Method and device for processing array plate
Patent Information
- Application Number
- PCT/JP2024/033604
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-09-29
- Filing Date
- 2024-09-20
- Publication Date
- 2025-04-03
AI Technical Summary
When multiple array plates are processed simultaneously, the prior art is difficult to effectively prevent contamination of samples and reagents between array plates, resulting in frequent replacement of pipette.tip that increases cost and labor hours while reducing analysis throughput.
An array plate processing device including a liquid supply system and a liquid discharge system is adopted. This device ensures liquid isolation between each array plate by serializing the liquid discharge and liquid supply operations, reducing the number of replacement times of pipette.tip.
Effectively prevent pollution between array boards, reduce the consumption and replacement of pipette.tip, improve analysis throughput, and reduce costs and labor hours.
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Figure JP2024033604_03042025_PF_FP_ABST
Abstract
Description
Array plate processing method and processing device
[0001] The present invention relates to a method and apparatus for processing an array plate.
[0002] Array plates, such as protein arrays, peptide arrays, and DNA arrays, are known in which a large number of substances, such as proteins, peptides, and nucleic acids, are immobilized in the form of spots on a substrate. By using an array plate, interactions between the large number of immobilized substances and substances in a specimen can be observed at once. Therefore, by using an array plate, interactions between the large number of substances immobilized in the form of spots and a large number of substances, including biological specimens such as blood, cell extracts, saliva, and interstitial fluid, can be comprehensively analyzed.
[0003] A known measurement method using an array plate involves selectively fluorescently labeling spots where an interaction of interest has occurred to obtain optical information. A confocal laser microscope is known as a device for observing fluorescently labeled specimens. A confocal laser microscope has an illumination optical system, a fluorescence detection optical system, and a two-dimensional scanning system. The fluorescence detection optical system has the function of detecting the amount of fluorescence from spots labeled with fluorescent probes. The two-dimensional scanning system has the function of acquiring a fluorescent image of the spot area on the array plate by two-dimensionally scanning the array plate or the optical system.
[0004] Japanese Patent Application Laid-Open No. 2023-12426 describes an inspection technology that uses a plate having multiple spots containing biological substances to perform a reaction process including labeling, and then performs a measurement process in which the labeled pattern is optically acquired. In the reaction process, reagents such as specimens, labels, and cleaning solutions are supplied to and discharged from the plate using pipette tips. The technology discloses that the pipette tips are replaced each time to prevent contamination of the reagents (mixing of the reagents; hereinafter, simply referred to as contamination).
[0005] JP 2023-12426 A
[0006] When multiple array plates are processed in parallel to increase analytical throughput, contamination of samples and reagents between the array plates may occur. To prevent contamination, the pipette tip replacement method described in Japanese Patent Laid-Open Publication No. 2023-12426 is applied, resulting in the use of a large number of pipette tips. This increases the cost of the pipette tips and the labor required to replace them, resulting in a decrease in analytical throughput.
[0007] An object of the present invention is to provide an array plate processing method and processing device that can prevent contamination between a plurality of array plates and reduce the consumption of pipette tips and the like.
[0008] The array plate processing method of the present invention is a method for processing array plates in which different specimens are reacted with multiple array plates including a common spot array using a processing device including a supply system for supplying liquid and a discharge system for discharging liquid, and includes the following steps: a discharge step for sequentially discharging contact liquid that comes into contact with the spot array for each array plate using the discharge system; a specimen supply step for supplying a specimen selected from multiple specimens for each array plate using the supply system; a stop liquid supply step for sequentially supplying a reaction stop liquid to the multiple array plates using the supply system to stop the reaction between at least a portion of the spot array and the specimen; a buffer solution supply step for sequentially supplying a predetermined buffer solution to the multiple array plates using the supply system; a discharge preparation step for replacing a part of the discharge system when the contact liquid discharged by the discharge system is changed; and a supply preparation step for replacing a part of the supply system when the liquid supplied by the supply system is changed.
[0009] The array plate processing device of the present invention comprises a mounting section on which a plurality of array plates are arranged and mounted, a supply system that supplies liquid to at least one of the plurality of array plates mounted on the mounting section, a discharge system that discharges liquid held by at least one of the plurality of array plates mounted on the mounting section when the array plate holds liquid, a moving section that changes the relative position of the mounting section with respect to the supply system, a loading section that loads dispensing tips into at least one of the supply system and the discharge system, a release section that releases the loading of the dispensing tips from at least one of the supply system and the discharge system, and a liquid storage section in which the liquid to be supplied to the supply system is stored.
[0010] According to the present invention, an array plate processing method and processing device are realized that can prevent contamination between a plurality of array plates and reduce the consumption of pipette tips and the like.
[0011] FIG. 1 is a diagram for explaining a method for processing an array plate according to embodiment 1. FIG. 2 is a schematic diagram showing a general configuration of a processing apparatus for an array plate according to embodiment 1. FIG. 3 is a diagram for explaining a method for processing an array plate according to embodiment 2. FIG. 4 is a schematic diagram showing a general configuration of a processing apparatus for an array plate according to embodiment 2. FIG. 5 is a diagram for explaining a method for processing an array plate according to embodiment 3. FIG. 6 is a schematic diagram showing a general configuration of a processing apparatus for an array plate according to embodiment 3. FIG. 7 is a diagram for explaining a method for processing an array plate according to embodiment 4. FIG. 8 is a schematic diagram showing a general configuration of a processing apparatus for an array plate according to embodiment 4.
[0012] Preferred embodiments will be described in detail below with reference to the drawings. In the following description, components common to multiple drawings are designated by common reference numerals. Therefore, the common components will be described with mutual reference to multiple drawings, and descriptions of components designated by common reference numerals will be omitted as appropriate.
[0013] -Embodiment 1- Hereinafter, embodiment 1 will be described with reference to FIGS.
[0014] FIG. 1 is a diagram for explaining a method for processing an array plate according to the first embodiment.
[0015] <Analyzing Process S1000 and Tip Replacement Process S2000> First, the individual processes constituting the analyzing process S1000 will be described. In the analyzing process S1000, S1100, S1200, S1300, S1400, S1500, S1600, S1500, S1700, S1500, S1600, S1500, and S1800, which will be described below, are executed in sequence.
[0016] The analysis step S1000 is an array plate processing method in which a processing device including a supply system for supplying liquid and a discharge system for discharging liquid is used to react different specimens with multiple array plates including a common spot array. A spot array refers to multiple spots arranged in a predetermined state (e.g., an array). In this embodiment, common processing is performed on the multiple array plates except for the processing of reacting different specimens with the multiple array plates. The common processing includes a reaction stopping step S1400, a washing solution supplying step S1600, a label supplying step S1700, and a preservation solution supplying step S1800, which are performed on the multiple array plates.
[0017] [Preservation Solution Discharge Step (S1100)] The preservation solution discharge step S1100 is a step of sequentially discharging the preservation solution in contact with the spot array for each array plate. In this step, the preservation solution held on the array plate to prevent deterioration of the multiple spots provided on the array plate is discharged.
[0018] As a holding mechanism, the array plate can be provided with a frame that acts as a bank for storing liquid, or the array plate can be placed in an appropriate container. These frames or containers can hold liquids such as the specimen, stop solution, washing solution, label, observation solution, and reagents used in the following steps on the array plate.
[0019] [Sample Supplying Step (S1200)] The sample supplying step S1200 is a step of supplying a sample selected from multiple samples to each array plate. This step brings the sample into contact with the spots, causing some or all of the targets to react with different biological substances contained in the spots. The reaction includes binding between the targets and biological substances, chemical reactions, and enzymatic reactions.
[0020] A reagent may be added to the sample depending on the purpose. The sample is added in an amount that will at least cover the spot. The reaction between the substance in the sample and the biological substance is carried out at a temperature suitable for the reaction for a desired period of time.
[0021] [Sample Discharge Step (S1300)] The sample discharge step S1300 is a step of sequentially discharging the samples in contact with the spot array for each array plate. This step discharges the samples supplied in the sample supply step S1200. After this step, targets bound to the biological substance in the sample supply step S1200 remain on the spot side, while unreacted targets or targets after chemical or enzymatic reactions with the biological substance are discharged.
[0022] The sample on the spot is aspirated and discharged with a pipette. The sample may be discharged by tilting the array plate or a container containing the array plate relative to the horizontal. Alternatively, the sample may be discharged by decantation by simply tilting the array plate without using a pipette, and then the liquid may be discharged by aspirating with a pipette. Note that discharging refers to reducing the volume of the remaining liquid to less than 50% of the volume of the liquid before discharging. More preferably, the discharge step reduces the volume of the remaining liquid to less than 10% of the volume of the liquid before discharging.
