JP6959644B2 - Electrophoresis fully automatic processing device and its method - Google Patents

Description

The present invention relates to a fully automatic electrophoresis processing device and a method thereof.

In recent years, capillary sequencing by the dideoxy method is often used to determine the base sequence of nucleic acids (DNA, RNA, etc.) and fragments thereof (oligonucleotides, nucleotides, etc.). In this method, four ordinary DNA synthesis systems are prepared, and low-concentration strand-stop nucleotides (terminators) are added thereto for reaction. As the terminator, only one of each of the four types of dideoxynucleotides (ddATP, ddGTP, ddCTP, ddTTP) is used. DNA polymerase synthesizes DNA while incorporating the deoxyribonucleotide corresponding to the template sequence, but sometimes the reaction stops there by incorporating the corresponding terminator. As a result, DNA fragments of various lengths corresponding to the base of the terminator used will be randomly generated. For example, in a system in which ddATP is added as a terminator, the base at the 3'end of the resulting DNA fragment becomes adenine. As a result, it is not necessary to simply synthesize DNA at the beginning, and the sequence can be properly determined with only four reaction systems.

In this method, DNA fragments of various lengths containing labeled dideoxynucleotides and the like are prepared by binding various dyes. This is done by separating the labeled DNA fragment with a gel-filled electrophoresis capillary and detecting the label to sequence four bases (A, C, G, T) (A, C, G, T). Sanger method: die terminator sequencing).

However, conventionally, the extraction process of nucleic acid from a sample, the synthesis process and amplification process of a fragment using a primer, DNA polymerase, and labeled dideoxynucleotide as a pretreatment for applying the extracted nucleic acid to a sequencer, and the labeled fragment. The electrophoresis process, the quality evaluation process of the product in each of these processes, and the sequencer process are performed by another dedicated device.

However, when analyzing such a base sequence, a highly accurate amplification process is required using the nucleic acid to be analyzed, the chemical substance to be used, and the produced product. In particular, since a nucleic acid other than the target nucleic acid is mixed, an erroneous conclusion may be drawn by amplifying the nucleic acid, or the target nucleic acid may be repeated many times from the beginning to the amplification after the amplification process. In order to analyze the base sequence of Nucleic Acid, it is particularly necessary for the success of the analysis to randomly divide the nucleic acid or a fragment thereof.

Therefore, in order to see whether the chemical substance solutions such as various biopolymers to be used, the target nucleic acid which is the extracted product, and the fragment of the target nucleic acid amplified for fragment production meet the processing purpose. Various physical chemical quantities, such as quantity, concentration, absorbance, viscosity, dispersibility, sedimentation rate, high, are manually extracted from the chemical solution to be used or the product extracted or fragmented. Molecular molecular weight, nucleic acid amplification amount, etc., or various physicochemical properties, for example, when measuring the presence or absence of the target nucleic acid or a fragment thereof, the amount thereof, etc., and determining the base sequence of the target nucleic acid, respectively. The measurement is performed by preparing an apparatus of the above, for example, an electrophoresis apparatus and the like. This is troublesome for the user, there is a risk of cross-contamination, and the current situation is that it requires researchers and technicians who are specialized in electrophoresis and nucleic acids, and doctors who are not specialized in this field. Etc. could not be easily used for clinical application.

For example, in order to measure the presence or absence or amount of the target nucleic acid labeled with a fluorescent substance, or the base sequence, it is necessary to receive the fluorescence generated by irradiating the excitation light as the measurement light. In this case, a solution of the target substance labeled with a fluorescent substance is placed in a temperature-controllable container by the PCR method, the solution is sealed with a translucent sealing lid or a sealing liquid, and then the sealing is performed. It is necessary to irradiate the excitation light through the lid or the sealing solution to receive the fluorescence.

Further, for example, in order to measure the absorbance of a chemical substance solution containing chemical substances such as various biopolymers such as nucleic acids and proteins, the target solution is contained in a quartz cell and placed on a predetermined side surface of the quartz cell. Light for measurement having a predetermined wavelength λ that can be vertically transmitted through the quartz cell and can be absorbed by the chemical substance (here, as light to be irradiated to the measurement target in order to obtain light to be detected. (For example, light for measuring absorbance, excitation light, etc.) is applied to measure the ratio (transmission) between the _{incident light intensity I 0 and the transmitted light intensity I, and A λ} = −log ₁₀ (I). Obtain the absorbance A _λ from / I _0).

In this case, as the light having a wavelength that can be absorbed by the nucleic acid, ultraviolet rays in the vicinity of 260 nm are used as the measurement light. This is because the bases constituting the nucleic acids of DNA, RNA and oligonucleotides have absorption peaks in the vicinity thereof. In general, in addition to nucleic acids, the absorbance of various biopolymer substances such as proteins, biological tissues, colloidal substances, aggregation of various substances, and various solutions (including suspensions) such as various solids is measured. In each case, measurement light having a suitable wavelength is required, and it is necessary to prepare a device capable of irradiating each dedicated measurement light.

By the way, when the measurement light used according to various measurement contents is irradiated or received from the outside such as a container containing a chemical substance solution to be measured, the measurement light passes through the wall, and the wall. Even if is a transparent member, the absorption of measurement light may not be negligible.

For example, when measuring the absorbance, glass, which is often used as a material for optical components, is special because its extinction coefficient increases remarkably in the wavelength region of ultraviolet rays and its transmittance decreases sharply, making it difficult to use. Dedicated optical components made of materials are used (for example, quartz glass [can be used at wavelengths of 200 nm and above], calcium fluoride, magnesium fluoride [can be used at 150 nm and above]), and cell containers made of these materials. The absorbance is measured by accommodating the solution to be measured inside and irradiating it with measurement light. However, not only are these materials expensive and can lead to increased manufacturing costs for the equipment, but when measured horizontally, the optical path length is limited to the distance between the opposite side walls of the container, and the top and bottom When measuring in the direction, there is a problem that the optical path length may be limited by the size of the container and the amount of liquid.

If the optical path length is limited, it may be difficult to obtain an appropriate optical path length and improve the measurement accuracy. For example, assuming that the intensity of the light for measurement is the same, if the solution to be measured has a low transmittance (high concentration), the optical path length is shortened, and if the transmittance is high (low concentration), the optical path length is short. The measurement accuracy can be improved by lengthening the length, and especially when the amount of the solution to be measured is small, the cell container for measurement cannot be filled and the specified optical path length cannot be obtained. There was a problem that there was a risk.

Therefore, in electrophoresis treatment such as nucleic acid sequencing treatment, extraction of the target substance from the sample, presence / absence of the extracted target substance, amount, presence / absence of processed target substance such as amplification, amount, labeling of the target substance, labeling of the target substance, It is necessary to master the labor of analysis by electrophoresis, for example, measurement of base sequence, the variety of devices used, specialized knowledge and techniques, and such things are, for example, genes using electrophoresis. It is supposed to hinder the generalization of analysis and the expansion of clinical application in hospitals and the like. Therefore, in clinical practice, it is possible to perform processing such as highly reliable and accurate nucleic acid amplification that prevents cross-contamination, reduces user's labor, and enables rapid and efficient electrophoresis processing. is important. Furthermore, it is necessary to consistently automate the process from extraction of the target substance to processing such as amplification and measurement, and it is also important to reduce the size of the device and to provide an inexpensive and highly accurate device.

Japanese Unexamined Patent Publication No. 2012-068234 JP-A-11-162920 International release WO2012 / 036296 Japanese Unexamined Patent Publication No. 2004-205415

Therefore, the present invention has been made to solve the above problems, and the first object thereof is electricity in which analysis of a target substance (for example, analysis of the base sequence of a target nucleic acid) is performed by capillary electrophoresis. When performing electrophoresis treatment (including sequence processing) in clinical practice, etc., cross-contamination is prevented and the user's labor is reduced, and the target substance (for example, target nucleic acid) is extracted from the sample, labeled, and labeled. Processing (for example, fragmentation and amplification of nucleic acid) and analysis of the target substance (for example, determination of the base sequence of nucleic acid) are consistently automated, and processing is executed quickly and efficiently without the intervention of the user. It is to provide a fully automated electrophoresis processing apparatus or a method thereof.

The second purpose is to evaluate the quality of the product and related chemical substances when analyzing the target substance using capillary electrophoresis, without using the same device manually or using other dedicated devices. By making it possible to do it using, it reduces the trouble of the user, prevents the invasion of foreign substances from the outside and contamination, uses highly reliable chemical substances, and has high quality. It is an object of the present invention to provide a fully automated electrophoresis processing apparatus and a method thereof capable of obtaining a product and performing highly accurate analysis of a target substance.

The third purpose is to incorporate not only a dispensing device but also a processing device for chemical substances such as a nucleic acid amplification device based on the PCR method, a dedicated device for capillary electrophoresis, a control unit and an optical measuring device, and to incorporate parts, instruments and mechanisms. It is an object of the present invention to provide a fully automatic electrophoresis processing apparatus and a method thereof that can be efficiently processed and inexpensively manufactured and used without expanding the scale of the apparatus by being commonly used.

The fourth purpose is to perform high-precision analysis in spite of quick and efficient processing by enabling some or all of a plurality of types of target substances to be processed in parallel and with high accuracy. It is to provide a fully automatic electrophoresis processing apparatus capable of performing the above and a method thereof.

The first invention comprises a capillary electrophoresis unit which has a plurality of electrophoresis capillaries and allows a target substance to be electrophoresed in the capillary by applying a voltage, and an extraction process of the target substance from a sample. Electricity that enables the electrophoretic sample containing the target substance obtained through the processing of the substance and the quality evaluation of the product or chemical substance related to each treatment to be supplied to each of the capillaries of the capillary electrophoresis unit. Any one of at least one selected from the group consisting of the migration pretreatment unit, the measurement of light for each of the capillarys of the electrophoresis unit, and the measurement of light for the quality evaluation of the electrophoresis pretreatment unit. An optical selective measurement unit that enables light measurement, and a control unit that controls the extraction process of the target substance from the sample, the processing process of the target substance, the analysis process of the target substance, and the quality evaluation. Yes, and the light selection measurement unit photometric content or the product or each set of irradiation end is the end of the plurality of light guide capable of irradiating a measuring light determined by the chemical containing the target substance A plurality of sets of irradiation ends, and a plurality of sets that are located or positionably provided at a position corresponding to the irradiation end set and capable of receiving light generated based on the measurement light emitted from the irradiation end. When there are a plurality of sets of light-receiving end sets each having a light-receiving end, which is one end of each of the light guide paths, and an instruction for analysis processing or quality evaluation of a target substance by the control unit, the plurality of sets of irradiation ends. A pair of irradiation end sets and a set of light receiving end sets are selected from the set and a plurality of sets of light receiving end sets, and for each irradiation light receiving pair consisting of the corresponding pair of irradiation ends and light receiving ends, said sequential supplies a predetermined measurement light to the irradiation end, is an electrophoretic fully automatic processing apparatus for chromatic and illumination light receiving pair selecting measuring unit for measuring the intensity of light successively received by said light receiving end.

Here, the "capillary for electrophoresis" is a capillary tube used in capillary electrophoresis, and "capillary electrophoresis" has various separation methods, and the present invention can be applied to any of the separation methods. .. The separation method includes, for example, (1) a method in which a buffer solution is filled in a capillary and a sample is injected from one end (free zone electrophoresis method). (2) When multiple electrically neutral components are present in the sample, they are taken into an SDS micelle using an anionic surfactant called sodium dodecyl sulfate (SDS) and moved (electrodynamics). Chromatography method). (3) A method of forming polyacrylamide gel in the capillary. Alternatively, a method using a polymer solution (gel electrophoresis method). (4) The capillary is filled with a mixture of an amphoteric electrolyte having various isoelectric points and a sample, the positive electrode is immersed in an acid, and the acid is more acidic than the one having the lowest isoelectric point among the amphoteric electrolytes. The negative electrode is filled with a base, and the base is stronger than the amphoteric electrolyte having the highest isoelectric point (isoelectric point method). (5) A method in which a medium containing ions that electrophores faster than any of the components at the front end of the sample mixture, a medium having the opposite character at the rear end, and the sample solution are electrophoresed at an intermediate setting between the two (constant velocity electrophoresis). Migration method) and so on. The "electrophoretic capillary" is a sample for electrophoresis containing a buffer solution in which both ends of the capillary are inserted into a pair of liquid accommodating portions (for example, a movable fluid accommodating portion and a post-electrophoretic accommodating portion, which will be described later). It is immersed and electrophoresed by applying a high voltage of, for example, 10 to 30 kV. During the electrophoresis, the sample is gradually separated while moving in the capillary, and the sample content is detected in a cell provided in the middle of the capillary. The inner diameter of the capillary is 100 μ \ ochm or less, for example 50 μ \ ochm. The pitch between adjacent capillaries is, for example, 18 mm. The length of the capillary is, for example, about 80 cm. Capillaries are made of, for example, silica or glass.

The "target substance" is mainly a nucleic acid or a part thereof, but also includes other biochemical substances such as proteins, amino acids, sugar chains, and fats. The "processing process of the target substance" is a process of processing the target substance so as to be suitable for electrophoresis, for example, mixing of the target substance and the buffer solution, fragmentation processing when the target substance is nucleic acid or the like, and amplification processing. , Labeling processing, etc. The "capillary electrophoresis section" is provided with, for example, an electrophoresis capillary filled with a plurality of gels, one end of which is provided in each moving fluid storage section, and the other end is inserted into the post-migration storage section. One of the electrode pairs (negative electrode, positive electrode pair or cathode, anode) is provided in each accommodating portion, and a predetermined voltage is applied between the electrode pairs, and a fluorescent substance is used in the electrophoresis capillary. A labeled target substance or a fragment thereof, for example, a DNA fragment (electrophoretic sample) is run, and the base sequence is analyzed from the position of the fragment or the order of electrophoresis according to the size of the molecular weight. Since the electrophoresis sample is, for example, a mixture of phosphors corresponding to four types (A, C, G, T) of bases, measurement is performed by, for example, simultaneously detecting light having four wavelengths (for example). Sanger method). The "measurement of light with respect to the capillary" includes a case where the light is measured on the side wall of the capillary and a case where the light is measured on the side wall of the post-electrophoresis accommodating portion. Here, the "electrophoretic sample" is a sample supplied to an electrophoresis capillary, and is a target substance or a processed target substance for electrophoresis, a reagent required for the processing, or electrophoresis. It contains a reagent or a buffer solution necessary for the above.

For example, in "fragment generation", heat is applied to a fragment of the target nucleic acid to be sequenced to denature it from double-stranded to single-stranded, and further, it is low in template DNA, primers, DNA synthase, and nucleotides. By reacting in four reaction vessels to which one of the four concentrations of chain-stopping nucleotides (terminators) is added, fragments stopped at random lengths A, C, G, and T are produced (. Sanger method).

"Quality evaluation" is an evaluation of the quality of a product or a chemical substance used as a result of processing such as extraction treatment, fragment formation treatment, and amplification treatment, thereby finally performing quality evaluation. By ensuring that the results obtained are reliable, or by ascertaining which process was erroneous, the cause can be more easily identified and the product obtained as a result of the process or process. Quality can be improved.

Quality evaluation is performed, for example, by using the optical selective measurement unit to evaluate the molecular weight or concentration of the obtained target substance, for example, nucleic acid or a fragment thereof, in a flow tube, a capillary for electrophoresis, a reaction vessel or after migration. This is done by measuring the optical condition inside the housing. For example, the range of molecular weight is analyzed, the base sequence is analyzed, and the concentration of the nucleic acid or a fragment thereof is measured by photo-measuring the amplified amount or the absorbance of the nucleic acid. Quality assessments include, for example, detection or quantitative measurement of products, biochemicals, or measurement of concentration or absorbance of biochemical solutions. In addition, the "measurement" may include a colorimetric method, a turbidity method, and the like. Further, the "measurement" includes measurement of temporal changes such as the amount of amplification, the amount of biochemical substance, the amount of reaction, the concentration, or the absorbance, such as real-time PCR, enzyme activity, or reaction rate. Sometimes.
"Physical and chemical properties" means, for example, identification of a product or chemical substance to be measured, presence / absence of a target substance (target nucleic acid), identification of a product or structure of a chemical substance, base sequence, molecular structure, presence / absence of virus. , Presence or absence of bacteria, immunoassay, etc.
The "physicochemical value" is, for example, a chemical substance solution amount, a chemical substance amount, a concentration, an absorbance, a molecular weight, or the like.

The "optical state" includes light emission, coloration, discoloration, and light change, and the "variable light" includes reflection, absorption, and scattering of light.

The “chemical substance” corresponds to a substance used in a chemical reaction, in particular, a genetic substance such as a nucleic acid, a protein such as an immune substance, a saccharide, or a biochemical substance such as a peptide.

The "nucleic acid amplification method" includes, for example, PCR (polymerase chain reaction) method, LAMP (loop-mediated isothermal amplification) method, LCR (ligase chain reaction) method, SDA (strand displacement amplification) method, MTD (transcription mediated amplification). There are laws, etc. The "nucleic acid detection method" may detect a target nucleic acid using complementarity.

The "control unit" includes a computer (CPU) built in the fully automatic electrophoresis processing device, a program for driving the computer, and the like, and includes, for example, an input device such as a memory, a display device, a keyboard, a touch panel, and a mouse. Then, the signal is transmitted through the DA converter and the AD converter to the suction / discharge mechanism, the nozzle moving mechanism, the electrophoresis preprocessing unit having the nozzle head, the light source, the photoelectric conversion unit, the electrophoresis unit, etc., which will be described later. Is exchanged for control.

Here, the amount of the chemical substance solution that is sucked and held in the flow tube or contained in the photometric container is preferably a predetermined amount. "Light received at the light receiving end" means "light generated by irradiating the measurement light through the flow tube or the photometric container in the vertical direction, or in the flow tube or the photometric container. Is, for example, transmitted light, scattered light, or light related to light emission, color development, discoloration, or photometry of the chemical substance solution.

By deriving the absorbance from the intensity of the transmitted light of the chemical substance solution to be measured, for example, the control unit can obtain various physical quantities based on the absorbance and analyze the chemical substance solution.
For example, in order to analyze the concentration of various chemical substances (nucleic acid, lipid, protein, sugar, etc.), the concentration of the solution is derived from the absorbance as shown below based on Lambert-Beer's law.

The intensity of the measurement light (wavelength λ) before it is incident on the chemical substance solution in the flow tube is I ₀ , the intensity of the light after transmission is I, and the molar extinction coefficient (the wavelength λ and the chemistry to be measured). the normalized) in units molar concentration determined in accordance with the substance epsilon, if the final molar concentration to determine c, and optical path length is L, the ^{_{I = I 0 · 10 (-εcL}} ). On the other hand, from the relationship of _{absorbance A λ} = −log ₁₀ (I / I _0),
By determining the absorbance A _λ and therefore the transmittance I / I ₀ , the molar concentration c of the nucleic acid or the like contained in the solution can be determined from the following relational expression.
A _λ = εcL (1)
In reality, the measurement light does not travel in parallel as it is due to scattering or reflection, so it is preferable to correct this formula by using a calibration curve or a calibration formula in order to improve the accuracy.

If the chemical substance (sample) to be measured reacts with various enzymes (AST, ALT, lipase, LDH, γ \ och-GTP, etc.) and its concentration changes, the chemical substance solution permeates. The enzyme activity can be analyzed based on the absorbance derived from light.
The reaction rate, that is, the rate of change in the concentration of the chemical substance, dc / dt (concentration: the rate of change in mol / liter) is used to determine the enzymatic activity. Is expressed by the _{change in absorbance (dA λ} / dt) per unit time of the change in absorbance. That is,
dc / dt = (dA _λ / dt) · (1 / εL) (2).
ε is, for example, 6300 liters / (mol · cm) for NADH (nicotinamide adenine dinucleotide).
Then, the enzyme activity is expressed as follows. That is,
Enzyme activity = (dc / dt) · (V _t / V _s ) (3)
V _t = total volume (liter) of the chemical substance solution
V _s = sample capacity (liter)
Therefore, by substituting Eq. (3) into Eq. (2),
Enzyme activity = (dA _λ / dt) · V _t / (εLV _s ) (4).
However, the unit of enzyme is defined as 1U (Unit), which is the amount of enzyme that can convert 1 μ \ ochmol of substrate per minute in 1 liter of sample under the optimum conditions. , 1 U / liter, and is expressed by the following equation, which is a modification of the above equation (4).
Enzyme activity (U / liter) = ΔA _λ・ (V _t・ 10 ⁶ ) / (εLV _s )
ΔA _λ : Change in absorbance per minute
V _t : Total reactant capacity (m liter)
V _s : Sample capacity (m liter)
ε: Molar absorbance (liter / (mol · cm))
L: Optical path length (cm)
Is.

Further, the control unit measures the concentration of an unknown chemical substance solution (sample) and the absorbance of a substance (standard solution) having a known concentration, and creates a calibration curve showing the relationship between the concentration and the absorbance in a graph or table. back. Using the calibration curve or table, the concentration can be determined from the absorbance of an unknown chemical substance solution.

Here, for a certain chemical substance solution (A1), the corresponding absorbance for measurement light having a wavelength suitable for the measurement is A ₁ , the extinction coefficient is ε ₁ , and the concentration of the chemical substance is c ₁ . Regarding the internal standard (A0), the corresponding absorbance for standard measurement light having a wavelength suitable for the measurement is A ₀ , the extinction coefficient is ε ₀ , and the specified concentration of the internal standard is c ₀ . Further, assuming that the optical path length when the mixture is mixed in the flow tube and sucked is L (common as a mixed solution), the following equations can be obtained from Lambert-Beer's law.
A ₁ = ε ₁ c ₁ L
A ₀ = ε ₀ c ₀ L
When the optical path length is eliminated from these equations, the concentration c _{1 can be obtained from c 1} = (A ₁ ε ₀ c ₀ ) / (A ₀ ε ₁ ), and it is not affected by the variable optical path length. It is possible to obtain a highly reliable concentration based on the relative ratio to the internal standard.

In addition, the control unit can perform quantitative measurement of immune antibody (CPR, FDP, D-dimer, etc.). For the measurement of hemoglobin and the like in the sample, the antibody is fixed to the latex particles made of resin by using the antigen-antibody reaction, and the antigen-antibody reaction is caused with the antigen in the sample to aggregate the latex particles. If this agglutination reaction is regarded as a change in absorbance, the amount of change in absorbance increases depending on the amount of antigen in the sample. If a calibration curve is prepared using this standard solution having a known concentration, the amount of antigen in the sample can be measured from the amount of change in absorbance.

