JP7652068B2 - Analytical chip manufacturing apparatus, analytical chip manufacturing apparatus operation method, and analytical chip manufacturing method - Google Patents

Description

The present invention relates to an analytical chip manufacturing apparatus, an operating method of an analytical chip manufacturing apparatus, and a manufacturing method of an analytical chip.

Research into the analysis of genetic information in various organisms has begun. Information on numerous genes and their base sequences, including human genes, as well as on the proteins encoded by gene sequences and the glycans produced secondarily from these proteins, is being rapidly revealed. The functions of polymers such as genes, proteins and glycans whose sequences have been revealed can be investigated using a variety of methods. The main methods for investigating nucleic acids are northern blotting and southern blotting, which utilize the complementarity between various nucleic acids/nucleic acids to investigate the relationship between various genes and the expression of their biological functions. For proteins, protein function and expression can be investigated by utilizing protein/protein reactions, as typified by western blotting.

The DNA microarray method (analysis chip method) is a method for analyzing the expression of many genes at once. In principle, this method is the same as the conventional method described above in that it is a nucleic acid detection and quantification method based on a nucleic acid/nucleic acid hybridization reaction. This analysis chip method can be applied to the detection and quantification of proteins and sugar chains based on specific reactions between proteins/proteins, sugar chains/sugar chains, or sugar chains/proteins. This technology uses a substrate on which a large number of DNA fragments, proteins, and sugar chains are aligned and immobilized at high density on a flat plate or a substrate with a concave-convex pattern. A typical example of a specific method for using the analysis chip method is to hybridize a sample in which the expressed genes of the cells under study are labeled with fluorescent dyes or the like on the convex parts formed on the substrate, to bind complementary nucleic acids (DNA or RNA) to each other, and to read the sites at high speed with a high-resolution fluorescence detection device (scanner). There is also a method for detecting responses such as current values based on electrochemical reactions. In this way, the amount of each gene in the sample can be quickly estimated. Moreover, analytical chips are used not only in gene expression analysis for estimating the amount of expressed genes, but also as a means for detecting single nucleotide substitutions (SNPs) in genes.

A typical method for producing an analytical chip is the spotting method using a spotting member. Typical methods include a method in which a solution containing pre-synthesized DNA (spot solution) is spotted onto the upper end surface of a convex portion on a substrate using a metal pin such as stainless steel (see, for example, Patent Document 1), and a method in which a spot solution ejected from a nozzle using an inkjet method is spotted onto the upper end surface of a convex portion. Typically, hundreds to tens of thousands of types of DNA are applied to each of multiple convex portions formed in a matrix array on the substrate.

JP 2006-201035 A

In Patent Document 1, multiple pins are used as spotting members to simultaneously spot the upper end surfaces of multiple convex portions on a substrate; however, if the arrangement direction of the pins is misaligned with the arrangement direction of the convex portions on the substrate when the pins are positioned on the substrate (convex portions), there is a risk that the spot solution will not be properly spotted on at least some of the convex portions.

The present invention has been made in consideration of the above-mentioned problems, and aims to provide an analytical chip manufacturing apparatus, an operating method of the analytical chip manufacturing apparatus, and a manufacturing method of an analytical chip, which are capable of reliably applying spotting to each of multiple convex portions when applying spotting to multiple convex portions using multiple spotting members.

In order to solve the above problems, the analytical chip manufacturing apparatus of the present invention is an analytical chip manufacturing apparatus having a substrate having a plurality of convex portions to which a plurality of types of selective binding substances are individually applied, the analytical chip manufacturing apparatus comprising: a turntable that rotates about a central axis, on which a substrate not coated with the selective binding substance is placed; a spotting head having a plurality of spotting members that spot the selective binding substance onto each convex portion on the substrate and that is movable on a scanning plane positioned parallel to the upper portion of the turntable; and a control unit that controls, for each substrate, the rotation of the turntable and the movement of the spotting head on the scanning plane, and the application of the selective binding substance to the convex portions on the substrate, the control unit rotates the turntable and/or moves the spotting head to a position where, as viewed from the central axis direction of the turntable, each spotting member of the spotting head overlaps with a convex portion on the substrate corresponding to each spotting member, thereby applying the selective binding substance to each convex portion.

In addition, the analytical chip manufacturing device according to the present invention is characterized in that, in the above invention, at least a portion of the multiple convex portions on the substrate and the multiple spotting members arranged on the spotting head are all arranged on a straight line, the spotting head is movable in two directions that intersect with each other on the scanning plane, the control unit calculates a first angle between a first arrangement direction parallel to a straight line passing through the multiple spotting members arranged on the spotting head and one direction in which the spotting head can move, calculates a second angle between a second arrangement direction that is parallel to a straight line passing through the multiple convex portions arranged on the substrate placed on the rotating table and is formed outward from the central axis, and the one direction in which the spotting head can move, and rotates the rotating table so that the difference between the first angle and the second angle is minimized.

In addition, the analytical chip manufacturing apparatus of the present invention, in the above invention, is characterized in that it comprises a first imaging unit that images the deposition head and a second imaging unit that images the substrate placed on the rotating table, and the control unit detects the first arrangement direction based on a first image captured by the first imaging unit and detects the second arrangement direction based on a second image captured by the second imaging unit.

In addition, in the analytical chip manufacturing apparatus of the present invention, in the above invention, the control unit detects the first arrangement direction by detecting the positions of the multiple spotting members of the spotting head based on the first image.

In addition, the analytical chip manufacturing apparatus of the present invention is characterized in that, in the above invention, the control unit detects the second arrangement direction by detecting the positions of multiple convex portions on the substrate based on the second image.

In addition, the analytical chip manufacturing apparatus of the present invention is characterized in that, in the above invention, the control unit detects the second array direction by detecting a label portion formed on the substrate based on the second image.

In addition, the analytical chip manufacturing apparatus of the present invention is characterized in that, in the above invention, a plurality of the substrates are placed on the rotating table, and each substrate is placed at a position different from the position through which the central axis of the rotating table passes.

In addition, the analytical chip manufacturing apparatus of the present invention is characterized in that, in the above invention, a plurality of the rotating tables are provided, and one of the substrates is placed on each rotating table.

In addition, the analytical chip manufacturing apparatus of the present invention is characterized in that, in the above invention, the central axis of the rotating table passes through the substrate placed on the rotating table.

In addition, the analytical chip manufacturing apparatus of the present invention is characterized in that, in the above invention, the central axis of the rotating table passes through the center of gravity of the substrate.

In addition, the analytical chip manufacturing apparatus according to the present invention is characterized in that, in the above invention, it is provided with a holding table that holds each rotating table so that it can rotate freely around its respective central axis.

