WO2006132209A1

WO2006132209A1 - Automatic analyzer

Info

Publication number: WO2006132209A1
Application number: PCT/JP2006/311276
Authority: WO
Inventors: Isao Yamazaki; Ryuji Tao
Original assignee: Hitachi High-Technologies Corporation
Priority date: 2005-06-08
Filing date: 2006-06-06
Publication date: 2006-12-14
Also published as: JP4969061B2; JP2006343164A

Abstract

An automatic analyzer which is high in speed and degree of freedom, can reduce the number of times of mechanically dispensing a specimen and a reagent, and can analyze a plurality of specimens by selecting necessary items. The automatic analyzer comprises a droplet carrying device formed with two surfaces thereof facing each other on at least one of which are formed a plurality of electrodes, a plurality of analysis routes (80) that allow specimen droplets and reagent droplets to be mixed, reacted and optically measured within the droplet carrying device, a specimen distributing mechanism capable of distributing specimen droplets into a plurality of analysis routes, a reagent distributing mechanism capable of distributing reagent droplets into a plurality of analysis routes, and a control device (12) for controlling each mechanism so as to select a combination of a specimen and a reagent and guide it to an analysis route and calculating the concentrations of components contained in a specimen from the results of an optical measurement.

Description

Specification

Automatic analyzer

Technical field

The present invention relates to an automatic analyzer that performs qualitative 'quantitative analysis of biological components such as blood and urine.

In particular, the present invention relates to an automatic analyzer that is small in size, can be loaded with more reagents, and has a high throughput per hour.

Background art

[0002] Automatic analyzers that automatically analyze biological samples such as blood and output the results are highly efficient for large hospitals, small and medium hospitals with a large number of patients, and inspection centers that undertake clinic power tests. It is necessary to perform analysis well, and it becomes a device.

[0003] Such an automatic analyzer is desired to be compact and capable of performing more types of analysis and to have a high processing speed, and various types of automatic analyzers have been proposed. For example, in Patent Document 1, a plurality of reaction cells are arranged on the circumference, a rotatable reaction disk is used, samples and reagents are dispensed into individual reaction cells with a probe, and the change in absorbance of the mixed solution is measured with a photometer. Discloses an apparatus for detecting the concentration of a specific component of a specimen.

[0004] In this method, all the reaction cells are measured by passing through the photometer by the rotation of the reaction disk. Therefore, only one photometer is required, and all the cells vary under the same conditions. A small analysis is possible. In addition, specimens and reagents can be dispensed into any reaction cell, so the necessary analyzes can be performed in any order and analysis with high throughput is possible.

However, in this method, the reaction cell needs to contain a reaction solution (sample + reagent) larger than the luminous flux diameter of the photometer, and a certain amount or more of the sample Z reagent is required. In addition, in order to increase the processing speed, it is necessary to increase the number of reaction cells. On the other hand, there is a problem in that the reaction cell requires a certain volume, which inevitably increases the size of the apparatus.

[0006] On the other hand, Non-Patent Document 1 applies a technique for manipulating droplets between flat plates on which electrode arrays called electro-watching are arranged to react a specimen with a reagent and use an LED. An example of detecting the absorbance of reaction droplets in an optical system and analyzing the concentration of four types of items was introduced. ing. The droplet transfer technology by electro-etching has advantages such as high reliability because it can handle a small amount of droplets and no mechanical movement mechanism is possible, and there is a possibility of realizing a small and high-throughput analyzer. There is.

[0007] Patent Document 1: Japanese Patent Laid-Open No. 4 71184

Special Reference 1: Clinical diagnostics on human whole blooa, plasma, serum, urine ^ sail va, sweat, and tears on a digital microfluidic platform μ TAS2003

Disclosure of the invention

Problems to be solved by the invention

[0008] With the technique described in Non-Patent Document 1, it is possible to analyze specific items, but it is not possible to automatically select and analyze necessary items from multiple types of items for multiple specimens. ,.

[0009] An object of the present invention is to provide a high-speed and high-precision automatic analyzer capable of reducing the number of mechanical dispensing of specimens and reagents and automatically selecting and analyzing necessary items for a plurality of specimens. It is to provide.

Means for solving the problem

The problem solving means of the present invention is as follows.

[0011] A liquid droplet transport device formed by facing two surfaces on which at least one surface has a plurality of electrodes, and a sample droplet and a reagent droplet are mixed, reacted, and optical in the liquid droplet transport device Select multiple analysis paths to be measured, sample distribution mechanism that can distribute sample droplets to multiple analysis paths, reagent distribution mechanism that can distribute reagent droplets to multiple analysis paths, and a combination of sample and reagent Then, each mechanism is controlled so as to guide it to the analysis path, and a control device for calculating the concentration of the component contained in the sample from the result of the optical measurement is provided.

[0012] More preferably, the configuration is as follows.

[0013] A liquid transport mechanism including at least one pair of plate-like members opposed to each other at a predetermined interval and holding a liquid in a gap, wherein the liquid is carried to at least one of the at least one pair of plate-like members. A plurality of liquid transport paths in which a plurality of electrodes are arranged at predetermined intervals along the direction in which the sample transport path is provided, and the liquid transport path includes at least a sample transport path for transporting the sample liquid in a radial manner and a crossing the sample transport path A liquid transport mechanism including a reagent transport path for supplying reagents to the plurality of sample transport paths, and a sample distribution unit for supplying a sample to the sample transport path An automatic analyzer comprising: a distribution mechanism; a reagent distribution mechanism that supplies a reagent to the reagent conveyance path; and a measurement mechanism that optically analyzes a reaction between the sample and the reagent in the liquid conveyance path.