[0023] [Reaction Stopping Step (S1400)] The reaction stopping step S1400 is a stop solution supplying step in which a stop solution that stops the reaction between at least a portion of the spot array and the sample is sequentially supplied to multiple array plates. The stop solution containing an inhibitor is supplied onto the array plate. In this step, the inhibitor binds to the biological substance contained in the spot, thereby preventing the reaction between the biological substance and the sample from proceeding after this step.
[0024] [Contact Liquid Discharge Step (S1500)] The contact liquid discharge step S1500 is a step of sequentially discharging the liquid on the array plate for each array plate. The contact liquid refers to the liquid in contact with the spots on the array plate. Contact liquids include specimens, stop solutions, washing solutions, labeling solutions, preservative solutions, etc., but in this step, it refers to the discharge of liquids other than specimens. The discharge method, etc. is performed in the same way as in the specimen discharge step S1300.
[0025] [Washing Liquid Supply Step (S1600)] The washing liquid supply step S1600 is a step of sequentially supplying a washing liquid to multiple array plates. The washing liquid is supplied in this step, and the contact liquid (washing liquid) discharge step S1500 is performed after washing, thereby washing the array plate. Washing (washing liquid supply step S1600 and washing liquid discharge step S1500) may be repeated. Examples of washing liquids that can be used include water, physiological saline, phosphate buffer, Tris-HCl buffer, other buffers, and other solutions to which surfactants, preservatives, nonspecific adsorption inhibitors, glycerol, and other additives are added as appropriate. Typically, TBST, a Tris buffer containing polysorbate, can be used as the washing liquid. The washing liquid may be used directly as a storage liquid or observation liquid. This step is part of the buffer supply step.
[0026] [Label Supplying Step (S1700)] The label supplying step S1700 is a step of sequentially supplying labeling substances to multiple array plates. To visualize the spots that have reacted with the targets, the targets or the spots that have reacted with the targets are labeled, i.e., a labeling substance is bound to the targets or introduced into the spots that have reacted with the targets. Labeling substances that can be optically detected are used. Labeling substances include fluorescent substances, chemiluminescent substances, phosphorescent substances, dyes, gold nanoparticles, fluorescent particles, enzymes for enzymatic chemiluminescence or color reactions, and microparticles that absorb specific wavelengths. Labeling substances may also include antibodies, ligands, or other binding moieties. The binding or introduction of labeling substances includes binding the labeling substance via hydrophobic interaction, electrostatic interaction, van der Waals interaction, hydrogen bonding, or covalent bonding, introduction during PCR or synthesis, and other known labeling methods. Typically, the labeling substance is a fluorescent substance. Fluorescent substances are advantageous in that they provide stable emission, do not require substrates, can label regions specifically, and are suitable for two-dimensional analysis, or can be used for multiple labeling using fluorescent substances with different wavelengths. The type of fluorescent substance is appropriately selected according to the reaction system and optical system. Those skilled in the art can select a fluorescent substance with appropriate excitation wavelength, fluorescence wavelength, and properties according to the optical system and experimental system.
[0027] [Preservation Solution Supplying Step (S1800)] The preservation solution supplying step S1800 is a step of sequentially supplying a preservation solution to multiple array plates. The preservation solution maintains the state of the spots on the array plate after the reaction, for example, by preventing the spots on the array plate from drying out or the labeled substance from oxidizing. In this step, the preservation solution is supplied onto the array plate and brought into contact with the spots. A washing solution or other reagent solution may be used as the preservation solution as is, and in that case, the step of bringing them into contact corresponds to this step. This step is part of the buffer solution supplying step. The buffer solution refers to a washing solution, an observation solution, a preservation solution, a dilution solution, etc., and in this embodiment, it includes at least one selected from these solutions.
[0028] When optical information is acquired after the preservation solution is supplied, it is desirable to use a solution that has a refractive index close to that of the substrate of the array plate and that does not emit fluorescence when irradiated with excitation light. A glycerol solution is preferably used as a solution that satisfies these conditions, but the solution can be selected appropriately based on the properties of the labeling substance, biological substance, and specimen.
[0029] Next, the tip replacement step S2000 will be described.
[0030] [Array Plate Number for Discharge (S2100)] A to J in S2100 indicate the array plate number when discharging the liquid on the array plate. In this embodiment, the processing of 10 plates is exemplified, but the present invention is not limited to this.
[0031] [Array Plate Number for Liquid Supply (S2200)] A to J in S2200 indicate the array plate number when liquid is supplied onto the array plate. Note that numbers that are the same as the plate numbers in S2100 indicate the same plate. In this embodiment, the processing of 10 plates is described, but this is not limited to this.
[0032] [Pipette Tip Replacement Status (S2300)] S2300 shows the pipette tip replacement status for each array plate in each discharge step and each supply step of the analysis process S1000. In S2300, the numbers indicate the number of tips used after pipette tips have been replaced, and the triangle symbol indicates that the pipette tips are being reused without being replaced.
[0033] The term "pipette tip" may be alternatively referred to as a "dispensing tip" or simply as a "tip." Furthermore, when distinguishing between the intended use and the usage process of a liquid supply step and a liquid discharge step, the term "tip" may be alternatively referred to as a "liquid supply tip" or a "liquid discharge tip."
[0034] <Tip replacement in each step of the analysis process S1000> In this embodiment, a discharge preparation step and a supply preparation step are performed. The discharge preparation step is performed when the liquid discharged by the discharge system is changed, and is a step of replacing a part of the discharge system, in this case, replacing pipette tips. The supply preparation step is performed when the liquid supplied by the supply system is changed, and is a step of replacing a part of the supply system, in this case, replacing pipette tips.
[0035] The discharge preparation step is performed between the sample discharge steps S1300, which are performed for each array plate, so that the array plate does not come into contact with multiple liquids. In the discharge preparation step, the timing at which the liquid is changed is the timing at which each sample is changed during the period between the sample supply steps S1200, which are performed successively for two array plates.
[0036] The supply preparation step is performed between the sample supply steps S1200, which are performed for each array plate, so that the array plate does not come into contact with multiple samples. The timings at which the liquid is changed in the supply preparation step include the following: (1) the timing at which each sample is changed during the period between the sample supply steps S1200 performed for two consecutive array plates; (2) the timing at which the liquid is changed to a stop solution when the reaction stopping step 1400 is performed after the sample discharge step S1300; (3) the timing at which the liquid is changed to a cleaning solution when the washing solution supply step S1600 is performed after the contact solution discharge step S1500; (4) the timing at which the liquid is changed to a labeling substance when the labeling solution supply step S1700 is performed after the contact solution discharge step S1500 of the cleaning solution; and (5) the timing at which the liquid is changed to a cleaning solution when the washing solution supply step S1600 is performed after the contact solution discharge step S1500 of the labeling substance. (6) The timing at which the liquid is changed to the preservation liquid when the preservation liquid supplying step S1800 is performed after the contact liquid discharging step S1500 of the cleaning liquid.
[0037] Here, the timing of changing the sample (1) will be described with reference to the sample supplying step S1200 before and after it.
[0038] The sample A is supplied onto the Nth plate, and the sample B is supplied onto the N+1th plate. [1] A step of aspirating sample A from a reagent container using pipette tip a and a pipettor, and supplying sample A onto the Nth plate. [2] A step of removing pipette tip a from the pipettor and discarding it, out of the pipette tip a and pipettor that supplied sample A. [3] A step of attaching a virgin (empty) pipette tip b to the pipettor. [4] A step of aspirating sample B from a reagent container using pipette tip b and a pipettor, and supplying sample B onto the N+1th plate.
[0039] The timing of the supply preparation step for replacing sample A with sample B in these two sequential sample supply steps S1200 ([1] and [4]) is the timing between sample supply step [1] and sample supply step [4], where supply preparation steps [2] and [3] are performed. By performing the supply preparation step in this manner, the pipette tip a is not reused between the two sequential sample supply steps S1200 ([1] and [4]), reducing the risk of cross-contamination of sample A for the Nth plate with the essential sample B for the N+1th plate.
[0040] The discharge steps, excluding the specimen discharge step S1300, are performed for at least two of the multiple array plates from which liquid is continuously discharged without replacing a part of the discharge system, such as a tip. The reaction stop step S1400, the washing solution supply step S1600, the label supply step S1700, and the preservation solution supply step S1800 are performed for at least two of the multiple array plates from which liquid is continuously supplied without replacing a part of the supply system, such as a tip.
[0041] In the preservation solution discharge step S1100, a tip is attached to the pipette to discharge the preservation solution from the array plate, and the same tip is reused to discharge the solution from plates A to J. In this step, the sample has not yet been supplied onto the array plate, and sample contamination will not occur, so the tip is reused.
[0042] In the sample supply step S1200, when supplying samples to plate A, the first tip is replaced with a second tip because reusing the first tip would result in contamination of the sample with the preservative solution. Also, to prevent sample contamination between array plates, tips are replaced for each array plate.