In addition, the method of operating the analytical chip manufacturing apparatus of the present invention is an analytical chip manufacturing apparatus having a substrate with a plurality of convex portions to which a plurality of types of selective binding substances are individually applied, the manufacturing apparatus comprising: a turntable that rotates about a central axis on which a substrate not coated with the selective binding substance is placed; a spotting head having a plurality of spotting members that spot the selective binding substance onto each convex portion on the substrate and that is movable on a scanning plane positioned parallel to the upper portion of the turntable; and a control unit that controls the rotation of the turntable, the movement of the spotting head on the scanning plane, and the application of the selective binding substance to each convex portion, characterized in that the control unit performs, for each substrate, the rotation of the turntable and/or the movement of the spotting head to a position where each spotting member of the spotting head overlaps with a convex portion on the substrate corresponding to each spotting member, as viewed from the central axis direction of the turntable, and the movement of the spotting head.

The manufacturing method of the analytical chip according to the present invention is characterized in that, when viewed from the direction of the central axis of a turntable on which a substrate not coated with a selective binding substance is placed, the method has a plurality of spotting members that individually apply a plurality of types of the selective binding substance to each convex portion on the substrate, and rotates the turntable and/or moves the spotting head to a position where each spotting member of a spotting head that can move on a scanning plane positioned parallel to the top of the turntable overlaps with the convex portion on the substrate corresponding to each spotting member, and applies the selective binding substance to each convex portion for each substrate.

According to the present invention, when spotting solution onto multiple convex portions using multiple spotting members, the effect is achieved that the spotting solution can be reliably spotted onto each convex portion.

FIG. 1 is a diagram showing a schematic configuration of an analytical chip manufacturing apparatus according to one embodiment of the present invention. FIG. 2 is a cross-sectional view of the substrate shown in FIG. 1 taken along line AA. FIG. 3 is a perspective view showing a schematic configuration of a spotting head in an analytical chip manufacturing apparatus according to one embodiment of the present invention. FIG. 4 is a diagram illustrating collection of a spot solution. FIG. 5 is a diagram for explaining the application of the spot solution. FIG. 6 is a diagram for explaining calculation of the angle between the arrangement direction of the pins and the movement direction of the spotting head. FIG. 7 is a diagram for explaining calculation of the angle formed between the arrangement direction of the convex portions on the substrate and the movement direction of the spotting head. FIG. 8 is a flow chart for explaining the spotting process of the spotting solution in the analytical chip manufacturing apparatus according to one embodiment of the present invention. FIG. 9 is a diagram showing the configuration of an analytical chip manufacturing apparatus according to the first modified example of the present invention. FIG. 10 is a diagram showing a schematic configuration of an analytical chip manufacturing apparatus according to the second modified example of the present invention. FIG. 11 is a diagram showing a schematic configuration of an analytical chip manufacturing apparatus according to the third modified example of the present invention.

Below, the form for implementing the present invention will be described in detail with reference to the drawings. Note that the present invention is not limited to the following embodiment. Furthermore, each figure referred to in the following description merely shows the shape, size, and positional relationship roughly to the extent that the contents of the present invention can be understood. In other words, the present invention is not limited to only the shape, size, and positional relationship exemplified in each figure. Furthermore, in the description of the drawings, the same parts are given the same reference numerals.

The analytical chip that is the subject of this invention is a chip in which a solution containing selective binding substances such as DNA, proteins, and glycans (referred to as a spot solution in this invention) is applied to and immobilized on the surface of a carrier, such as a substrate such as a glass substrate or a plastic substrate.

The analytical chip according to the present invention is used to measure the presence or absence, amount, properties, etc. of a test substance by dropping a sample onto the reaction portion of the analytical chip. Specific examples include biochips that measure the presence or absence, amount, etc. of a test substance by a reaction between a selective binding substance immobilized on a carrier surface and the test substance. More specific examples include DNA chips on which nucleic acids are immobilized on a carrier surface, protein chips on which proteins such as antibodies are immobilized on a carrier surface, glycan chips on which glycans are immobilized on a carrier surface, and cell chips on which cells are immobilized on a carrier surface.

(Embodiment)
Fig. 1 is a diagram showing a schematic configuration of an analytical chip manufacturing apparatus according to an embodiment of the present invention. The analytical chip manufacturing apparatus 1 shown in Fig. 1 includes a spotting processing device 10 that performs spotting processing, and a control device 20 that controls the driving of the spotting processing device 10.

The substrate 100 constituting the analytical chip comprises a base portion 101 and a plurality of convex portions 102 formed within the base portion 101. The base portion 101 has a rectangular outer edge and is tray-shaped with the outer edge rising up. The inner bottom surface of the base portion 101 extends in a flat plate shape, and the convex portions 102 are partially formed. The material of the base portion 101 is preferably a general slide glass or a plastic of a similar size. In addition, the substrate 100 preferably has a surface of a color or material that absorbs light, such as black, in order to suppress light (e.g., autofluorescence) emitted by the substrate 100 itself when detecting the signal intensity.

Figure 2 is a cross-sectional view of the substrate shown in Figure 1 taken along line A-A. A plurality of convex portions 102 (eight in this embodiment) are formed inside the base portion 101. The convex portions 102 protrude in a convex shape from the inner bottom surface of the base portion 101. Here, the upper end surface of the convex portions 102 is flat, and a spotting solution containing a selective binding substance is spotted on the upper end surface, immobilizing the selective binding substance. The upper end surface of the convex portions 102 corresponds to the immobilization region of the selective binding substance in the spotting solution, and is the region to which the spotting solution is applied.

The number of protrusions 102 can be set to any number, for example, two, four, eight, etc. The protrusions 102 are arranged in a matrix. In this embodiment, eight protrusions 102 are arranged in four rows and two columns (4 x 2).

In the present invention, the selective binding substance refers to various substances that can selectively bind to a test substance directly or indirectly. Representative examples of selective binding substances that can bind to a test substance include nucleic acids, proteins, peptides, sugars, and lipids.

Among the selective binding substances, the nucleic acid may be DNA or RNA, or may be PNA or LNA. The DNA may be, but is not limited to, chromosomal DNA, viral DNA, bacterial or fungal DNA, cDNA obtained by reverse transcribing RNA, or fragments thereof. The RNA may be, but is not limited to, messenger RNA, ribosomal RNA, small RNA, microRNA, or fragments thereof. The nucleic acid may also include chemically synthesized DNA or RNA. A single-stranded nucleic acid having a specific base sequence selectively hybridizes and binds to a single-stranded nucleic acid having a base sequence complementary to the base sequence or a portion thereof, and therefore corresponds to the selective binding substance referred to in the present invention. The nucleic acid may be derived from a natural product such as a living cell, or may be synthesized by a nucleic acid synthesizer. Preparation of DNA or RNA from living cells can be performed by known methods, for example, DNA extraction can be performed by the method of Blin et al. (Blin et al., Nucleic Acids Res. 3: 2303 (1976)) or the like, and RNA extraction can be performed by the method of Favaloro et al. (Favororo et al., Methods Enzymol. 65: 718 (1980)) or the like. Examples of nucleic acids to be immobilized include linear or circular plasmid DNA or chromosomal DNA, DNA fragments obtained by cleaving these with restriction enzymes or chemically, DNA synthesized in a test tube with an enzyme or the like, or chemically synthesized oligonucleotides.