[0014] The automatic analyzer may include a photometer that measures the optical properties of the droplet and a moving mechanism that moves the photometer, and the photometer can be configured to perform optical measurement through a plurality of analysis paths. Good.

[0015] The reagent storage is a reagent disk that can be rotated by mounting a plurality of reagent containers on the circumference, and the reagent dispensing mechanism sucks the reagent from the reagent container at a specific position on the reagent disk. Then, the reagent probe may be ejected to a specific position of the liquid droplet transport device.

[0016] The reagent probe may suck the amount of reagent required for a plurality of analyzes at a time and discharge it to the droplet transport device.

[0017] There may be a reagent reservoir in the droplet transport device, and the reagent droplet may be transported to the analysis path after being held in the reagent reservoir.

[0018] In addition, the reagent reservoir holds the amount of droplets required for a plurality of analyzes as a unit, and is divided into droplets required for one analysis in a sorting path connected to the reagent reservoir. It may also be transported to the analysis path.

[0019] The reagent reservoir may be configured to hold a plurality of droplets and exchange them in the order and transport them to the analysis path.

[0020] Further, a plurality of reagent reservoirs are provided, and the reagents held in each reagent reservoir may be the same type of reagent.

[0021] In addition, the type of reagent held in each reagent reservoir is not fixed, and different types of reagents may be held in a common reagent reservoir.

[0022] The sample dispensing mechanism is a sample probe that sucks the sample from the sample container and discharges the sample to a specific position of the droplet transport device, and the sample probe sucks the amount of samples required for a plurality of analyzes at a time. May be.

[0023] There is a specimen reservoir in the droplet transport device, and the specimen droplet may be transported to the analysis path after being held in the specimen reservoir.

[0024] In addition, the specimen reservoir integrally holds the amount of liquid droplets required for a plurality of analyzes, and is divided into the amount of liquid droplets required for one analysis in a sorting path connected to the specimen reservoir. In the analysis path Transport it.

[0025] Further, the specimen reservoir may be configured to hold a plurality of droplets and to transport them to the analysis path by changing the order.

[0026] Further, it may have a dilution mechanism for diluting the specimen at different dilution rates, and the diluted specimen may be supplied to the droplet transport device.

[0027] The sample dispensing mechanism may be a sample probe that aspirates the sample container force sample, and the sample may be diluted at the sample discharge position of the droplet transport device.

[0028] The analysis path, the sample distribution mechanism, and the reagent distribution mechanism each include a plurality of electrode arrays, and the electrode arrays that form the analysis path intersect the electrode arrays that form the sample distribution mechanism and the reagent distribution mechanism. In addition, the droplets may move between the respective electrode rows through the intersection.

[0029] Alternatively, a voltage may be applied to a plurality of continuous electrodes to hold one droplet, and droplets having different volumes may be conveyed on a common electrode array.

[0030] In addition, the droplet transport device is circular, the electrode arrays that form a plurality of analysis paths are aligned in the radial direction, and the electrode arrays that form the sample distribution mechanism and the reagent distribution mechanism are aligned in the circumferential direction. Good.

[0031] Further, a plurality of analysis paths may be arranged on the circumference, and the photometer may rotate to perform optical measurement.

[0032] Either or both of the transport path for distributing the specimen droplets to the analysis path and the transport path for distributing the reagent droplets to the analysis path can be selected from a plurality of paths. Good.

The invention's effect

[0033] It is possible to provide a high-speed and high-degree of freedom automatic analyzer capable of selecting and analyzing necessary items for a plurality of samples with a small number of mechanical dispensing of samples and reagents. . Brief Description of Drawings

FIG. 1 is a perspective view showing a schematic configuration of an analyzer according to a first embodiment.

FIG. 2 is a cross-sectional view showing the main part of the analysis substrate of the first embodiment.

FIG. 3 is a top view showing a schematic configuration of the analysis substrate of the first embodiment.

FIG. 4 is a top view showing the main part of the analysis flow path of the first embodiment. FIG. 5 is a top view showing a reagent port and a reagent reservoir main part of the first embodiment.

FIG. 6 is a cross-sectional view showing the main part of the reagent port of the first embodiment.

FIG. 7 is a cross-sectional view showing the main part of the drainage port of the first embodiment.

FIG. 8 is a perspective view showing a schematic configuration of an analyzer according to a second embodiment.

FIG. 9 is a top view showing a schematic configuration of the analysis substrate of the second embodiment.

FIG. 10 is a cross-sectional view showing the main part of the sample port of the first embodiment.

Explanation of symbols

[0035] 10 ... Analytical substrate, 12 ... Control device, 13 ... Display device, 20 ... Sample disk, 21 ... Sample container, 22 ... Sample probe, 23 ... Diluent Probe 24 ... Sample port 25 ... Dilution port 26 ... Wash port 30 ... First reagent probe 31 ... First reagent port 3 5 ... Second reagent probe 37 ... Second reagent port 40 ··· Reagent container, ·························································································································· Mechanism 60 ... First substrate 61 ... Common electrode 62, 66, 68 ... Water repellent film 63 ... Second substrate 64 ... Control electrode 65 ... Insulating film 67 ... Paser, 70 ··· droplet, 71… oil, 73… waste fluid, 75… analyte fluid, 76… diluent, 80 ··· analysis channel, 81 ··· drain channel, 82 ·· 2 reagent channels, 83 ... sample channels, 8 "1st reagent Road, reservoir 85 ... reagent, 86 ... sample reservoir, 87 ... supply passage, 88 ... relay electrode, 90, 91 ... path

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described with reference to the drawings.