The control unit obtains the absorbance of the one or two or more types of chemical substances based on the one or two or more types of transmitted light, and based on the absorbance, the concentration of the one or two or more types of chemical substances, etc. Can be sought. Similarly, the physicochemical properties or numerical values of the one or more kinds of chemical substance solutions can be obtained based on the one or more kinds of transmitted light, scattered light and the like.

Before Symbol light selecting measuring unit has an irradiation end is the product or the one end of the plurality of light guide capable of irradiating a measuring light determined by the chemical containing photometric content or the target substance each set A plurality of sets of irradiation end sets and a plurality of sets of irradiation end sets and a plurality of sets that are positioned or positionably provided at positions corresponding to the irradiation end sets and capable of receiving light generated based on the measurement light emitted from the irradiation ends. A plurality of sets of light receiving ends having light receiving ends, which are one end of each light guide path, and the plurality of sets of irradiation end sets when the control unit gives an instruction for analysis processing or quality evaluation of a target substance. And a pair of irradiation end sets and a set of light receiving end sets are selected from a plurality of sets of light receiving end sets, and the irradiation is performed for each irradiation light receiving pair consisting of the corresponding pair of irradiation ends and light receiving ends. This is a fully automatic electrophoresis processing device having an irradiation light receiving pair selective measuring unit that sequentially supplies predetermined measurement light to the ends and measures the intensity of the light sequentially received by the light receiving ends.

"Measurement light" is light emitted to measure the physicochemical properties or numerical values of the chemical substance solution to be measured, and the measurement content (for example, the presence or absence of a labeling substance) and the size of the chemical substance or product. It is light having a wavelength corresponding to the molecular weight and the like. For example, in the case of measuring absorbance, in the case of nucleic acids such as DNA, RNA, and oligonucleotides, ultraviolet light near 260 nm is appropriate. This is because the base of the nucleic acid has an absorption peak near this (A: 259 nm, T: 267 nm, G: 253 nm, C: 267 nm). The value of absorption will be affected by the structure (single-stranded, double-stranded), length, and base composition of the nucleic acid. For other substances, for example, white light is used. When a fluorescent substance is used as the labeling substance, it is excitation light having a wavelength corresponding to the fluorescence. The "irradiation end (or light receiving end)" is an end portion of a light guide path capable of irradiating (or receiving) light, and may have an optical element such as a lens. The "light guide path" is a passage capable of guiding light, and is formed in an elongated shape along the light guide direction. It is a fiber.

Here, the “plurality” is, for example, the case (n) which is the same as the “plurality”, that is, the number (n) of the electrophoresis capillaries. Including the number of accommodating unit groups described later, the number of nozzles, and the number of accommodating unit rows belonging to all accommodating unit groups, the case is not necessarily limited to n, and in the case of a multiple of the number of capillaries, for example, 2n, It may be 3n or the like. This is because many types of reagents may be used for pretreatment or complicated treatment may be performed.

The "irradiation end set (light receiving end set)" is a set including the plurality of irradiation ends (or light receiving ends). In the present invention, a plurality of sets of each of these irradiation end sets and light receiving end sets are included. At that time, the number of irradiation end sets and the number of light receiving end sets do not always match. Therefore, the selection of the pair of irradiation end sets and the light receiving end sets may be duplicated when the number of sets is small. In "selection", for example, only the light source that emits the corresponding measurement light is turned on and the other light sources are turned off, or the light guide path connecting the light source and the irradiation end is set to the light guide state. By putting the light guide path connected to other light sources in a non-light guide state, and by turning on only the photoelectric conversion unit that receives the corresponding light and turning off the other photoelectric conversion units. Alternatively, the light guide path connecting the photoelectric conversion unit and the light receiving end is placed in a light guide state, and the light guide path connected to the other photoelectric conversion unit is in a non-light guide state.

In the second invention, the irradiation / light receiving pair selective measuring unit emits one or two or more light sources that emit a predetermined measurement light selected according to the instruction, and one or two or more light sources that convert the received light into an electric signal. Two or more photoelectric conversion units, and one or two or more irradiation end sets and one or more light receiving end sets are selected from a plurality of irradiation end sets and a plurality of light receiving end sets based on the above instructions. A connection or cutoff between the light source and an irradiation end belonging to the selected irradiation end set, and a connection or disconnection between one or more of the photoelectric conversion units and a light receiving end belonging to the selected light receiving end set. This is a fully automatic electrophoresis processing device having a pair selection interlocking switching unit that switches the cutoff in conjunction with each irradiation / light receiving pair.

Since it is a "one or two or more light sources", one or two or more irradiation measurement ends, which will be described later, are provided to be optically connected to these. Since it is a "one or two or more photoelectric conversion units", one or two or more light receiving measurement ends described later are provided which are optically connected to these. “Switching” refers to, for example, relative movement at a predetermined speed, for example, reciprocating motion or oscillating, along a predetermined direction between a plurality of pairs of end-set arrangements described below and a plurality of pairs of measurement end-set arrangements described below. It is repeated at a predetermined cycle according to.
Here, the “1 light source” is, for example, a white light light source that irradiates measurement light of white light (including ultraviolet rays) having a wavelength in the range of 220 to 350 nm, and the “2 or more light sources” is, for example, , 6 types of variable light sources set so as to be able to irradiate 6 types of excitation light (for example, 496 nm, 527 nm, 555 nm, 587 nm, 593 nm, 647 nm). On the other hand, the "1 photoelectric conversion unit" is, for example, a photoelectric conversion unit provided via a spectroscope, and the "2 or more photoelectric conversion units" is, for example, a plurality of bandpass filters (for example, 517 nm). , 549nm, 580nm, 599nm, 613nm, 653nm, these wavelengths correspond to fluorescent materials, FAM, HEX, TAMURA, ROX, Texas Red, Cy5). Is.

Further, as the "light source", for example, an LED, a deuterium lamp (for example, Hamamatsu Photonics Co., Ltd., L10691D), a halogen lamp, or the like is used, and a continuous wavelength from the ultraviolet region to the visible region is used. Can be irradiated on the sample. The "photomultiplier conversion unit" converts the intensity of light into a corresponding electric signal and digital signal, and is, for example, a PMT (photomultiplier tube) with amplification, an ADP, a CCD image sensor, a photodiode, or the like. It is a light receiving element.

In the third invention, in the irradiation light receiving pair selective measurement unit, the irradiation connection end of each of the other ends of the plurality of light guide paths, each of which has one irradiation end whose one end belongs to the irradiation end set, is provided. The plurality of irradiation connection ends to which the plurality of light receiving connections belong, and the plurality of light receiving connection ends to which the other end of each of the plurality of light guide paths having one light receiving end having one light receiving end belonging to the light receiving end set belong to the plurality of light receiving connection ends. There are a plurality of light receiving connection end sets, and the irradiation connection ends or the light receiving connection ends belonging to the same set are arranged in a row at predetermined intervals along a predetermined direction and belong to different sets that can be paired. The irradiation connection end or the light receiving connection end further has a plurality of pair connection end array having a connection end arrangement surface arranged in parallel at intervals along a direction orthogonal to the predetermined direction. The pair selection interlocking switching unit is optically connected to the light source that can be turned on and off, and one or two or more irradiation measurement ends provided so as to be sequentially connectable to the irradiation connection ends belonging to the irradiation connection end set are in the predetermined direction. It is optically connected to a plurality of sets of irradiation measurement ends provided in a row at predetermined intervals along the above, and the photoelectric conversion unit that can be turned on and off, and sequentially connected to the light receiving connection ends belonging to the light receiving connection end set. The above-mentioned is The plurality of pairs of measurement end set arrays having measurement end array surfaces arranged at intervals, and the connection end array surface and the measurement end array surface facing each other and sliding along the predetermined direction. The multiple-pair connection end-set array and the multiple-pair measurement end-set array are relatively moved to simultaneously connect the selected irradiation connection end and light-receiving connection end to the irradiation measurement end and light-receiving measurement end. Alternatively, for each irradiation-receiving pair of selected pairs, the connection or blocking between the irradiation end and the light source in the ON state is connected to the photoelectric conversion unit in which the light-receiving end and the light-receiving end are in the ON state. It is a fully automatic electrophoresis processing device that has a switching mechanism that is sequentially performed in conjunction with connection and disconnection.

In this case, the connection end arrangement surface of the plurality of pairs of connection end set array may be one plane, one curved surface, or multiple planes or multiple curved surfaces. Each of the irradiation connection ends is arranged in a row along a predetermined direction (for example, in the horizontal direction or in the column direction (Y-axis direction) or row direction (X-axis direction) of a plurality of accommodating portions arranged in a matrix. The irradiation connection ends of the above are arranged, and each of the light receiving connection end sets is arranged with a plurality of light receiving connection ends in a row along the predetermined direction, so that they are parallel to each other and orthogonal to the predetermined direction. (For example, in the vertical direction (Z-axis direction) or in the row direction (X-axis direction) or column direction (Y-axis direction) of the plurality of accommodating portions arranged in the matrix) in parallel with each other at a predetermined distance. They are arranged (examples of a predetermined direction and a direction orthogonal to the predetermined direction can be interchanged with each other). At that time, the irradiation end belonging to the irradiation connection end set and the light receiving end belonging to the light receiving connection end set that can be paired are described above. They are arranged at intervals along the directions orthogonal to the predetermined direction. At that time, when there are a plurality of irradiation connection end sets and light receiving connection end sets that can be paired, when they are arranged in parallel in the orthogonal directions. Therefore, when either the irradiation connection end set or the light receiving connection end set is common, the pair spacing needs to be different. It is also possible to arrange them in series with the same pair spacing.

On the other hand, the measurement end array surface of the plurality of pairs of measurement end set array may be one plane, one curved surface, multiple planes, or multiple curved surfaces (for example, a divisible plane). In that case, the plurality of pairs of irradiation connection ends, the plurality of pairs of irradiation measurement ends connected to the plurality of light sources to be connected to the light receiving connection set, and the light receiving measurement ends connected to the plurality of photoelectric conversion units to be connected are used. Each set is arranged in a single column along the predetermined direction (for example, the column direction (Y-axis direction) or the row direction (X-axis direction) of a plurality of accommodating units arranged in a horizontal direction or a matrix) ( The irradiation measurement end set and the light reception measurement end set, which can be paired with each other when there is only one, are arranged in a direction orthogonal to the predetermined direction (for example, in the vertical direction (Z-axis direction) or in the matrix shape). The plurality of housing units arranged are arranged at positions corresponding to each pair along the row direction (X-axis direction) or the column direction (Y-axis direction) with the pair spacing in the connection end arrangement surface. (Examples of a predetermined direction and a direction orthogonal to it can be interchanged).

When the array planes are arranged in a divisible manner, the one including the corresponding pair of light sources 84 and the photoelectric conversion unit 83 (paired end body) can be divided into units. Is preferable. Each of these divided array planes is formed by a combination of divisible paired measurement end sets, and each divided array can be arbitrarily inserted and removed for each paired measurement end according to the processing content. As described above, the pair spacing between the plurality of pairs of the irradiation connection end set and the light receiving connection end set on the connection end arrangement surface and the corresponding plurality of pairs of the irradiation measurement ends on the measurement end arrangement surface. The pair spacing between the set and the light receiving measurement end set is provided to be equal. Here, the "pair spacing" is the spacing between the irradiation connection end set and the light receiving connection end set that can be paired on the connection end array surface in the direction orthogonal to the predetermined direction, or the irradiation measurement end set that can be paired. And the distance on the measurement end array surface in the direction orthogonal to the predetermined direction between the light receiving measurement end set and the pair spacing on the corresponding connection end array surface and the pair spacing on the measurement end array surface are equal. .. Here, the paired measurement end body is housed in, for example, a frame body capable of connecting and accommodating a plurality of the paired measurement end bodies in order to form the paired measurement end assembly array. Further, in order to form the plurality of pairs of measurement end arrays 811, for example, the plurality of pairs of measurement end arrays or the pair of measurement ends are housed in a frame capable of accommodating the plurality of pairs of measurement ends.

The "single row" is preferably a straight line when the arrangement surface is a flat surface, for example. The relative movement directions of the plurality of pairs of connection end sets and the plurality of pairs of measurement end sets are in the direction along the connection end rows of each set and the measurement end rows of each set, that is, in the predetermined direction. It is relatively movable along, and the first connection end row and the first measurement end row overlap, and the second connection end row and the second measurement end row overlap and switch. They are arranged so that they are linked by movement. In this case, since each switching of one or two or more irradiation / light receiving pairs can be shared by the switching mechanism of 1, it is possible to prevent the expansion of the scale of the apparatus. Here, "on (state)" means an active state and a state in which a circuit is established in an electric circuit, and "off (state)" means an inactive state and a state in which an electric circuit is established. say.

According to a fourth aspect of the present invention, the electrophoresis pretreatment unit communicates with a suction / discharge mechanism for sucking and discharging a gas, and a plurality of nozzles and the nozzles to which a flow tube capable of sucking and discharging a liquid is detachably attached. A magnetic part that can apply and remove a magnetic field from the outside to the flow tube attached to the flow tube, a liquid storage part that houses various chemical substance solutions including a sample to be inspected and a magnetic particle suspension, and a temperature. A stage having at least each reaction vessel whose temperature can be controlled by an elevator and having a plurality of groups of accommodating units provided corresponding to each nozzle, and the nozzle and the stage can be relatively moved. The first set of one of the irradiation end set and the light receiving end set of the light selection measuring unit is provided in the nozzle or the suction / discharge mechanism, and the second set of the one is provided. The irradiation end set and the other first set of the light receiving end set are paired with the one first set so as to be provided in contact with or close to the outer surface of the electrophoretic capillary or the post-migration accommodating portion. The other second set is provided in the nozzle or suction / discharge mechanism, and contacts or contacts the outer surface of each electrophoresis capillary or the post-migration accommodating portion so as to be paired with the one second set. It is a fully automatic electrophoresis processing device installed in close proximity.

The suction / discharge mechanism, the nozzle, and the magnetic force portion are preferably provided on the nozzle head. In this case, the nozzle moving mechanism, for example, in a stage where the stage and the nozzle head are fixed, when only the nozzle is moved with respect to the stage, the nozzle fixed to the nozzle head is ejected to the stage. When moving relative to the head, the nozzle may be provided so as to be relatively movable with respect to the nozzle head, and the nozzle head may be made movable relative to the stage.

It is preferable that the stage is provided with a chip accommodating portion for accommodating the flow pipe with the mounting opening facing upward so that the flow pipe can be mounted on the nozzle by lowering the nozzle by the nozzle moving mechanism. Further, it is preferable to provide a reaction vessel capable of temperature control in addition to the liquid accommodating portion. It is preferable that the control unit controls the nozzle moving mechanism so that the flow pipe is attached to the nozzle by the relative descent of the nozzle. In this case, it is preferable that the nozzle head is provided with a detachable mechanism for detaching the flow pipe from the nozzle by controlling the nozzle moving mechanism. As a result, cross-contamination can be prevented and a flow tube suitable for the amount of liquid to be measured can be used by attaching / detaching the flow tube or the like without human intervention.

Here, "relative" indicates that it holds in relation to other objects to be compared. Therefore, in the case of "relative movement", when one of the objects (for example, a nozzle) is moving and the other of the objects (for example, a stage) is stationary, one of the objects is stationary and the object is stationary. There are cases where the other moves, or both (when the speeds are different).

"Magnetic particles" are magnetic particles, the size of which is, for example, about 1 nm to several tens of μ \ ochm. The size, mass, material, structure (single domain, surface coated with various coating substances, etc.), its properties (paramagnetism, superparamagnetism, ferromagnetism, ferrimagnetism, etc., magnitude of magnetic force), etc. are processed. It can be determined according to the purpose. Coating materials include organic substances that give rise to various functional groups, ionic substances that give rise to ions, and surface stabilizers that prevent aggregation and precipitation due to magnetic fields (aliphatic gee, polycarboxylic acids and their substitution products and derivatives. Etc.), specific binding substances (ligants, receptors, etc.), medicinal active substances, etc.

The first set of one of a plurality of pairs of irradiation end sets or light receiving end sets is provided on the nozzle or suction / discharge mechanism, that is, the nozzle head, and the second set of the one is provided on the electrophoresis capillary or the post-electrophoresis accommodating portion. The other first set of the plurality of pairs of irradiation end sets or light receiving end sets is provided in the nozzle or suction / discharge mechanism, and the other second set is provided in the electrophoresis capillary or the post-electrophoresis accommodating portion. ing. However, the light source or photoelectric conversion unit does not necessarily have to be provided in the same nozzle head, stage, or capillary unit as the irradiation end or the light receiving end. When the first set of one is paired with the first set of the other, it is not necessary to attach a flow pipe to the nozzle. In that case, the nozzle has a suction / discharge mechanism such as a cylinder. Will not need to communicate. Here, the “plurality” of the “plurality of nozzles” or the “plurality of accommodating portions” is, for example, the same as the number (n) of the plurality of nozzles corresponding to the plurality of nozzles, that is, the number (n) of the electrophoresis capillaries (n). ), Or in the case of a multiple of the number of the capillaries (particularly in the case of the number of nozzles or the number of rows of accommodating parts), for example, 2n, 3n and the like. This is because many types of reagents may be used for pretreatment or complicated treatment may be performed.

The "flow pipe" is a tubular member having the mouth portion at the lower end and a mounting opening at the upper end which is detachably attached to the nozzle. The flow tube is formed to be thinner than the nozzle having a mouth at the tip and accommodating the chemical substance solution to be measured, and thicker than the thin tube communicating with the thin tube and having the mounting opening. It is preferably a chip-shaped container having a thick tube. The flow tube having a thin tube formed thinner than a nozzle has a cross-sectional shape and size through which the measurement light can pass. For example, the internal space of the flow tube has a cylindrical shape with a circular cross section. For example, the inner diameter thereof is 0.05 mm to 10 mm, preferably 0.1 mm to 5 mm, and more preferably about 0.5 mm to 1 mm. The size and shape of this cross section are determined based on the shape or size of the irradiation end and the light receiving end. As a result, it has an axial or vertical length in which the optical path length can be set according to the chemical substance solution having a small liquid volume (for example, about 0.1 μ \ ochL to 10 μ \ ochL). In addition, the internal space of the flow pipe may be truncated cone-shaped or prismatic.

The flow tube is a flow tube for dispensing that agitates the liquid in one liquid storage part, moves the liquid between a plurality of liquid storage parts, and dispenses by sucking and discharging the liquid, and the solution sucked inside. It contains a flow tube for measuring light in which the intensity of transmitted light along the vertical direction is measured. For the photometric flow tube, for example, it is preferable that the side wall portion is formed of a black substance as a light-shielding member or a translucent material is applied with a black paint to block external light. "External light" is mainly visible light or ultraviolet light, and when it is formed of a black substance, it is formed by kneading a black pigment into a resin and molding it. The flow tube for dispensing or the flow tube for minute amount dispensing and the flow tube for metering may be used together, or they may be formed as different ones. Since the flow tube is detachably attached to the nozzle, a attachment / detachment mechanism for attaching / detaching the flow tube from the nozzle is provided, for example, in the nozzle head described later. The irradiation end set and the light receiving end set may be provided only in a part of a plurality of nozzles or a multiple of the nozzles or a suction / discharge mechanism. For example, it may be provided only in the nozzle or the suction / discharge mechanism at intervals of the second pitch (a pitch that is a plurality of times the first pitch of the nozzle). The flow pipe may also be attached to a part of the nozzle. For example, it is a case where it is mounted only on the nozzles at the interval of the second pitch. This is because in the arrangement of the accommodating units of the accommodating unit group, the accommodating unit for measuring light, the reaction vessel, and the measurement area are concentrated in the accommodating unit row corresponding to the nozzle, and exist in the accommodating unit row corresponding to other nozzles. This is a case where it does not occur, and it depends on the arrangement of the housing.

The fifth invention further comprises the other third set of the irradiation end set and the light receiving end set, and the other third set is outside the flow tube, and the mouth portion of the flow tube is the same. It is a fully automatic electrophoresis processing device that can be positioned upward and can be paired with the first set of the one.

In this case, the other third set may be provided in the light receiving region of the stage or may be provided at the bottom of the photometric container provided on the stage. The photometric container has a cylindrical recess formed at substantially the center of the bottom of the photometric container, the lower end of the photometric flow tube can be inserted or loosely inserted from above, and the transparent container has a tubular recess. It is preferable that the light region is formed in the narrow bottom portion of the recess, and the narrow side wall portion of the recess is formed so as to block light from the external light.
Since the mouth of the flow tube can be inserted into the "light measuring container", the cross section thereof is larger than the cross section of the thin tube of the flow tube, and when measuring a chemical substance solution having a small amount of liquid, It is more appropriate to suck and hold the chemical substance solution in a flow tube having a smaller cross section according to the amount of liquid and the content of measurement by using the suction and discharge mechanism, rather than storing the chemical substance solution in a light measuring container. The optical path length can be set, which is preferable in terms of photometric measurement.

In this case, the entire optical path passing through the chemical substance solution to be measured can be shielded from light, and external light can be prevented from entering the optical path to perform highly accurate measurement. The recess is formed in a thin cylinder shape having an opening having a cross-sectional area sufficiently smaller than the opening of the photometric container to the extent that the lower end of the flow tube can be inserted or loosely inserted. Here, it is preferable that the narrow bottom portion of the recess is optically connected to the light receiving end surface of the light receiving end in close contact with or in close contact with each other without an air layer. As a result, the optical path length can be set from the upper end surface of the liquid contained in the flow tube to the light receiving end without going through the air layer. The "substantially center" is preferably the "center".