Proteins include antibodies and antigen-binding fragments of antibodies, such as Fab fragments and F(ab')2 fragments, as well as various antigens. Antibodies and their antigen-binding fragments selectively bind to their corresponding antigens, and antigens selectively bind to their corresponding antibodies, so they are considered "selective binding substances."

Examples of sugars include various monosaccharides, oligosaccharides, polysaccharides, and other sugar chains.

The lipids may be simple lipids or complex lipids.

In addition, antigenic substances other than the above-mentioned nucleic acids, proteins, sugars, and lipids can also be immobilized. Also, cells may be immobilized on the surface of the carrier as a selective binding substance.

Among these selective binding substances, particularly preferred ones include DNA, RNA, proteins, peptides, sugars, glycans, and lipids.

These selective binding substances are applied to the surface of the carrier as a spotting solution and immobilized. The spotting solution may also contain other salts for adjusting the buffer. Examples of such salts include phosphate buffer, citrate buffer, citrate phosphate buffer, borate buffer, and tartrate buffer.

When the selective binding substance is immobilized on the carrier surface by a covalent bond, the spotting solution may contain a condensing agent. As the condensing agent, a carbodiimide for forming an amide bond, particularly the water-soluble carbodiimide 3-(3-dimethylaminopropyl)-1-ethylcarbodiimide (EDC) or its hydrochloride, may be preferably used. When EDC is used as the condensing agent, a solution in which EDC and sodium chloride are mixed may be used in the spotting solution.

It is preferable that the analytical chip has a structure in which at least the space in which the convex portion 102 is formed in the base portion 101 is sealed by a cover or the like (not shown) when reacting with the test substance. For example, the inner surface of the cover can be formed in a concave shape so that the upper end surface of the convex portion 102 does not directly contact the cover. In addition, when a flat cover is used, a structure can be adopted in which the convex portion 102 is provided in a concave portion formed in the base portion 101, and the depth of the concave portion is such that the upper end surface of the convex portion 102 does not contact the inner surface of the cover when the cover is placed on the substrate. The cover used in this case may be made of any material, such as glass, various polymers (e.g., polystyrene, polymethyl methacrylate, polycarbonate, polyolefin), silicone, etc.

The spotting treatment device 10 includes a rotating table 11, a spotting head 12, a moving mechanism 13, a first imaging unit 14, a second imaging unit 15, a spot solution holding unit 16, a cleaning unit 17, and a drying unit 18. In the spotting treatment device 10 shown in FIG. 1, the left-right direction is the X direction (the right direction is the positive direction), the up-down direction is the Y direction (the up direction is the positive direction), and the direction perpendicular to the paper surface is the Z direction (the direction toward the viewer is the positive direction).

The rotating table 11 is disk-shaped and places the substrate 100 on which the spotting process is to be performed. The rotating table 11 is rotatable around a central axis N. In FIG. 1, the central axis N extends in a direction perpendicular to the paper surface (Z direction). The surface on the rotating table 11 on which the substrate 100 is placed is parallel to the XY plane. The substrates 100 are arranged in a circumferential direction of a circle centered on the central axis N, at a position that is not passed by the central axis N of the rotating table 11. Therefore, the substrates 100 revolve around the central axis N as the rotating table 11 rotates.

The spotting head 12 has a holding section 121 that holds a plurality of pins 122 that spot the spot solution on the substrate 100. FIG. 3 is a perspective view that shows a schematic configuration of the spotting head in an analytical chip manufacturing apparatus according to one embodiment of the present invention. The pins 122 extend in a rod shape from the holding section 121. The spotting head 12 shown in FIG. 1 is provided with eight pins 122 in accordance with the number of protrusions 102 of the substrate 100. The multiple pins 122 are arranged in two orthogonal directions (in a matrix). In the substrate 100 shown in FIG. 1, the multiple pins 122 are arranged in a 4×2 (piece) arrangement that corresponds to the arrangement of the protrusions 102. The pins 122 correspond to the spotting members.

The movement mechanism 13 holds the holder 121 of the spotting head 12, and moves the spotting head 12 under the control of the control device 20. The movement mechanism 13 drives the spotting head 12 to move in the X, Y, and Z directions. Specifically, the movement mechanism 13 moves the spotting head 12 on the XY plane, which is the scanning plane. Furthermore, this scanning plane can be shifted in the Z direction.

The moving mechanism 13 has a first shaft 131 extending in the X direction, a first moving part 132 that moves in the X direction along the first shaft 131, a second moving part 133 held by the first moving part 132 and movable in the Z direction, and a second shaft 134 that extends in the Y direction from the second moving part 133 and holds the spotting head 12 movably in the Y direction.

The first imaging unit 14 captures an image of the side of the spotting head 12 on which the pins 122 are disposed.
The second imaging section 15 captures an image of the surface of the substrate 100 on which the convex portions 102 are formed.

The first imaging unit 14 and the second imaging unit 15 are configured using, for example, a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal Oxide Semiconductor) image sensor. The first imaging unit 14 and the second imaging unit 15 may be configured to be movable in order to change the imaging field of view of the first imaging unit 14 and the second imaging unit 15. In that case, it is possible to move the first imaging unit 14 and the second imaging unit 15 in order to capture an image for detecting the arrangement direction of the pins 122 or the arrangement direction of the protrusions 102.

The spot solution holding unit 16 is provided with a replaceable plate 161. The plate 161 is formed with a plurality of holes 162 (eight in this embodiment). The holes 162 contain spot solutions. The holes 162 are arranged in accordance with the arrangement of the pins 122, and the pins 122 are inserted into each hole 162 by the movement of the moving mechanism 13. The plate 161 may be replaced manually by the user or mechanically. When replacing mechanically, for example, a refrigerator compartment that stores a plurality of plates 161 containing spot solutions is provided at the bottom of the spot solution holding unit 16, and the plate 161 to be replaced is removed from the refrigerator compartment and placed in the spot solution holding unit 16.

The cleaning unit 17 is supplied with a cleaning liquid such as water (pure water), physiological saline, or an aqueous solution containing a surfactant, and cleans the pins 122 arranged in the cleaning unit 17 by immersion, stirring, or the like.
The drying section 18 is for removing cleaning liquid adhering to the pins after cleaning. For example, the pins after cleaning are inserted into the drying section 18, and the cleaning liquid adhering to the pins is removed by wind pressure.

The control device 20 includes a drive unit 21, a calculation unit 22, a memory unit 23, and a control unit 24. The control device 20 is configured using one or more processors, such as a CPU (Central Processing Unit), FPGA (Field Programmable Gate Array), or ASIC (Application Specific Integrated Circuit), and a memory.

The drive unit 21 drives and controls each part of the spotting processing device 10 based on a control signal from the control unit 24. For example, the drive unit 21 sends a pulse signal to each part to move the rotating table 11 and the moving mechanism 13 in a set direction and distance, and causes the first imaging unit 14 and the second imaging unit 15 to perform imaging processing.