[0037] (Example 1)

FIG. 1 is a perspective view of a first embodiment of the present invention. A reagent disk 41, a first reagent probe 30, and a second reagent probe 35 are disposed in a ring-shaped analysis substrate 10. A sample disk 20, a sample probe 22, a photometer 50 supported by a moving mechanism 51, a control device 12, and a display device 13 are arranged outside the analysis substrate 10. A plurality of reagent containers 40 are mounted on the reagent disk 41. A plurality of sample containers 21 are mounted on the sample disk 20. The first reagent probe 30, the second reagent probe 35, and the sample probe 22 can be independently moved up and down and rotated. Each probe is connected to a syringe pump (not shown). First reagent port 31 and second on the probe path Reagent port 37, sample port 24, and wash port 26 are located. In addition, the analysis substrate

Four drain ports 48 are provided in 10 and a drain tube 47 is connected to them.

The photometer 50 includes a light source that emits light in a wide wavelength range, a diffraction grating, and a detector that detects light of a plurality of wavelengths.

FIG. 2 is a schematic diagram showing a cross section of the analysis substrate 10 of the first embodiment. The analysis substrate 10 includes a first substrate 60 and a second substrate 63. A common electrode 61 is formed on the lower surface of the first substrate 60, and is further covered with a water repellent film 62. A plurality of control electrodes 64 are disposed on the upper surface of the second substrate 63, and are covered with an insulating film 65 and a water repellent film 66. The common electrode 61 and the control electrode 64 are connected to the control device 12 by wiring not shown. The first substrate 60, the common electrode 61, the water repellent film 62, the second substrate 63, the control electrode 64, the insulating film 65, and the water repellent film 66 are all made of a material that transmits light. The end surface of the analysis substrate 10 is sealed with a spacer 67, and the first substrate 60 and the second substrate 63 are separated by a gap of 0.5 mm. This gap is filled with oil 71 that does not mix with the aqueous solution, and water-soluble droplets 70 are retained.

FIG. 3 is a top view of the analysis substrate 10 of the first embodiment. A large number of analysis flow paths 80 extending in the radial direction are arranged in a circle. A drainage flow channel 81, a second reagent flow channel 82, a sample flow channel 83, and a first reagent flow channel 84 are arranged in the circumferential direction so as to cross the analysis flow channel 80. 84 includes a sample port 24, a plurality of sample reservoirs 86, a first reagent port 31, a second reagent port 37, a plurality of reagent reservoirs 85, and a plurality of drainage ports 48. A supply flow path 87 is disposed above. About 100 force reagent reservoirs 85, which are omitted in the figure, are arranged on the entire circumference.

FIG. 4 is a top view showing an electrode arrangement of a part of the analysis substrate 10 of the first embodiment. In the figure, each solid square frame represents a control electrode 64. The analysis channel 80 is composed of 23 electrodes with al force aligned in the radial direction up to a23. In this embodiment, each electrode is a square having a side of about 2.8 mm. Electrodes al, 3, a5, and al2 have a relay electrode 88 disposed between the adjacent analysis flow paths, and the first reagent flow path 84, sample flow path 83, and second reagent flow that are transport flow paths in the circumferential direction. A passage 82 and a drainage passage 81 are formed. The width of the relay electrode 88 is It is smaller than the width of the electrode forming the path 80. The electrodes al8, al9, and a20 are photometric areas.

FIG. 5 is a top view showing another partial electrode arrangement of the analysis substrate 10 of the first embodiment. Similar to the first reagent channel 84, the supply channel 87 is composed of electrode rows arranged in the circumferential direction. A first reagent port 31 is arranged between the first reagent channel 84 and the supply channel 87, and electrodes are connected from the first reagent port 31 to the supply channel 87. An electrode reagent reservoir 85 having a size larger than that of the other electrodes is arranged in the middle of the electrode train connected from the supply channel 87 to the first reagent channel 84. In the case of this example, this electrode is circular with a diameter of 14 mm.

FIG. 6 is a cross-sectional view showing the structure of the first reagent port 31 of the first embodiment. The first reagent port 31 protrudes upward from the analysis substrate 10 and has a hole therethrough. A water repellent film 68 is formed on the inner surface. The first reagent probe 30 is inserted into the first reagent port 31 to form a structure in which the droplet 70 is discharged inside the analysis substrate 10.

The second reagent port 37 and the sample port 24 have the same structure as the first reagent port 31.

The sample reservoir 86 has the same shape as the reagent reservoir 85.

FIG. 7 is a cross-sectional view showing the structure of the drainage port 48 of the first embodiment. The drainage port 48 protrudes upward from the analysis substrate 10 and has a hole therethrough. Furthermore, the drainage tube 47 penetrates the side force. There is space inside.

Next, the operation of the first embodiment will be described.

[0047] On the reagent disk 41, two types of reagents, a first reagent and a second reagent, are placed in a reagent container 40 and loaded corresponding to each analysis item.