The photometric container is formed, for example, with a cylindrical thick cylinder portion that can be fitted under the closed lid (the upper side can be fitted to the nozzle) and a thinner cylinder portion than the thick cylinder portion (hence, the nozzle). A thin cylinder having a cylindrical shape with a flat bottom in the horizontal direction on the inside and outside at the lower end, and a thick cylinder that communicates with the thick cylinder and the thin cylinder and is sandwiched between them. It has a tapered middle portion formed so as to have an inner diameter and an outer diameter intermediate between the portion and the thin cylinder portion. In the intermediate portion, a cylindrical receiving portion for fitting and receiving the sealing portion of the sealing lid is formed near the center thereof. The outer diameter of the thin cylinder portion is, for example, 3.0 mm, the inner diameter is 2.5 mm, and the thickness of the bottom portion of the thin cylinder portion is, for example, 0.5 mm. As a result, the measurement light emitted from the irradiation end described later in the axial direction of the thin cylinder portion of the photometric reaction vessel is surely transmitted through the bottom portion, and the air layer is formed by the light receiving end described later which is in close contact with the bottom portion on the lower side. It is possible to reliably receive the transmitted light without going through. In addition, since the chemical substance solution is housed in a thin cylinder having a cross section that allows the light for measurement to pass through, the amount of liquid required for measurement is suppressed, and light measurement of a small volume of liquid is possible.
Further, an appropriate optical path length can be set according to the amount of liquid contained within the range of the vertical length of the thin cylinder portion, and for measurement without contacting the irradiation end and the light receiving end with the solution. It can irradiate and receive light, prevents cross-contamination, and is highly reliable.

In addition, the control unit may control the chemical substance solution to be sucked above the position separated from the mouth of the flow pipe by a certain interval. This makes it possible to prevent liquid leakage from the mouth at the lower end of the flow tube, stabilize the optical path length, and obtain highly accurate physicochemical properties or numerical values (for example, absorbance). In addition, the optical path in the flow tube along the vertical common axis connecting the irradiation end and the light receiving end includes the wall of the flow tube and is not blocked by substances other than the chemical substance solution and air. Including, it is not necessary to form a substance that is transparent to the measurement light, and it is possible to measure physicochemical properties or numerical values (for example, absorbance) at low cost and with high accuracy.

Here, for example, in a flow tube having a total length of about 3 cm to 20 cm, the fixed interval is, for example, 0.5 mm to 10 mm, preferably 1 mm to 5 mm, and the portion containing the chemical substance solution or the mixed solution is For example, it is 1 mm to 15 mm. As a result, it is possible to prevent liquid leakage from the mouth of the flow tube, stabilize the optical path length, and obtain various numerical values or properties including highly reliable absorbance and concentration.

In addition, for example, a plurality of liquid storage units capable of accommodating a chemical substance solution, an extraction reagent, an amplification reagent, a labeling reagent such as a fluorescent substance or a chemiluminescent substance, or a reagent such as an enzyme, and 1 or 2 having temperature controllability. The above reaction container or the photometric container is provided in a cartridge container formed in a single row and arranged in a single row or in a plurality of rows, and is arranged in a substantially rectangular substrate of the cartridge container in the longitudinal direction thereof. It is preferable that a partition wall having a predetermined height is formed on one side of the edge. The partition wall is for preventing the mixing of droplets of reagents and the like from other cartridge containers when a plurality of the cartridge containers are used side by side. The length of the substrate in the longitudinal direction of the cartridge container is, for example, 150 mm to 200 mm.

In the sixth invention, when the control unit instructs the measurement of the presence or absence or amount of the target substance labeled with a fluorescent substance in the product or chemical substance solution, the product or chemical substance solution is instructed. The nozzle is moved to the accommodating portion in which the is housed, and the pair selection interlocking switching unit is the first set of one of the irradiation end set and the light receiving end set, and the irradiation end set and the light receiving end set. In the other first set, a pair of the irradiation measurement end set and the light reception measurement end set that can be connected to the irradiation end and the light receiving end to which they belong are selected, and 1 or 2 belonging to the selected irradiation measurement end set. Only one or more light sources that use excitation light of one or more kinds of wavelengths optically connected to the above irradiation measurement end as measurement light are turned on, and one or one or one or a plurality of light receiving measurement ends belonging to the selected light receiving measurement end set. Only the photoelectric conversion unit via the bandpass filter that can pass the fluorescence excited by the excitation light that is optically connected to the plurality of light receiving measurement ends is turned on, and the irradiation end and the light receiving end, the irradiation measuring end, and the light receiving light are turned on. The connection and disconnection between the measurement end and the measurement end are sequentially switched, and when the control unit instructs the analysis process using the electrophoresis of the target substance, the electrophoresis sample is accommodated. One end of each of the electrophoresis capillaries is inserted into each movable liquid accommodating portion, and the pair selection interlocking switching portion is the second set of one of the irradiation end set and the light receiving end set, and the irradiation end set. And a pair of the irradiation measurement end set and the light receiving measurement end set that can be connected to the irradiation end and the light receiving end to which they belong are selected as the other second set of the light receiving end set, and the selected irradiation measurement end set is selected. Only one or more kinds of excitation light having one or more kinds of wavelengths optically connected to one or more irradiation measurement ends belonging to the above, or one or more kinds of light sources using white light as measurement light are turned on and selected. Only the photoelectric conversion unit or the spectrophotometer via the bandpass filter capable of passing the fluorescence excited by the excitation light, which is optically connected to one or more light receiving measurement ends belonging to the light receiving measurement end set, is turned on. This is a fully automatic electrophoresis processing device that sequentially switches the connection and disconnection between the irradiation end and the light receiving end and the irradiation measurement end and the light receiving measurement end.

The "first set of one of the irradiation end set and the light receiving end set" and the "first set of the other of the irradiation end set and the light receiving end set" are "irradiation end set" and "light receiving end set" (in no particular order). The two are paired with the nozzle or the suction / discharge mechanism, for example, the lower end of the nozzle, the lower end of the plunger sliding in the cylinder of the suction / discharge mechanism provided above the nozzle, or the nozzle. It is a concave portion, a convex portion, or the like provided, and is provided with the irradiation end face or the light receiving end face facing downward. It is mainly used for the measurement of qPCR. When analyzing the base sequence using electrophoresis, it is preferable to irradiate four types of excitation light in order to measure four types of fluorescence corresponding to the bases A, C, G, and T. Therefore, for example, four types of light sources are used. The case where the absorbance of the electrophoresis capillary is measured is, for example, the case where the measurement is performed separately based on the size of the protein.

The "second set of one of the irradiation end set and the light receiving end set" and the "second set of the other of the irradiation end set and the light receiving end set" are "irradiation end set" and "light receiving end set" (in no particular order). Both are provided as a pair in close proximity to or in contact with the outer surface of each of the plurality of electrophoresis capillaries or post-electrophoretic accommodating portions. It is mainly used for analysis of a target substance by an electrophoresis unit, for example, for determining the base sequence of a target nucleic acid.

The "first set of one of the irradiation end set and the light receiving end set" and the "third set of the other of the irradiation end set and the light receiving end set" are either "irradiation end set" or "light receiving end set". One is the nozzle or the suction / discharge mechanism, for example, the lower end of the nozzle, the lower end of a plunger that slides in the cylinder of the suction / discharge mechanism provided on the upper side of the nozzle, or a concave or convex portion provided on the nozzle. A portion or the like, which is provided with the irradiation end face or the light receiving end face facing downward, and the other of the “irradiation end set” or the “light receiving end set” is directly connected to the stage or transparent to the light measuring container of the accommodating part group. A plurality of light regions are arranged at a second pitch on the bottom surface, and the irradiation end face or the light receiving end face is provided with the irradiation end face or the light receiving end face facing upward. It is mainly used when the control unit instructs the measurement of the absorbance of the product or chemical substance solution.

In order to enable measurement of absorbance or concentration, at least one of the one or more light sources is further connected via a white light source that emits white light as measurement light and one spectroscope. A plurality of photoelectric conversion units are provided. When the measurement of the absorbance or concentration of the product or chemical substance solution is instructed, a flow tube having a mouth at the lower end is attached to the nozzle so as to be removable, and the product or chemical to be measured is to be measured. The substance solution is sucked into the flow tube and stored and held, or stored and held in a light measuring container, and the pair selection interlocking switching unit is the first set of one of the irradiation end set and the light receiving end set, and the irradiation. The irradiation measurement end and the light reception measurement end that can be connected to the irradiation end and the light reception end to which they belong are selected for the other first set of the end set and the light receiving end set, and optically with the selected irradiation measurement end. The connected white light source is turned on, the photoelectric conversion unit connected to one spectroscope optically connected to the selected light receiving measurement end is turned on, and the irradiation end, the light receiving end, and the irradiation are turned on. The connection and disconnection between the measurement end and the light receiving measurement end are sequentially switched in conjunction with each other. It is preferable to use it by the control unit or in a state where there is a vertical line that commonly passes through the end face of the irradiation end belonging to the irradiation light receiving pair and the end face of the light receiving end, that is, a vertical common axis. .. Further, it is preferable that the vertical common axis passes through the mouth of the flow pipe mounted on the nozzle. By providing any one of the irradiation light receiving pairs on the vertical common axis of at least one nozzle or the flow tube of the suction discharge mechanism and providing the other on the stage, the nozzle moving mechanism described later is used. Since the light receiving end and the irradiation end can be easily and surely positioned on the vertical common axis, the irradiation of the measurement light can be easily and surely performed along the vertical common axis direction of the flow tube. .. The "vertical direction" is the direction when the flow pipe is attached to the nozzle, and preferably corresponds to the direction along the vertical common axis of the flow pipe or the suction / discharge direction of the flow pipe.

More preferably, the "one of the irradiation / light receiving pairs" (element) provided in the nozzle or the suction / discharge mechanism is the "irradiation end", and the "other of the irradiation / light receiving pairs" is the "light receiving end". As a result, the measurement light emitted from the irradiation edge is more reliably irradiated to the chemical substance solution than when it is irradiated upward from the mouth or bottom, and the entire amount or the main part of the light passes through the flow tube. Can be made to. In particular, when the flow pipe is formed to be tapered like a chip-shaped container, the degree is high.

According to the seventh invention, in the electrophoresis pretreatment unit, the nozzles are provided so as to be movable only in the column direction and the vertical direction, and are arranged in a row at the first pitch along the row direction. Each of the accommodating portions is provided so as to extend in a row or a plurality of rows along the column direction and arranged at a second pitch along the row direction, and in the capillary electrophoresis section, the electricity is provided. The electrophoresis capillary extends along the column direction and is provided arranged in the row direction at a third pitch, and is attached to one or more groups of nozzles arranged at the second pitch among the nozzles. A group of movable fluid accommodating portions composed of the plurality of movable fluid accommodating portions arranged in a row at a variable pitch along the row direction so that a plurality of flow tubes can be inserted into each accommodating portion all at once. Alternatively, a variable pitch liquid accommodating pedestal in which a plurality of groups of the movable liquid accommodating portions are provided in parallel at intervals in the column direction, and the pedestal is placed along the row direction at each of the first pitches or in the electrophoresis pretreatment. A gantry moving unit provided so as to move between the unit and the capillary electrophoresis unit, and a pitch conversion mechanism provided so that the variable pitch can be converted between the second pitch and the third pitch. One end of the electrophoresis capillary is a fully automatic electrophoresis processing device provided so as to be able to be inserted into a plurality of movable fluid accommodating portions belonging to one group of movable fluid accommodating portions all at once.

Here, the "column direction" and the "row direction" are two directions orthogonal to each other along the arrangement direction when the accommodating portions of the accommodating portion group are arranged in a matrix on a horizontal plane, for example, a Cartesian coordinate system. (X, Y, Z) in the Y-axis direction and the X-axis direction. In this case, the Z-axis direction is the vertical direction orthogonal to the stage. "Pitch" refers to the distance between the centers of the arranged elements when the same or different elements (eg, container, well, liquid reservoir, nozzle, etc.) are arranged at equal intervals.
The "first pitch" is the pitch in which the nozzles are arranged, the distance between one row of housing units belonging to each storage unit group, and the distance at which the variable-pitch liquid storage stand can move. Corresponds to one of. The "second pitch" is the same as the first pitch or is a plurality of times the first pitch, and the "plurality" of a plurality of times is equal to the number of rows of the accommodation unit row belonging to the accommodation unit group. Further, it is the same as the number of groups of the movable liquid accommodating portion group of the variable pitch liquid accommodating stand. The case where the second pitch is equal to the first pitch is the case where each of the accommodating portions extends in a row along the row direction, and the flow pipes of the group mounted on the nozzle are all at once. This is a case where each accommodating portion is provided so as to be insertable. When the second pitch is a plurality of times the first pitch, the number of rows of each containment group is multiple, so that many reagents and reaction vessels are used to increase the length of each row of the containment group. Since it can be accommodated without any need, the stage and therefore the device scale can be compactly formed. In this case, the arrangement of each row is not the same, but it has 1 flow tube accommodating part and 1 liquid accommodating part or 1 reaction vessel. In this case, the flow tubes and the sealing lids may be arranged in the accommodating section row in a row or (plural-1) rows so as to have a plurality of groups of flow tubes and sealing lids arranged at the second pitch. Yes (see Figures 1 and 4).

The "third pitch" is generally different from the "second pitch". The number of flow tubes arranged at the "second pitch" is preferably equal to the number of the electrophoresis capillaries. Then, the total number of nozzles is one or more times the number of accommodating unit groups, and each accommodating unit group is provided with one or a plurality of accommodating unit rows at the first pitch. For example, the second pitch is 44 mm and the third pitch is 18 mm.

In each of the housing units, it is not necessary to provide an irradiation end and a light receiving end for the nozzle group corresponding to the storage unit row in which the light measurement is not performed.
When the nozzle moving mechanism is provided so as to be movable only in the column direction and the vertical direction, a cross-sectional nozzle having one nozzle movable only in the row direction and the vertical direction is provided from the common accommodation area. It is preferable that each of the housing groups is supplied with a commonly used reagent that is independent of the sample and is supplied to the reaction vessel. As a result, the number of reagents stored in the stage in advance can be reduced, and the stage can be formed compactly. Further, in the variable pitch liquid accommodating stand, it is preferable that the movable liquid accommodating portions are arranged in parallel at intervals along a direction orthogonal to the arrangement direction of the movable liquid accommodating portions.

The eighth invention is a capillary electrophoresis step in which a target substance is electrophoresed by applying a voltage into a plurality of electrophoresis capillaries, an extraction process and a processing process of the target substance from a sample, and each process. Used in the electrophoresis pretreatment step and the electrophoresis step of making it possible to supply an electrophoresis sample containing the target substance obtained through quality evaluation of the product or chemical substance to each of the electrophoresis capillaries. A light selective measurement step that enables any at least one measurement to be performed by selecting from a group consisting of light measurements for each capillary and light measurements for the quality evaluation in the electrophoresis pretreatment step. When the analyzing step to analyze the quality evaluation and objective substance for each process, it has a, the light selection measuring step, the measurement light is determined by the product or the chemical containing photometric content or the target substance A plurality of sets of irradiation end sets having an irradiation end, which is one end of each of the plurality of irradiation paths, in each set, and an irradiation end set located at a position corresponding to the irradiation end set or provided so as to be positioned. A plurality of sets of light-receiving end sets having a light-receiving end, which is one end of each of a plurality of light guide paths capable of receiving light generated based on the measurement light emitted from the light guide path, are provided. When an instruction for analysis processing or quality evaluation based on electrophoresis is given, a pair of irradiation end sets and a set of light receiving ends are paired from the plurality of sets of irradiation end sets and multiple sets of light receiving end sets. A set is selected, and a predetermined measurement light is sequentially supplied to the irradiation end for each irradiation light receiving pair consisting of the corresponding pair of irradiation ends and the light receiving ends, and the intensity of the light sequentially received by the light receiving ends is measured. it is an electrophoretic fully automatic processing method for chromatic illumination light receiving pair selection measuring step for.

In the ninth invention, in the irradiation / light receiving pair selection measurement step, a pair of irradiation end sets and a light receiving end set are selected from a plurality of sets of irradiation end sets and a plurality of sets of light receiving end sets based on the above instructions. Then, the connection or blocking between one or two or more light sources that emit a predetermined measurement light selected according to the instruction and the irradiation end belonging to the selected irradiation end set, and the received light are electrophoresed. A pair selection interlocking switching step of interlocking and switching between one or two or more photoelectric conversion units that convert signals and a light receiving end belonging to the selected light receiving end set for each irradiation light receiving pair. This is a fully automatic electrophoresis processing method.

According to a tenth invention, in the pair selection interlocking switching step, the irradiation connection end of each of the other ends of the plurality of light guide paths having one irradiation end having one irradiation end belonging to the irradiation end group is the irradiation connection end. A plurality of irradiation connection ends and a light receiving end to which each of the other ends of the plurality of light guide paths having one light receiving end having one light receiving end belonging to the light receiving end set belong to the plurality of light receiving connections. There are a plurality of connection end sets, and the irradiation connection ends or the light receiving connection ends belonging to the same set are arranged in a row at predetermined intervals along a predetermined direction, and belong to different sets that can be paired. The irradiation connection end or the light receiving connection end can be turned on and off with a plurality of pair connection end array having a connection end array surface arranged in parallel with a pair spacing along a direction orthogonal to the predetermined direction. One or two or more irradiation measurement ends that are optically connected to the light source and are provided so as to be sequentially connectable to the irradiation connection ends belonging to the irradiation connection end set are provided in a row at predetermined intervals along the predetermined direction. 1. A plurality of sets of light receiving measurement end sets, each of which is provided in a row at predetermined intervals along the predetermined direction, are arranged with the pair spacing along the direction orthogonal to the predetermined direction. The irradiation of the selected irradiation ends by relatively moving the plurality of pairs of measurement end array having the above-mentioned The connection end and the light receiving connection end and the irradiation measurement end and the light receiving measurement end are connected or disconnected in conjunction with each other, and each pair of the irradiation end and the light receiving end of the selected pair is turned on with the irradiation end. This is a fully automatic electrophoresis processing method in which the connection with the light source is cut off in sequence in conjunction with the connection and cutoff between the light receiving end and the photoelectric conversion unit in the ON state.

According to the eleventh invention, the electrophoresis pretreatment step communicates with a suction / discharge mechanism for sucking and discharging a gas, and a plurality of nozzles and the nozzles to which a flow tube capable of sucking and discharging a liquid is detachably attached. The flow tube mounted on the is provided with a magnetic force portion capable of applying and removing a magnetic field from the outside, and a liquid storage portion for accommodating various chemical substance solutions including a sample to be inspected and a magnetic particle suspension. And a stage having at least each reaction vessel whose temperature can be controlled by a temperature evaporator and having a plurality of groups of accommodating portions provided corresponding to each nozzle, and a relative between the nozzle and the stage. The light selective measurement step includes a moving nozzle moving step, in which the first set of one of the irradiation end set and the light receiving end set is provided on the nozzle or the suction / discharge mechanism, and the second set of the one is provided. The irradiation end set and the other first set of the light receiving end set are paired with the one first set, which is provided in contact with or close to the electrophoretic capillary or the outer surface of each post-electrophoresis accommodating portion. As described above in the nozzle or suction / discharge mechanism, the other second set contacts or contacts the outer surface of the electrophoresis capillary or the post-electrophoresis accommodating portion so as to be paired with the one second set. This is a fully automatic electrophoresis processing method in which measurements are taken by being provided close to each other. Here, "plurality" preferably corresponds to the plurality of pieces.

In the twelfth invention, the light selective measurement step further includes the other third set of the irradiation end set and the light receiving end set, and the other third set is outside the flow tube. This is a fully automatic electrophoresis processing method in which the mouth of the flow pipe can be positioned above the mouth of the flow pipe and the measurement is performed so as to form a pair with the first set of the one.

In a thirteenth invention, the optical selective measurement step is instructed to measure the presence or absence or amount of a fluorescent substance-labeled target substance in the product or chemical solution, if the product or chemical is instructed to measure the presence or absence of the target substance. After moving the nozzle to the accommodating portion in which the substance solution is contained, the first set of one of the irradiation end set and the light receiving end set, and the other first set of the irradiation end set and the light receiving end set. A pair of the irradiation measurement end set and the light reception measurement end set that can be connected to the irradiation end and the light receiving end to which each belongs is selected, and one or two or more irradiation measurements belonging to the selected irradiation measurement end set are selected. Only one or two or more light sources whose measurement light is excitation light of one or more kinds of wavelengths optically connected to the end is turned on, and one or two or more light receivers belonging to the selected light receiving measurement end set are turned on. Only the photoelectric conversion unit is turned on via a bandpass filter that can pass fluorescence excited by the excitation light that is optically connected to the measurement end, and the irradiation end and the light receiving end and the irradiation measurement end and the light receiving measurement end are turned on. It has a pair-selection interlocking switching step that sequentially switches the connection and disconnection between the two, and when instructed to perform an analysis process by electrophoresis of the target substance, the electrophoretic sample is accommodated. After inserting one end of the electrophoretic capillary into the movable liquid accommodating portion, the second set of one of the irradiation end set and the light receiving end set, and the other second set of the irradiation end set and the light receiving end set. For the two sets, a pair of the irradiation measurement end set and the light receiving measurement end set that can be connected to the irradiation end and the light receiving end to which they belong are selected, and one or more irradiation measurement ends belonging to the selected irradiation measurement end set are selected. Only one or more types of light sources that are optically connected to one or more kinds of excitation light or white light as measurement light are turned on, and one or more members belong to the selected light receiving measurement end group. Only the photoelectric conversion unit or the spectrophotometer via the bandpass filter capable of passing the fluorescence excited by the excitation light, which is optically connected to the light receiving measurement end of the above, is turned on, and the irradiation end and the light receiving end and the irradiation measurement are performed. This is a fully automatic electrophoresis processing method having a pair-selection interlocking switching step of sequentially switching the connection and disconnection between the end and the light receiving measurement end.

In the fourteenth invention, in the electrophoresis pretreatment step, the nozzles are provided in a row in a row along the row direction at a first pitch, and can move only in the column direction and the vertical direction. Each of the accommodating portions is arranged in a row or a plurality of columns along the column direction and at a second pitch corresponding to the first pitch or a plurality of times thereof along the row direction. A variable-pitch liquid storage stand provided with one group or a plurality of groups of movable liquid storage parts composed of the plurality of movable liquid storage parts arranged in a row or a plurality of rows at a second pitch along the row direction. In addition, the flow tubes mounted on the plurality of nozzles arranged at the second pitch discharge and accommodate the moving fluid in a group of the moving fluid accommodating portions, and the gantry is accommodated along the row direction of the first group. It is moved pitch by pitch or to the capillary electrophoresis section, and the capillary electrophoresis step converts the second pitch of each movable liquid storage section of the variable pitch liquid storage stand into a third pitch, and the electrical conduction This is a fully automatic electrophoresis processing method in which one end of a capillary is inserted and a predetermined voltage is applied between the ends of the capillary to perform electrophoresis of a target substance contained in the electrophoresis sample.