The calculation unit 22 executes calculation processing to determine the amount of rotation of the rotary table and the position of the spotting head 12 by the moving mechanism 13. The calculation unit 22 has an angle calculation unit 221 and a position determination unit 222.

The angle calculation unit 221 calculates the angle between the arrangement direction of the pins 122 arranged on the spotting head 12 and the movement direction of the spotting head 12, and the angle between the arrangement direction of the convex portions 102 of the substrate 100 and the movement direction of the spotting head 12.

The position determination unit 222 determines the rotation position of the rotating table 11 and the movement position of the spotting head 12 by the movement mechanism 13 based on the angle calculated by the angle calculation unit 221.

The memory unit 23 stores information including various programs for operating the manufacturing equipment 1 and various parameters necessary for the operation of the manufacturing equipment 1.

The control unit 24 comprehensively controls each part of the manufacturing equipment 1.

Next, an example of a method for using the analytical chip will be described. First, a test substance such as a nucleic acid is extracted from a specimen. Then, a label, for example a fluorescent label, is bound to the extracted test substance. The labeled test substance is reacted with a selective binding substance on the DNA chip. In the reaction process, the test substance is reacted with the selective binding substance immobilized on the upper end surface of the convex portion 102 by stirring for example at 32°C for several hours. In the stirring process, the solution containing the test substance is stirred by moving the analytical chip by, for example, rotation, vibration, or a combination of these, or by moving stirring beads enclosed in a cover covering the analytical chip.

Samples used in the present invention include, but are not limited to, bodily fluids such as blood, serum, plasma, urine, stool, cerebrospinal fluid, saliva, various tissue fluids, and various foods and beverages and their dilutions.

Examples of test substances used in the present invention include, but are not limited to, nucleic acids to be measured, such as genes of pathogens or viruses, genes responsible for genetic diseases, and parts thereof, various biological components having antigenicity, and antibodies against pathogens or viruses. The test substances can be reacted with selective binding substances, for example, by hybridization reaction in the case of nucleic acids, or by antigen-antibody reaction in the case of proteins.

The nucleic acid to be tested may be nucleic acid extracted from blood or cells and labeled with a fluorescent substance or the like, or may be amplified by a nucleic acid amplification method such as PCR using the nucleic acid as a template. When a nucleic acid amplification product is used as the test substance, it is possible to label the amplified nucleic acid by performing amplification in the presence of a nucleoside triphosphate labeled with a fluorescent substance or the like. In addition, when the test substance is an antigen or an antibody, the test substance, the antigen or antibody, may be directly labeled by a conventional method, or the test substance, the antigen or antibody, may be bound to a selective binding substance, and the carrier may be washed, and the labeled antibody or antigen that undergoes an antigen-antibody reaction with the antigen or antibody may be reacted to measure the label bound to the carrier. Furthermore, when an unamplified nucleic acid is used as the test substance, a method in which, for example, the phosphate group at the 5' end of the nucleic acid is removed with alkaline phosphatase, the test substance is labeled with a fluorescent substance, and then reacted with a selective binding substance and the bound label is measured; or a method in which the test substance is captured by a selective binding substance (capture probe), a detection probe labeled with a fluorescent substance or the like is bound to the test substance, and the label of the detection probe is measured (sandwich hybridization method) is suitably used.

After the reaction process, the analytical chip is washed to remove any substances that have not reacted with the selective binding substance. After the washing process, the analytical chip is centrifuged and dried using a general centrifuge designed specifically for chips and slide glasses.

If the test substance is fluorescently labeled, the analytical chip after washing and drying is used to read the image using a high-resolution fluorescence detection device or the like, and to quantify the signal intensity (fluorescence intensity). Suitable high-resolution fluorescence detection devices include, but are not limited to, 3D-Gene (registered trademark) Scanner (manufactured by Toray Industries, Inc.), SureScan microarray scanner (manufactured by Agilent Technologies, Inc.), and GenePix (manufactured by Molecular Devices, Inc.).

Next, the method of spotting the spot solution when manufacturing the analytical chip will be described with reference to Figs. 3 to 8. Fig. 4 is a diagram explaining the collection of the spot solution. Fig. 5 is a diagram explaining the spotting of the spot solution. The pin 122 (spotting head 12) is moved by the driving of the moving mechanism 13 under the control of the control unit 24.

In the spotting process, first, the pins 122 are inserted into the holes 162 containing the spot solutions _{Q1 to Q4} (see FIG. 4A), and the spot solutions Q1 to _Q4 are applied to the tips of the pins 122 (see FIG. 4B).

Then, the pin 122 with the spot solution attached to its tip is placed on top of the substrate 100 to be spotted (see FIG. 5(a)), and the spot solution is brought into contact with the convex portion 102, thereby transferring the spot solution from the pin 122 to the convex portion 102 (see FIG. 5(b)).

In this case, if the position of the pin 122 is misaligned with the position of the convex portion 102, the spot solution may not be properly applied to the convex portion 102. In this embodiment, the spotting head 12 and the substrate 100 are positioned so that the arrangement direction of the pins 122 and the arrangement direction of the convex portion 102 are aligned.

At this time, the angle calculation unit 221 first calculates the angle between the arrangement direction of the pins 122 arranged on the spotting head 12 and the movement direction of the spotting head 12. Figure 6 is a diagram for explaining the calculation of the angle between the arrangement direction of the pins and the movement direction of the spotting head. Note that the first imaging unit 14 and the second imaging unit 15 will be described as images captured by an optical system with an optical axis parallel to the Z direction.

The angle calculation unit 221 acquires an image of the spotting head 12 captured by the first imaging unit 14. Based on the captured image, the angle calculation unit 221 generates a straight line L _P passing through all the pins 122 arranged in a predetermined direction from the arrangement of the pins 122. In this embodiment, a straight line passing through all the pins 122 arranged approximately parallel to the X direction is generated. For example, the angle calculation unit 221 extracts the contour of the outer periphery of each pin 122 by contour extraction and obtains the center of the contour. The angle calculation unit 221 obtains an approximation line for the position of each obtained center, and sets this as the straight line L _P. The angle calculation unit 221 calculates the angle θ _P between the straight line L _P and a straight line L _N parallel to the movement direction of the spotting head 12 (here, the longitudinal axis direction (X direction) of the first shaft 131).

The angle calculation unit 221 also calculates the angle between the arrangement direction of the convex portions 102 of the substrate 100 and the moving direction of the spotting head 12. FIG. 7 is a diagram for explaining the calculation of the angle between the arrangement direction of the convex portions of the substrate and the moving direction of the spotting head. The angle calculation unit 221 acquires an image of the substrate 100 captured by the second imaging unit 15. The angle calculation unit 221 generates a straight line L _C passing through all the convex portions 102 arranged in a predetermined direction from the arrangement of the convex portions 102 based on the captured image. In this embodiment, a straight line is generated that passes through all the convex portions 102 arranged substantially parallel to the arrangement direction of the spotting head 12 (here, the arrangement direction of the convex portions 102 arranged in the X direction when placed at the spotting position). The arrangement direction of the convex portions 102 through which this straight line passes is the direction from the center (center axis N) of the rotating table 11 toward the outside. The angle calculation unit 221 extracts the contour of the outer periphery of each convex portion 102 by contour extraction, for example, and finds the center of the contour. The angle calculation unit 221 finds an approximation line for each of the found center positions, and sets this line as line L _C. The angle calculation unit 221 calculates the angle θ _C between line L _C and line L _N that is parallel to the movement direction of the spotting head 12 (here, the longitudinal axis direction (X direction) of the first shaft 131).