[0048] The dispensing of the reagent of a certain item to the analysis substrate 10 is performed as follows. Rotate 41 so that the reagent container 40 containing the first reagent of the item is at the suction position of the first reagent probe 30, and aspirate 80 microliters of the first reagent with the first reagent probe 30. The first reagent probe 30 is raised and rotated and inserted into the first reagent port 31. After insertion, dispense 80 microliters of reagent. A voltage is sequentially applied to the control electrode 64 along the path 90 connecting from the first reagent port 31 to the reagent reservoir 85 selected for the reagent in conjunction with the reagent discharge. The discharged reagent enters the region sandwiched between the water-repellent films 62 and 66 as droplets 70, but suction force is generated by electro-etching on the control electrode 64 to which voltage is applied. Therefore, it is guided to the reagent reservoir 85 through the route 90. When the discharge from the first reagent probe 30 is completed, the voltage application to the control electrode 64 on the path 90 is sequentially cut off, and only the reagent reservoir 85 is applied and the reagent is held on the reagent reservoir 85. .

[0049] For the second reagent, the same operation as that for the first reagent is performed, and the second reagent probe 35 sucks 40 microliters of the second reagent from the reagent container 40 and discharges it from the second reagent port 37. The second

It is transported to and held by the reagent reservoir 85 selected separately from 1 reagent.

[0050] After the reagent is discharged, the first reagent probe 30 and the second reagent probe 35 move to the cleaning port 26, and the inner surface and outer surface of the probe are cleaned with cleaning water.

[0051] The first reagent and the second reagent of all items to be analyzed are dispensed and held on 85 different from each other.

[0052] The dispensing of the reagent to the analysis substrate 10 is performed at the start of the operation and when the amount of the reagent held in each reagent reservoir 85 falls below a predetermined amount.

[0053] On the sample disk 20, a sample of known concentration for calibration and accuracy control and a sample to be analyzed are placed in a sample container 21 and mounted.

[0054] The sample is dispensed onto the analysis substrate 10 as follows. The sample disk 20 rotates so that the sample container 21 containing the target specimen is positioned at the suction position of the sample probe 22, and the sample probe 22 sucks the specimen from the sample container 21. The amount of aspiration is greater than that required for testing all items analyzed on the sample. The sample probe 22 is raised and rotated and inserted into the sample port 24. After insertion, the aspirated specimen is discharged. A voltage is sequentially applied to the control electrode 64 in conjunction with the specimen discharge along a path connecting from the sample probe 22 to the sample reservoir 86 selected corresponding to the specimen. The discharged specimen becomes a droplet 70 and enters the portion sandwiched between the water-repellent films 62 and 66. Since a suction force is generated by electroetching on the control electrode 64 to which a voltage is applied, the path is routed. It leads to sample reservoir 86. When the discharge from the sample probe 22 is completed, the voltage application to the control electrode 64 on the path is sequentially cut, and the sample is held on the sample reservoir 86, leaving only the application of the sample reservoir 86. The sample probe 22 moves to the cleaning port 26 after dispensing, and the inner and outer surfaces of the probe are cleaned with cleaning water.

[0055] An analysis of an item of a sample is performed as follows. [0056] The control device 12 selects one of the reagent reservoir 85 in which the first reagent used for the analysis is retained, the reagent reservoir 85 in which the second reagent is retained, and the empty analysis channel 80. .

[0057] A voltage higher than that applied to the reagent reservoir 85 is applied to four electrodes continuous from the reagent reservoir 85 holding the first reagent to the outer peripheral side. By cutting off the application of the second electrode among the four electrodes after a certain period of time, a first reagent droplet of about 8 microliters is formed on the third and fourth electrodes. By sequentially moving the electrode to which the voltage is applied from the reagent reservoir 85 along the path 91 passing through the first reagent channel 84, the droplet of the first reagent is conveyed to the selected analysis channel 80. .

[0058] The specimen is applied to the sample reservoir 86 to three electrodes that are continuous from the sample reservoir 86 to the outer peripheral side, and a voltage is applied to the sample reservoir 86 higher than the sample reservoir 86. By cutting off the application, approximately 4 microliters of analyte droplets are formed on the third electrode.

[0059] The specimen droplet is conveyed to the selected analysis channel 80 by sequentially moving the electrode that is applied with voltage along the path in the sample channel 83. After collecting the required amount of sample, the sample remaining in the sample reservoir 86 is transported to the drain port 48 and discarded.

[0060] In the analysis flow path 80, first, the specimen droplet is held in alO, and the first reagent droplet is held in a7 and a8.

Next, the specimen droplet is transported to a20 by sequentially moving the application electrode from alO. Subsequently, the first reagent droplet is transported to al8 and al9 by sequentially moving the application electrodes a7 and a8. Here, the specimen and the first reagent droplet are combined to form a first reaction solution, which is held on the three electrodes al8, al9, and a20. Next, by reciprocating the position where voltage is applied between a16 and a23, the droplet reciprocates, and the specimen and the first reagent in the droplet of the first reaction liquid are agitated and leveled. Become one. The applied electrode is then fixed to al8, al9, a20, and the droplet is held for 5 minutes during the first reaction time.

[0062] The photometer 50 is turned by the moving mechanism 51 at a speed of one rotation in 30 seconds. When passing through the analysis flow path 80, light is applied to the droplets on al8, al9, and a20, and the amount of transmitted light of the selected wavelength is measured and transmitted to the controller 12. The controller 12 calculates the absorbance. Periodic measurements are taken during the first reaction time. [0063] During the first reaction time, a second reagent is prepared. Reagent reservoir 85 holding the second reagent is also applied to three electrodes that continue to the outer circumference, and a voltage higher than that applied to reagent reservoir 85 is applied, and the second electrode of the three electrodes is applied after a certain period of time. To form a second reagent droplet of about 4 microliters on the third electrode. The second reagent droplets are transported to the electrode al4 of the selected analysis channel 80 by sequentially moving the electrodes applying the voltage along the path passing through the second reagent channel 82.