[0043] In the sample discharge step S1300, similar to the sample supply step S1200, the chip is replaced for each array plate to prevent sample contamination between array plates.
[0044] In the reaction stopping step S1400, if the 21st tip is used when supplying stop solution to plate A, the sample from plate J will adhere to the tip and be mixed into the stop solution bottle. If that stop solution is supplied to each array plate, sample contamination will occur between the array plates. Therefore, the tip is replaced to prevent sample contamination between the array plates.
[0045] Since the same stop solution is supplied from plate B onwards, the reuse of the tip prevents contamination of samples between plates or with other liquids. However, if the tip of the tip comes into contact with the liquid on the array plate when supplying stop solution to each array plate, contamination of samples between array plates or with other liquids may occur. Therefore, the position of the tip tip must be controlled so that it does not come into contact with the liquid on the array plate when supplying liquid.
[0046] In the contact liquid discharge step S1500 after the reaction stopping step S1400, the tips are reused for all array plates without changing them. Because the contact liquid on plate A is the same as the contact liquid supplied immediately before, reusing the tips will not result in contamination that will affect the reaction. In the discharge from B onwards, samples from plates prior to the array plate being discharged may be attached to the tips, but because the stop liquid prevents the reaction of the biological substances on the array plate from proceeding, even if sample contamination occurs, it will not affect the reaction.
[0047] In the washing solution supply step (buffer solution supply step) S1600, label supply step S1700, and preservation solution supply step S1800, only the tip for the first array plate (A plate) is replaced, and the tip is reused for the second and subsequent plates (B plate and subsequent plates). The reason for replacing the tip is that the buffer solution supplied to A plate is different from the solution discharged immediately before, which could result in contamination of the buffer solution container with another solution. The reason for reusing the tip is that, as in the reaction termination step S1300, the same solution is supplied to B plate and subsequent plates, so reusing the tip does not result in contamination with other solutions. However, if the tip of the tip comes into contact with the solution on the array plate when supplying the solution to each plate, contamination with other solutions will occur. Therefore, the position of the tip tip must be controlled so that it does not come into contact with the solution on the array plate when supplying the solution.
[0048] If chips are exchanged between array plates in all steps of the analysis process S1000, 120 chips would be used, but by performing chip exchange in this embodiment, the number of chips used can be reduced to 26. The number of chips reduced also changes depending on the number of steps and the number of plates.
[0049] <Configuration of Array Plate Treatment Device> Hereinafter, an array plate treatment device for supplying and discharging liquid in this embodiment will be described.
[0050] FIG. 2 is a schematic diagram showing the general configuration of an array plate processing apparatus 1000 according to this embodiment.
[0051] In Fig. 2, 100 denotes an array plate. Here, a plurality of array plates 10 (in the illustrated example, ten array plates 10 A to J) are appropriately held on a mounting section so that they can be processed in parallel. As shown in Fig. 2, they may be held on the mounting section arranged horizontally, or they may be held on the mounting section arranged vertically, in a grid, in a circle, or the like. Furthermore, the number of plates is not limited to ten as shown in Fig. 2.
[0052] Reference numeral 200 denotes a specimen, which is stored in a predetermined liquid storage portion. The specimen 200 is reacted with a spot on the array plate 100. The amount of specimen 200 required for the number of array plates 10 is prepared. Reference numeral 300 denotes a pipette, and 400 denotes a pipette tip. The tip 400 is attached to the pipette 300 and is used to supply and discharge a predetermined liquid.
[0053] Reference numerals 500, 600, and 700 denote moving units that change the relative position of the mounting unit with respect to the supply system (relatively move translationally). Specifically, these units are stages for moving the pipette 300 (and the attached tip 400) to a desired position, including on each array plate 100. The X-movement stage 500 moves the pipette 300 in the X direction, the Y-movement stage 600 moves the pipette 300 in the Y direction, and the Z-movement stage 700 moves the pipette 300 in the Z direction. The Z-movement stage 700 is attached to either the X-movement stage 500 or the Y-movement stage 600. The pipette 300 is attached to the Z-direction moving stage 700 and can move within the XY plane (horizontal plane) and in the Z direction (vertical). Although not shown, actuators and control systems are used to move the XYZ-movement stages 500, 600, and 700. In this embodiment, the XYZ-movement stages 500, 600, and 700 are illustrated as linearly moving, but this is not limited thereto. For example, a moving stage may also be used.
[0054] Reference numeral 800 denotes a tip storage area for holding replacement tips 400. The XYZ moving stages 500, 600, and 700 function as loading units that load tips 400 into at least one of the supply system and the discharge system. The pipette 300 functions as a releasing unit that releases the loading of the tip 400 from at least one of the supply system and the discharge system. In its function as a loading unit, the pipette 300 is moved horizontally to a desired tip position in the tip storage area, and then moved vertically to attach the tip to the pipette 300. In its function as a releasing unit, the pipette 300 removes a used tip 400 from the pipette 300 at a predetermined position. When replacing a used tip 400, it may be disposed of in a waste tip storage area 900, which is a tip disposal area, or in an empty space in the tip storage area 800.
[0055] The supply system is coupled to a supply system moving unit having multiple degrees of freedom of movement so as to move relative to the mounting unit, the loading unit, and the releasing unit. The discharge system is coupled to a discharge system moving unit having multiple degrees of freedom of movement so as to move relative to the mounting unit, the loading unit, and the releasing unit. The supply system moving unit has multiple degrees of freedom of movement and is equipped with a movement mechanism that shares at least some of the degrees of freedom of movement with the discharge system moving unit. In this embodiment, the configuration including the pipette 300, the tip 400 used, and the XYZ movement stages 500, 600, and 700 serves as both a supply system and a discharge system for a predetermined liquid. The XYZ movement stages 500, 600, and 700 function as a supply system moving unit in the supply system and a discharge system moving unit in the discharge system. The supply system supplies a predetermined liquid to at least one of the multiple array plates 100 placed on the mounting unit. The discharge system discharges the liquid held by the array plate 100 when at least one of the multiple array plates 100 placed on the mounting unit holds the predetermined liquid.
[0056] Reference numeral 1000 denotes a drainage container for draining liquids discharged in the sample and reagent discharge step. Reference numerals 1100, 1200, 1300, and 1400 denote reagents used in the reaction process, and are stored in designated reservoirs. Reference numeral 1100 denotes a stop solution used in the reaction stop step, 1200 denotes a washing solution used in the washing step, 1300 denotes a labeling substance used in the label supply step, and 1400 denotes a preservative solution for preventing drying on the array plate 100.
[0057] Reference numeral 10 denotes a controller that controls the operations of the XYZ moving stages 500, 600, and 700 and the pipette 300. These operations include the movement of the pipette 300 by the XYZ moving stages 500, 600, and 700, a loading operation for loading the tip 400 into the pipette 300, the aspirating and discharging of a sample or reagent by the pipette 300, and a release operation for detaching the tip 400 from the pipette 300. Under the control of the controller 10, the supply system replaces a part of the supply system (e.g., a tip) when the liquid to be supplied is changed. Similarly, under the control of the controller 10, the discharge system replaces a part of the discharge system (e.g., a tip) when the liquid to be discharged is changed. Specifically, each step of the analysis process S1000 in FIG. 1 is executed by the driving of each component by the controller 10. The controller 10 is electrically connected to the XYZ moving stages 500, 600, and 700 and the pipette 300. The controller 10 has a central processing unit (CPU), and the CPU executes an operating program to realize each drive.
[0058] <Operation of Array Plate Processing Apparatus> The operation of the processing apparatus 1000 according to this embodiment will be described below with reference to Figures 1 and 2. Here, the pipette 300, tip 400, and XYZ moving stages 500, 600, and 700 are configured as a common component for the discharge system and the supply system.
[0059] In the preservation solution discharge step S1100, the XYZ moving stages 500, 600, and 700 attach the tip 400 from the tip holder 800 to the pipette 300 and move the pipette 300 above plate A, where the pipette 300 aspirates the preservation solution on plate A into the tip 400. While maintaining the aspirated state, the pipette 300 is moved above the drainage container 1900, and the aspirated preservation solution is discharged into the drainage container 1900. Without replacing the tip 400, the drainage operation of the preservation solution is repeated for plates B to J in the same manner as for plate A, thereby discharging the preservation solution on plates B to J. After discharging the preservation solution from plate J is completed, the XYZ moving stages 500, 600, and 700 move the pipette 300 to the waste tip holder 900, where the pipette 300 removes the tip 400 and places it in the waste tip holder 900.