The position determination unit 222 determines the rotational position of the turntable 11 (the arrangement of the substrate 100 to be spotted) and the movement position of the spotting head 12 by the movement mechanism 13, based on the angles θ _P and θ _C calculated by the angle calculation unit 221. The position determination unit 222 calculates the difference θ _D between the angles θ _P and θ _C. This difference θ _D corresponds to the deviation in the X direction between the arrangement direction of the pins 122 and the arrangement direction of the protrusions 102.

The position determination unit 222 determines the position of the substrate 100 to be the target of spotting, which is the position obtained by rotating the turntable 11 by θ _B from the reference spotting position (for example, the reference position P _B shown in FIG. 1). That is, the position determination unit 222 determines the rotation angle (θ _B ) of the turntable 11 at which the difference (difference θ _D ) between the angle θ _P and the angle θ _C is minimum. This allows the arrangement direction of the pins 122 and the arrangement direction of the protrusions 102 to be parallel. Depending on the characteristics related to the rotation of the turntable 11, the characteristics related to the drive of the moving mechanism 13, the arrangement area of the protrusions, and the area of the upper ends of the protrusions, the rotation angle (θ _B ) may be set, for example, within a range of θ _D ±0.1°. More preferably, it may be set within a range of θ _D ±0.06°.

Furthermore, the position determination unit 222 determines a position above the substrate 100 after the rotation of the turntable 11 as a position for placing the spotting head 12. A virtual coordinate space is set in the spotting processing device 10, and the position determination unit 222 determines coordinates located a predetermined distance above in the Z direction in the XY coordinates of the substrate 100 placed at the spotting position as the position of the spotting head 12. Here, the coordinates of the substrate and the spotting head 12 refer to the coordinates where the representative points of each component are located.
The position determination unit 222 may correct the position (coordinates) of the spotting head 12 depending on the position and orientation of the substrate 100 in the captured image.

Next, the flow of the spotting process of the spot solution in the manufacturing apparatus 1 will be described with reference to Figure 8. Figure 8 is a flowchart illustrating the spotting process of the spot solution in an analytical chip manufacturing apparatus according to one embodiment of the present invention.

First, the substrate 100 is subjected to a surface treatment and then placed on the rotating table 11. In the surface treatment, processes such as the introduction of functional groups required for immobilizing the selective binding substance on the substrate surface are carried out. For example, in the case of a substrate made of polymethyl methacrylate (PMMA), hydrolysis of the PMMA side chains is carried out using an alkaline aqueous solution.

In the manufacturing apparatus 1, in order to detect the arrangement direction of the pins 122, the first imaging unit 14 captures an image of the spotting head 12 (step S101).

Thereafter, the angle calculation unit 221 detects the arrangement direction of the pins 122 based on the captured image of the spotting head 12 (step S102). As described above, the angle calculation unit 221 generates a straight line L _P that passes through all the pins 122 that are arranged in a predetermined direction from the arrangement of the pins 122 (see FIG. 6 ).

The angle calculation unit 221 calculates the angle θ _P (arrangement angle) between the generated straight line L _P and a straight line L _N parallel to the movement direction of the spotting head 12 (step S103). The arrangement angle calculated in step S103 is stored in the memory unit 23, and the arrangement angle can be used until the spotting head 12 is replaced.

Here, the control unit 24 assigns a spotting process number n to the multiple substrates 100 placed on the turntable 11. The number n corresponds to the number of substrates 100 placed on the turntable 11. If the maximum value of the number n is n _MAX , in this embodiment, n _MAX = 8 (see FIG. 1). The control unit 24 sets the number n of the substrate to be spotted to n = 1 (step S104). Under the control of the control unit 24, the drive unit 21 rotates the turntable 11 to move the substrate 100 with n = 1 to a reference position (reference position P _B ). Note that the substrate 100 placed on the turntable 11 at this time is a substrate on which the spotting solution has not been applied.

In step S105, the angle calculation unit 221 detects the arrangement direction of the convex portions 102 of the n-th substrate 100. At this time, the second imaging unit 15 captures an image of the substrate 100. Based on the captured image, the angle calculation unit 221 generates a straight line L _C that passes through all the convex portions 102 lined up in a predetermined direction from the arrangement of the convex portions 102 (see FIG. 7 ).

The angle calculation unit 221 calculates the angle θ _C between the generated straight line L _C and a straight line L _N parallel to the moving direction of the spotting head 12 (step S106).

Thereafter, the position determination unit 222 determines the position of the nth substrate 100 (the rotation angle of the turntable 11) and the position of the spotting head 12 (movement position) by the movement mechanism 13 based on the angles θ _P and θ _C calculated by the angle calculation unit 221 (step S107). The position determination unit 222 determines the position of the substrate 100 to be spotted as the position of the turntable 11 rotated from the reference position P _B by a rotation angle at which the difference θ _D between the angles θ _P and θ _C is minimum. The position determination unit 222 also determines the position above the substrate 100 after rotation by the rotation angle at which the difference θ _D is minimum as the position at which the spotting head 12 is to be positioned, and records this in the memory unit 23.

Next, the control unit 24 increments the value of the number n of the substrate 100 by 1 (step S108).

Thereafter, the control unit 24 judges whether the reset number n is greater than the maximum value n _MAX (here, n=8) (step S109). When the control unit 24 judges that n is equal to or less than n _MAX (step S109: No), the control unit 24 returns to step S105 and executes processing on the substrate 100 corresponding to the reset number n. On the other hand, when the control unit 24 judges that n is greater than n _MAX (step S109: Yes), the control unit 24 executes spotting processing on all substrates 100 placed on the turntable 11 (step S110). The driving unit 21 moves the spotting head 12 to the spot solution holder 16 and applies the spot solution to the pins 122 (see FIG. 4). After the spot solution is applied to the pins 122, under the control of the control unit 24, the turntable 11 is rotated according to the substrate 100 to be spotted, and the spotting head 12 is moved by the moving mechanism 13, so that the n-th substrate 100 and the spotting head 12 are positioned at the position determined in step S107 (the position recorded in the memory unit 23). After positioning the substrate 100 and the spotting head 12, the control unit 24 lowers the spotting head 12 in the Z direction to bring the spot solution into contact with the convex portion 102 and spot the solution (see FIG. 5). The control unit 24 performs the above-mentioned process on each substrate 100 in a preset order (for example, n=1, 2, 3, ..., n).
Furthermore, if it is determined in step S109 that n is greater than n _MAX (step S109: Yes), before proceeding to step S110, a position confirmation step can be added in which the second imaging unit 15 detects the arrangement direction of the convex portions again at the position recorded in the memory unit 23 to confirm whether the position recorded in the memory unit 23 is appropriate.