[0064] After the first reaction time has elapsed, the droplets of the second reagent are transferred to al8 by sequentially moving the application electrode from al4. Here, the second reagent is combined with the first reaction solution to form the second reaction solution. Next, by reciprocating the position where voltage is applied between al6 and a23, the droplet reciprocates, and the second reaction liquid is stirred and becomes uniform. The applied electrode is then fixed to al8, al9, a20, a21, and the droplet is held for 5 minutes during the second reaction time. Periodic measurements are taken with the photometer during the second reaction time.

After the second reaction time, the droplets of the second reaction liquid pass through the drainage flow path 81 and are conveyed to the drainage port 48. The droplet 70 of the second reaction liquid enters the drainage port 48 due to the surface force with the water repellent films 62 and 69 and rises due to the difference in specific gravity with the oil 71. The floated waste liquid 73 is sucked into the drainage tube 47 and discharged.

[0066] During the second reaction time, after the sample for the next analysis and the first reagent droplets wait on the electrodes alO and a7, a8, the analysis is completed and the second reaction solution is discharged. The next analysis will begin immediately.

[0067] While analysis of an item of a sample is performed in one analysis channel 80, analysis of another sample or another item proceeds in parallel in another analysis channel 80.

[0068] The control device 12 derives the relationship between the change in absorbance and the concentration obtained by analyzing the sample for calibration for each analysis item, and stores it as calibration data. For the analyte, the concentration of the analysis item is calculated using the calibration data, transmitted to the display device 13 and displayed. Also, periodically analyze the sample for quality control, and if the result does not fall within the prescribed range, send an abnormal alarm to the display device 13.

In addition, the control device monitors the state of the entire device. Individual control electrodes during maintenance 6 When a voltage is applied to 4 and the capacitance and current between the common electrode 61 are detected and abnormal, the electrode is memorized and the analysis flow path 80 containing it is controlled not to be used for analysis. To do.

[0070] In the case of the present embodiment, a function of supplying specimen droplets and reagent droplets to each of the plurality of analysis channels 80, a function of mixing droplets, a function of transporting specimens, reagents, and mixtures thereof, Since there is a built-in area with the function of reacting the mixture and it can be performed in parallel without synchronizing with other analysis channels, multiple analyzes can be freely started, progressed and terminated in the free analysis channel 80. Therefore, it is possible to use a plurality of analysis flow paths 80 with less free time, and to realize an analyzer having a high processing capacity per unit time.

[0071] Further, in the present embodiment, the analysis substrate is fixed and the photometer is configured to rotate. Therefore, even during photometry of any analysis flow path, droplet movement and mixing are performed. In addition, it is possible to perform an operation such as agitation and to realize an analyzer having a high throughput.

[0072] In addition, since operations such as droplet movement, mixing, and stirring can be performed in parallel in a plurality of analysis flow paths, it is possible to take a longer time for each operation, and a reasonable speed. By operating with, it is possible to avoid adverse effects such as heat generation and flow turbulence, and stable and highly accurate analysis is possible.

[0073] Further, since the droplet conveyance, mixing, and stirring are performed only by controlling the voltage application to the electrodes, the mechanism is not complicated even if these functions are incorporated in each of the many analysis flow paths, and simple. A small, highly reliable analyzer with a configuration can be realized.

[0074] Further, in the case of the present embodiment, the specimen and the reagent can be transported to all the analysis flow paths 80, and any analysis flow path can be analyzed for any item, and the processing capacity is efficient. High analysis is possible.

[0075] In the case of the present embodiment, each of the plurality of analysis flow channels 80 has a built-in region having a function of temporarily storing a sample, a reagent, or a mixture thereof. It is possible to efficiently supply samples and reagents to multiple analysis channels that do not require the timing of supplying sample droplets and reagent droplets from the reagent channels to the analysis channel 80 to match the progress of the analysis. Analysis with high throughput is possible.

[0076] In the present example, the specimen and the reagent do not react with the aqueous solution in the analysis substrate! Since it is wrapped in a film and does not change in quality due to evaporation, it is not necessary to synchronize the supply to the analysis board with the timing of the analysis.

[0077] Further, in this embodiment, the analysis of all items can be performed in any analysis flow path, and the analysis can be started and advanced at any timing in any analysis flow path. Since any analysis channel is selected and executed, analysis with a high processing capacity is possible by efficiently using the analysis channel.

[0078] Further, since the analysis channel can be freely selected by the control device, the analysis that requires quick processing is close to the sample reservoir, and the conveyance time can be shortened by selecting it to be performed in the analysis channel. The analysis results can be output in a short time.

[0079] In the present embodiment, since the same photometer is used for all the analysis flow paths 80, the same characteristics can be analyzed in any flow path, and high accuracy with little variation is possible. Analysis is possible.

[0080] Further, in the case of the present embodiment, since the photometer is scanned and used, only one photometer and a detection electric system are required, and a low-cost analyzer can be realized.

In the case of the present embodiment, since the same photometer is used for all the analysis channels, the calibration is not necessary for all the analysis channels.

Save time and reduce running costs.

[0082] In the case of the present embodiment, the reaction droplets remain stationary during the reaction time! /, And periodic measurement is performed at the same place, so that the change in the shape of the droplets, bubbles, etc. Therefore, it is possible to perform highly accurate analysis without being subject to changes in the conditions.