[0060] Next, the process moves to a specimen supplying step S1200. In the specimen supplying step S1200, the XYZ moving stages 500, 600, and 700 attach a new tip 400 from the tip storage area 800 to the pipette 300, and the pipette 300 aspirates the specimen 200. The XYZ moving stages 500, 600, and 700 move the pipette 300 aspirating the specimen 200 above array plate A, and the pipette 300 supplies the specimen 200 onto plate A. After supplying, the XYZ moving stages 500, 600, and 700 move the pipette 300 to a discarded tip storage area 900, and the pipette 300 removes the tip 400 and discards it in the discarded tip storage area 900. Thereafter, the XYZ moving stages 500, 600, and 700 move the pipette 300 to the tip storage area 800, where a new tip 400 is attached, and the pipette 300 aspirates the specimen 200 and supplies it onto plate B. The above operations are similarly repeated for plates C to J, supplying specimens to all of the array plates 100.
[0061] Once the biological material contained in the spots on plates 100A-J has sufficiently reacted with the specimen 200, the process proceeds to the specimen discharge step S1300. In the specimen discharge step S1300, the XYZ movement stages 500, 600, and 700 move the pipette 300 to the tip holder 800, and a new tip 400 is attached. The XYZ movement stages 500, 600, and 700 move the pipette 300 above plate A, and the pipette 300 aspirates the specimen 200 on plate A into the tip 400. While the pipette 300 maintains the aspirated state, the XYZ movement stages 500, 600, and 700 move the pipette 300 above the drainage container 1900, and the pipette 300 discharges the aspirated specimen 200 into the drainage container 1900. After discharging, the XYZ moving stages 500, 600, and 700 move the pipette 300 to the waste tip storage area 900, where the pipette 300 removes the tip and places it in the waste tip storage area 900. The XYZ moving stages 500, 600, and 700 then move the pipette 300 to the tip storage area 800, attach a new tip 400, and move the pipette 300 onto plate B, where the pipette 300 aspirates the sample in the same manner as for plate A. The above operations are repeated for plates C to J in the same way, and the sample 200 is discharged from each of plates A to J.
[0062] Next, the process moves to the reaction stopping step S1400. In the reaction stopping step S1400, the XYZ moving stages 500, 600, and 700 move the pipette 300 to the tip holder 800, attach the tip 400, and aspirate the stop solution 1100. The pipette 300 aspirating the stop solution 1100 is moved above array plate A, and the stop solution 1100 is supplied onto plate A. After supply, the XYZ moving stages 500, 600, and 700 move above the stop solution 1100, and the pipette 300 aspirates the stop solution 1100, moves above plate B, and supplies the stop solution 1100. The above operations are similarly repeated for plates C to J.
[0063] Once the stop solution 1100 has been supplied onto all of the array plates 100, the process proceeds to the contact liquid discharge step S1500. In the contact liquid discharge step S1500, the XYZ moving stages 500, 600, and 700 move the pipette 300 onto plate A without replacing the tip 400, and the pipette 300 aspirates the stop solution 1100 on plate A. While maintaining the aspirated state of the pipette 300, the XYZ moving stages 500, 600, and 700 move the pipette 300 onto the drainage container 1900, and the pipette 300 discharges the aspirated stop solution 1100 into the drainage container 1900. The above operations are similarly repeated for plates B to J, and the stop solution 1100 on plates B to J is discharged.
[0064] The following operations are performed in the washing solution supplying step (buffer solution supplying step) S1600, the labeling solution supplying step S1700, and the preservation solution supplying step (buffer solution supplying step) S1800. The XYZ movement stages 500, 600, and 700 move the pipette 300 to the tip storage area 800 and attach a new tip 400. The pipette 300 aspirates a predetermined liquid, such as washing solution 1200 (a buffer solution), labeling substance 1300, or preservation solution 1400 (a buffer solution). The XYZ movement stages 500, 600, and 700 move the pipette 300 aspirating the predetermined liquid above array plate A, and the pipette 300 supplies the predetermined liquid onto plate A. After supplying the predetermined liquid, the XYZ movement stages 500, 600, and 700 move above the washing solution 1200, labeling substance 1300, or preservation solution 1400, and the pipette 300 aspirates the predetermined liquid. The XYZ moving stages 500, 600, and 700 move the pipette 300 onto plate B, and the pipette 300 supplies a predetermined liquid. The above operations are repeated for plates C to J in the same manner.
[0065] As described above, the processing method and processing apparatus 1000 of this embodiment can prevent contamination between a plurality of array plates and reduce the amount of chips consumed.
[0066] In the first embodiment, the supply system and the discharge system are operated as a single system, but the supply system and the discharge system may be separate systems. By using separate systems, the supply process and the discharge process can be carried out in parallel, which makes it possible to reduce the number of steps required for the reaction process of the array plate.
[0067] The second embodiment will be described below with reference to Figures 3 and 4. In the analysis step S1000, S1100, S1200, S1300, S1400, S1500, S1600, S1500, S1700, S1500, S1600, S1500, and S1800, which will be described below, are executed in sequence.
[0068] FIG. 3 is a diagram for explaining the method for processing an array plate according to the second embodiment.
[0069] [Pipette Tip Replacement Status (S2301)] This shows the tip replacement status for each array plate in each supply step and each discharge step of the analysis process S1000. In S2301, the numbers indicate the number of tips used by the supply and discharge pipettes after tips have been replaced. The ● symbol indicates that the discharge pipette is reusing the tip without replacing it, and the ○ symbol indicates that the supply pipette is reusing the tip without replacing it.
[0070] <Replacing Tips in Each Step of Analysis Process S1000> The preservative solution discharge step S1100 is the same as in the case of one system in the first embodiment.
[0071] In the sample supply step S1200, a tip is attached to a supply pipette and the sample is supplied. To prevent sample contamination between plates, the tip is replaced for each plate.
[0072] In the sample discharge step S1300, the tip that discharged the preservative solution is reused to discharge the sample from plate A. This is because reusing the tip will not cause sample contamination. However, from plate B onwards, tips are replaced for each plate to prevent sample contamination between plates.
[0073] In the reaction stopping step S1400, if the 10th tip from the sample supplying step is reused, sample contamination will occur, so the tip is replaced with a new one on plate A. Since the same stop solution is supplied from plate B onwards, reusing the tip will not cause sample contamination between plates or contamination with other liquids.
[0074] The steps after the contact liquid discharge step S1500 are the same as those in the case of one system in the first embodiment.
[0075] If chips are exchanged between array plates in all steps of the analysis process S1000, 120 chips would be used, but by performing chip exchange in this embodiment, the number of chips used can be reduced to 25. The number of chips reduced also changes depending on the number of steps and the number of plates.
[0076] <Configuration of Array Plate Treatment Device> Hereinafter, an array plate treatment device for supplying and discharging liquid in this embodiment will be described.
[0077] FIG. 4 is a schematic diagram showing the general configuration of an array plate processing apparatus 2000 according to this embodiment.
[0078] In this embodiment, the discharge system includes a pipette 300, a tip 400, and XYZ moving stages 500, 600, and 700 as a discharge system moving section, and 301 is a supply system pipette (supply pipette), and 401 is a supply system pipette tip (supply tip).
[0079] Reference numerals 501, 601, and 701 denote stages for moving the supply pipette 301. 501 denotes a stage for moving in the X direction, 601 denotes a stage for moving in the Y direction, and 701 denotes a stage for moving in the Z direction. The Z movement stage 701 is attached to either the X movement stage 501 or the Y movement stage 601. The pipette 300 is attached to the Z movement stage 701 and can move within the XY plane (horizontal plane) and in the Z direction (vertical). Although not shown, actuators and a control system are used to move the XYZ movement stages 501, 601, and 701. In this embodiment, a case in which the XYZ movement stages 501, 601, and 701 each move linearly is illustrated, but this is not limited thereto, and a moving stage, for example, may also be used. In this embodiment, the supply system is configured to include the supply pipette 301, the supply tip 401, and the XYZ movement stages 501, 601, and 701 as a supply system moving unit.
[0080] The controller 10 controls various operations of the discharge system and the supply system. The discharge system controls the movement of the discharge pipette 300 and the loading of the discharge tip 400 by the XYZ moving stages 500, 600, and 700, the various operations of aspirating and discharging specimens and reagents by the discharge pipette 300, and the release operation of detaching the discharge tip 400 from the discharge pipette 300. The supply system controls the movement of the supply pipette 301 and the loading of the supply tip 401 by the XYZ moving stages 501, 601, and 701, the various operations of aspirating and discharging specimens and reagents by the supply pipette 301, and the release operation of detaching the supply tip 401 from the supply pipette 301. Under the control of the controller 10, the supply system replaces a part of the supply system (e.g., a tip) when the liquid to be supplied is changed. Similarly, under the control of the controller 10, the discharge system replaces a part of the discharge system (e.g., a tip) when the liquid to be discharged is changed. 3 is executed by driving each step by the controller 10. The controller 10 is electrically connected to the XYZ movement stages 500, 600, 700, and the discharge pipette 300, as well as the XYZ movement stages 501, 601, 701, and the supply pipette 301.