According to the first invention or the eighth invention, when performing capillary electrophoresis processing including analysis of the base sequence of a target nucleic acid in clinical practice or the like, cross-contamination is prevented and the user's labor is reduced. , From extraction of target substance (for example, target nucleic acid) from sample to processing such as labeling, fragmentation, amplification, and analysis using electrophoresis of target substance (for example, determination of base sequence). It can be automated and the process can be executed quickly and efficiently without the intervention of the user. In addition, the quality evaluation of the product and related chemical substances when performing analysis using electrophoresis of the target substance (for example, analysis of the base sequence of the target nucleic acid) can be performed manually or according to the content to be measured. By eliminating the need to use a dedicated device and making it possible to use the same device, the user's labor is reduced, and foreign matter from the outside and contamination are reliably prevented. It is possible to use highly reliable chemical substances, obtain high-quality products, and perform highly accurate electrophoretic analysis of the target substances. Furthermore, by incorporating not only a dispensing device but also a nucleic acid amplification device based on the PCR method, a dedicated electrophoresis device, a control unit and an optical measuring device (optical selective measuring unit), and by using parts, instruments and mechanisms in common. It can be processed efficiently and can be manufactured and used at low cost without expanding the scale of the apparatus.

Using multiple sets of light guide assembly, a plurality of sets of irradiation end sets having an illumination end or receiving end which is one end portion of each light guide in each set, or located at a position corresponding to the irradiation end group or A nozzle in which a storage unit or a flow tube containing a product or chemical substance to be analyzed or quality evaluated by electrophoresis of a target substance is mounted on a plurality of sets of light receiving ends that are provided so as to be positioned. Alternatively, by providing the suction / discharge mechanism, the position on the stage, the measuring container, the capillary for electrophoresis, or the side wall of the accommodating portion after electrophoresis, the light for measurement is supplied and received through the light guide path, thereby performing various situations. By concentrating the optical measurement for the object in the above on one common optical measuring instrument, the same operation can be performed compactly, easily, and efficiently and reliably without expanding or complicating the scale of the apparatus. ..

According to the second invention or the ninth invention, a pair of irradiation end sets and light receiving end sets are selected from a plurality of sets of irradiation end sets and a plurality of sets of light receiving end sets, and are selected according to instructions. Each pair of irradiation end and light receiving end belonging to each set, the corresponding light source, and the corresponding photoelectric conversion unit are connected and cut off in conjunction with each other. Therefore, it is highly versatile because it is possible to perform various measurements on one chemical substance solution by combining various light sources or blocking from the light sources and various photoelectric conversion units. In addition, since multiple types of measurements can be performed simultaneously for a plurality of chemical substance solutions, the efficiency is high, and since it is not necessary to provide a light source or a photoelectric conversion unit for each of a plurality of chemical substance solutions, the scale of the device It is possible to prevent the expansion of the manufacturing cost and the increase of the manufacturing cost.

According to the third or tenth invention, the connection and disconnection of a large number of irradiation ends and one or more light sources and the connection and disconnection of a large number of light receiving ends and one or more photoelectric conversion units are performed. Since it can be realized by moving along a relative straight line between the multiple pair connection end set array and the multiple pair measurement end set array by the common interlocking switching mechanism, the sample to be subjected to multiple electrophoresis processing. Since the analysis process of the target substance and the quality evaluation of the product or chemical substance solution can be performed simultaneously and simultaneously with one device, it is possible to prevent the expansion of the device scale and the increase in the number of parts, and the efficiency. Will be high. Further, the irradiation connection end set and the light receiving connection end set which can be a pair arranged in the plurality of pair connection end set array, and the irradiation measurement end which can be a pair provided in the multiple pair measurement set array which slides facing the same. Since the sets and the light receiving measurement end sets are arranged along the row direction and the column direction, it is easy to expand by adding them and shrink by reducing them according to the user's needs, and it is highly flexible.

According to the fourth or eleventh invention, the nozzle or suction / discharge mechanism provided in the apparatus, the capillary for electrophoresis is provided with a pair of irradiation end set and light receiving end set, respectively, and they are used as a light guide path. Are arranged in a row along a predetermined direction as an irradiation connection end set and a light receiving end set so that they can be connected and blocked at the same time as a pair on a plurality of pairs of connection end sets of the optical selection measurement unit. By arranging them at predetermined intervals in the orthogonal directions, it is possible to reliably and easily connect to the light source and the photoelectric conversion part by linear motion, so that not only the base sequence of the target nucleic acid can be analyzed but also its quality. Since the evaluation can be performed by one device, the entire device is compact and highly efficient.

By providing an irradiation end or a light receiving end for the nozzle or suction / discharge mechanism without changing its basic form and basic function, a nozzle, suction / discharge mechanism or special parts dedicated to photometric processing can be provided separately from the dispensing process. Using the same nozzle and suction / discharge mechanism as the normal dispensing process without providing and without interfering with the suction / discharge function, the normal dispensing process and photometric processing can be performed by attaching a flow tube to the nozzle. Since it can be performed, processing is easy and work efficiency is high.

According to the fifth or twelfth invention, a liquid required for measurement is obtained by holding or accommodating a chemical substance solution in a flow tube or a light measuring container in a columnar shape having a cross section that allows measurement light to pass through. It suppresses the amount and enables measurement of physicochemical properties or numerical values (for example, absorbance) for a small volume of liquid. In addition, since the measurement light is not blocked by the flow tube for accommodating the chemical substance solution or the light measurement flow tube having a translucent region, the optical influence on the measurement light can be eliminated or reduced to achieve highly accurate physical chemistry. Physical properties or numerical values (eg, absorbance) can be obtained. In addition, since the light for measurement is not blocked by the translucent region of the flow tube or the light measurement container, it is inexpensive without using a flow tube or a light measurement container manufactured only with a special material according to the type of measurement light. A member that is opaque to the measuring light (for example, a black substance) can be used for the flow tube or the measuring container to prevent the ingress of light from the outside and have highly accurate physicochemical properties or numerical values (for example). For example, the concentration) can be measured. Here, the term "thin columnar" means, for example, that the nozzle is formed thinner than the cross section of the nozzle, and is formed by accommodating and holding the liquid in the flow tube or the photometric container.

An appropriate optical path length (for example, in the case of transmitted light or scattered light) can be set according to the amount of the sucked liquid within the range of the length in the vertical direction of the flow tube, and the irradiation end and the light receiving end can be regarded as a solution. The measurement light can be irradiated and received without contact. Therefore, it is highly reliable by preventing cross-contamination due to contact between the light receiving end and the irradiation end and the solution, and the optical path length is not fixed by the size of the container, and an appropriate optical path length is set according to the amount of liquid. It is highly versatile because it can measure physicochemical properties or numerical values (for example, absorbance) according to various liquid volumes.

Further, by using a highly quantitative suction / discharge mechanism and a control unit, the optical path length can be accurately determined and stabilized, and highly reliable measurement can be performed.
Further, by using a plurality of nozzles, it is possible to measure the properties or numerical values of a plurality of chemical substance solutions in parallel, and to sequentially measure various properties or numerical values for one chemical substance solution. Is possible and highly efficient.

According to the sixth or thirteenth invention, a plurality of pairs of irradiation end set and light receiving end set, one or more light sources capable of emitting one or more kinds of excitation light or white light, and one or more applicable light sources. Connecting and blocking with one or more photoelectric converters or spectrophotometers via a type of fluorescence bandpass filter is performed in conjunction with each selected pair of irradiated end sets and light receiving end sets. The presence or absence or amount of the target substance labeled with one or more fluorescent substances for multiple product or chemical solutions containing the target substance, or the presence or absence of the target substance using absorbance. It is highly versatile because it can easily and efficiently correspond to various capillary electrophoresis methods by using a pair selection interlocking switching device or process of 1.

According to the seventh invention or the fourteenth invention, the movable liquid storage unit group consisting of the plurality of movable liquid storage parts arranged at the second pitch is one group or a plurality of groups (for example, orthogonal to the arrangement direction). (Arranged at intervals in the direction) is provided on the variable pitch liquid accommodating pedestal, and the electrophoresis sample produced by the electrophoresis pretreatment unit is accommodated in one group thereof, and the variable pitch liquid accommodating pedestal is electrophoresed. A position where one end of a plurality of rows of electrophoresis capillaries arranged at a third pitch is securely inserted and brought into contact with each of the movable fluid accommodating portions belonging to the first group of movable fluid accommodating portions. Can be moved to. Therefore, the process in the electrophoresis unit can be reliably, smoothly, and quickly executed without human intervention. Further, with respect to the other movable liquid accommodating portions, the movable liquid accommodating portions arranged at the second pitch are aligned in the row direction of a certain accommodating portion row of each accommodating portion group, and then the gantry is placed. By moving at each first pitch, it becomes possible to move the liquid between the accommodation unit rows belonging to each accommodation unit group using the flow pipe attached to the nozzle. Therefore, by moving the variable-pitch liquid accommodating pedestal without using the nozzle head moving mechanism or the crossing head, the accommodating portions arranged in the row direction at the first pitch of the same accommodating portion group can be moved. The liquid can be moved efficiently with a simple mechanism without expanding the scale of the device.

It is a block diagram which shows the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention. It is a perspective view which shows the state which the moving liquid accommodating part is located in the electrophoresis pre-processing part in the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention. It is a perspective view which shows the state in which the moving liquid accommodating part is located in the capillary electrophoresis part in the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention. It is a top view which mainly shows the stage and the variable pitch liquid accommodating stand of the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention. It is a side view which shows the variable pitch liquid accommodating stand which concerns on embodiment of this invention. It is a side view of the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention, and a partially enlarged perspective view thereof. It is a perspective view which shows the installation place of the light selection measurement part of the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention. It is a figure which shows the whole picture of the optical selective measurement part which concerns on 1st Example of Embodiment of this invention. It is sectional drawing which shows the pair of irradiation ends and light receiving ends of the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention. It is a flow chart which shows the electrophoresis fully automatic processing method which concerns on 1st Example of Embodiment of this invention. It is a graph which shows the amplification by the PCR method using the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention. It is a figure which shows the whole picture of the light selective measurement part which concerns on the 2nd Example which concerns on embodiment of this invention. It is a figure and the graph which shows the measurement of the absorbance using the light selective measurement part which concerns on the 2nd Example of the Embodiment of this invention. It is a graph which shows the analysis of the base sequence using the electrophoresis fully automatic processing apparatus which concerns on embodiment of this invention.

The fully automatic electrophoresis processing apparatus 10 according to the embodiment of the present invention will be described with reference to FIG.
The electrophoresis fully automatic processing device 10 has a plurality of (n) electrophoresis capillaries filled with gel, and a voltage is applied to the inside of the capillaries to migrate the target substance in the capillaries. Enables the electrophoresis unit 5, extraction processing of the target substance from a plurality of types of samples, processing processing of the target substance (for example, generation and amplification processing of a fragment of the target nucleic acid), and a product or chemical substance in each treatment. Pretreatment units 3 and 4 for supplying a plurality of types of electrophoresis samples (for example, a plurality of types of electrophoresis samples containing the fragment) obtained through the quality evaluation of the above to the electrophoresis unit, and the above-mentioned Arbitrary at least one measurement selected from the group consisting of the measurement of light in each of the capillaries of the electrophoresis unit 5 and the measurement of light for the quality evaluation in each processing of the electrophoresis pretreatment unit. The optical selective measurement unit 8 capable of performing the above, the extraction process of the target substance from the sample, the processing process of the target substance (for example, the generation and amplification process of a fragment of the target nucleic acid), and the electrophoresis of the target substance. The CPU + program + memory 9 as a control unit that controls the analysis process used (for example, the analysis process of the base sequence of the target nucleic acid) and the quality evaluation of the product or the chemical substance solution in each process, and the CPU + program. + It has an operation panel 94 such as a touch-type tablet, a keyboard, and a switch that performs operations such as instructions from the user to the memory 9.

The electrophoresis pretreatment units 3 and 4 include one or more types of chemical substance solutions, a liquid storage unit for accommodating various reagents, a flow tube (for dispensing) 2 ₁ to 2 _n , 2 ₁ to 2 _n , and minute amounts. A flow tube accommodating section for accommodating a quantity (for dispensing) flow tube (also serving as a metering flow tube), a drilling tip, etc., and a container row containing one or more temperature-controllable reaction vessels. Each has said accommodating rows extending along the Y-axis direction (column direction) and arranged over two columns at intervals of the first pitch along the X-axis direction (row direction), and X. _{Stage 3 having a plurality of housing groups 3 1 to} 3 _n arranged at a second pitch (twice the first pitch) along the axial direction (row direction), and suction and discharge for sucking and discharging gas. _{Two nozzle groups 4 1 to 4 n} , which communicate with the mechanism 41 and the suction / discharge mechanism 41, are arranged along the X-axis direction at the first pitch, and are alternately arranged every other at the second pitch. 4 _'1-4' each belonging plurality of nozzles _n, and the nozzle head 4 having a nozzle support 44 in which the nozzles are supported said plurality of relatively movable nozzles of said plurality of relative to the stage 3 It has a nozzle moving mechanism (nozzle head moving mechanism 49 and nozzle Z-axis moving portion 42). Therefore, each of the two nozzle groups, 1 nozzle, corresponds to each of the accommodating unit groups 3 _{1 to} 3 _{n of 1.}

The chemical substance solution to be measured is, for example, a nucleic acid solution when the target substance is nucleic acid, and various reagents include, for example, a reagent for nucleic acid extraction, a reagent for nucleic acid amplification, a reagent for real-time PCR, and a labeling substance. , Various carrier suspensions containing magnetic particles. The flow tubes 2 _{1 to} 2 _n and 2 ₁ to 2 _n (see, for example, FIG. 13 (a)) are capable of sucking and discharging liquid at the lower end, and can be sucked and discharged in each housing of the housing group or in a reaction vessel (light measuring container). simultaneously insertable mouth portion 2a in the containing) has the nozzle group _{4 1 ~4 n, 4 '1} ~4' fitting opening 2b which is detachably attached to the _n to the upper end, the flow The tube may have a dispensing flow tube (dispensing tip) used for dispensing and a metering flow tube used for light measurement, or both may be used in combination with one type of flow tube.

In each of the storage unit groups 3 _{1 to} 3 _n of the stage 3, a sample (contained in the storage unit 35 in the sample region in the case described later), the one or two or more kinds of the chemical substance solutions, various reagents, etc. _{33 1 to} 33 _{n of} the liquid storage section, the dispensing flow tube used as the dispensing tip, the light measuring flow tube or the minute amount dispensing flow tube for measuring light, and the drilling tip are the nozzle group. _{4 1 ~4 n, 4 '1} ~4' n can be mounted and made as the accommodating portion group of the fitting opening 2b is housed in the upper 31 ₁ to 31 _n, the reaction vessel capable of temperature control 32 _{1 to} 32 _n , 32'1 to 32'n (including a photometric vessel), and a sealed lid accommodating portion 34 _{1 to 34 n} that seals the reaction vessel during temperature control, but in this example, each accommodating unit. Each group is arranged in two rows. These sealing lids 34 are provided so as to be piercable by the piercing tip after mounting the reaction vessel. The stage 3 is provided with a temperature elevator 39 having a Perche element for temperature control, a heat block, and the like.

Hereinafter, in order to simplify the explanation, reference numerals 61 and 63 are used as irradiation end sets and reference numerals 71, 73 and 75 are used as light receiving end sets (for these, the irradiation end set and the light receiving end set can be interchanged). Is). These are the reaction vessels (including the photometric container) to be measured by light, and the accommodations in the first row of _{each accommodation group 3 1 to} 3 _{n provided with the light receiving end set 75 of the photometric region 38 described later.} parts provided in the nozzle group 4 ₁ to 4 _n corresponding to the columns, have is provided nozzle group 4 _'1 ~4' _n corresponding to the second row of the accommodating portion rows of the accommodation unit group 3 ₁ to 3 _n Suppose there is no. Then, the optical selective measurement unit 8 includes at least one (for light measurement) flow tube 2 ₁ to 2 _n , the reaction vessel 32 _{1 to} 32 _n (including the light measurement container), an electrophoresis capillary, or a post-migration storage unit. On the other hand, two sets of irradiation end sets 61, 63 _{consisting of two or more irradiation ends 61 1 to 61 n} and 63 _{1 to 63 n} capable of irradiating the one or two or more types of measurement light, and the irradiation end. _{61 1 ~61 n, 63 1 ~63} n it can receive light from two or more light receiving end _{71 1 ~71 n, 73 1 ~73} n, 75 1 ~75 n, 77 1 4 pair consisting to 77 _n When there is an instruction of analysis processing or quality evaluation using the electrophoretic electrophoresis of the target substance by the light receiving end sets 71, 73, 75, 77 of the above and the control unit (9), among the plurality of sets of irradiation end sets. One set of irradiation end sets is selected from the above and a predetermined measurement light is sequentially supplied, and one set of light receiving end sets is selected from the plurality of sets of light receiving end sets to form a pair of irradiation light receiving pairs. It has an irradiation / light receiving pair selective measurement unit 80 that sequentially measures the intensity of the light.

Here, the irradiation ends 61 _{1 to 61 n} of the irradiation end assembly 61 are provided in the nozzles 4 ₁ to 4 _n or the suction / discharge mechanism 44 _{1 to} 44 _{n, and the irradiation ends 63 1 to} 63 _{n of the} irradiation end assembly 63 are provided. Is provided in the electrophoresis capillary, and the light receiving ends 71 _{1 to 71 n of the} light receiving end set 71 are provided in the nozzles 4 ₁ to 4 _n or the suction and discharge mechanism 44 _{1 to} 44 _n, and the light receiving end set 71 is provided. The light receiving ends 73 _{1 to 73 n} of 73 are provided in the electrophoresis capillary or the post-electrophoresis accommodating portion, and the light receiving end set 75 is provided in the light measuring region 38 of the stage 3, and the light receiving ends 75 ₁ to 73 n are provided. The 75 _n are arranged at intervals according to the arrangement of the housing group 3 _{1 to} 3 _n. Each light receiving end 77 ₁ to 77 _n of the receiving end sets 77 are provided at the bottom of the metering container (32 ₁ ~32 _n).

Therefore, five pairs of irradiation end sets and light receiving end sets (61,71), (61,75), (61,77), (63,73) are formed. In the case of two pairs of irradiation end sets and light receiving end sets (61, 75) and (61, 77), the irradiation ends 61 _{1 to 61 n} and the light receiving ends 75 ₁ to 75 _n or the light receiving ends 77 _{1 to 77 n.} The pair with is preferably on a vertical common axis that commonly passes through the mouth portion 2a and the mounting opening 2b of the flow pipes 2 ₁ to 2 _{n mounted on the nozzles 4 1} to 4 _n. Further, wherein the metering container (32 ₁ ~32 _n), has a bottom translucent region of light-transmitting property with respect to the chemical solution or the like can accommodate the measuring light is formed. In this example, the irradiation end set 61 corresponds to the "first set of one of the irradiation end set and the light receiving end set", and the irradiation end set 63 is the first of the "irradiation end set and the light receiving end set". The light-receiving end set 71 corresponds to the other first set of the "irradiation end set and the light-receiving end set", and the light-receiving end set 73 corresponds to the other of the "irradiation end set and the light-receiving end set". The light receiving end set 75 or the light receiving end set 77 corresponds to the "second set of the irradiation end set and the other third set of the light receiving end set".

The irradiation / light receiving pair selective measurement unit 80 includes a light source 84 that emits a predetermined measurement light selected based on the instruction of the control unit (9), and a photoelectric conversion unit 83 that converts the received light into an electric signal. And, based on the instruction of the control unit (9), a pair of irradiation end sets and light receiving end sets are selected from a plurality of sets of irradiation end sets and a plurality of sets of light receiving end sets, and the selected 1 or 2 is selected. The connection or disconnection between the light source 84 and the irradiation end belonging to the selected irradiation end set, and the light receiving end belonging to the selected one or more photoelectric conversion units 83 and the selected light receiving end set. It has a pair selection interlocking switching unit 81 that interlocks and switches between the irradiation end and the light receiving end (irradiation light receiving pair) for each of the corresponding irradiation end and the light receiving end (irradiation light receiving pair).

Further, the irradiation light receiving pair selective measurement unit 80 has a plurality of light guide paths 161 and 163, one of which has _{one irradiation end 61 1 to 61 n and 63 1 to} 63 _n belonging to the irradiation end set 61, 63. irradiation connecting end _{62 1 ~62 n, 64 1 ~64} n belongs the plurality irradiation connection end pairs to each other end with each of 62, 64 and the one end the receiving end sets 71, 73, 75, the other ends of the plurality of light guides 171,173,175,177 have each having a plurality of light receiving end 71 ₁ -71 _n of _{77, 73 1 ~73 n, 75} 1 ~75 n, 77 1 ~77 n There are a plurality of light receiving connection end sets 72, 74, 76, 78 to which a plurality of light receiving connection ends 72 _{1 to} 72 _{n , 74 1} to 74 _{n , 76 1 to 76 n , 78 1 to 78 n belong, and each of them.} The irradiation connection ends or the light receiving connection ends belonging to the same set are arranged in a row at predetermined intervals along a predetermined direction (for example, the row direction), and the irradiation connection ends or the light receiving connection ends that can be pairs belonging to different sets are arranged with each other. Further comprises a plurality of paired end assembly arrays 82 having connection end array planes arranged in parallel at intervals along a direction orthogonal to the predetermined direction (eg, column direction).

As the plurality of light sources, for example, there are cases where a plurality of types of specific wavelength light sources are provided, or a plurality of tunable wavelength light sources set for each specific wavelength are used. As the plurality of photoelectric conversion units, a case where a plurality of photoelectric conversion units are provided via a bandpass filter corresponding to a plurality of types of light of a specific wavelength, or a photoelectric conversion unit is provided corresponding to each wavelength via a spectroscope. It may be provided.

Wherein the nozzle head 4, the nozzle Z-axis moving unit 42 that moves along the Z-axis direction with respect to further the nozzle group _{4 1 ~4 n, 4 '1} ~4' the nozzle head 4 in unison _n, and the nozzle group _{4 1 ~4 n, 4 '1} ~4' the flow is attached to the _n tube 2 ₁ ~2 _n, 2 ₁ magnetic mechanism 43 capable of exerting a magnetic force in a to 2 _n, said nozzle and the group _{4 1 ~4 n, 4 '1} ~4' desorption mechanism 45 for detachable simultaneously the flow tube _{2 1 ~2 n, 2 1 ~2} n from _n. Here, the nozzle _{4 1 ~4 n, 4 '1} ~4' n the Z-axis direction that together with the nozzle Z-axis moving unit 42 that is movable with the nozzle head moving mechanism 49 to said nozzle moving mechanism Corresponds to 49 and 42.