In the above-described embodiment, the arrangement direction of the pins 122 arranged on the spotting head 12 and the arrangement direction of the convex portions 102 of the substrate 100 are detected, and the rotating table 11 and the spotting head 12 are moved to a position where the arrangement directions are aligned to perform the spotting process. According to this embodiment, the spotting process is performed in a manner that suppresses misalignment between the positions of the pins 122 and the positions of the convex portions 102. Therefore, when spotting solution onto multiple convex portions using multiple pins, the spot solution can be reliably spotted onto each convex portion.

In the above-described embodiment, instead of using a pin that applies the spot solution to the upper end surface of the convex portion by contact with the spot solution, a nozzle that ejects the spot solution from the inside by an inkjet method may be used to apply the spot solution to the convex portion 102.

In the above-mentioned embodiment, an example was described in which the arrangement directions of the pins 122 and the protrusions 102 were detected from their images, but it would also be possible to provide the holding unit 121 or the base unit 101 with indicators indicating the arrangement directions of the pins 122 and the protrusions 102, and to detect each arrangement direction by detecting these indicators. The indicators may be characters, or may be figures such as a square (□), a circle (◯), or a straight line (-), or a combination of these, as long as it is possible to detect the arrangement direction.

In addition, in the above-mentioned embodiment, an example was described in which the number of pins 122 and the number of convex portions 102 of the substrate 100 are the same, and spotting on one substrate 100 is completed in one spotting process. However, if the number of pins 122 is fewer than the number of convex portions 102, the spotting head 12 can be moved back and forth relative to the substrate 100. If the number of pins 122 is greater than the number of convex portions 102, the arrangement of the spot solution contained in the plate 161 of the spot solution holding unit can be adjusted to match the convex portions, and the pins 122 that apply the spot solution can be controlled.

(Variation 1)
Next, modified example 1 will be described with reference to Fig. 9. Fig. 9 is a diagram showing the configuration of an analytical chip manufacturing apparatus according to modified example 1 of the present invention. The analytical chip manufacturing apparatus 1A according to modified example 1 includes a spotting processing apparatus 10A instead of the spotting processing apparatus 10 of the analytical chip manufacturing apparatus 1 described above. In the analytical chip manufacturing apparatus 1A, the configuration other than the spotting processing apparatus 10A is the same as the configuration described in the embodiment.

The spotting treatment device 10A includes a plurality of rotating tables 11A, a spotting head 12, a moving mechanism 13, a first imaging section 14, a second imaging section 15, a spot solution holding section 16, a cleaning section 17, and a drying section 18. The first imaging section 14, the spot solution holding section 16, the cleaning section 17, and the drying section 18 are the same as those in the above-described embodiment. The moving mechanism 13 is the same as those in the above-described embodiment, except that the lengths of the first shaft 131 and the second shaft 134 differ depending on the arrangement of the rotating table 11A.

The turntable 11A is disk-shaped and has one substrate 100 placed thereon. The turntable 11A is rotatable around a central axis _N1 under the control of the control device 20. In FIG. 9, the central axis _N1 extends in a direction perpendicular to the paper (Z direction). The surface of the turntable 11A on which the substrate 100 is placed is parallel to the XY plane. In addition, when the substrate 100 is placed on the turntable 11A, the central axis _N1 passes through the substrate 100. In this modified example 1, an example in which the central axis N1 passes through the center of gravity of the substrate 100 will be described, but the present invention is not limited to this, and the central axis _N1 may pass through a position shifted from the center of gravity.

In this first modified example, the second imaging unit 15 is provided so as to be movable relative to each rotating table 11A. The second imaging unit 15 is moved by a moving mechanism (not shown). The second imaging unit 15 may be attached to the spotting head 12 and move together with the spotting head 12, or may move along the moving mechanism 13 separately from the spotting head 12, or a known moving mechanism other than the moving mechanism 13 may be used.

The calculation unit 22 executes a calculation process to determine the amount of rotation of the rotary table 11A based on the image of the substrate 100. Specifically, the angle calculation unit 221 calculates the angle θ P1 (corresponding to the above-mentioned angle θ P) between the arrangement direction of the pins 122 arranged on the spotting head 12 (corresponding to the above-mentioned straight line L _P ) and the movement direction of the spotting head 12 (corresponding to the above-mentioned straight line L _N ), and the angle θ _C1 (corresponding to the above-mentioned angle θ _{C )} between the arrangement direction of the convex portions 102 of the substrate 100 (e.g., corresponding to the above-mentioned straight line L _C ) and the movement direction of the spotting head 12. Here, the angle calculation unit 221 calculates the angle θ _C1 between the arrangement direction of the convex portions 102 of the substrate 100 and the movement direction of the spotting head ₁₂ for each rotary table 11A.

Thereafter, the position determination unit 222 determines the rotation angle around the central axis _N1 of the turntable 11A based on the angle calculated by the angle calculation unit 221. Specifically, the position determination unit 222 calculates the difference (difference _θD1 ) between the angle _θP1 and the angle _θC1 , and determines the rotation angle ( _θB1 ) of the turntable 11A at which the difference _θD1 is minimum. In this modified example 1, the movement position of the spotting head 12 by the moving mechanism 13 is a position determined based on the image of the substrate 100 captured by the second imaging unit 15. This movement position is determined, for example, by extracting the outline of the substrate 100 and aligning the outline with the spotting head 12. In addition, this movement position is determined for each turntable 11A based on the position of the central axis _N1 of each turntable 11A.

The rotating table 11A on which the substrate 100 to be spot-applied is placed is rotated at a rotation angle determined by the position determination unit 222 under the control of the control device 20.

The movement mechanism 13 moves the spotting head 12 to the movement position described above under the control of the control device 20. The movement mechanism 13 drives the spotting head 12 to move in the X, Y, and Z directions. The spotting head 12 moves up and down in the Z direction at the movement position, thereby spotting the spot solution onto the convex portion 102 of the substrate 100.

In the above-mentioned modified example 1, the arrangement direction of the pins 122 arranged on the spotting head 12 and the arrangement direction of the convex portions 102 of the substrate 100 placed on the rotating table 11A are detected, and the rotating table 11A is rotated to a position where the arrangement directions are aligned to perform the spotting process. According to this modified example 1, the spotting process is performed in a manner that suppresses the occurrence of misalignment between the positions of the pins 122 and the positions of the convex portions 102, so that when spotting solution onto multiple convex portions using multiple pins, the spot solution can be reliably spotted onto each convex portion.

In the above-mentioned variant example 1, a configuration in which one second imaging unit 15 is movably arranged relative to each rotating table 11A has been described as an example, but multiple units may be provided, or the second imaging unit 15 may be provided individually for each rotating table 11A.