[0081] 3 and 4, the operation of the processing apparatus 2000 according to this embodiment will be described. Here, the pipette 300, the tip 400, and the XYZ moving stages 500, 600, and 700 form a discharge system, and the pipette 301, the tip 401, and the XYZ moving stages 501, 601, and 701 form a supply system.
[0082] The preservation solution discharge step S1100 and the specimen supply step S1200 are performed in parallel. First, the XYZ movement stages 500, 600, and 700 move the discharge pipette 300 to the tip holder 800 and attach a new discharge tip 400, and the discharge pipette 300 aspirates the preservation solution on plate A into the discharge tip 400. While the discharge pipette 300 is aspirating the preservation solution, the XYZ movement stages 501, 601, and 701 move the supply pipette 301 to the tip holder 800 and attach a new supply tip 401, and the supply pipette 301 aspirates the specimen 200. The XYZ movement stages 501, 601, and 701 move the supply pipette 301, which is aspirating the specimen 200, to plate A, and the supply pipette 301 supplies the specimen 200 onto plate A. While the supply pipette 301 supplies the sample onto the plate, the XYZ movement stages 500, 600, and 700 move the discharge pipette 300 above the waste container 1900 while the discharge pipette 300 maintains the aspirated state of the preservation solution. The discharge pipette 300 discharges the aspirated preservation solution into the waste container 1900. After the supply pipette 301 supplies the sample 200, the XYZ movement stages 501, 601, and 701 move the supply pipette 301 to the waste tip holder 900, and the supply pipette 301 removes the supply pipette 301 and places it in the waste tip holder 900. The XYZ movement stages 500, 600, and 700 move the discharge pipette 300 above plate B without changing the discharge tip 400 of the discharge pipette 300, and the discharge pipette 300 aspirates the preservation solution. The XYZ moving stages 501, 601, and 701 move the supply pipette 301 to the tip storage area 800 and attach a new supply tip 401, and the supply pipette 301 aspirates the specimen 200 and supplies it onto plate B. The above operations are similarly repeated for plates C to J, discharging the preservative solution from all of the array plates 100 and supplying the specimen 200.
[0083] Once the biological material contained in the spots on plates A to J has sufficiently reacted with the specimen 200, the specimen discharge step S1300 and the reaction stopping step S1400 are performed in parallel. First, the XYZ moving stages 500, 600, and 700 attach the discharge tip 400 that has discharged the preservative solution to the discharge pipette 300, and move the discharge pipette 300 to plate A. The discharge pipette 300 aspirates the specimen 200 on plate A into the discharge tip 400. While the discharge pipette 300 is attaching the tip and aspirating the specimen, the XYZ moving stages 501, 601, and 701 move the supply pipette 301 to the tip holder 800, attach a new supply tip 401, and the supply pipette 301 aspirates the stop solution 1100. After the discharge pipette 300, which has aspirated the specimen 200 on plate A, moves above the waste container 1900, the XYZ moving stages 501, 601, and 701 move the supply pipette 301, which has aspirated the stop solution 1100, above plate A. The supply pipette 301 supplies the stop solution 1100 onto plate A. While the supply pipette 301 is supplying the stop solution 1100 onto plate A, the discharge pipette 300 discharges the aspirated specimen 200 into the waste container 1900. After the discharge, the XYZ moving stages 500, 600, and 700 move the discharge pipette 300 to the waste tip holder 900, and the discharge pipette 300 removes the discharge tip 400 and places it in the waste tip holder 900. While the discharge pipette 300 is disposing of the tip, the supply pipette 301 moves above the stop solution 1100 and waits until it supplies the stop solution 1100 to the next plate B. The standby position of the supply pipette 301 may be above the stop solution 1100, or may be set at a position that does not interfere with the pipette operation of the discharge system.
[0084] Thereafter, the XYZ moving stages 500, 600, and 700 move the discharge pipette 300 to the tip holder 800, attach a new discharge tip 400, and move the discharge pipette 300 onto plate B. The discharge pipette 300 aspirates the sample 200 on plate B into the discharge tip 400. While the discharge pipette 300 is attaching the tip and aspirating the sample 200 on plate B, the supply pipette 301 aspirates and prepares to supply the stop solution 1100. After the discharge pipette 300 that has aspirated the sample 200 on plate B has moved above the waste liquid container 1900, the XYZ moving stages 501, 601, and 701 move the supply pipette 301 that has aspirated the stop solution 1100 onto plate B. The supply pipette 301 supplies the stop solution 1100 onto plate B. While the supply pipette 301 supplies the stop solution 1100 onto plate B, the supply pipette 300 discharges the aspirated specimen 200 into the waste container 1900. After discharging, the XYZ moving stages 500, 600, and 700 move the discharge pipette 300 to the waste tip holder 900, where the discharge pipette 300 removes the discharge tip 400 and places it in the waste tip holder 900. While the discharge pipette 300 discards the discharge tip 400, the supply pipette 301 moves above the stop solution 1100 and waits until the stop solution 1100 is supplied to the next array plate 100. The above operations are similarly repeated for plates C to I. For plate J, the same process is performed up to the step of discharging the specimen 200 into the waste container 1900, and the plate is then left waiting above the waste container 1900, without tip replacement. The standby position of the discharge pipette 300 may be above the waste container 900, or a separate standby position may be provided.
[0085] Once the stop solution 1100 has been supplied onto all of the array plates 100 and the reactions of the spots on the array plate 100 have been stopped, the process proceeds to a contact liquid discharge step S1500 and a washing liquid supply step S1600. The XYZ moving stages 500, 600, and 700 move the discharge pipette 300, which has been waiting above the drainage container 1900, onto plate A, and the discharge pipette 300 aspirates the stop solution on plate A. While the discharge pipette 300 is aspirating the stop solution 1100, the XYZ moving stages 501, 601, and 701 move the supply pipette 301 to the tip holder 800, where a new tip 401 is attached, and the supply pipette 301 aspirates the washing liquid 1200. After the pipette 300 that has aspirated the stop solution 1100 on plate A has moved above the waste liquid container 1900, the XYZ moving stages 501, 601, and 701 move the supply pipette 301 that has aspirated the washing liquid 1200 above plate A. The supply pipette 301 supplies the washing liquid 1200 onto plate A. While the supply pipette 301 is supplying the washing liquid 1200 onto plate A, the discharge pipette 300 discharges the stop solution 1100 that it had aspirated into the waste liquid container 1900 and waits above the waste liquid container 1900. After the supply pipette 301 has supplied the reaction washing liquid 1100 onto plate A, the XYZ moving stages 501, 601, and 701 move the supply pipette 301 above the washing liquid 1200 and waits.
[0086] Next, the XYZ moving stages 500, 600, and 700 move the discharge pipette 300 above plate B, and the discharge pipette 300 aspirates the stop solution 1100 on plate B. While the discharge pipette 300 is aspirating the stop solution 1100, the supply pipette 301 aspirates the washing solution 1200. After the discharge pipette 300 moves from above plate B to above the waste liquid container 1900, the supply pipette 301 moves above plate B and supplies the washing solution 1200. These operations are similarly repeated for plates C to J. The subsequent steps (contact liquid discharge step S1500 to preservation liquid supply step S1800) are also performed in the same procedure.
[0087] As described above, the processing method and processing apparatus 2000 of this embodiment can prevent contamination between multiple array plates and reduce the amount of chips consumed. Furthermore, in this embodiment, the supply system and discharge system are separate, so the supply process and discharge process can be carried out in parallel, thereby reducing the number of steps required for reaction processing of the array plates.
[0088] Third Embodiment In a third embodiment, similar to the second embodiment, the supply system and the discharge system are separate systems, and a plurality of supply pipettes are provided in the supply system.
[0089] The second embodiment will be described below with reference to Figures 5 and 6. In the analysis step S1000, S1100, S1200, S1300, S1400, S1500, S1600, S1500, S1700, S1500, S1600, S1500, and S1800, which will be described below, are executed in sequence.
[0090] FIG. 5 is a diagram for explaining a method for processing an array plate according to the third embodiment.
[0091] [Pipette Tip Replacement Status (S2302)] This shows the tip replacement status for each array plate in each supply step and each discharge step of the analysis process S1000. In S2302, the numbers indicate the number of tips used by the pipettes in the supply and discharge systems after they have been replaced. The circle symbol indicates that the pipette in supply system 1 is reusing the tip without replacing it, the double circle symbol indicates that the pipette in supply system 2 is reusing the tip without replacing it, and the black circle symbol indicates that the pipette in the discharge system is reusing the tip without replacing it.