The nozzle head 4 is further movable relative to the stage 3 or the nozzle head 4 so as to traverse the _{entire housing group 3 1 to} 3 _{n along the X-axis direction.} It said transverse head 46 which dispensing tip 2 ₀ of 1 for sucking and discharging the liquid through the insertable tip into the reaction vessel or the liquid accommodating portion of the housing part group 3 ₁ to 3 _n is detachably mounted And a crossing head moving mechanism 47 for moving the crossing head 46 along the X-axis direction. The common accommodation region 3 ₀ with at least a chip accommodation portion for accommodating a plurality of dispensing tips 2 ₀ which is capable mounted detachably to the cross head 46 provided in the ₁ to 3 _n outer該全accommodating portion group 3 the It is provided on the stage 3.

The said common receiving area 3 _0, other, the total accommodation unit group 3 ₁ to 3 _n various liquid reagents or the like to the sample and independent of the common fed to the reaction vessel, for example, is in the target nucleic acids objective substance In some cases, a liquid storage unit is provided that houses an enzyme that requires temperature control for real-time PCR, a primer or probe for use in labeling, or a large amount of water, a buffer, or the like. As a result, the scale of the entire containment group 3 _{1 to} 3 _{n can be reduced.} Further, in the apparatus 10 according to the present embodiment, the apparatus 10 is movably provided between the electrophoresis unit 5 and the electrophoresis pretreatment units 3 and 4, and each of them is provided in a row along the X-axis direction. in parallel two groups of movable fluid receiving unit group _{36 1 ~36 n, 36 '1} ~36' n that a movable liquid storage unit of the plurality of (n) which are arranged at a predetermined pitch at intervals in the Y-axis direction The variable pitch liquid accommodating pedestal 36 provided and the pedestal moving provided so that the variable pitch liquid accommodating pedestal 36 can be moved between the electrophoresis unit 5 and the electrophoresis pretreatment units 3 and 4 along the X-axis direction. The variable-pitch liquid accommodating pedestal 36 has a unit 37, and the predetermined pitch is arranged along the X-axis direction of the second pitch and the plurality of electrophoresis capillaries of the electrophoresis unit 5. A pitch conversion mechanism is provided so as to be able to convert between the third pitch and the third pitch.

In the CPU + program + memory 9, the extraction / reaction control unit 91 that instructs the nozzle moving mechanism (49, 42), the suction / discharge mechanism 41, the magnetic force mechanism 43, and the temperature elevator 39 to extract or react. With respect to the electrophoresis control unit 95 that controls the electrophoresis unit 5, the nozzle moving mechanisms 49 and 42, the suction / discharge mechanism 41, and the light selection measurement unit 8 based on the previously specified photometric content. A photometric control unit 92 that controls the photometric content, and transmitted light, scattered light, or light emission, color development, discoloration, or light change related to a product, chemical substance, or labeling substance obtained from the photometric measurement unit 8. It has a photometric analysis unit 93 that performs analysis and quality evaluation using electrophoresis of the target substance based on the intensity of.

Subsequently, based on FIGS. 2 to 13, the fully automatic electrophoresis processing device 10 according to the embodiment of the present invention described with reference to FIG. 1 will be shown more specifically. The fully automatic electrophoresis processing device 100 when the target nucleic acid is used as the target substance will be described.

As shown in FIG. 2, the electrophoretic fully automatic processing apparatus 100 includes one or more kinds of chemical substance solutions, various reagents, a flow tube for dispensing 2 ₁ to 2 _n , 2 ₁ to 2 _n , and a chip for drilling. One or two or more accommodating portions for accommodating the sealing lid 34, such as 23 ₁ to 23 _n , or a bottom portion having a translucent region formed which is temperature controllable and transparent to the measurement light determined by the measurement content. Two or more reaction vessels including a photophoresis vessel having a A plurality (in this example, each of the accommodating sections) arranged at intervals of a second pitch (twice the first pitch in this example) along the X-axis direction (row direction). The stage 3 is provided with a loading hole into which the accommodating portions 3 _{1 to} 36 of ₆ ) can be loaded as a cartridge container, the suction / discharge mechanism 41 for sucking and discharging gas, and the suction / discharge mechanism 41 are communicated with each other. and, the nozzles are arranged along the X-axis direction at a first pitch, each second two groups of nozzle group arranged alternately in every other at a pitch 41 _{to 6,} 4 _'1-4 ' ₆ (A nozzle having the same subscript number as the accommodating unit group corresponds to the accommodating unit group having the same subscript number), and the nozzle head 4 and the stage 3 are relative to each other. A nozzle head moving mechanism (not shown) that can move along the Y-axis direction, the optical selection measuring unit 8 (shown in FIGS. 6, 7, and 8), and a row direction (shown in FIGS. 6, 7, and 8) in two columns. X-axis direction) a plurality arranged in a variable pitch along the (movable liquid storage unit group 36 ₁ to 36 ₆ of the second group each having a movable housing portion of the six in the example), 36 _{'1-36' 6} The variable pitch liquid accommodating pedestal 36 provided and the gantry moving portion 37 that enables the pedestal 36 to move along the row direction are arranged at a third pitch along the X-axis direction so as to be curved in the Z-axis direction. (in this example, six) a plurality of the gel is filled for electrophoresis comprising a electrophoretic capillary 51 _{1-51 6,} the fragments generated from the target nucleic acid for analyzing a plurality of types of nucleotide sequence the voltage on the sample by applying and an electrophoresis unit 5 which enables migration the capillary 51 _{1-51 6.} The variable-pitch liquid accommodating stand 36 has a pitch conversion mechanism that enables pitch conversion between the third pitch and the second pitch.

Wherein the nozzle head 4, further detachably in the housing portion can be a liquid suction discharge insertable mouth 2a, the nozzle groups 4 ₁ to 4 _n, 4 to _'1 to 4' _n the upper end to the lower end 2n book having a mounting opening 2b to be attached to the flow tube _{2 1 ~2 n, 2 1 ~2} n of (12 in this example), the nozzle _{4 1 ~4 n, 4 '1} ~4' in unison _n to the stage 3 and the nozzle Z-axis moving unit 42 to be movable along the Z-axis direction, the nozzle groups _{4 1 ~4 n, 4 '1} ~4' flow tube attached to the _n 2 _{1 ~2 n,} 2 forward and backward movement of the magnet relative to ₁ to 2 _n said flow tube 2 ₁ to 2 _n as it is possible to exert and remove a magnetic force simultaneously to the inside of, 2 ₁ to 2 _n a magnetic mechanism 43 capable provided, the nozzle groups _{4 1 ~4 n, 4 '1} ~4' flow tube attached to the _n 2 _{1 ~2 n,} 2 ₁ a to 2 _n can be detached from the nozzle A detachable mechanism 45 is provided. Here, the combination of the nozzle Z-axis moving portion 42 and the nozzle head moving mechanism 49 (not shown) corresponds to the nozzle moving mechanism.

Incidentally, in the present embodiment, the nozzle group 4 _{'1-4' 6,} like the nozzle groups 41 _{to 6,} the flow tube 2 ₁ to 2 ₆ is mounted, thus sucking and discharging mechanism 41 However, the difference is that the pair of irradiation end sets and light receiving end sets (61,71), which will be described later, are not provided. The housing portion row corresponding to the nozzle group 4 _{'1-4' 6} because the reaction vessel such that the light measurement is made is not provided.

The nozzle head 4 is supported by a Y-axis moving body 425 that can move in the Y-axis direction by the nozzle head moving mechanism 49. The nozzle head moving mechanism 49 has a rail laid in the Y-axis direction provided on the substrate 13 of the electrophoretic fully automatic processing device 100, and a timing belt hung on a rotor along the Y-axis direction. The Y-axis moving body 425 is connected to the timing belt and can be moved in the Y-axis direction by the timing belt.

As shown in FIGS. 2, 3, 6 or 7, the Y-axis moving body 425 of the nozzle head 4 is rotationally driven by a motor 421 provided on a beam 425a extending in the X-axis direction and the motor 421. A Z-axis attached to a ball screw 422 (see FIG. 7) provided so as to extend downward and a nut portion (not shown) screwed with the ball screw 422 by rotation of the ball screw 422. A moving body (the nozzle support) 44 and a guide rail (not shown) provided on the Y-axis moving body 425 and laid along the Z-axis direction are provided.

As shown in FIGS. 2, 3, 6 or 7, the suction / discharge mechanism 41 of the nozzle head 4 is a gas suction / discharge motor supported by the Z-axis moving body (nozzle support) 44. 411, a ball screw connected via a coupling 412 rotationally driven by the motor 411, and a plunger drive plate 413 (see FIG. 6) that is connected to a nut portion screwed with the ball screw and can move up and down. It has a plurality of (six in this example) plungers 414 that engage with the plunger drive plate 413 and slide in a plurality of (six in this example) cylinders 416. The plunger 414 is wound with a coil-shaped spring provided in the cylinder 416 and is always urged downward with respect to the cylinder 416.

As shown in FIGS. 2, 3, 6 or 7, the plurality of cylinders 416 are supported by a cylinder support member 415 attached to the Z-axis moving body 44 at the upper end thereof, extend downward, and extend downward at the lower end thereof. It is attached to the nozzle support member 417 attached to the Z-axis moving body 44. Nozzles of the nozzle groups 41 _{to 6,} 4 _{'1-4' 6} on the lower side of the nozzle support member 417 are arranged alternately, and movably detachable member 452 is provided for the nozzle support member 417 ing.

2, 3, 6 or 7, wherein the nozzle head 4, the nozzle groups 41 _{to 6,} 4 _{'1-4' 6} flow tube 2 mounted on 21 _{to 6} , 2 ₁ to 2 ₆ has a detachment mechanism 45 for detaching a desorption mechanism 45 has the detachable member 452, the desorption member 452 is the nozzle group 41 _{to 6,} 4 _'1-4 'larger than the outer diameter of the nozzles _6, but the nozzle groups ₄₁ to _6, 4' each nozzle inside has a smaller inner diameter than the outer diameter of _{1-4 '6n} to attached the flow tube Detachable holes or gaps are formed to penetrate. It passes through both ends of the nozzle support member 417, passes through springs 453 attached to both ends of the detachable member 452, the lower side is fixed to the detachable member 452, and the upper end penetrates the cylinder support member 415 and reaches the upper side thereof. , Two poles 451 located below the plunger drive plate 413 at a predetermined distance, spirally wound around the pole 451 at the upper end thereof, and the lower end thereof is attached to the pole 451 and the lower end thereof is a cylinder support member. It has a spring 453 attached to the 415. By moving the plunger drive plate 413 to a position lower than the height position for suction and discharge, the detachable member 452 is moved downward to detach the flow pipe. When the plunger drive plate 413 is returned to the suction / discharge height position, the detachable member 452 is retracted to the original position by the spring 453.

As shown in FIG. 2, FIG. 3, or FIG. 6, the nozzle head 4 further includes a crossing head 46 and a crossing head moving mechanism 47 for moving the crossing head along the X-axis direction (row direction). It is provided. Therefore, the crossing head 46 itself can move in the Y-axis direction together with the nozzle head 4. The crossing head 46 drives a nozzle support member 462 on which the nozzle 461 is supported, a cylinder 466 provided on the nozzle support member 462 and communicating with the nozzle 461, and a plunger sliding in the cylinder 466 in the vertical direction. Motor 464, a plunger drive plate 467 that drives the plunger, two poles 463 located below the plunger drive plate 467 at a predetermined distance, and a spirally wound around the pole 463. The upper end has a spring attached to the pole 463. It said plunger drive plate 467 performs the desorption of desorption member 465 by moving at a position lower than the height position for the suction and discharge is moved downward pipette tip 2 _0. When the plunger drive plate 467 is returned to the suction / discharge height position, the detachable member 465 is retracted to the original position by the spring. Reference numeral 464 is a motor for driving the plunger for suction and discharge.

The crossing head 46 is provided so as to be movable in the X-axis direction and the Z-axis direction by the crossing head moving mechanism 47. The crossing head moving mechanism 47 includes an X-axis moving body 475 to which the crossing head 46 is movably attached in the Z-axis direction, and an X-axis moving body support that movably supports the X-axis moving body 475 in the X-axis direction. It has a plate 473, a timing belt 474 provided on the X-axis moving body support plate 473 and connected to the X-axis moving body 475, and pulleys 474a and 474b over which the timing belt 474 is bridged. The X-axis moving body 475 has a motor 472, a ball screw 476 rotationally driven by the motor 472, and a nut portion screwed with the ball screw 476 and to which the crossing head 46 is attached.

As shown in FIGS. 2, 3, 5 or 6, the electrophoresis fully automatic processing apparatus 100 further includes the variable pitch liquid accommodating pedestal 36 and the variable pitch liquid accommodating pedestal 36 in the capillary electrophoresis unit. A gantry moving unit 37 is provided so as to be movable between the 5 and the electrophoresis pretreatment units 3 and 4.
The variable pitch liquid container mount 36 has a movable liquid storage unit 36 ₁ to 36 ₆ of a plurality arranged in a variable pitch along the row direction (X axis direction) in a row-like (six in this example) A plurality (6 in this example) provided at intervals in the row direction (Y-axis direction) from the first movable liquid storage group and the first movable liquid storage group and arranged at the second pitch. a second movable liquid storage unit group having a movable fluid receiving unit 36 _{'1-36' 6,} the variable pitch, the housing part group 3 ₁ to 3 ₆ second from said pitch capillary electrophoresis unit 5 of the those having a convertible pitch changing mechanism in the third pitch of the electrophoretic capillary 51 _{1-51 6} provided.

The pitch conversion mechanism is slidably guided by the gantry main body 361, the guide rail 361a horizontally provided on the gantry main body 361 along the X-axis direction, and the guide rail 361a along the X-axis direction. , supporting said six to two movable liquid storage unit comprising a pair of each group are arranged in parallel provided at the upper end of the movable fluid receiving unit group 36 ₁ to 36 _6, 36 _{'1-36' 6} having a plate 365 _{1 to 365 6,} and six links 366 _{1 to 366 6} for connecting the adjacent support plates, the.

The support plate 365 ₁ is fixed to the gantry main body 361, _{and one end of the guide rail 361a is supported by the support plate 365 1} and the other end is supported by a side plate 361c provided in the gantry main body. The adjacent support plates 365 _{1 to} 365 ₆ are connected by kinematic pairs at predetermined nodes via _six links 366 _{1 to 366 6.} Further, of the six support plates 365 _{1 to} 365 ₆ , the timing belt 364 for moving the _five support plates 365 _{1 to} 365 _{5 excluding the support plate 365 6} at the end in the X-axis direction, and the The pulleys 363a and 363b over which the timing belt 364 is laid, and the motor 363 that rotationally drives the pulleys 363a are provided on the gantry main body 361. The support plate 365 _{1 at the} other end is coupled to the timing belt 364.

Further, as shown in FIG. 2 or FIG. 3 or FIG. 6, the gantry moving unit 37 transfers the gantry main body 361 from the electrophoresis pretreatment units 3 and 4 to the electrophoresis unit 5 along the X-axis direction. The support plates 365 _{1 to} 365 _{6 provided with the movable liquid accommodating portions 36 1 to} 36 ₆ and 36 ' _{1 to} 36' _{6 of the} variable pitch liquid accommodating stand 36 are slidably accommodated for movement. The support plate accommodating portion 374, the timing belt 372 that connects the gantry main body 361 to the connecting portion 362 provided on the gantry main body 361 so as to be movable along the X-axis direction, and the timing belt 372 It has a first pulley 372a that is bridged, a second pulley (not shown) that is rotationally driven by a motor 371, and a frame 373 that incorporates the variable pitch liquid accommodating pedestal 36 and the pedestal moving portion 37.

Subsequently, the stage 3 of the electrophoresis fully automatic processing apparatus 100 according to the embodiment of the present invention will be described with reference to FIG.
The stage 3 is formed in a plate shape, and the storage unit groups 3 _{1 to} 3 _n (each storage unit group consists of two rows, n = 6) in a plurality of rows (12 in this example) are in the row direction (Y). Arranged as cartridge containers along the axial direction). Each of the containment groups 3 _{1 to} 3 _n includes a reaction region 32 in which quantitative PCR and a Sanger sequence reaction are performed, a region 33 in which DNA is extracted and an extract is contained, and a flow tube (two types of flow tubes for dispensing 2). ₂₁ to _6, 2 ₁ to 2 _6, 22 ₁ to 22 _6, the (for metering) small amounts dispensing flow pipe 21 ₁ to 21 _6, the drilling tip 23 _{1-23 6,} 23 ₁ to 23 ₆₎ It has a flow tube accommodating area 31 for accommodating, a sample area 35 for accommodating samples, and a variable pitch liquid accommodating stand 36 for accommodating the above-mentioned electrophoresis sample and the like.

In the reaction region 32, a sealing lid 34 capable of sealing the openings _{of the reaction vessels 321 1 to 321 6} , the photometric reaction vessels 322 _{1 to 322 6} , and the reaction vessels 321 _{1 to 321 6} , 322 _{1 to 322 6 can be sealed.} the accommodation portion 34 _{1-34 6} accommodating portion is provided. Incidentally, the sealing lid 34, the by perforating tip 23 _{1-23 6,} 23 ₁ to 23 ₆ or piercing member 123 is provided so as to be perforated.

The DNA extraction region 33 includes an extraction reagent for extracting a target nucleic acid from a sample, a cartridge container 332 containing a magnetic particle suspension, and an extract tube 331 containing an extract from the sample. doing. The sample area 35 is provided with, for example, a blood collection tube 351 and a 1.5 ml tube 352.

Subsequently, the electrophoresis section 5 of the electrophoresis fully automatic processing apparatus 100 according to the embodiment of the present invention will be described with reference to FIGS. 2, 3, 6, and 7.

The said capillary electrophoresis unit 5, a plurality of electrophoresis capillary 51 _{1-51 6} (in this case six) the gel is filled inside, inserted one end of each of the capillary 51 _{1-51 6} 6 pieces arranged on the variable pitch liquid accommodating stand 36, moved from the electrophoresis pretreatment units 3 and 4 in the X-axis direction, and arranged at a third pitch converted from the second pitch. the first movable liquid storage unit 36 ₁ to 36 ₆ of the movable liquid storage unit group, an electrophoresis after accommodating portion to the other end portion is inserted in each said capillary 51 _{1-51 6} (not shown) of the with the capillary holder 52 that holds the capillary 51 _{1-51 6} at a third pitch in the one end side holds the capillary 51 _{1-51 6} at the other end, the capillary 51 _{1-51 6} capillary and holder 53, the capillary said held by the holder 52 movable liquid storage unit 36 ₁ to 36 ₆ has a pair of irradiation end set and light receiving end sets provided adjacent or in contact with the outer wall (63, 73) of having a negative electrode 54 _{1-54 6} provided insertable within, and said capillary holder 53 positive electrode 55 provided so as to be inserted into the electrophoresis after receiving portion (not shown) is held. One end portion and the said electrophoresis capillary 51 _{1-51 6} negative electrodes 54 ₁ to 54 _6, after the variable pitch liquid container mount 36 has moved into the capillary electrophoresis unit 5, one end lifting mechanism (not shown) is inserted into the capillary 51 _1-51 by lowering each end of the ₆ first movable liquid each movable liquid storage portion group accommodation portion 36 _{1-36 6,} the end portion The variable pitch liquid accommodating pedestal 36 is moved after the one end portion is raised by the elevating mechanism and pulled out from the movable liquid accommodating portion.

Subsequently, the optical measurement system of the fully automatic electrophoresis processing device 100 according to the present embodiment will be described in detail with reference to FIGS. 7, 8 and 9.

FIG. 7 shows an irradiation light receiving pair selective measurement unit 80 mounted on the back surface of the optical selective measurement unit 8 of the electrophoretic fully automatic processing apparatus 100 according to the present embodiment. The light receiving pair selective measurement unit 80 includes an on / off light source 84 that emits selected predetermined measurement light, an on / off possible photoelectric conversion unit 83 that converts the received light into an electric signal, and a plurality of pairs of connection ends. It has a body 82 and a pair selection interlocking switching unit 81.

As shown in FIG. 7, the pair selection interlocking switching unit 81 has a plurality of pairs of measurement end set array 811 having a measurement end arrangement surface 813 and a switching mechanism (814,815,816). The switching mechanism is hooked between a pulley 815 attached to the Y-axis moving body 425 of the nozzle head 4 and a pulley (not shown) rotationally driven by a motor 816 along the X-axis direction. A plurality of pairs of connection end assembly 82 having a passed timing belt 814 and connected to the timing belt 814 can slide with respect to the plurality of pair measurement end assembly 811 along the X-axis direction. It is provided.

8 (a) is irradiated receiving pairs of first irradiation end sets of a pair of light-selecting measuring unit 8 according to the embodiment and light receiving end sets of this embodiment (61, 71) (61 _1, 71 ₁ ) there is shown a portion of a ~ (61 _6, 71 _6), are those provided in the nozzle group ₄₁ to _6.
FIG. 8 (b), there is shown a radiation receiving pair of one-irradiation end set and light receiving end sets of (63, 73) (63 _1, 73 ₁₎ to (63 _6, 73 _6), the electric is provided in the measuring unit of the electrophoresis capillary 51 _{1-51 6,} for example, a light receiving end and radiation end the capillaries 51 _{1-51 6} example, so as to sandwich opposite the radially outer wall surface of the capillary It is provided so as to be aligned in the same radial direction or at a predetermined angle.

FIG. 8C shows a pair of irradiation end sets and light receiving end sets (61, 71), (63, 73) from the plurality of sets of irradiation end sets 61, 63 and the plurality of sets of light receiving end sets 71, 73. ) Is selected, each pair of the irradiation end and the light receiving end belonging to the selected set is used as each irradiation light receiving pair, and a predetermined measurement light is sequentially supplied to the irradiation end, and the light sequentially received by the light receiving end. It shows the irradiation light-receiving pair selective measurement unit 80 which sequentially measures the intensity of.