(Variation 2)
Next, modified example 2 will be described with reference to Fig. 10. Fig. 10 is a diagram showing a schematic configuration of an analytical chip manufacturing apparatus according to modified example 2 of the present invention. The analytical chip manufacturing apparatus 1B according to modified example 2 includes a spotting processing apparatus 10B instead of the spotting processing apparatus 10 of the analytical chip manufacturing apparatus 1 described above. In the analytical chip manufacturing apparatus 1B, the configuration other than the spotting processing apparatus 10B is the same as the configuration described in the embodiment.

The spotting processing device 10B includes a plurality of rotating tables 11B, a holding table 11C that holds the rotating tables 11B, a spotting head 12, a moving mechanism 13, a first imaging unit 14, a second imaging unit 15, a spot solution holding unit 16, a cleaning unit 17, and a drying unit 18. The first imaging unit 14, the second imaging unit 15, the spot solution holding unit 16, the cleaning unit 17, and the drying unit 18 are the same as those in the above-described embodiment.

The turntable 11B is disk-shaped and has one substrate 100 placed thereon. The turntable 11B can rotate around a central axis _N2 under the control of the control device 20. In FIG. 10, the central axis N2 extends in a direction perpendicular to the paper (Z direction). The surface of the turntable 11B on which the substrate 100 is placed is parallel to the XY plane. In addition, when the substrate 100 is placed on the turntable 11B, the central axis _N2 passes through the substrate 100. In this modified example 2, an example in which the central axis _N2 passes through the center of gravity of the substrate 100 will be described, but the present invention is not limited to this, and the central axis _N2 may pass through a position shifted from the center of gravity.

The holding table 11C is disk-shaped and holds each rotating table 11B rotatably around a central axis _N2 . The holding table 11C is rotatable around a central axis _N3 as a rotation axis under the control of the control device 20. In Fig. 10, the central axis _N3 extends in a direction perpendicular to the paper surface (Z direction). In the holding table 11C, the rotating table 11B is disposed around the central axis _N3 . In this case, the central axis _N3 does not pass through the rotating table 11B.
The holding table 11C rotates about the central axis _N3 to position the turntable 11B, on which the substrate 100 to be spotted is placed, at a position for imaging by the second imaging unit 15. The imaging position is set, for example, so that the central axis _N2 of the turntable 11B is located on the reference position P _B. In this modified example 2, the second imaging unit 15 images the substrate 100 placed at a position where the spotting head 12 will perform spotting.

In the second modification, the calculation unit 22 executes a calculation process to determine the amount of rotation of the turntable 11B and the position of the spotting head 12 by the moving mechanism 13, based on an image of the substrate 100. Specifically, similar to the first modification, the position determination unit 222 calculates the difference (difference θ _D1 ) between the angle θ _P1 and the angle θ _C1 for the substrate 100 on the turntable 11B placed at the spotting position, and determines the rotation angle (θ _B1 ) of the turntable 11B at which the difference θ _D1 is minimum.

The rotating table 11B on which the substrate 100 to be spot-applied is placed is rotated at a rotation angle determined by the position determination unit 222 under the control of the control device 20.

The movement mechanism 13 moves the spotting head 12 under the control of the control device 20. The movement mechanism 13 drives the spotting head 12 to move in the X, Y, and Z directions. The spotting head 12 moves up and down in the Z direction relative to the rotating table 11B located on the reference position P _B , thereby spotting the spot solution onto the convex portions 102 of the substrate 100.

In the above-mentioned modified example 2, the arrangement direction of the pins 122 arranged on the spotting head 12 and the arrangement direction of the convex portions 102 of the substrate 100 placed on the rotating table 11B are detected, and the rotating table 11B is rotated to a position where the arrangement directions are aligned to perform the spotting process. According to this modified example 2, the spotting process is performed in a manner that suppresses the occurrence of misalignment between the positions of the pins 122 and the positions of the convex portions 102, so that when spotting solution onto multiple convex portions using multiple pins, the spot solution can be reliably spotted onto each convex portion.

(Variation 3)
Next, modified example 3 will be described with reference to Fig. 11. Fig. 11 is a diagram showing a schematic configuration of an analytical chip manufacturing apparatus according to modified example 3 of the present invention. The analytical chip manufacturing apparatus 1C according to modified example 3 includes a spotting processing apparatus 10C instead of the spotting processing apparatus 10 of the analytical chip manufacturing apparatus 1 described above. In the analytical chip manufacturing apparatus 1C, the configuration other than the spotting processing apparatus 10C is the same as the configuration described in the embodiment.

The spotting processing device 10C includes a plurality of rotating tables 11B, a holding table 11D that holds the rotating tables 11B, a spotting head 12, a moving mechanism 13, a first imaging section 14, a second imaging section 15, a spot solution holding section 16, a cleaning section 17, and a drying section 18. The rotating table 11B, the first imaging section 14, the second imaging section 15, the spot solution holding section 16, the cleaning section 17, and the drying section 18 are the same as those in the above-described embodiment.

The holding table 11D extends in the Y direction and holds each rotating table 11B rotatably around a central axis _N2 . The holding table 11D moves the rotating table 11B in the Y direction under the control of the control device 20. The holding table 11D moves the rotating table 11B in one direction (downward in FIG. 11 ) to sequentially position the multiple substrates 100 at the spotting positions by the spotting head 12.

In the third modification, the calculation unit 22 executes calculation processing to determine the amount of rotation of the turntable 11B and the position of the spotting head 12 by the moving mechanism 13, based on the image of the substrate 100. Specifically, similar to the first modification, the position determination unit 222 calculates the difference (difference θ _D1 ) between the angle θ _P1 and the angle θ _C1 for the substrate 100 on the turntable 11B placed at the spotting position, and determines the rotation angle (θ _B1 ) of the turntable 11B at which the difference θ _D1 is minimum.

The rotating table 11B on which the substrate 100 to be spot-applied is placed is rotated at a rotation angle determined by the position determination unit 222 under the control of the control device 20.

The movement mechanism 13 moves the spotting head 12 under the control of the control device 20. The movement mechanism 13 drives the spotting head 12 to move in the X, Y, and Z directions. The spotting head 12 moves up and down in the Z direction relative to the rotating table 11B located on the reference position P _B , thereby spotting the spot solution onto the convex portions 102 of the substrate 100.

In the above-mentioned modified example 3, the arrangement direction of the pins 122 arranged on the spotting head 12 and the arrangement direction of the convex portions 102 of the substrate 100 placed on the rotating table 11B are detected, and the rotating table 11B is rotated to a position where the arrangement directions are aligned to perform the spotting process. According to this modified example 3, the spotting process is performed in a manner that suppresses misalignment between the positions of the pins 122 and the positions of the convex portions 102, so that when spotting solution onto multiple convex portions using multiple pins, the spot solution can be reliably spotted onto each convex portion.

The holding table 11D that moves the rotating table 11B is not limited to the configurations of variants 2 and 3, and may be configured to move the rotating table 11B in the X direction or to move the rotating table 11B along a partially curved path.