[0083] In the case of the present embodiment, since the specimen, reagent droplets are transported, mixed, and stirred only by controlling the voltage application to the electrodes, the analysis substrate 10 has a light intensity with no mechanical operation. Since the total 50 rotates without stopping and can perform photometry, the integration time of each photometry can be extended, noise is reduced! And high-precision analysis is possible.

[0084] In addition, in the case of this example, since the photometry time of the photometer can be increased, it is possible to analyze the absorbance even when the optical path length of the reaction solution is short, and the amount of sample and reagent is small and the running cost is low. Can be realized.

[0085] In the case of this example, the inner surfaces of the analysis substrate, sample port, and reagent port are all repelled. Covered with a water film, and the inside is not dissolved with an aqueous solution. The analysis is performed with oil, so the specimen and reagent droplets do not come into direct contact with the wall, so the wall is contaminated with the specimen and reagent. Highly accurate analysis without carryover is possible.

[0086] In the case of the present embodiment, since the dispensing with the reagent probe from the reagent container 40 to the analysis substrate 10 is performed in an amount required for 10 analyzes at a time, the operation of the reagent disk and the reagent probe The number of analyzes is less than the number of analyses, and an analysis device with high throughput can be realized even with a low-speed dispensing mechanism.

[0087] Further, in the case of the present embodiment, a reagent disk and a reagent probe are used, and the reagent probe is washed at the washing port, so that different reagents can be supplied by a common dispensing mechanism. High-precision analysis without difference is possible. Also, a low-cost and space-saving analyzer with fewer dispensing mechanisms can be realized.

In the present embodiment, since the reagent container is mounted on the reagent disk, reagent replacement can be easily performed without the need to connect the reagent container and the analysis substrate with a pipe.

[0089] Further, in the case of the present embodiment, since the dispensing with the sample probe 22 from the specimen container 21 to the analysis substrate 10 is performed in a single operation, the number of operations of the sample probe 22 is reduced. The number of analyzes is less than the number of analyses, and an analyzer with high throughput can be realized even with a low-speed dispensing mechanism.

[0090] In the case of this example, since the reagent and the specimen are held in the reagent reservoir 85 and the sample reservoir 86, respectively, a predetermined amount is collected and transported to the analysis channel. Without being limited, it is possible to perform analysis by reacting samples and reagents in any combination, and it is possible to realize an analyzer with high throughput and high analysis efficiency.

[0091] In the case of the present embodiment, the size of each control electrode in the analysis flow channel is a size that holds microliter droplets. The sample, first reagent, second reagent, first reaction liquid, and second reaction liquid have 4, 8, 4, 12, and 16 microliter droplets, respectively, so they are 1, 2, 1, Held by one, three and four electrodes. In this way, it is configured to handle a plurality of droplets that are an integral multiple of the amount held by one control electrode, and to hold the droplets to a plurality of electrodes. Various types of droplets can be transported. This makes it possible to freely set the path of specimens, reagents, drainage, etc. Is possible. In particular, in the present embodiment, the flow path for supplying the sample and reagent and the flow path for the drainage liquid are arranged so as to intersect with the analysis flow path, so that the liquid droplets can freely come and go between them. All analyzes can be performed in any analysis channel, enabling efficient analysis with a high degree of freedom.

[0092] In the case of this embodiment, the path for transporting liquid droplets to the analysis flow path selected from the sample port and the reagent port and the path for transporting liquid droplets from the analysis flow path to the drainage port are different. It passes through the analysis flow path, but where to pass can be selected from a plurality of paths. This makes it possible to select a route that does not interfere with other analyses, and to realize an analyzer with a high processing capacity.

[0093] Furthermore, in the case of the present embodiment, analysis of each item can be performed in any analysis flow path, and since a transfer path can be selected from a plurality of paths, even if there are defective electrodes, avoid them. Minute prayers are possible. For this reason, it is possible to improve the reliability of the apparatus, and to reduce the running cost by reducing the frequency of replacing the board, so that even if a defect occurs on a part of the analysis board, the analysis cannot be performed.

[0094] In the case of the present embodiment, there are separate specimen and reagent droplet standby areas on the analysis flow path 80 and reaction areas, and the reaction area droplets are discharged without passing through the standby area. As a result, the next analysis can be performed immediately after the end of one analysis, and an analysis with high throughput and high efficiency is possible.

[0095] In the case of the present embodiment, since the analysis substrate 10 is circular, the photometer 50 can perform photometry of all the analysis flow paths 80 by a rotational motion, and there is no need to stop or change the direction. Therefore, it is possible to realize a highly reliable analyzer that does not waste time.

In the present example, the analysis substrate 10 has a circular shape, and the first reagent channel 84, the sample channel 83, and the second reagent channel 82 are formed in a circumferential shape. Reagents can be efficiently transported to all analysis channels 80.

[0097] In the present embodiment, the width of the relay electrode 88 is narrower than the width of the electrode forming the analysis flow path 80, so that the size of the analysis substrate 10 can be reduced, and the space-saving is reduced. An analysis device can be realized.

[0098] In this example, the photometer 50 was used to measure absorbance. It may also be one that measures fluorescence. In that case, the combination of these items increases the types of items that can be analyzed, and there is an advantage that immunoassay can be realized with the same device.

[0099] Further, in this embodiment, the force of scanning one photometer may scan two or more sets of photometers! /. In that case, there is an advantage that changes in absorbance can be measured at short intervals.