FIG. 8C shows the plurality of pairs of the paired connection end set array 82 of the irradiation light receiving pair selection measurement unit 80 and the multiple pair measurement end set array 811 of the pair selection interlocking switching unit 81.

Plurality several pairs connecting end assembly array 82 is irradiated connecting end 62 _{1-62 6} 64 _{1-64 6} said plurality having a first end with each respective other ends of the two pairs of the irradiation end sets 61 and 63 (the six in the example) belonging two sets of irradiation connection end pairs 62, 64 and a plurality of the one end portion has a plurality of light receiving end 71 _{1-71 6,} 73 ₁ to 73 ₆ of the receiving end sets 71 and 73 There are two sets of light receiving connection ends 72 and 74 to which a plurality of light receiving connection ends (six in this example) each of the other ends of the optical fibers 171 and 173 as the light guide path of the above belong to the same set. The irradiation connection ends or the light receiving connection ends belonging to the above are arranged in a row at predetermined intervals along the row direction (X-axis direction), and the irradiation connection ends and the light receiving connection ends belonging to different pairs that can be paired are in the row direction. With a plurality of pairs of connection end array bodies 82 having connection end array planes arranged in parallel with a pair spacing along a direction (in this example, the column direction, that is, the Y axis direction) orthogonal to (X-axis direction). It has the plurality of pairs of measurement end set array 811 of the pair selection interlocking switching unit 81. The irradiation connection ends and the light receiving connection ends belonging to different pairs that cannot be paired with them are spaced apart from each other by a predetermined distance along the row direction (X-axis direction) or in the column direction (Y-axis direction). Can be arranged in parallel with different pairs of intervals (see FIG. 12).

As shown in FIG. 8C, the plurality of pairs of measurement end sets 811 are optically connected to the light source 84 that can be turned on and off, and the irradiation connection ends 62 _{1 to} 62 of the irradiation connection end sets 62 and 64 are formed. _6, 64 ₁ to 64 ₆ and sequentially connectable to provided the one or more radiation measuring end 841a~841d, 842a~842d are each provided with a plurality of sets of illumination measuring portion sets 841 and 842, which can be turned on and off wherein the photoelectric conversion unit 83 optically connected, receiving connection end 72 _{1-72 6} 74 _{72d 6} sequentially connectable to one or more light receiving measurements provided in the light receiving connection end pairs 72, 74 A plurality of sets of light receiving measurement end sets 831 and 832 provided with ends 831a to 831d and 832a to 832d each have a measurement end array surface 813 arranged in parallel along a predetermined direction (X-axis direction in this example). Correspondence is in code order). Here, the irradiation measurement end set 841 and the light receiving measurement end set 831 that can be paired are the irradiation measurement end and the light receiving measurement end (841a, 831a) to (841d, 831d) provided at intervals of the pair that can be paired. A pairable paired measurement end set 8111 is formed in each paired measurement end body, and the pairable irradiation measurement end set 842 and the light receiving measurement end set 832 form a pairable irradiation measurement end and light receiving measurement end (842a, A pair-measurement end set array 8112 that can be divided into pair-measurement ends for each of 832a) to (842d, 832d) is formed. The paired measurement end set arrangements 8111 and 8112 include a pair of corresponding light sources 84 and a photoelectric conversion unit 83 for each pair of measurement ends.

Here, the switching mechanism (814,815,816) so that the connection end array surface and the measurement end array surface 813 face each other and slide along the predetermined direction (in this example, the row direction, that is, the X-axis direction). Moves the plurality of pairs of end assembly array 82 relative to the plurality of pairs of measurement endpoint array 811. Then, irradiation connecting end group selected as pairs and receiving the connection end pairs (62, 72), (64, 74) to each connection end pairs belonging (62 _1, 72 ₁₎ to (62 _6, 72 _6), ( 64 _1, 74 ₁₎ to (64 _6, 74 ₆₎ and, receiving the measurement end to be connected to the photoelectric conversion unit 83 in the radiation measuring portion set and the selected oN state to connect the light source 84 in the selected on-state Each measurement end pair (841a, 831a) to (841d, 831d) belonging to the first measurement end set pair (841,831) consisting of a pair, or belongs to the second measurement end set pair (842,832). Allows connection and disconnection of each pair of measurement end pairs (842a, 832a) to (842d, 832d), and is turned on for each pair of irradiation end and light receiving end (irradiation light receiving pair) connected to these. The connection or disconnection between the light source in the state and the photoelectric conversion unit in the on state is sequentially performed in conjunction with each other. If one of the pair of the first measurement end set or the pair of the second measurement end set is selected and the corresponding light source and photoelectric conversion unit are in the ON state, the other is not selected. , The corresponding light source and photoelectric conversion unit are turned off.

Here, each of the irradiation end 61 _{1-61 6} irradiation end group 61, because those used to measure the qPCR, irradiation connection end of the irradiation connecting end assembly 62 of a plurality of pairs of connection end assembly array 82 62 ₁ the to 62 ₆ and the light source 84 connected through a radiation measuring portion 841a~841d of the irradiation measuring portion sets 841 of the plurality of pairs measuring end assembly array 811, for example, four colors of the excitation light (e.g., wavelength There are four types of LEDs that emit light (496 nm, wavelength 527 nm, wavelength 555 nm, wavelength 587 nm). Then, the light receiving end 71 _{1-71 6} receiving end sets 71 forming a pair is selected, receiving the connection end of the light receiving connection end pairs 72 of the pairs connecting end assembly array 82 72 _{1-72 6} and more The photoelectric conversion unit 83 connected via the light receiving measurement ends 831a to 831d of the light receiving measurement end group 831 of the paired measuring end assembly 811 is via a bandpass filter having a wavelength of 517 nm for receiving fluorescence of four colors. High-sensitivity photodiode connected via a bandpass filter with a wavelength of 549 nm, a high-sensitivity photodiode connected via a bandpass filter with a wavelength of 580 nm, and a bandpass filter with a wavelength of 599 nm. It is a high-sensitivity photodiode connected via. These correspond to the fluorescent substances FAM, HEX, TAMURA, and ROX, respectively.

Furthermore, the irradiation end 63 _{1-63 6} of the irradiation end group 63, because those used to measure relates to an electrophoretic capillary 51 _{1-51 6,} irradiation connection thereof with pairs connecting end assembly array 82 through an irradiation measuring portion 842a~842d irradiation measuring portion sets 842 irradiated connection end 64 _{1-64 6} and said plurality of pairs measuring end assembly array 811 of the end sets 64, for example, emits four colors of the excitation light 4 It is a kind of LED. Then, the light receiving end 73 _{1-73 6} receiving end sets 73 forming a pair are selected, these light receiving connection end pairs connecting end assembly array 82 set 74 to _{72d 6} and the plurality of pairs measuring portion sets It is a high-sensitivity photodiode connected via a bandpass filter of a corresponding wavelength connected via the light-receiving measurement ends 832a to 832d of the light-receiving measurement end set 832 of the array 811. The plurality of pairs of measurement end set array 811 can be divided into measurements for each pair of irradiation measurement ends and light reception measurement ends, and partially replaces a light source and a photoelectric conversion unit having another wavelength range. It is possible and versatile.

FIG. 9A shows a nozzle 4 _n (n = 1 to 6) according to the embodiment of the present invention and a suction / discharge mechanism 41 _{n communicating with the nozzle 4 n} . The nozzle 4 _n communicates with said flow tube 2 _n fitting opening 2b is provided to be mounted in 2 _n said flow tube. A hollow portion is formed inside the nozzle 4 _{n , and optical fibers 161 n} and 171 _n as the light guide path are provided in the center passing through the central axis thereof, and the tips thereof are a pair of irradiation end 61 _n and light receiving end 71 _{n. The lens 1 n} is supported in a state where a gap communicating with the tip opening of the _{nozzle 4 n} is provided in the center of the tip portion of the nozzle 4 _n on the lower side thereof. The gap communicates with the cylinder 416 via the suction / discharge flow path 416d and the suction / discharge port 416e, and communicates with the pressure sensor 416f through the lateral hole 416g.

The cylinder 416 has a cavity inside and a plunger 414 slidably provided with the cavity. The cavity is provided with a small diameter region 416a, a large diameter region 416b having an inner diameter larger than that of the small diameter region 416a, and a floating region 416c provided between the small diameter region 416a and the large diameter region 416b. It has a thin shaft portion 414a that slides with the small diameter region 416a, and a thick shaft portion 414b that slides with the large diameter region 416b. Can move without sliding. Thereby, each of the suction and discharge mechanisms 41 _{1 to} 41 _n of 1 communicating with each nozzle 4 ₁ to 4 _{n of} 1 enables dispensing of both a minute amount and a large amount of liquid.

FIG. 9B shows the optical inside of the reaction vessel via the perforable translucent membrane 34a which is attached to the sealing lid 34 attached to the opening of the reaction vessel 322 and has the translucency of the sealing lid 34. It shows the case of measuring a state.

Subsequently, based on FIG. 10, a case where the canine genome is analyzed as a target substance will be described with respect to the operation of the electrophoresis fully automatic processing device 100 according to the embodiment of the present invention.
The blood collection tube provided in the sample region 35 provided on the stage 3 of the electrophoretic fully automatic processing device 100 contains whole blood collected from six different dogs. A case where the canine genome is extracted from the whole blood, the concentration of the extracted DNA is measured, the quality is evaluated, and the base sequence of the canine genome is analyzed will be described.

Therefore, a serum solution obtained by diluting whole dog blood with physiological saline is stored in the liquid storage portion of the sample region 35. Further, each liquid storage portion of the DNA extraction region 33 is prepacked with an extraction reagent and a washing liquid in advance.
In step S1, the operation panel 94 directs the processing of the canine genome from the sample.

In step S2, the extraction / reaction control unit 91 of the CPU + program + memory 9 of the electrophoretic fully automatic processing device 100 supports the nozzle head moving mechanism 49 and moves the nozzle head 4 in the Y-axis direction. Te, by moving the nozzle groups 41 _{to 6,} 4 _{'1-4' 6} over the perforating tip is housed in said flow tube receiving area 31, descends with the nozzle Z-axis moving unit 42 the drilling tip 23 _{1-23 6,} 23 ₁ to 23 ₆ is attached to the nozzle groups 41 _{to 6,} 4 _{'1-4' 6} by the DNA extracted using the nozzle head moving mechanism 49 By locating the drilling tip above the first liquid storage portion of the region 33 and lowering the nozzle by the nozzle Z-axis moving portion 42, a film covering the opening of the liquid storage portion is punched in the same manner. Then, the nozzle head moving mechanism 49 moves the nozzle head in the Y-axis direction to sequentially drill other liquid accommodating portions and reaction vessels. The DNA extraction region 33 contains the separation / extraction solution as follows. For example, Lysis 1 is 40 μ \ ochL in the first liquid storage part, Lysis 2 is 200 μ \ ochL in the second liquid storage part, and 500 μ \ ochL of the binding buffer liquid is in the third liquid storage part. , The fourth liquid storage part contains a magnetic particle suspension, the fifth liquid storage part contains 700 μ \ ochL of cleaning liquid 1, and the sixth liquid storage part contains 700 μ \ ochL of cleaning liquid 2. In the liquid storage part of the above, 50 μ \ ochL of distilled water is stored as a dissociation liquid, and in the eighth liquid storage part, isopropyl alcohol (isopropanol) used for removing proteins or the like as a part of the protein separation / extraction solution is contained. It shall be contained. It is housed only in the first housing portion row of the first column of each of the accommodating part group 3 ₁ to 3 ₆ (cartridge container 332).

Next, the nozzle head moving mechanism 49 moves the nozzle head moving mechanism 49 again in the Y-axis direction, moves the nozzle head moving mechanism 49 to the flow tube accommodating area 31, attaches and detaches the drilling tip by the detaching mechanism 45, and then reattaches the nozzle head moving mechanism 49. is moved in the Y-axis direction, the nozzle groups 41 _{to 6,} 4 _{'1-4' 6} is lowered by the nozzle Z-axis moving unit 42, flow tube housing of the respective housing part group 3 ₁ to 3 ₆ thereby mounting the first column of the accommodating part flow for dispensing is contained only in the column tube 22 _{1-22 6} region 31 only on the nozzle groups 41 _{to 6} (as shown in FIG. 4, the flow tube in accommodating area 31, housing portion corresponding to the nozzle group 4 _{'1-4' 6} is empty).

Then, after moving to the sample region 35 where the sample is accommodated, by using the nozzle Z-axis moving unit 42, is lowered inserting mouth portion 2a of the tube 22 ₁ to 22 _6, the suction and discharge mechanism For the suspension of whole blood contained in the sample region by raising and lowering the plunger drive plate 413 of 41, the sample is suspended in the liquid by repeating suction and discharge, and then the sample is suspended. sucking the Nigoeki flow tubes 22 _{1-22 6.} The sample sample suspension is moved along the Y-axis by the nozzle head moving mechanism 49 to the first liquid storage part of the liquid storage part containing Lysis 1 (enzyme) as a solution for separation and extraction. Te, by inserting the mouth portion 2a of the flow tube 22 _{1-22 6} repeats the suction and discharge to agitate and said Lysis 1 and the sample suspension through the pores of the perforated films.

Next, by suction the entire amount of the stirred liquid by said flow tube 22 _{1-22 6,} by incubation houses by the temperature elevator 39 to the set temperature-controllable reaction vessel 55 ° C.. As a result, the protein contained in the sample is destroyed to reduce the molecular weight. After a predetermined time, leaving the reaction mixture to the reaction vessel, accommodating the flow tube 22 _{1-22 6} to the second liquid storage portion with the nozzle head moving mechanism 49 and the suction and discharge mechanism 41 is the total amount of liquid was aspirated and the transferred using said flow tube 22 _{1-22 6} by the nozzle head moving mechanism 49, the third liquid receptacle to pass through the hole of the film said opening Is inserted and the reaction solution is discharged.

Next, the binding buffer solution as the separation / extraction solution contained in the third liquid container and the reaction solution are stirred to further dehydrate the solubilized protein and disperse nucleic acids and the like in the solution. ..

Then the mouth portions in the liquid containing portion of the third with the flow tube 22 _{1-22 6} and inserted through the hole of the film, the flow by the nozzle moving unit 42 to suck the whole amount It raises the tube 22 ₁ to 22 _6, and transferring the reaction solution until the fourth liquid storage portion, stirring the magnetic particle suspension and the reaction solution contained in the liquid containing portion of the fourth .. A cation structure in which Na + ions are bonded to the hydroxyl groups formed on the surface of the magnetic particles contained in the magnetic particle suspension is formed. Therefore, the negatively charged DNA is captured by the magnetic particles.

Next, magnet provided by arranging the magnet of the magnetic force mechanism 43 onto a capillary of the flow tube 22 ₁ to 21 ₆ to the magnet support member extending in the Y-axis direction so as to correspond to each of the flow tubes 22 _{1-22 6} reciprocating mechanism adsorbing the by close simultaneously with (not shown) along the Y-axis direction on the inner wall of the capillary of the flow tube 22 _{1-22 6} magnetic particles. The magnetic particles in a state of being adsorbed to the inner wall of the capillary of the flow tube 22 _{1-22 6,} wherein the nozzle Z-axis is raised by the moving unit 42, the nozzle head moving mechanism 49 flow pipe 22 _1-22 using ₆ is moved from the 4th liquid storage part to the 5th liquid storage part, and the thin tube is inserted through the hole of the film.

While removing the magnetic force to the narrow tube by spaced all together the magnets of the magnetic force mechanism 43 from the flow tube 22 _{1-22 6} capillaries, the cleaning liquid contained in the liquid containing portion of the fifth By repeating suction and discharge with respect to 1 (NaCl, SDS, isopropanol), the magnetic particles are separated from the inner wall and stirred in the washing liquid 1 to wash the protein. Then, in a state in which the magnetic particles be brought close to the narrow tube of the magnetic mechanism said flow tube 22 _{1-22 6} again magnets 43 was adsorbed to the inner wall of the tubule, the nozzle the flow tube 22 _{1-22 6} The Z-axis moving portion 42 and the nozzle head moving mechanism 49 are used to move the fifth liquid accommodating portion to the sixth liquid accommodating portion.

Then inserted through the hole of the film using a nozzle Z-axis moving unit 42 tubules of the flow tube 22 _{1-22 6.} While removing the magnetic force to the narrow tube by separating the magnet of the magnetic force mechanism 43 from capillary of the flow tube 22 _{1-22 6,} the cleaning liquid is accommodated in the liquid accommodating portion of said 6 2 (isopropanol ), The magnetic particles are stirred in a liquid to remove NaCl and SDS, and the protein is washed. Then, in a state in which the magnetic particles be brought close to the narrow tube of the magnetic mechanism said flow tube 22 _{1-22 6} again magnets 43 was adsorbed to the inner wall of the tubule, the nozzle the flow tube 22 _{1-22 6} After being raised by the Z-axis moving portion 42, the nozzle head moving mechanism 49 moves the distilled water from the sixth liquid accommodating portion to the seventh liquid accommodating portion.

Then, by the nozzle Z-axis moving unit 42, a thin tube of said flow tube 22 _{1-22 6} is lowered through the hole, in a state in which the magnetic force exerted on the flow tube 22 _{1-22 6} within tubules By repeating the suction and discharge of the distilled water at a slow flow velocity, the cleaning liquid 2 (isopropanol) is replaced with water and removed. Thereafter, the magnet of the magnetic force mechanism 43 and stirred by repeating suction and discharge of the magnetic particles in a state that is separated by removing the magnetic force from the capillary of the flow tube 22 _{1-22 6} in distilled water as the dissociation solution , The nucleic acid held by the magnetic particles is dissociated (eluting) from the magnetic particles into the liquid. Thereafter, the magnetic particles have a magnetic field in the capillary is adsorbed to the inner wall by for approximating the magnet capillary of the flow tube 22 _{1-22 6,} containing the extracted nucleic acid or the like to the liquid containing portion of the eighth Leave the solution. Said flow tube 22 _{1-22 6} is moved to the flow tube receiving area 31 by the nozzle head moving mechanism 49, the flow tube 22 which has adsorbed the magnetic particles from the nozzle 41 _{to 8} using the desorption mechanism 45 the _{1-22 6} together with the magnetic particles to desorb into the receptacle.

In step S3, a small amount of 5 μ \ ochL of the DNA extracted in step S2 is measured using a real-time PCR reagent using a FAM fluorescent substance or the like in order to measure the concentration thereof.
In this example, in the stage 3 of the fully automated fluorescence _{processing apparatus 100, the reaction vessels 322 1 to 322 6} for real-time PCR measurement in FIG. 5 have two types at both ends of the amplification region of the target nucleic acid to be amplified. In addition to the primer, as a fluorescent probe that complementarily binds in the amplified region, a fluorescent probe having a fluorescence reporter and a quencher next to it having four pairs of base sequences, such as fluorescent substance HEX, fluorescent substance TAMURA, and fluorescence. Contains a real-time PCR reagent labeled with the substance ROX and the fluorescent substance Texas Red. These reagents are dispensed from a common housing area 3 ₀ to each reaction vessel using the cross head 46.

Next, the nozzle head 4 with nozzle head moving mechanism 49 is moved to above the flow tube receiving area 31, said nozzle 41 _{to 6} with the nozzle Z-axis moving unit 42, 4 _'1 by lowering the ~ 4 _'6, is mounted a small amount dispensing flow pipe 21 ₁ to 21 ₆ only the nozzle 4 ₁ to 4 _8.該装wearing the flow tube 21 ₁ to 21 ₆ extracted nucleic acid solution stored in the liquid containing portion of the eighth using, for example, among the 50.mu. \ och1, small amounts, for example, aspirating each 5 [mu] \ och1.

In step S4, the extracted nucleic acid is moved in the Y-axis direction by using the nozzle head moving mechanism 49 and is moved in the Z-axis direction by using the nozzle Z-axis moving portion 42 and is stored in the liquid containing portion. Discharge 5 μ \ ochL of the solution into the reaction vessels 322 _{1 to 322 6} and mix. On the other hand, each of the 45 μ \ ochL nucleic acid solutions left in the eighth liquid storage portion is moved in the Y-axis direction using the nozzle head moving mechanism 49, and the minute amount dispensing flow tubes 21 _{1 to} 21 are used. It sucked into _6, housed in the variable movable liquid storage portion group 36 of the first group of pitch liquid container mount 36 _{'1-36' 6.}

Then, by the nozzle head moving mechanism 49 positions the flow tube 21 ₁ to 21 ₆ above the flow tube receiving area 31, flow tube housing area flow tube 21 ₁ to 21 ₆ by the detachment mechanism 45 Detachable within 31. The nozzle assembly 4 by the nozzle head moving mechanism 49 _{1-4 6,} 4 _'1-4' sealing cover housing portion 34 of the ₆ the reaction region 32 _1-34 The nozzle group 4 by positioning falling above the _{6 1-4 6} sealing lid 34 is mounted on the housing portion row of the first column of each of the accommodating part group 3 ₁ to 3 _6, again, after being positioned above the reaction vessel 322 _{1-322 6,} The nozzle is lowered by the nozzle Z-axis moving portion 42, and the sealing lid 34 is fitted into the openings of the _{reaction vessels 322 1 to 322 6.}

Next, according to the qPCR method, the temperature elevator 39 _{controls and amplifies the temperatures of the reaction vessels 322 1 to 322 6} all at once, and the irradiation light receiving pair selective measuring unit 80 of the light selective measuring unit 8. by, irradiation end sets 61 and receiving end sets 71 pair provided in the nozzle 41 _{to 6} is selected, i.e., the irradiation end and receiving end of the plurality of pairs (61 _1, 71 ₁₎ to (61 ₆ , 71 ₆₎ is selected, therefore, the corresponding one-to-irradiated connecting end assembly 62 and the light receiving connection end pairs 72 of the pairs connecting end assembly array 82, therefore, a pair of a plurality pairs measurement end assembly array 811 The irradiation measurement end set 841,842 and the light receiving measurement end set 831,832 are selected, and the plurality of pairs of end set array 82 are moved with respect to the multiple pair measurement end set 811 at a predetermined speed in the X-axis direction. Then, it is repeatedly reciprocated at a predetermined predetermined cycle. Thereby, each of the selected pair of connection ends (62, 72) of the plurality of pairs of connection ends array 82 corresponds to the fluorescent material used in the corresponding plurality of pairs of measurement ends array 811 in sequence. Repeat connection and disconnection for a pair of measurement ends (841,831). The reciprocating motion is performed in a predetermined cycle of, for example, 2 to 3 seconds for one temperature cycle of the PCR method (for example, 30 seconds, for example, 40 cycles are repeated) to repeat optical connection and disconnection.