[0092] In the supply system, tips are replaced when each sample and each supply liquid is changed. However, if there are multiple steps in the process flow that supply the same liquid, the number of tip replacements can be reduced by having a dedicated supply system pipette for that liquid. In the analysis process S1000 of this embodiment, there are two cleaning liquid supply steps S1600, so once a new tip is installed, the tip is reused as is. As a result, if tips were replaced between array plates in all steps of the analysis process S1000, 120 tips would be used. However, by performing tip replacement in this embodiment, the number of tips used can be reduced to 24. The number of tips reduced also changes depending on the number of steps and the number of plates.
[0093] <Configuration of Array Plate Treatment Device> Hereinafter, an array plate treatment device for supplying and discharging liquid in this embodiment will be described.
[0094] FIG. 6 is a schematic diagram showing the general configuration of an array plate processing apparatus 3000 according to this embodiment.
[0095] In this embodiment, the discharge system is configured to include a pipette 300, a tip 400, and XYZ moving stages 500, 600, and 700 as a discharge system moving section. 301 is a pipette of supply system 1, and 401 is a pipette tip of supply system 1. 302 is a pipette of supply system 2, and 402 is a pipette tip of supply system 2.
[0096] In this embodiment, supply systems 1 and 2 use a common moving stage in the X and Y directions, and two different moving stages in the Z direction. Specifically, X moving stage 501 and Y moving stage 601 are common to supply systems 1 and 2, Z moving stage 701 is included in supply system 1, and Z moving stage 702 is included in supply system 2. In this embodiment, supply system 1 is a configuration including a supply pipette 301, a supply tip 401, and XYZ moving stages 501, 601, and 701 as supply system moving units. Supply system 2 is a configuration including a supply pipette 302, a supply tip 402, and XYZ moving stages 501, 601, and 702 as other supply system moving units. Note that the configuration of the XYZ moving stage is not limited to the above, and any stage configuration that allows multiple pipettes to be moved in the supply system may be used.
[0097] The controller 10 controls various operations for each of the discharge system and the supply systems 1 and 2. The discharge system controls the movement of the discharge pipette 300 and the loading of the discharge tip 400 by the XYZ moving stages 500, 600, and 700, the various operations of aspirating and discharging specimens and reagents by the discharge pipette 300, and the release operation of detaching the discharge tip 400 from the discharge pipette 300. The supply system 1 controls the movement of the supply pipette 301 and the loading of the supply tip 401 by the XYZ moving stages 501, 601, and 701, the various operations of aspirating and discharging liquid by the supply pipette 301, and the release operation of detaching the supply tip 401 from the supply pipette 301. The supply system 2 controls the movement of the supply pipette 302 and the loading of the supply tip 402 by the XYZ movement stages 501, 601, and 702, the various operations of aspirating and discharging liquid by the supply pipette 302, and the release operation of detaching the supply tip 402 from the supply pipette 302. Under the control of the controller 10, the supply system replaces a part of the supply system (e.g., a tip) when the liquid to be supplied is changed. Similarly, under the control of the controller 10, the discharge system replaces a part of the discharge system (e.g., a tip) when the liquid to be discharged is changed. Specifically, each step of the analysis process S1000 in FIG. 5 is executed by each drive by the controller 10. The controller 10 is electrically connected to the XYZ movement stages 500, 600, and 700, the discharge pipette 300, the XYZ movement stages 501, 601, 701, and 702, and the supply pipettes 301 and 302.
[0098] <Operation of Array Plate Processing Apparatus> The operation of the processing apparatus 3000 according to this embodiment will be described below with reference to Figures 5 and 6. Here, the pipette 300, tip 400, and XYZ moving stages 500, 600, and 700 form a discharge system. The pipette 301, tip 401, and XYZ moving stages 501, 601, and 701 form supply system 1, and the pipette 302, tip 402, and XYZ moving stages 501, 601, and 702 form supply system 2.
[0099] First, the steps from the preservation solution discharge step S1100 to the stop solution contact solution discharge step S1500 are performed in the same manner as in the second embodiment.
[0100] In the contact liquid discharge step S1500 of the stop liquid, while the discharge pipette 300 is aspirating the stop liquid 1100, the supply system performs the washing liquid supply step S1600. In the washing liquid supply step S1600, the XYZ moving stages 501, 601, and 702 of the supply system 2 move the supply pipette 302 to the tip holder 800 and attach a new tip 402. The supply pipette 302 aspirates the washing liquid 1200. After the pipette 300 that aspirated the reaction stop liquid on plate A moves above the waste liquid container 1900, the XYZ moving stages 501, 601, and 702 of the supply system 2 move the supply pipette 302 that aspirated the washing liquid 1200 above plate A. The supply pipette 302 supplies the washing liquid 1200 onto plate A. While the supply pipette 302 supplies the washing liquid 1200 onto plate A, the discharge pipette 300 discharges the stop liquid 1200 that it had aspirated into the waste liquid container 1900 and waits above the waste liquid container 1900. After the supply pipette 302 supplies the washing liquid 1200 onto plate A, the XYZ moving stages 501, 601, and 702 of the supply system 2 move the supply pipette 302 above the washing liquid 1200 and waits there.
[0101] Next, the XYZ moving stages 500, 600, and 700 of the discharge system move the discharge pipette 300 above plate B, and the discharge pipette 300 aspirates the stop solution on plate B. While the discharge pipette 300 is aspirating the stop solution 1100, the supply pipette 302 aspirates the washing solution 1200. After the discharge pipette 300 moves from above plate B to above the waste liquid container 1900, the XYZ moving stages 501, 601, and 702 of the supply system 2 move the supply pipette 302 above plate B, and the supply pipette 302 supplies the washing solution 1200 onto plate B. These operations are similarly repeated for plates C to J. After the washing solution has been supplied to all plates, the tip 402 is not discarded but remains held in the supply pipette 302. Thereafter, the steps S1500 for discharging the contact liquid of the washing solution to S1500 for discharging the contact liquid of the labeling substance are performed in the same manner as in embodiment 2. In the second cleaning liquid supply step S1600, the pipette 302 is used to supply the cleaning liquid 1200, and the tip 402 used in the first cleaning liquid supply step S1600 is reused. The operation of the supply pipette 302 is performed in the same manner as the operation of the supply pipette 301 in embodiment 2. The subsequent contact liquid discharge step S1500 and preservation liquid supply step S1800 are performed in the same manner as in embodiment 2.
[0102] As described above, the processing method and processing apparatus 3000 of this embodiment can prevent contamination between multiple array plates and reduce the amount of tips consumed. Furthermore, in this embodiment, by separating the supply system and the discharge system, the supply process and the discharge process can be carried out in parallel, thereby reducing the number of steps required for reaction processing of the array plate. Furthermore, in this embodiment, the configuration of the supply system having multiple pipettes reduces the amount of tips consumed.
[0103] Fourth Embodiment In a fourth embodiment, similar to the second embodiment, the supply system and the discharge system are separate systems, and a chip storage area for storing chips in the supply system is provided.
[0104] The fourth embodiment will be described below with reference to Figures 7 and 8. In the analysis step S1000, S1100, S1200, S1300, S1400, S1500, S1600, S1500, S1700, S1500, S1600, S1500, and S1800, which will be described below, are executed in sequence.
[0105] FIG. 7 is a diagram for explaining the method for processing an array plate according to the fourth embodiment.
[0106] [Pipette Tip Replacement Status (S2303)] This shows the tip replacement status for each array plate in each supply step and each discharge step of the analysis process S1000. In S2303, the numbers indicate the number of tips used by the supply and discharge pipettes after tips have been replaced. A circle indicates that the supply pipette is reusing its tip without replacing it, and a black circle indicates that the discharge pipette is reusing its tip without replacing it.
[0107] In the pipette tip replacement situation (S2302) in embodiment 3, when there are multiple steps in the process flow that supply the same liquid, it was explained that a dedicated supply pipette is provided for that liquid. In this embodiment, a tip storage area is provided for temporarily storing tips, and tips dedicated to the above liquid can be stored without being discarded and attached to the pipette when used again.
[0108] Since the analysis process S1000 includes two washing solution supplying steps S1600, a new chip is attached, washing solution is supplied to all plates, and then the chip is stored in the chip storage area. If the washing solution supplying step S1600 is performed again, the stored chip is reused. As a result, while exchanging chips between arrays and plates in all steps of the analysis process S1000 would require 120 chips, by performing the chip exchange in this embodiment, the number of chips used can be reduced to 24. The number of chips reduced also changes depending on the number of steps and the number of plates.
[0109] <Configuration of Array Plate Treatment Device> Hereinafter, an array plate treatment device for supplying and discharging liquid in this embodiment will be described.
[0110] FIG. 8 is a schematic diagram showing the general configuration of an array plate processing apparatus 4000 according to this embodiment.
[0111] The processing device 4000 according to this embodiment has a configuration similar to that shown in FIG. 6 of the second embodiment, and in addition has a chip storage area 1500 as a chip storage section for temporarily storing used chips.