[0100] In this embodiment, the analysis substrate is a disc-shaped integrated structure, but may be divided into a plurality of fan-shaped substrates. In that case, it is possible to configure so that the droplets can move to another substrate, but it is also possible to configure so that oil and droplets do not move independently for each substrate. At that time, each divided substrate should have a sample port, reagent port, and drainage port. In this case, since each substrate is small, the equipment for manufacturing the substrate is small, and can be manufactured at low cost. In addition, there is an advantage that the board and oil can be changed easily.

[0101] In the case of the present embodiment, the four transport channels in the circumferential direction are specially used for transporting droplets of the same use as the sample, the first reagent, the second reagent, and the drainage, respectively. However, it can be used to select any flow path without specialization. Furthermore, it is possible to control to select a flow path that can reach the target transport position quickly by fixing the transport direction for each flow path and providing a clockwise flow path and a counterclockwise flow path. In this case, an analysis device with higher efficiency and higher throughput can be realized.

[0102] In FIG. 1, the liquid transport mechanism has a disk shape, but each sample transport path is provided with a sample supply path and a reagent supply path, and the sample supply path and the reagent supply path are closed. You just need to make a loop. That is, if the sample transport path is radial, the same effect can be obtained even in a square shape.

[0103] Further, as described in Non-Patent Document 1, the measurement mechanism need not be a rotating photometer, and an LED as described above may be provided in each sample transport path.

[Example 2]

Next, a second embodiment of the present invention will be described. FIG. 8 is a perspective view of a second embodiment of the present invention, FIG. 9 is a top view of the analysis substrate 10, and FIG. 10 is a cross-sectional view showing a portion of the sample port 24. The main difference from the first embodiment is that the moving mechanism 51 and the photometer 50 are arranged inside the analysis substrate 10. The reagent disk 41, the first reagent probe 30, and the second reagent probe 35 are arranged outside the analysis substrate 10, and the dilution port 25 is installed close to the sample port 24. In other words, the opening / closing mechanism 42 is installed close to the reagent disk 41, and there is no reagent reservoir 85 and sample reservoir 86. The arrangement of the analysis flow path 80 is the same as in FIG. 4, but unlike the first embodiment, the electrode al is on the outer peripheral side and the electrode a23 is on the inner peripheral side.

The dilution port 25 installed in the vicinity of the sample port 24 protrudes upward from the analysis substrate 10 in the same manner as the sample port 24, and the diluent probe 23 is inserted therein. The diluent probe 23 is connected to a diluent pump (not shown) and can discharge the diluent by controlling the amount.

A snap cap 43 is provided at the opening of the reagent container 40 and can be opened and closed by the opening / closing mechanism 42.

[0107] In the second embodiment, the reagent is supplied to the analysis substrate 10 as follows. First, the snap cap 43 is opened by the opening / closing mechanism 42. Next, the reagent disk 41 is rotated to move the reagent container 40 to the suction position. In the case of the first reagent, aspirate 80 microliters with the first reagent probe 30 and discharge it to the first reagent port 31. At that time, 8 microliters are intermittently discharged in 10 batches, and each small droplet is transported to the first reagent channel 84. The droplet goes around the first reagent channel 84 until it is needed for analysis. In the case of the second reagent, aspirate 40 microliters with the second reagent probe 35 and discharge it to the second reagent port 37. At that time, 4 microliters are ejected intermittently in 10 batches, and each small droplet is transported to the second reagent channel 82. The droplet circulates in the second reagent channel 82 until needed for analysis. After the suction, the reagent container 40 is closed with the snap cap 43 by the opening / closing mechanism 42.

[0108] The sample is supplied to the analysis substrate 10 as follows. The sample disk 20 rotates, and the sample probe 22 sucks the specimen from the sample container 21. Move sample probe 22 and insert into sample port 24. Discharge is performed as many times as the number of analyzes performed on the sample plus the number of spares for retesting. Prior to the discharge of the sample from the sample probe 22, the diluted solution is discharged from the dilution solution probe 23. The discharge amount of the diluted solution and the sample is controlled by the control device 12 so as to be an amount determined according to the analysis item. From sample probe 22 The discharged specimen liquid 75 is conveyed to the selected analysis flow path 80 via the sample flow path 83 while being mixed with the dilution liquid 76 discharged from the dilution liquid probe 23. The preliminary droplets for retesting do not enter the analysis flow path 80, but go around the sample flow path 83.

[0109] The analysis procedure in the analysis flow path 80 is the same as in the first embodiment. When the second reaction time is over and the analysis is finished, the controller 12 calculates the concentration of the analysis item, and if the result is out of the predetermined range, a retest is performed using a spare droplet for retesting. carry out. If retesting is not required, preliminary droplets for retesting are discharged from drain port 48.

[0110] In the case of this example, a plurality of samples and reagents for analysis are separated into droplets of the size required for each analysis when injected into the analysis substrate 10 and are supplied to the transport flow path. Therefore, a compact analyzer can be realized.

[0111] Further, in the case of the present embodiment, since the sample and the reagent are dispensed from the probe in a single dispensing amount and separated into droplets, the volume of the droplets can be accurately controlled, Highly accurate analysis is possible.

[0112] Further, in the case of the present embodiment, since the reagent is not stored in a large-capacity liquid reservoir, an analyzer with a small amount of reagent waste and a low running cost can be realized.

[0113] In the case of the present embodiment, since the specimen is discharged into the diluent and separated into droplets, even in specimens having different characteristics such as viscosity, the difference in characteristics is mitigated by the diluent, and accuracy is improved. High-volume dispensing is possible, and high-precision analysis is possible.