The selection of the irradiation light receiving pair is optically connected to the pair of irradiation measurement end sets 841 and the light receiving measurement end set 831 which should be connected to the selected pair of irradiation end sets 61 and the light receiving end set 71. This is performed by turning on the light source 84 and the photoelectric conversion unit 83 to be turned on, and turning off the other light sources 84 and the photoelectric conversion unit 83. If the photometric analysis unit 93 graphs the obtained fluorescence intensity with the obtained fluorescence intensity as the vertical axis and each temperature cycle as the horizontal axis, the amplification curves shown in FIG. 11 can be obtained. This makes it possible to obtain amplification curves in parallel for 6 samples at the same time.

In step S5, the photometric analysis unit 93 determines whether or not the amount of the target nucleic acid is sufficiently present in the nucleic acid solution, and if it is not sufficiently present, the process proceeds to step S9 and the process is completed. If it is determined that a sufficient amount of the target nucleic acid is present in the nucleic acid solution, the process proceeds to step S6.

In step S6, the variable-pitch liquid storage pedestal 36 is moved along the X-axis direction by the first pitch, so that the variable-pitch liquid storage pedestal 36 is provided on the variable-pitch liquid storage pedestal 36 and contains the nucleic acid solution 45 μ \ ochL. the movable liquid storage unit 36 _{'1-36' 6,} is moved to a position along the second housing part columns from the first housing portion rows of the accommodation unit group 3 ₁ to 3 _6. Next, the nozzle head 4 is moved to the upper side of the flow tube accommodating area 31 by using the nozzle head moving mechanism 49, and the nozzle group 4 ₁ to 4 ₆ , 4'using the nozzle Z-axis moving portion 42. 'by lowering the _6, the dispensing flow tube 2 ₁ to 2 _6, 2 ₁ to 2 ₆ nozzle group 41 _{to 6,} 4' _1-4 each is attached to the _{1-4 '6.} The nozzle head 4 is moved in the Y axis direction, after the position above the variable pitch liquid container mount 36, by lowering, the dispensing flow tube attached to the nozzle group 4 _{'1-4' 6} 2 ₁ to 2 ₆ movable housing portion 36 _'1-36' is inserted into the ₆ sucks the nucleic acid solution 45μ \ ochL, nozzle groups 41 _{to 6} mounted a dispensing flow tube 2 ₁ ~ ₂₆ descends the space outside the support plates 365 _{1 to} 365 ₆ that support the movable liquid accommodating portions 36 _{1 to} 36 ₆ , 36 ' _{1 to} 36' ₆ , and collides with the variable pitch liquid accommodating stand 36. There is nothing to do. This is because the variable pitch liquid accommodating stand 36 has a variable pitch with the second pitch as the maximum pitch, so that a gap is formed between the adjacent movable liquid accommodating portions.

By moving the nucleic acid solution of the 45μ \ ochL housed in the flow pipe 2 ₁ to 2 ₆ mounted to the nozzle group 4 _{'1-4' 6,} the nozzle head 4 in the Y-axis direction, the flow tube 2 ₁ to 2 _6, 2 ₁ to 2 ₆ after being positioned above the reaction vessel 321 _{1-321 6} and the reaction vessel 321 _{1-321 6} and are provided alternately six relief hole 324 , by lowering, discharging the nucleic acid solution 45μ \ ochL dispensing flow tube 2 ₁ to 2 ₆ mounted to the nozzle group 4 _{'1-4' 6} is inserted into the reaction vessel 321 _{1-321 6} and, flow tube 2 ₁ to 2 ₆ mounted to the nozzle groups ₄₁ to ₆ descends the relief hole 324, does not collide with the housing part group 3 ₁ to 3 _6. Incidentally, in the reaction vessel 321 _{1-321 6,} using the cross head 46, beforehand based on the Sanger method from the common receiving area 3 _0, primers, DNA polymerase, labeled labeled with four different fluorescent substance Dideoxynucleotides (ddATP, ddGTP, ddCTP, ddTTP) have been dispensed.

In step S7, the nozzle head 7 is moved to the flow tube accommodating area 31, and the flow tubes 2 ₁ to ₂₆ and 2 ₁ to ₂₆ are simultaneously attached and detached by the flow tube attachment / detachment mechanism 45. wherein after positioning the nozzle head 7 above the sealing cover housing portion 34 _{1-34 6,} the sealing lid 34 is attached to the nozzle groups ₄₁ to ₆ by lowering the reaction vessel 321 ₁ the nozzle head 7 After being located above ~ 321 _6, the sealing lid 34 is fitted into the opening by lowering to seal the reaction vessel, and then the reaction vessels 321 _{1 to 321 6} are moved to the temperature elevator 39. Using the PCR method, a fragment of the target nucleic acid is produced and amplified.

Then, the nucleic acid solution that is fragmented is generated, the drilling tip 23 _{1-23 6} of the nozzle head 4 to move in the Y axis direction the flow tube receiving area 31, 23 ₁ to 23 ₆ accommodating portion of after overlying, lowered attached to each nozzle ₄₁ to _8, then again moved in the Y-axis direction, and piercing the sealing lid 34 for closing the reaction vessel 321 _{1-321 6,} the nozzle 4 again _{1-4 8,} 4 _{'1-4' 6} the flow tube 2 ₁ to 2 _6, 2 ₁ to 2 ₆ mounted on, sucking the generated fragmented nucleic acid solution to flow tube, said nozzle using head moving mechanism 49, housed in the movable liquid storage unit group 36 ₁ to 36 ₆ of the variable pitch liquid container mount 36, the variable pitch liquid storage rack 36 is moved in the X-axis direction by the gantry movement portion 37 the move to electrophoresis unit 5, at the same time, the pitch of the movable Doeki accommodating portion 36 _{1-36 6,} converting the second pitch in the third pitch Te.

In step S8, the n pieces (this example of the fragments of the target nucleic acids are generated to the respective movable liquid storage unit 36 ₁ to 36 ₆ electrophoresis sample is housed included in the random electrophoresis section 5 6 one end portion and the negative electrode 54 _{1-54 6} of the electrophoresis capillary 51 _{1-51 6} of the present) is inserted, by a predetermined voltage between the electrode pairs is applied, a fragment of the target nucleic acid electrophoresis do.

Then, by the irradiation light receiving pair selecting measuring unit 80 of the light selection measuring unit 8, a capillary holder 53 for holding the capillary 51 _{1-51 6} near the other end of the electrophoresis capillary 51 _{1-51 6} the pair irradiation end sets 63 and receiving end sets 73 of which is provided close to or in contact with the outer surface of each electrophoretic capillary 51 _{1-51 6} is selected, i.e., the irradiation end and receiving end of the plurality of pairs ( 63 _1, 73 ₁₎ to (63 _6, 73 ₆₎ is selected, therefore, the corresponding one-to-irradiated connecting end sets of 64 and the light receiving connection end pairs 74 pairs connecting end assembly array 82, therefore, a plurality of pairs A pair of the irradiation measurement end set 842 and the light receiving measurement end set 832 arranged in the pair measurement end set array 8112 of the measurement end set array 811 are selected, and a plurality of pairs of the plurality of pairs of the connection end set array 82 are combined. It is moved with respect to the measurement end set array 811 at a predetermined speed in the X-axis direction, and further reciprocated repeatedly at a predetermined predetermined cycle. Thereby, each of the selected pair of connection ends (64,74) of the plurality of pairs of connection ends array 82 is sequentially subjected to a pair corresponding to the fluorescent substance used in the corresponding plurality of pairs measurement end assembly arrangement 811. The connection and disconnection are repeated for the measurement end set (842, 832) of.

The selection of the irradiation / light receiving pair is optically connected to the pair of irradiation measurement end sets 842 and the light receiving measurement end set 832, which should be connected to the selected pair of irradiation end sets 63 and light receiving end set 73. This is performed by turning on the light source 84 and the photoelectric conversion unit 83 to be turned on, and turning off the other light sources 84 and the photoelectric conversion unit 83. If the photometric analysis unit 93 graphs the obtained fluorescence intensity on the vertical axis and the detection time (fragment size) on the horizontal axis, each type of fluorescence for each capillary is shown in FIG. 14 (a). An intensity graph will be obtained. By superimposing the fluorescence intensity data, a base sequence can be obtained as shown in FIG. 14 (b). Therefore, the nucleotide sequences of 6 samples can be determined in parallel at the same time. The analysis process by the photometric analysis unit 93 corresponds to the process in the analysis step.

Subsequently, the optical selective measurement unit 8'according to the second embodiment according to the embodiment of the present invention will be described.
12 (a) is a second pair of irradiation end sets of light selecting measuring unit 8 'according to the embodiment and light receiving end sets of the present invention (61, 71) irradiation light receiving pairs (61 _1, 71 ₁₎ there is shown a portion of a ~ (61 _6, 71 _6), are those provided in the nozzle group ₄₁ to _6. The same reference numerals may be used for the portions that overlap with the optical selection measurement unit 8 according to the first embodiment, and the description thereof may be omitted.
12 (b) is a view illustrating the light irradiating and receiving pair of irradiation end set and light receiving end sets (63, 73) (63 _1, 73 ₁₎ to (63 _6, 73 _6), a capillary for the electrophoretic 51 _1-51 provided on the measuring unit _6, for example, as a light receiving end and radiation end sandwich facing each capillary 51 _{1-51 6} in the radial direction, the same radius with respect to the outer wall surface of each capillary It is provided so that it is aligned in the direction or at a predetermined angle.

FIG. 12 (c), which shows a part of the irradiation light receiving pairs of pair irradiation end set and light receiving end sets of (61,75) (61 _1, 75 ₁₎ to (61 _6, 75 _6), irradiation end assembly 61 _{1-61 6} is provided in the nozzle group 41 _{to 6,} the receiving end sets 75 _{1-75 6,} the metering area 38 X-axis direction (row direction) along the second It is arranged at a pitch, and are arranged so as to be positioned in the first housing portion rows of the accommodation unit group 3 ₁ to 3 _6. Moreover, the the receiving end and the irradiation end of each irradiation light receiving pair, provided to be positioned in a vertical common axis line connecting the mouth portion 2a and the mounting opening 2b of the flow tube attached to the nozzle 4 _{1-4 6} ing.

FIG. 12 (d) shows a pair of irradiation end sets and light receiving end sets (61, 71), (63) from the plurality of sets of irradiation end sets 61, 63 and the plurality of sets of light receiving end sets 71, 73, 75. , 73), (61, 75) are selected, the pair of the irradiation end and the light receiving end belonging to the selected set is set as the irradiation light receiving pair, and a predetermined measurement light is sequentially supplied to the irradiation end, and the light receiving is received. The irradiation light-receiving pair selective measurement unit 80 which measures the intensity of light received sequentially by an edge is shown.

FIG. 12D shows the plurality of pairs of the paired connection end set array 82'of the irradiation light receiving pair selective measurement unit 80'and the multiple pair measurement end set array 811'of the pair selection interlocking switching unit 81'. Is.

Plurality several pairs connecting end assembly array 82 'is irradiated connecting end 62 _{1-62 6} having one end with the other end of the two pairs of the irradiation end sets 61 and 63 are each 64 _{1-64 6} wherein the plurality number (six in this example) belonging two sets irradiation connection end pairs 62, 64 and of the one end a plurality of light receiving ends of the light receiving end sets 71, 73, 75 71 _{1-71 6} 73 _{1-73 6} , 75 _1-75 plurality is receiving connection end of the other end portion has respective optical fiber 171, 173, 175, as a plurality of light guides having ₆ (six in this example) belonging three sets of light receiving connection end pairs There are 72, 74, and 76, and the irradiation connection end or the light receiving connection end belonging to each of the same set is arranged in a row along the row direction (X-axis direction) at predetermined intervals to form different sets that can be paired. The irradiation connection end and the light receiving connection end to which the light receiving connection end belongs are arranged in parallel with a pair spacing along the direction (in this example, the column direction, that is, the Y axis direction) orthogonal to the row direction (X-axis direction). It has a plurality of pairs of connected end-set arrays 82'having an array surface and the plurality of pairs of measurement end-set arrays 811' of the pair selection interlocking switching unit 81'. The irradiation connection ends and the light receiving connection ends belonging to different sets that cannot be paired with them are positioned at predetermined intervals along the row direction (X-axis direction) (see FIG. 8) or in the column direction (Y-axis direction). ) Can be arranged in parallel with a pair spacing different from the pair spacing.

As shown in FIG. 12 (d), the plurality of pairs of measurement end sets 811'are optically connected to the light source 84 that can be turned on and off, and the irradiation connection ends 62 ₁ to the irradiation connection ends 62, 64 of the irradiation connection end sets 62, 64. 62 _6, 64 ₁ to 64 ₆ and sequentially connectable to provided the one or more radiation measuring end 841a~841d, 842a~842d, 843a, a plurality of sets of 843b is provided each irradiation measuring portion sets 841 and 842 , and 843, on-off possible the photoelectric conversion unit 83 and is optically connected, receiving connection end 72 _{1-72 6} of the light receiving connection end pairs 72, 74, 76, 74 to _{72d 6,} 76 ₁ to 76 ₆ A plurality of sets of light receiving measurement ends 831a to 831d, 832a to 832d, 833a, and 833b, which are provided so as to be sequentially connectable to the light receiving measurement ends 831a to 831d, 832a to 832d, 833a, and 833b. It has measurement end array planes 813 arranged along (in this example, the X-axis direction) (correspondence is in sign order). Here, the irradiation measurement end set 843 and the light receiving measurement end set 833 that can be paired can be divided into the irradiation measurement end and the light receiving measurement end (843a, 833a) to (843b, 833b) that can be paired. The paired measurement end set array 8113 is formed.

Here, the switching mechanism (814,815,816) is such that the connection end array surface and the measurement end array surface 813 face each other and slide along the predetermined direction (in this example, the row direction, that is, the X-axis direction). ) Moves the plurality of pairs of end-set arrangements 82 relative to the plurality of pairs of measurement end-set arrangements 811. Then, irradiation connecting end group selected as pairs and receiving the connection end pairs (62, 72), (64, 74), each connection end pairs belonging to (62, 76) (62 _1, 72 ₁₎ to (62 ₆ , 72 _6), (64 _1, 74 ₁₎ to (64 _6, 74 _6), connected to the light source 84 in a, are selected to the oN state (62 _1, 76 ₁₎ to (62 _6, 76 ₆₎ A pair (841,831) of a first measurement end set consisting of an irradiation measurement end set and a light receiving measurement end set connected to a photoelectric conversion unit 83 which is selected and turned on (arranged in a pair measurement end set array 8111). Each of the measurement end pairs (841a, 831a) to (841d, 831d) belonging to the second measurement end pair (842,832) (arranged in the pair measurement end set array 8112). Measurement end pairs (842a, 832a) to (842d, 832d), or measurement end pairs (843a, 833a) to (843b) belonging to a third measurement end set (arranged in the pair measurement end set array 8113). , 833b) enables connection and disconnection of each pair, and for each pair of irradiation end and light receiving end (irradiation light receiving pair) connected to these, the light source in the on state and the photoelectric in the on state. Connection or disconnection with the conversion unit is performed in conjunction with each other. One of the three pairs of the first measurement end set, the pair of the second measurement end set, and the third measurement end set is selected, and the corresponding light source and photoelectric conversion unit are in the ON state. In this case, since the other 2 is not selected, the corresponding light source and the photoelectric conversion unit are in the off state. The paired measurement end assembly 8113 includes a corresponding light source 84 and a photoelectric conversion unit 83, one pair for each pair of measurement ends.

Here, in the second embodiment, in addition to the measurement of qPCR described in the first embodiment, it is also possible to measure the absorbance, whereby the absorbance is measured instead of qPCR. By doing so, the concentration of nucleic acid can be used for measurement.
In this case, the irradiation end 61 _{1-61 6} of the irradiation end sets 61, irradiation connecting end 62 _{1-62 6} and a plurality of pairs measuring portion sets array of irradiation connecting end assembly 62 a plurality of pairs of connection ends assembly array 82 As the light source 84, for example, a deuterium lamp that emits ultraviolet rays having a wavelength of 260 nm and a wavelength of 280 nm is turned on and the other light sources are turned off via the irradiation measurement ends 843a and 843b of the irradiation measurement end set 843 of 811'. As an optical connection. Then, the light receiving end 75 _{1-75 6} receiving end sets 75 forming a pair are selected, the light receiving connection end 76 _{1-76 6} and a plurality of pairs of pairs connecting end assembly array 82 'of the receiving connection end pairs 76 The line sensor type spectrophotometer is turned on as the photoelectric conversion unit 83 and the other photoelectric conversion units are turned off via the light receiving measurement ends 833a and 833b of the light receiving measurement end group 833 of the measuring end set array 811'. , Optically connect.

In the second example, unlike the case of the first example, in step S4, the target nucleic acid is measured by measuring the absorbance of the nucleic acid solution instead of the qPCR method as a quality evaluation process of the target nucleic acid. Measure the amount of.

This will be described with reference to FIGS. 2, 4, 12, and 13. The description of the part overlapping with the first embodiment has been omitted. Step S4, when aspiration of the said eighth extracted nucleic acid solution 5 [mu] \ och1 contained in the liquid accommodating portion with the small amount dispensing flow pipe 21 ₁ to 21 _6, the nozzle Z-axis moving unit after raising the 42, wherein a top of the light receiving end 75 _{1-75 6} of the photometric region 38 of the stage 3 by using the nozzle head moving mechanism 49, provided at the lower end of the nozzle ₄₁ to ₆ wherein the irradiation end 61 _{1-61 6} receiving end 75 _{1-75 6,} positioned to come to a vertical common axis line connecting the fitting opening 2b and the mouth portion 2a of the flow tube 21 ₁ to 21 _6.

Next, the 'the irradiation light receiving pair selecting measuring section 80' of the light selection measuring unit 8, irradiation end sets 61 and receiving end sets 75 pair provided in the nozzle 41 _{to 6} is selected, i.e. , irradiation end and receiving end of the plurality of pairs (61 _1, 75 ₁₎ to (61 _6, 75 ₆₎ is selected, therefore, a plurality of pairs connecting end assembly array 82 'of the corresponding pair irradiation connecting end sets of 62 And the light receiving connection end set 76, and therefore the pair of irradiation measurement end sets 843 and the light receiving measurement end set 833 of the multiple pair measurement end set array 811'are selected to form the plurality of pair connection end set array 82. It is moved at a predetermined speed in the X-axis direction with respect to the paired measurement end set array 811', and further reciprocated repeatedly at a predetermined predetermined cycle. The measurement ends thereby sequentially connecting each selected pair of connection ends (62,76) of the plurality of pairs of connection ends array 82'to the corresponding pair of pairs of measurement ends array 811'. The connection and disconnection are repeated for the measurement end set (843, 833). FIG. 13B shows the connection and disconnection.
As a result, for example, the light source 84 of the white light by the deuterium lamp (or xenon lamp) is turned on, and the measurement light of the white light (including ultraviolet rays) having wavelengths of 260 nm and 280 nm is irradiated, and the light receiving end 75 ₁ 75 an electric signal the photoelectric conversion unit 83 in the oN state for wavelengths 260nm and 280nm through a spectroscope the intensity of the transmitted light of said solution from said measuring portion sets 832 lens is received via the provided ₆ Obtain strength data as.

Next, the photometric analysis unit 93 of the CPU + program + memory 9 as the control unit obtains the absorbance of the nucleic acid solution based on the _{intensity data I 0 and the intensity data I.}

That is, as described above, the photometric analysis unit 93 obtains the absorbance of the wavelength λ of the chemical substance solution A from A _λ = −log ₁₀ (I / I _o ) from _{the incident light intensity I 0 obtained in advance.} Then, assuming that the concentration of the chemical substance solution A is c, the known extinction coefficient ε \ och (molar extinction coefficient, = 0.002 mg / mL) of the chemical substance solution A (dNTP) is used. The concentration c can be obtained from the relational expression A _{λ = ε \ ochcL.}

At that time, it is preferable to obtain the concentration c from the relationship formula obtained in advance from the _{absorbance A 260} or A _{280 at} the peak wavelength λ = 260 nm and 280 nm of the absorbance curve, using the optical path length L or the amount of the liquid. Figure 13 shows the intensity data of each nucleic acid solution corresponding to the flow tube 21 ₁ to 21 ₆ containing a nucleic acid solution of canine genome extracted from whole blood of the dogs thus obtained. An example of the absorbance A ₂₆₀ is shown, and the photometric analysis unit 93 can obtain the concentration from the _{absorbance A 260} or A _{280 by using the relational expression obtained in advance.} The vertical axis represents the wavelength 260nm in FIG. 13 (c), and is indicative of the intensity data I in 280 nm, horizontal axis corresponds to the illumination light receiving pairs of each flow tube 21 ₁ to 21 _6, and the nozzle 4 _{1-4 6} It represents the X coordinate along the X-axis direction with respect to the plurality of pairs of connection end set array 82'and the plurality of pairs of measurement end set array 811'. The measurement is carried out sequentially within a predetermined period (1 second) of 1 while advancing in one direction at a predetermined speed, for example, along the X-axis direction, for example, 0.1 mm at a speed of 1 msec.

In the above description, only the case where six electrophoresis capillaries and flow tubes are provided and six storage groups are provided has been described, but the present invention is not limited to six. Further, the paired irradiation end and the light receiving end can be exchanged, and the above description is not limited to the case.

Further, the shape, structure, and function of each component described above are not limited to the examples described in the embodiments. For example, in the above description, a timing belt is used for the nozzle head moving mechanism and a ball screw is used for the nozzle moving part. However, the timing belt and the ball screw can be arbitrarily replaced, and other mechanisms can be used. Can be configured in the same manner by using. In the above description, it is assumed that the X-axis, the Y-axis, and the Z-axis form a Cartesian coordinate system. Further, although the row direction and the column direction correspond to the X-axis direction and the Y-axis direction, they may correspond to the Y-axis direction and the X-axis direction.

In the above description, the absorbance was measured using a spectroscope on the light receiving portion side, but it is also possible to measure using a filter. When a multi-channel spectroscope or the like including a photoelectric conversion unit is used as the spectroscope, the light receiving switching unit becomes unnecessary. It is also possible to use a spectroscope or a filter on the irradiation unit side.