[0112] The tip storage area 1500 is configured to be able to store tips that have been removed by pipettes on the tip storage area 1500, and to allow tips to be attached by pressing the pipette against the tip storage area 1500. While Fig. 8 illustrates an example in which one tip is stored in the tip storage area 1500, the present invention is not limited to this configuration, and if there are multiple types of liquids that are used repeatedly, the tip storage area 1500 may be configured to be able to store multiple tips.
[0113] <Operation of Array Plate Processing Apparatus> The operation of the processing apparatus 4000 according to this embodiment will be described below with reference to Figures 7 and 8. Here, the pipette 300, tip 400, and XYZ moving stages 500, 600, and 700 form a discharge system, and the pipette 301, tip 401, and XYZ moving stages 501, 601, and 701 form a supply system.
[0114] First, the steps from the preservation liquid discharge step S1100 to the cleaning liquid supply step S1600 are performed in the same manner as in the second embodiment.
[0115] After supplying the cleaning liquid onto all of the array plates 100, the XYZ moving stages 501, 601, and 701 move the supply pipette 301 with the used tip attached thereto onto the tip storage area 1500. The supply pipette 301 removes the tip 401 and stores it in the tip storage area 1500.
[0116] Thereafter, as in embodiment 2, the contact liquid discharge step S1500 of the cleaning liquid and the label supply step S1700 are performed in parallel, and the contact liquid discharge step S1500 of the label substance and the second cleaning liquid supply step S1600 are performed in parallel. While the discharge pipette 300 is discharging the contact liquid from plate A, the XYZ movement stages 501, 601, and 701 move the supply pipette 301 to above the tip holder 1500 and attach the previously removed tip 401 to the supply pipette 301. Thereafter, the XYZ movement stages 501, 601, and 701 move the supply pipette 301 above the cleaning liquid 1200, and the supply pipette 301 aspirates the cleaning liquid 1200 and supplies it to plate A.
[0117] The subsequent contact liquid discharging step S1500 and preservation liquid supplying step S1800 are performed in the same manner as in the second embodiment.
[0118] As described above, the processing method and processing apparatus 4000 of this embodiment can prevent contamination between multiple array plates and reduce the amount of tips consumed. Furthermore, in this embodiment, by separating the supply system and the discharge system, the supply process and the discharge process can be carried out in parallel, thereby reducing the number of steps required for reaction processing of the array plate. Furthermore, in this embodiment, the configuration of the supply system having multiple pipettes reduces the amount of tips consumed.
[0119] Other Embodiments In the array plate processing apparatus according to Embodiments 1 to 4, the controller 10 is a computer having a CPU, RAM, ROM, a storage medium such as an HDD, a display unit, and an operation unit. Naturally, the controller 10 is not limited to this form and may be an information terminal such as a PDA, a tablet PC, or a mobile phone. The display unit of the controller 10 may be any of various display devices such as a liquid crystal display device. The operation unit of the controller 10 may be any of various input devices such as a keyboard or a touch panel. A computer program for controlling the battery structure removal system is stored in the ROM or the storage medium. This computer program is a program for implementing various functions including the operations of XYZ moving stages 500, 600, 700, 501, 601, 701, and 702 and pipettes 300, 301, and 302, and corresponds to S1000 (S1100, S1200, S1300, S1400, S1500, S1600, S1500, S1700, S1500, S1600, S1500, and S1800) in Figures 1, 3, 5, and 7. The CPU of controller 10 reads the computer program from ROM or a storage medium and executes it using RAM as a work area. In this way, controller 10 controls each part of the inspection apparatus.
[0120] It should be noted that the above-described embodiments are merely examples of specific embodiments for carrying out the present invention, and the technical scope of the present invention should not be interpreted as being limited by these embodiments. In other words, the present invention can be carried out in various forms without departing from its technical concept or main features.
[0121] The disclosure of this embodiment includes the following methods and configurations.
[0122] (Method 1) A method for processing array plates, using a processing device including a supply system for supplying liquid and a discharge system for discharging liquid, in which different specimens are reacted with multiple array plates including a common spot array, the method comprising: a discharge step for sequentially discharging contact liquid that comes into contact with the spot array for each array plate using the discharge system; a specimen supply step for supplying a specimen selected from multiple specimens for each array plate using the supply system; a stop liquid supply step for sequentially supplying a reaction stop liquid to the multiple array plates using the supply system to stop a reaction between at least a portion of the spot array and the specimen; a buffer solution supply step for sequentially supplying a predetermined buffer solution to the multiple array plates using the supply system; a discharge preparation step for replacing a part of the discharge system, which is performed when the contact liquid discharged by the discharge system is changed; and a supply preparation step for replacing a part of the supply system, which is performed when the liquid supplied by the supply system is changed.
[0123] (Method 2) The method for treating an array plate according to Method 1, wherein the discharge preparation step is performed for each array plate during the discharge step after the sample supply step and before the stop solution supply step.
[0124] (Method 3) The method for treating an array plate according to Method 1 or 2, wherein the discharge preparation step is performed for each array plate between the discharge steps so that the array plate does not come into contact with a plurality of the specimens.
[0125] (Method 4) The method for treating an array plate according to any one of Methods 1 to 3, wherein the timing at which the contact liquid is changed is the period between two successive discharge steps.
[0126] (Method 5) The method for treating an array plate according to any one of Methods 1 to 4, wherein the supply preparation step is performed between the sample supply steps that are performed for each array plate.
[0127] (Method 6) The method for treating an array plate according to any one of Methods 1 to 5, wherein the supply preparation step is performed between the sample supply steps, which are performed for each array plate, so that the array plate does not come into contact with multiple samples.
[0128] (Method 7) The method for treating an array plate according to any one of Methods 1 to 6, wherein the timing at which the liquid is changed is a period between two successive steps selected from the sample supplying step, the stop solution supplying step, and the buffer solution supplying step.
[0129] (Method 8) The method for treating an array plate according to any one of Methods 1 to 7, wherein the sample supplying step, the stop solution supplying step, and the buffer solution supplying step are performed so that the supplied liquids come into contact with the spot array.
[0130] (Method 9) The method for treating an array plate according to any one of Methods 1 to 8, wherein the common spot array in the plurality of array plates includes a plurality of spots in which different biological substances are arranged in an array.
[0131] (Method 10) The method for treating an array plate according to any one of Methods 1 to 9, wherein a common treatment is carried out on the plurality of array plates except for the treatment of reacting the plates with different specimens.
[0132] (Method 11) The array plate processing method according to Method 10, wherein the common processing includes the stop solution supplying step and the buffer solution supplying step, which are performed on the plurality of array plates.
[0133] (Method 12) The method for treating an array plate according to any one of Methods 1 to 11, wherein the predetermined buffer solution includes at least one selected from a washing solution, an observation solution, a storage solution, and a dilution solution.
[0134] (Method 13) The method for treating an array plate according to any one of Methods 1 to 12, wherein the part of the discharge system includes a part that comes into contact with the contact liquid.
[0135] (Method 14) The method for treating an array plate according to any one of Methods 1 to 13, wherein the discharge steps, excluding the step of discharging the sample, are performed without replacing a part of the discharge system for at least two array plates from which liquid is continuously discharged among the plurality of array plates.
[0136] (Method 15) The method for treating an array plate according to any one of Methods 1 to 14, wherein the buffer solution supplying step and the stop solution supplying step are performed for at least two array plates to which liquid is continuously supplied among the plurality of array plates without replacing a part of the supply system.
[0137] (Configuration 1) An array plate processing device comprising: a mounting section on which a plurality of array plates are arranged and mounted; a supply system that supplies liquid to at least one of the plurality of array plates mounted on the mounting section; a discharge system that discharges liquid held by at least one of the plurality of array plates mounted on the mounting section when the array plate holds liquid; a moving section that changes the relative position of the mounting section with respect to the supply system; a loading section that loads dispensing tips into at least one of the supply system and the discharge system; a release section that releases the loading of the dispensing tips from at least one of the supply system and the discharge system; and a liquid storage section in which the liquid to be supplied to the supply system is stored.
[0138] (Configuration 2) The array plate processing apparatus according to Configuration 1, wherein the part of the supply system and the part of the discharge system that are replaced are the dispensing tips.
[0139] (Configuration 3) The array plate processing apparatus according to configuration 1 or 2, wherein the supply system replaces a part of the supply system when the liquid to be supplied is changed.
[0140] (Configuration 4) The array plate processing apparatus according to any one of configurations 1 to 3, wherein the discharge system replaces a part of the discharge system when the liquid to be discharged is changed.
[0141] (Configuration 5) The array plate processing apparatus according to any one of Configurations 1 to 4, further comprising a tip disposal unit that discards the dispensing tip after the discharging has been released.