The analytical chip manufacturing apparatus, the operating method of the analytical chip manufacturing apparatus, and the analytical chip manufacturing method of the present invention are useful for reliably applying spot solution to each convex portion when applying spot solution to multiple convex portions using multiple pins.

REFERENCE SIGNS LIST 1, 1A, 1B, 1C Analytical chip manufacturing apparatus 10, 10A, 10B, 10C Spotting processing apparatus 11, 11A, 11B Rotating table 11C, 11D Holding table 12 Spotting head 13 Moving mechanism 14 First imaging section 15 Second imaging section 16 Spot solution holding section 17 Cleaning section 18 Drying section 20 Control device 21 Driving section 22 Calculation section 23 Memory section 24 Control section 100 Substrate 101 Base section 102 Convex section 121 Holding section 122 Pin 131 First shaft 132 First moving section 133 Second moving section 134 Second shaft 161 Plate 162 Hole 221 Angle calculation section 222 Position determination section

Claims (12)

An analytical chip manufacturing apparatus comprising a substrate having a plurality of convex portions on which a plurality of types of selective binding substances are individually applied,
a rotating table that rotates about a central axis, on which a substrate not coated with the selective binding substance is placed;
a spotting head having a plurality of spotting members for spotting the selective binding substance on each of the convex portions on the substrate, the spotting head being movable on a scanning plane positioned parallel to an upper portion of the rotary table;
a control unit that controls, for each of the substrates, the rotation of the rotary table, the movement of the deposition head in the scanning plane, and the application of the selective binding substance to the convex portions on the substrate;
Equipped with
At least a portion of the plurality of convex portions on the substrate and the plurality of spotting members disposed on the spotting head are both arranged on a straight line,
the spotting head is movable in two directions intersecting each other on the scanning plane;
The control unit is
Calculating a first angle between a first arrangement direction parallel to a straight line passing through the plurality of spotting members arranged on the spotting head and one direction in which the spotting head can move;
calculating a second angle between a second arrangement direction that is parallel to a straight line passing through a plurality of convex portions arranged on the substrate placed on the rotary table and that is formed from the central axis toward an outside and the one direction in which the deposition head is movable;
rotating the rotary table so that a difference between the first angle and the second angle is minimized;
By doing so,
the rotary table is rotated to a position where each spotting member of the spotting head overlaps with a convex portion on the substrate corresponding to each spotting member when viewed from the central axis direction of the rotary table, and the selective binding substance is applied to each convex portion;
An analytical chip manufacturing apparatus comprising: A first imaging unit that images the spotting head;
A second imaging unit that captures an image of the substrate placed on the turntable;
Equipped with
The control unit is
Detecting the first arrangement direction based on a first image captured by the first imaging unit;
detecting the second array direction based on a second image captured by the second imaging unit;
2. The analytical chip manufacturing apparatus according to claim 1 . The control unit is
detecting the first arrangement direction by detecting positions of the plurality of spotting members of the spotting head based on the first image;
3. The analytical chip manufacturing apparatus according to claim 2 . The control unit is
detecting the second arrangement direction by detecting positions of a plurality of convex portions on the substrate based on the second image;
3. The analytical chip manufacturing apparatus according to claim 2 . The control unit is
detecting the second arrangement direction by detecting a mark portion formed on the substrate based on the second image;
3. The analytical chip manufacturing apparatus according to claim 2 . A plurality of the substrates are placed on the rotating table,
Each substrate is placed at a position different from a position through which the central axis of the rotary table passes.
2. The analytical chip manufacturing apparatus according to claim 1 . A plurality of the rotary tables are provided,
One of the substrates is placed on each of the rotary tables.
2. The analytical chip manufacturing apparatus according to claim 1 . The central axis of the rotary table passes through the substrate placed on the rotary table.
The analytical chip manufacturing apparatus according to claim 7 . the central axis of the rotary table passes through the center of gravity of the substrate;
The analytical chip manufacturing apparatus according to claim 8 . a holding table for holding each of the rotary tables so as to be rotatable about its respective central axis;
The analytical chip manufacturing apparatus according to claim 7 , further comprising: An analytical chip manufacturing apparatus having a substrate with a plurality of convex portions on which a plurality of types of selective binding substances are individually applied, the manufacturing apparatus comprising: a turntable that rotates about a central axis, on which a substrate not coated with the selective binding substance is placed; a spotting head having a plurality of spotting members that spot the selective binding substance onto each of the convex portions on the substrate and capable of moving on a scanning plane that is positioned parallel to an upper portion of the turntable; and a control unit that controls the rotation of the turntable, the movement of the spotting head on the scanning plane, and the application of the selective binding substance to each of the convex portions, the manufacturing apparatus comprising:
At least a portion of the plurality of convex portions on the substrate and the plurality of spotting members disposed on the spotting head are both arranged on a straight line,
the spotting head is movable in two directions intersecting each other on the scanning plane;
The control unit:
Calculating a first angle between a first arrangement direction parallel to a straight line passing through the plurality of spotting members arranged on the spotting head and one direction in which the spotting head can move;
calculating a second angle between a second arrangement direction that is parallel to a straight line passing through a plurality of convex portions arranged on the substrate placed on the rotary table and that is formed from the central axis toward an outside and the one direction in which the deposition head is movable;
rotating the rotary table so that a difference between the first angle and the second angle is minimized;
By doing so,
rotating the rotary table to a position where each spotting member of the spotting head overlaps with a convex portion on the substrate corresponding to each spotting member when viewed from the central axis direction of the rotary table , and applying the selective binding substance to each convex portion for each substrate;
A method for operating an analytical chip manufacturing apparatus comprising the steps of: A method for manufacturing an analytical chip, comprising the steps of: applying a plurality of spotting members to respective convex portions of a substrate on which the selective binding substances have not been applied, the method comprising the steps of: manufacturing an analytical chip using a spotting head movable in two directions intersecting each other on a scanning plane parallel to an upper portion of a rotary table on which the substrate is placed;
At least a portion of the plurality of convex portions on the substrate and the plurality of spotting members disposed on the spotting head are both arranged on a straight line,
a first arrangement direction parallel to a line passing through the plurality of spotting members arranged on the spotting head and a first angle formed by a direction in which the spotting head can move, a second arrangement direction parallel to a line passing through the plurality of convex portions arranged on the substrate placed on the turntable and formed from the central axis toward the outside, and a second angle formed by the direction in which the spotting head can move, the second arrangement direction being parallel to a line passing through the plurality of convex portions arranged on the substrate placed on the turntable and formed from the central axis toward the outside, the second arrangement direction being parallel to a line passing through the plurality of convex portions arranged on the substrate placed on the turntable, and the first angle formed by the direction in which the spotting head can move, the second arrangement direction being parallel to a line passing through the plurality of convex portions arranged on the substrate placed on the turntable and formed from the central axis toward the outside , the second arrangement direction being parallel to a line passing through the plurality of convex portions arranged on the substrate placed on the turntable, the second arrangement direction being ...
A method for producing an analytical chip comprising the steps of:

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