Further, in the above description, the measurement target is nucleic acid as a chemical substance, but the measurement target is not limited to this case, and other high molecular substances such as amino acids, proteins, sugar chains, fats and the like, and solids such as magnetic substances are used. It may be a chemical substance solution having various liquid amounts containing various chemical substances such as substances, bubbles, gases, and liquids.

In order to measure the difference in molecular size mainly of protein as a target substance by electrophoresis, for example, SDS polyacrylamide gel electrophoresis is used. In this case, irradiation end set and light receiving end sets of a pair provided in the capillary which is selected (63, 73) in the irradiation receiving end pair belonging (63 _1, 73 ₁₎ to (63 _6, 73 _6), via a pair of irradiation connecting end set and receiving a connection end sets of irradiation connection end and receiving the connection end of the pair belonging to the (64, 74) (64 _1, 74 ₁₎ to (64 _6, 74 _6), a pair Optically with a pair of measurement end set having a pair of irradiation measurement ends and light receiving measurement ends (842a, 832a) to (842b, 832b) belonging to the irradiation measurement end set and the light receiving measurement end set (842,832). Will connect. At that time, each separable paired measurement end body forming the paired measurement end assembly is replaced with one that is optically connected to a deuterium lamp that emits ultraviolet rays having a wavelength of 260 nm or 280 nm, respectively, and the deuterium lamp is replaced. It was turned on and the other light source off, and by the oFF state of the other photoelectric conversion unit is turned on the line sensor type spectrophotometer, ultraviolet of the electrophoretic capillary 51 _{1-51 6} This is done by measuring the absorbance used.

In the above description, necessary corrections and replacements shall be made in the paired irradiation end set and light receiving end set (61,71), (61,75), (61,77), (63,73). It is possible to switch between the irradiation end and the light receiving end.

The present invention relates to a fully automatic electrophoresis processing device and a method thereof. The present invention relates to fields requiring the handling of biopolymers such as genes, immune systems, amino acids, proteins and sugars, and small biomolecules, such as industrial fields, foods, agricultural products, agricultural fields such as fishery processing, and pharmaceutical fields. It is related to all fields such as health, health, immunity, diseases, medical fields such as heredity, and science fields such as chemistry or biology.

10,100 Electrophoresis fully automatic processing device 2 ₁ to 2 _n , 2 ₁ to 2 _n Dispensing flow tube 21 _{1 to 21 n} Small amount dispensing flow tube (also used as photometric flow tube)
22 _{1 to} 22 _n Dispensing flow pipe
23 ₁ ~23 _n, 23 ₁ ~23 for _n drilling tip 3 Stage 3 ₁ to 3 _n accommodating portion group 34 ₁ to 34C _n sealing cover housing portion 34 the sealing lid _{32 1 ~32 n, 32 '1} ~32' n reaction container 4, the nozzle head _{4 1 ~4 n, 4 '1} ~4' n nozzle groups 41, 41 ₁ to 41 _n suction and discharge mechanism 416 dispensing cylinder 44 Z-axis moving body (nozzle support)
45 Detachment mechanism 49 Nozzle head movement mechanism 51 _{1 to} 51 _n Electrophoresis capillary 61 _{1 to 61 n} , 63 _{1 to} 63 _n Irradiation end (light selection measurement unit)
161,171,163,173,175,177
Light guide path (optical selection measurement unit)
71 _{1 to 71 n} , 73 _{1 to 73 n} , 75 ₁ to 75 _n , 77 _{1 to 77 n}
Light receiving end (light selective measurement unit)
8,8'Light selective measurement unit 80,80' Irradiation light receiving pair selective measurement unit (light selective measurement unit)
81, 81'pair selection interlocking switching unit (optical selection measurement unit)
82, 82'Multiple paired end assembly array (optical selective measurement unit)
83 Photoelectric conversion unit (optical selective measurement unit)
84 Light source (light selective measurement unit)
9 CPU + program + memory (control unit)
93 Photometric analysis unit (control unit)

Claims (14)

A capillary electrophoresis unit that has a plurality of capillarys for electrophoresis and allows a target substance to be electrophoresed in the capillary by applying a voltage.
An electrophoresis sample containing the target substance obtained through extraction treatment of the target substance from the sample, processing treatment of the target substance, and quality evaluation of the product or chemical substance related to each treatment is obtained from the capillary electrophoresis unit. An electrophoresis pretreatment unit that can be supplied to each of the above-mentioned capillaries,
Any at least one light measurement can be performed by selecting from the group consisting of light measurement for each of the capillaries of the electrophoresis unit and light measurement for the quality evaluation of the electrophoresis pretreatment unit. Light selection measurement unit and
The extraction process of the target substance from a sample, processing that purpose materials, analysis of the target substance, and possess a control unit for controlling the quality evaluation,
The optical selective measurement unit
A plurality of sets of irradiation end sets having an irradiation end, which is one end of each of a plurality of light guide paths capable of irradiating measurement light determined by the measurement content or the product containing the target substance or the chemical substance, and a plurality of sets of irradiation ends. , Each one end of a plurality of light guide paths that are located at a position corresponding to the irradiation end set or are positionably provided and can receive light generated based on the measurement light emitted from the irradiation end. Multiple sets of light receiving ends, each set having an end,
When the control unit gives an instruction for analysis processing or quality evaluation of the target substance, one set of irradiation end sets and one set of paired irradiation end sets from the plurality of sets of irradiation end sets and multiple sets of light receiving end sets. A light receiving end set is selected, and a predetermined measurement light is sequentially supplied to the irradiation end for each irradiation light receiving pair consisting of the corresponding pair of irradiation ends and the light receiving end, and the intensity of the light sequentially received by the light receiving end. electrical to have the irradiation light receiving pair selecting measuring unit for measuring the electrophoretic fully automatic processing apparatus. The irradiation light receiving pair selective measuring unit is
One or more light sources that emit a predetermined measurement light selected according to the above instructions, and
One or more photoelectric conversion units that convert the received light into an electric signal,
Based on the above instructions, a pair of irradiation end sets and light receiving end sets are selected from a plurality of sets of irradiation end sets and a plurality of sets of light receiving end sets, and one or more light sources and the selected irradiation end sets are selected. The connection or cutoff between the irradiation end belonging to the above and the connection or cutoff between one or two or more photoelectric conversion units and the light receiving end belonging to the selected light receiving end set are interlocked for each irradiation light receiving pair. electrophoresis fully automatic processing apparatus according to claim 1 having, a pair selected interlock switching unit for switching to. In the irradiation light receiving pair selective measurement unit, the irradiation connection to which one end of each of the other ends of the plurality of light guide paths having one irradiation end belonging to the irradiation end set belongs to the plurality of irradiation connection ends. The end set and the light receiving connection end set to which the plurality of light receiving connection ends each of the other ends of the plurality of light guide paths each having one light receiving end whose one end belongs to the light receiving end set belong. There are a plurality of sets of each, and the irradiation connection ends or the light receiving connection ends belonging to the same set are arranged in a row at predetermined intervals along a predetermined direction, and the irradiation connection ends or the light receiving connection ends belonging to different sets that can be paired with each other. The light-receiving connection ends further have a plurality of pairs of connection-end array having connection-end array planes arranged in parallel at intervals along a direction orthogonal to the predetermined direction.
The pair selection interlocking switching unit is
One or two or more irradiation measurement ends that are optically connected to the light source that can be turned on and off and are provided so as to be sequentially connectable to the irradiation connection ends belonging to the irradiation connection end set are predetermined in a row along the predetermined direction. 1 or 2 provided to be optically connected to a plurality of sets of irradiation measurement ends provided at intervals and the photoelectric conversion unit capable of being turned on and off, and sequentially connectable to the light receiving connection ends belonging to the light receiving connection end set. A plurality of sets of light receiving measurement ends, each of which is provided in a row at predetermined intervals along the predetermined direction, are arranged with the pair spacing along a direction orthogonal to the predetermined direction. Multiple pairs of measurement end-set arrays with measurement end array planes,
The plurality of pairs of connection end arrangements and the plurality of pairs of measurement end arrangements are relatively moved so that the connection end arrangement surface and the measurement end arrangement surface face each other and slide along the predetermined direction. Allows simultaneous connection or disconnection of the selected irradiation connection end and light reception connection end and the irradiation measurement end and light reception measurement end, and for each irradiation light reception pair of the selected pair, the irradiation end and the light reception end The electrophoresis according to claim 2 , further comprising a switching mechanism in which the connection or disconnection with the light source in the ON state is sequentially performed in conjunction with the connection and disconnection between the light receiving end and the photoelectric conversion unit in the ON state. Fully automatic processing device. The electrophoresis pretreatment unit is
A magnetic field is applied from the outside to a plurality of nozzles to which a flow tube capable of sucking and discharging a liquid is detachably attached and a flow tube attached to the nozzle, which communicates with a suction and discharge mechanism for sucking and discharging gas. A magnetic part that can be removed and
It has at least a liquid storage unit for accommodating various chemical substance solutions including a sample to be inspected and a suspension of magnetic particles and a reaction vessel whose temperature can be controlled by a temperature elevator, and is provided corresponding to each of the nozzles. A stage with multiple containment groups and
It has a nozzle moving mechanism that allows relative movement between the nozzle and the stage.
The first set of one of the irradiation end set and the light receiving end set of the light selective measurement unit is provided in the nozzle or the suction / discharge mechanism, and the second set of the one is the capillary for each electrophoresis or after each electrophoresis. The first set of the irradiation end set and the other first set of the light receiving end set is provided on the nozzle or the suction / discharge mechanism so as to be paired with the first set of the one, which is provided in contact with or close to the outer surface of the accommodating portion. The other second set is provided so as to be paired with the one second set and is provided in contact with or close to each of the electrophoresis capillaries or the outer surface of each post-electrophoretic accommodating portion. Item 3. The fully automatic electrophoresis processing apparatus according to Item 3. It further has a third set of the irradiation end set and the other third set of the light receiving end set, and the other third set is outside the flow tube, and the mouth portion of the flow tube can be positioned above the flow tube. The fully automatic electrophoresis processing device according to claim 4 , which is provided so as to be capable of pairing with the first set of the one. When the control unit instructs the measurement of the presence or absence or amount of the target substance labeled with a fluorescent substance in the product or chemical substance solution, when the control unit instructs the measurement.
Move the nozzle to the containment area where the product or chemical solution is contained and
The pair selection interlocking switching unit belongs to the first set of one of the irradiation end set and the light receiving end set, and the irradiation end and the light receiving end belonging to the other first set of the irradiation end set and the light receiving end set, respectively. One or more types that select a pair of the irradiation measurement end set and the light receiving measurement end set that can be connected to, and optically connect to one or two or more irradiation measurement ends belonging to the selected irradiation measurement end set. Only one or more light sources using the excitation light of the wavelength of (1) as the measurement light are turned on, and the excitation light optically connected to one or more light reception measurement ends belonging to the selected light reception measurement end set is used. Only the photoelectric transformation tube portion via the bandpass filter capable of passing the excited fluorescence is turned on, and the connection and cutoff between the irradiation end and the light receiving end and the irradiation measurement end and the light receiving measurement end are interlocked. Sequential switching,
When the control unit gives an instruction for analysis processing using electrophoresis of the target substance, one end of each electrophoresis capillary is contained in each moving fluid accommodating portion in which the electrophoresis sample is accommodated. To insert
The pair selection interlocking switching unit includes an irradiation end and a light receiving end that belong to the second set of one of the irradiation end set and the light receiving end set, and the other second set of the irradiation end set and the light receiving end set, respectively. One or a plurality of wavelengths that select a pair of the irradiation measurement end set and the light receiving measurement end set that can be connected and optically connect to one or a plurality of irradiation measurement ends belonging to the selected irradiation measurement end set. Only one or more types of light sources using the excitation light or white light as measurement light are turned on, and the excitation is optically connected to one or more light receiving measurement ends belonging to the selected light receiving measurement end set. Only the photoelectric conversion unit or spectrophotometer via a bandpass filter capable of passing fluorescence excited by light is turned on, and the connection and disconnection between the irradiation end and the light receiving end and the irradiation measurement end and the light receiving measurement end are cut off. The fully automatic electrophoretic processing apparatus according to claim 4 , wherein the devices are sequentially switched in conjunction with each other. In the electrophoresis pretreatment unit, the nozzles are provided so as to be movable only in the column direction and the vertical direction, and are provided so as to be arranged in a row along the row direction at a first pitch. The groups are provided so as to extend in a single row or a plurality of rows along the column direction and are arranged at a second pitch along the row direction. A plurality of flow tubes extending along the column direction and arranged in the row direction at a third pitch, and attached to a group of nozzles arranged at the second pitch among the nozzles. Are provided so that they can be inserted into each housing all at once.
A group of movable fluid accommodating portions or a group of movable fluid accommodating portions composed of the plurality of movable fluid accommodating portions arranged in a row at a variable pitch along the row direction are arranged in parallel at intervals in the column direction. A plurality of groups of variable-pitch liquid accommodating pedestals are provided so as to move the gantry along the row direction for each of the first pitches or between the electrophoresis pretreatment unit and the capillary electrophoresis unit. It has a gantry moving portion and a pitch conversion mechanism provided so that the variable pitch can be converted between the second pitch and the third pitch, and one end of the electrophoresis capillary is a group. The fully automatic electrophoresis processing device according to claim 6 , which is provided so as to be able to be inserted into a plurality of the movable liquid storage units belonging to the movable liquid storage unit group all at once. A capillary electrophoresis step in which a target substance is electrophoresed by applying a voltage into a plurality of capillary electrophoresis steps,
An electrophoresis sample containing the target substance obtained through extraction treatment and processing treatment of the target substance from the sample and quality evaluation of the product or chemical substance related to each treatment is supplied to each of the electrophoresis capillaries. The electrophoretic pretreatment process that enables
Select from the group consisting of light measurements for each capillary used in the capillary electrophoresis step and light measurements for quality evaluation in the electrophoresis pretreatment step, and any at least one measurement. The optical selective measurement process to be performed and
Possess the analyzing step to analyze the quality evaluation and objective substance for each treatment, wherein the light selection measuring step, capable of emitting measurement light is determined by the product or the chemical containing photometric content or the target substance A plurality of sets of irradiation ends having an irradiation end, which is one end of each of the plurality of light guide paths, and a position corresponding to the irradiation end set or provided so as to be positioned and irradiating from the irradiation end. A plurality of sets of light-receiving end sets having a light-receiving end, which is one end of each of a plurality of light guide paths capable of receiving light generated based on the measured light, are provided, and electrophoresis of the target substance is performed. When an instruction is given for analysis processing or quality evaluation based on the above, a pair of irradiation end sets and a set of light receiving end sets are selected from the plurality of sets of irradiation end sets and multiple sets of light receiving end sets. Irradiation that selects and sequentially supplies a predetermined measurement light to the irradiation end for each irradiation light receiving pair consisting of the corresponding pair of irradiation ends and the light receiving end, and measures the intensity of the light sequentially received by the light receiving end. electrophoresis fully automatic processing method for chromatic light receiving pair selection measuring step. The irradiation light receiving pair selective measurement step is
Based on the above instructions, a pair of irradiation end sets and light receiving end sets are selected from a plurality of sets of irradiation end sets and a plurality of sets of light receiving end sets, and a predetermined measurement light selected according to the instruction is emitted. A selection of one or more light sources to be emitted, a connection or cutoff between the selected irradiation ends belonging to the irradiation end set, and one or more photoelectric conversion units for converting the received light into an electric signal. The fully automatic electrophoresis processing method according to claim 8 , further comprising a pair selection interlocking switching step of interlocking and switching the connection or disconnection with the light receiving end belonging to the light receiving end set for each irradiation light receiving pair. In the pair selection interlocking switching step, the irradiation connection end to which the plurality of irradiation connection ends of each of the other ends of the plurality of light guide paths each having one irradiation end belonging to the irradiation end set belongs to the one end. Each of the set and the light receiving connection end set having the plurality of light receiving connection ends each of the other ends of the plurality of light guide paths having one light receiving end having one light receiving end belonging to the light receiving end set. There are a plurality of sets, and the irradiation connection ends or the light receiving connection ends belonging to the same set are arranged in a row at predetermined intervals along a predetermined direction, and the irradiation connection ends or the light receiving light belonging to different sets that can be paired. The connection ends are optically connected to a plurality of pairs of connection end array having a connection end array surface arranged in parallel at intervals along a direction orthogonal to the predetermined direction, and the light source that can be turned on and off. A plurality of sets of irradiation in which one or more irradiation measurement ends provided so as to be sequentially connectable to the irradiation connection ends belonging to the irradiation connection end set are provided in a row at predetermined intervals along the predetermined direction. One or two or more light receiving measurement ends that are optically connected to the measurement end set and the photoelectric conversion unit that can be turned on and off and are provided so as to be sequentially connectable to the light receiving connection ends belonging to the light receiving connection end set are in the predetermined direction. Multiple pairs of measurement ends having a pair of measurement end array planes in which a plurality of sets of light receiving measurement end sets provided in a row at predetermined intervals are arranged at intervals along a direction orthogonal to the predetermined direction. With a set array,
The irradiation connection end, the light receiving connection end, the irradiation measurement end, and the selected irradiation connection end, the light receiving connection end, and the irradiation measurement end are relatively moved so that the connection end arrangement surface and the measurement end arrangement surface face each other and slide along the predetermined direction. Each of the light receiving measurement ends is connected or cut off in conjunction with each other, and for each pair of the irradiation end and the light receiving end of the selected pair, the connection cutoff between the irradiation end and the light source in the ON state is the light receiving end. The fully automatic electrophoresis processing method according to claim 9 , which is sequentially performed in conjunction with the connection and disconnection of the photoelectric conversion unit in the ON state. The electrophoresis pretreatment step is
A magnetic field is applied from the outside to a plurality of nozzles to which a flow tube capable of sucking and discharging a liquid is detachably attached and a flow tube attached to the nozzle, which communicates with a suction and discharge mechanism for sucking and discharging a gas. At least each of the reaction vessels, which are provided with a magnetic force unit that can be removed and whose temperature can be controlled by a liquid storage unit and a temperature elevator, which accommodate various chemical substance solutions including a sample to be inspected and a magnetic particle suspension. It has a stage having a plurality of groups of accommodating portions provided corresponding to each nozzle, and a nozzle moving step of relatively moving between the nozzle and the stage.
In the light selective measurement step, the first set of one of the irradiation end set and the light receiving end set is provided in the nozzle or the suction / discharge mechanism, and the second set of the one is the capillary for electrophoresis or after each electrophoresis. The first set of the irradiation end set and the other first set of the light receiving end set is provided on the nozzle or the suction / discharge mechanism so as to be paired with the first set of the one, which is provided in contact with or close to the outer surface of the accommodating portion. The second set of the other is provided so as to be paired with the second set of the one, and can be measured by being provided in contact with or close to the outer surface of the electrophoresis capillary or the post-electrophoretic accommodating portion. The fully automatic electrophoresis processing method according to claim 10. The light selective measurement step further includes the other third set of the irradiation end set and the light receiving end set, and the other third set is outside the flow tube and the mouth portion of the flow tube is. The fully automatic electrophoresis processing method according to claim 11 , wherein the measurement can be performed so as to be positioned above the first set and paired with the first set. The optical selective measurement step is
When instructed to measure the presence or absence or amount of a fluorescent substance-labeled target substance in the product or chemical solution,
After moving the nozzle to a containment containing the product or chemical solution,
A pair that can be connected to the irradiation end and the light receiving end that belong to the first set of one of the irradiation end set and the light receiving end set, and the other first set of the irradiation end set and the light receiving end set, respectively. The irradiation measurement end set and the light reception measurement end set are selected, and excitation light of one or a plurality of wavelengths optically connected to one or more irradiation measurement ends belonging to the selected irradiation measurement end set is measured. Only one or two or more light sources to be used as light are turned on, and the fluorescence excited by the excitation light is optically connected to one or two or more light receiving measurement ends belonging to the selected light receiving measurement end set. Pair-selective interlocking switching that turns on only the photoelectric conversion unit via a possible bandpass filter and sequentially switches the connection and disconnection between the irradiation end and the light receiving end and the irradiation measurement end and the light receiving measurement end. Have a process,
When instructed to analyze the target substance by electrophoresis,
After inserting one end of the electrophoresis capillary into the moving liquid accommodating portion in which the electrophoresis sample is accommodated,
A pair of the above, which can be connected to the irradiation end and the light receiving end to which the second set of one of the irradiation end set and the light receiving end set and the other second set of the irradiation end set and the light receiving end set belong to each other. The irradiation measurement end set and the light reception measurement end set are selected, and one or more kinds of excitation light or white light having one or more kinds of wavelengths optically connected to one or more irradiation measurement ends belonging to the selected irradiation measurement end set are emitted. Only one or more types of light sources used as measurement light are turned on, and pass through the fluorescence excited by the excitation light that is optically connected to one or more light receiving measurement ends belonging to the selected light receiving measurement end set. A pair in which only the photoelectric conversion unit or the spectrophotometer via a possible bandpass filter is turned on, and the connection and disconnection between the irradiation end and the light receiving end and the irradiation measurement end and the light receiving measurement end are sequentially switched in conjunction with each other. The fully automatic electrophoresis processing method according to claim 11 , further comprising a selection-linked switching step. The electrophoresis pretreatment step is
The nozzles are arranged in a row along the row direction at a first pitch, and can be moved only along the column direction and the vertical direction, and each of the accommodating portions groups is arranged along the column direction. They are arranged in a single column or a plurality of columns and along the row direction at a first pitch or a second pitch corresponding to a plurality of times thereof.
Variable pitch liquid storage provided with one or more groups of movable liquid storage units composed of the plurality of movable liquid storage units arranged in a single row or a plurality of rows at a second pitch along the row direction. A flow pipe mounted on the plurality of nozzles arranged at a second pitch on the gantry discharges and accommodates the movable liquid in a group of the movable liquid accommodating portions, and the gantry is housed in the row direction along the first row direction. each of the pitch or move to a key Yapirari electrophoresis unit,
The capillary electrophoresis step is
The second pitch of each movable liquid accommodating portion of the variable pitch liquid accommodating stand is converted into a third pitch, one end of the electrophoresis capillary is inserted, and a predetermined voltage is applied between the ends of the capillary. The fully automatic electrophoresis processing method according to claim 13 , wherein the target substance contained in the electrophoresis sample is electrophoresed by applying the electrophoresis.

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