[0142] (Configuration 6) The array plate processing apparatus according to any one of configurations 1 to 5, wherein the liquid storage section is configured to have a plurality of containers for storing the liquid.
[0143] (Configuration 7) The array plate processing apparatus according to any one of configurations 1 to 6, wherein the array plate has a bank portion capable of storing the liquid supplied from the supply system, and the mounting portion is configured so that the array plate is mounted on the mounting portion so that the liquid is stored on the array plate.
[0144] (Configuration 8) The array plate processing apparatus according to any one of configurations 1 to 7, wherein the moving unit moves the placement unit in a translational manner relative to the placement unit.
[0145] (Configuration 9) The array plate processing apparatus according to any one of Configurations 1 to 8, wherein the supply system is coupled to a supply system moving unit having multiple degrees of freedom of movement so as to move relative to the placement unit, the loading unit, and the release unit.
[0146] (Configuration 10) The array plate processing device according to any one of Configurations 1 to 9, wherein the discharge system is coupled to a discharge system moving unit having multiple degrees of freedom of movement so as to move relative to the placement unit, the loading unit, and the release unit.
[0147] (Configuration 11) An array plate processing apparatus described in any one of configurations 1 to 7, wherein the supply system is coupled to a supply system moving section having multiple degrees of freedom of movement so as to move relative to the placement section, the loading section, and the release section, the discharge system is coupled to a discharge system moving section having multiple degrees of freedom of movement so as to move relative to the placement section, the loading section, and the release section, and the supply system moving section has multiple degrees of freedom of movement and is equipped with a moving mechanism that shares at least some of the degrees of freedom of movement with the discharge system moving section.
[0148] (Configuration 12) The array plate processing device according to any one of configurations 1 to 11, further comprising a tip storage unit for temporarily storing the used dispensing tips for reuse.
[0149] The present invention is not limited to the above-described embodiments, and various modifications and variations can be made without departing from the spirit and scope of the present invention. Therefore, the following claims are appended to apprise the public of the scope of the present invention.
[0150] This application claims priority based on Japanese Patent Application No. 2023-170455, filed on September 29, 2023, the entire contents of which are incorporated herein by reference.
[0151] S1000 Analysis step S1100 Preservation solution discharge step S1200 Sample supply step S1300 Sample discharge step S1400 Reaction stop step S1500 Contact solution discharge step S1600 Washing solution supply step S1700 Label supply step S1800 Preservation solution supply step 100 Array plate 200 Sample 300, 301, 302 Pipette 400, 401, 402 Pipette tip 500, 501 X-moving stage 600, 601 Y-moving stage 700, 701, 702 Z-moving stage 800 Tip holder 900 Discarded tip holder 1000 Drainage container 1100 Stopping solution 1200 Washing solution 1300 Labeling substance 1400 Preservation solution 1500 Tip holder
Claims
1. A method for processing an array plate, in which a processing device including a supply system for supplying liquid and a discharge system for discharging liquid is used to react different specimens with multiple array plates including a common spot array, the method comprising: a discharge step of sequentially discharging contact liquid that comes into contact with the spot array for each array plate using the discharge system; a specimen supply step of supplying a specimen selected from the multiple specimens for each array plate using the supply system; a stop liquid supply step of sequentially supplying a reaction stop liquid to the multiple array plates using the supply system to stop a reaction between at least a portion of the spot array and the specimen; a buffer supply step of sequentially supplying a predetermined buffer solution to the multiple array plates using the supply system; a discharge preparation step of replacing a part of the discharge system, which is performed when the contact liquid discharged by the discharge system is changed; and a supply preparation step of replacing a part of the supply system, which is performed when the liquid supplied by the supply system is changed.
2. The method for processing an array plate according to claim 1, wherein the discharge preparation step is performed for each array plate during the discharge step after the specimen supply step and before the stop solution supply step.
3. The method for treating an array plate according to claim 1 or 2, wherein the discharge preparation step is performed for each array plate between the discharge steps so that the array plate does not come into contact with a plurality of the specimens.
4. The method for treating an array plate according to any one of claims 1 to 3, wherein the timing at which the contact liquid is changed is a period between two successive discharge steps.
5. The array plate processing method according to any one of claims 1 to 4, wherein the supply preparation step is performed between the sample supply steps which are performed for each array plate.
6. The method for processing an array plate according to any one of claims 1 to 5, wherein the supply preparation step is performed between the sample supply steps which are performed for each array plate so that the array plate does not come into contact with a plurality of the samples.
7. A method for processing an array plate as described in any one of claims 1 to 6, wherein the timing at which the liquid is changed is the period between two successive processes selected from the sample supply process, the stop solution supply process, and the buffer solution supply process.
8. A method for treating an array plate, wherein the liquids supplied in the sample supplying step, the stop solution supplying step, and the buffer solution supplying step come into contact with the spot array.
9. A method for processing an array plate according to any one of claims 1 to 8, wherein the common spot array in a plurality of array plates includes a plurality of spots in which different biological substances are arranged in an array.
10. The method for processing an array plate according to any one of claims 1 to 9, wherein a common process is carried out on the plurality of array plates except for the process of reacting the plurality of array plates with different specimens.
11. The array plate processing method according to claim 10, wherein the common processing includes the stop solution supplying step and the buffer solution supplying step which are performed on the plurality of array plates.
12. The method for treating an array plate according to any one of claims 1 to 11, wherein the predetermined buffer solution includes at least one selected from the group consisting of a washing solution, an observation solution, a storage solution, and a dilution solution.
13. The method for treating an array plate according to any one of claims 1 to 12, wherein a part of the exhaust system includes a part that comes into contact with the contact liquid.
14. A method for processing an array plate according to any one of claims 1 to 13, wherein the discharge steps, excluding the step of discharging the sample, are performed for at least two of the plurality of array plates from which liquid is continuously discharged, without replacing a part of the discharge system.
15. A method for processing an array plate according to any one of claims 1 to 14, wherein the buffer solution supplying step and the stop solution supplying step are performed for at least two array plates among the plurality of array plates to which liquid is continuously supplied, without replacing a part of the supply system.
16. An array plate processing apparatus comprising: a mounting section on which a plurality of array plates are arranged and mounted; a supply system which supplies liquid to at least any of the plurality of array plates mounted on the mounting section; a discharge system which discharges liquid held by at least any of the plurality of array plates mounted on the mounting section when the array plates hold liquid; a moving section which changes the relative position of the mounting section with respect to the supply system; a loading section which loads dispensing tips into at least any of the supply system and the discharge system; a release section which releases the loading of the dispensing tips from at least any of the supply system and the discharge system; and a liquid storage section in which the liquid to be supplied to the supply system is stored.
17. The array plate processing apparatus according to claim 16, wherein the part of the supply system and the part of the discharge system that are replaced are the dispensing tips.
18. The array plate processing apparatus according to claim 16, wherein the supply system replaces a part of the supply system when the liquid to be supplied is changed.
19. The array plate processing apparatus according to any one of claims 16 to 18, wherein the discharge system replaces a part of the discharge system when the liquid to be discharged is changed.
20. The array plate processing apparatus according to any one of claims 16 to 19, further comprising a tip disposal unit that discards the unloaded dispensing tip.
21. The array plate processing apparatus according to any one of claims 16 to 20, wherein the liquid storage section is configured to have a plurality of containers for storing the liquid.
22. An array plate processing apparatus as described in any one of claims 16 to 21, wherein the array plate has a dike portion capable of storing the liquid supplied from the supply system, and the mounting portion is configured so that the array plate is mounted on the mounting portion so that the liquid is stored on the array plate.
23. The array plate processing apparatus according to any one of claims 16 to 22, wherein the moving section moves the placement section in a translational manner relative to the substrate.
24. An array plate processing apparatus according to any one of claims 16 to 23, wherein the supply system is coupled to a supply system moving section having a plurality of degrees of freedom of movement so as to move relative to the placement section, the loading section, and the release section.
25. An array plate processing apparatus according to any one of claims 16 to 24, wherein the discharge system is coupled to a discharge system moving section having a plurality of degrees of freedom of movement so as to move relative to the placement section, the loading section, and the release section.
26. An array plate processing apparatus as described in any one of claims 16 to 25, wherein the supply system is coupled to a supply system moving section having multiple degrees of freedom of movement so as to move relative to the placement section, the loading section, and the release section, the discharge system is coupled to a discharge system moving section having multiple degrees of freedom of movement so as to move relative to the placement section, the loading section, and the release section, and the supply system moving section has multiple degrees of freedom of movement and is equipped with a moving mechanism that shares at least some of the degrees of freedom of movement with the discharge system moving section.
27. The array plate processing apparatus according to any one of claims 16 to 26, further comprising a tip storage section for temporarily storing the used dispensing tips for reuse.
Citation Information
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