[0114] Furthermore, since the amount of the diluted solution and the amount of the specimen can be changed for each droplet, the optimal dilution rate can be set for the analysis item, and highly accurate analysis is possible.

[0115] Further, in the case of this example, the sample for retesting is made to circulate on the sample flow path 83 as droplets, and the sample is used for analysis when necessary for retesting. Since the number of sample disks 20 that need not leave the sample container 21 for retesting on the disk 20 is small, a space-saving analyzer can be realized.

[0116] Further, in this embodiment, since the reagent for a plurality of times is sucked from the reagent container at a time, the snap cap 43 can be closed by the opening / closing mechanism 42 after the reagent is sucked from the reagent container 40. In addition, evaporation and alteration of reagents can be prevented, and running costs can be reduced and analysis accuracy can be improved. [0117] In the case of the present embodiment, since the photometer 50 and the moving mechanism 51 are inside the analysis substrate 10, the rotational radius of the moving mechanism 51 is small, and a small and highly reliable analyzer is provided. realizable.

In the present embodiment, since the sample disk 20 and the reagent disk 41 are outside the analysis substrate 10, the specimen and reagent can be easily replaced and replenished even during operation. Industrial applicability

[0119] The present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the spirit of the present invention.

Claims

The scope of the claims

[1] A liquid transport mechanism comprising at least one pair of plate-like members that face each other at a predetermined interval and hold liquid in a gap,

At least one of the at least one pair of plate-like members includes a plurality of liquid transport paths in which a plurality of electrodes are arranged at predetermined intervals along the direction of transporting the liquid,

The liquid transport path includes at least a sample transport path (83) for transporting the sample liquid radially,

A reagent transport path (82, 84) that crosses the sample transport path and supplies reagents to the plurality of sample transport paths, and a liquid transport mechanism,

A sample distribution mechanism for supplying a sample to the sample transport path;

A reagent distribution mechanism for supplying a reagent to the reagent transport path;

A measurement mechanism (al8, al 9, a20) for optically analyzing the reaction between the specimen and the reagent in the liquid conveyance path;

An automatic analyzer characterized by comprising:

[2] The automatic analyzer according to claim 1,

The automatic analyzer according to claim 1, wherein the liquid transport path further includes a sample flow path that crosses the sample transport path (83) and supplies specimens to the plurality of sample transport paths (83).

[3] The automatic analyzer according to claim 2,

An automatic analyzer comprising: a plurality of sample supply mechanisms for supplying different specimens to the sample flow paths; and a plurality of reagent supply mechanisms for supplying different reagents to the reagent transport paths (82, 84). .

[4] The automatic analyzer according to claim 3,

The sample supply mechanism and the reagent supply mechanism are each provided with a sample reservoir (86) or a reagent reservoir (85) for temporarily storing a specimen or a reagent capable of performing analysis for a plurality of times. Automatic analyzer to do.

[5] In the automatic analyzer according to any one of claims 1 to 4,

The analysis is completed from the plurality of sample transport paths across the sample transport path. An automatic analyzer comprising a waste liquid channel (81) for discharging a reaction liquid.

[6] The automatic analyzer according to claim 5,

An automatic analyzer comprising: a waste liquid port (48) for taking waste liquid out of the liquid transport mechanism from the waste liquid flow path; and a waste liquid suction mechanism that is inserted into the waste liquid port and sucks the waste liquid.

[7] In the automatic analyzer according to any one of claims 1 to 6,

The measurement mechanism is a photometer (50) including a light source and a light receiver that receives light emitted from the light source and transmitted through the reaction solution, and a relative position between the photometer and the plurality of sample transport paths. An automatic analyzer equipped with a relative positional change mechanism for changing the relationship.

[8] The automatic analyzer according to claim 7,

2. The automatic analyzer according to claim 1, wherein the relative positional relationship changing mechanism is a moving mechanism of the photometer and rotationally moves on an outer periphery or an inner periphery of the sample transport path.

[9] In the automatic analyzer according to claim 4,!

The reagent reservoir is provided with a droplet dividing mechanism for dividing the reagent reservoir into a quantity of droplets required for one analysis in the reagent transport path connected to the reagent reservoir and transporting the droplet to the sample transport path. apparatus.

[10] The automatic analyzer according to claim 3,

The sample supply mechanism includes a sample probe (22) for aspirating a sample from a sample container, a sample probe moving mechanism for moving the sample probe, and a sample port (24) for inserting the sample probe. Automatic analyzer.

[11] In the automatic analyzer according to any one of claims 1 to 10,

An automatic analyzer comprising a diluent supply port for supplying a diluent for diluting a specimen in the vicinity of the sample port.

[12] A liquid transport mechanism comprising at least a pair of plate-like members facing each other at a predetermined interval and holding a liquid in the gap,

At least one of the at least one pair of plate-like members includes a plurality of liquid transport paths in which a plurality of electrodes are arranged at predetermined intervals along the direction of transporting the liquid, The liquid transport path has a function of supplying a specimen and a reagent, a function of transporting the specimen, the reagent and a mixture thereof, a function of temporarily storing the specimen, the reagent and a mixture thereof, and a function of reacting a mixture of the specimen and the reagent. Has the function of measuring the concentration of a specific substance in a specimen, reagent, mixture thereof, or reacted mixture,

An automatic analyzer characterized in that the supply of specimens and reagents, the transportation, storage, reaction, and measurement of specimens, reagents, and mixtures thereof are performed in parallel and asynchronously on multiple liquid transport paths.