Multiwell plate, electrochemical measurement method, measurement device, automatic measurement system, and manufacturing method

Abstract

To provide a multi-well plate capable of rapidly performing electrochemical measurement of measurement objects.SOLUTION: A multi-well plate includes: a plurality of upwardly-opening wells; at least two electrodes positioned at the bottom of each of the wells; and a pillar-shaped conductive member that is electrically in contact with one of the electrodes and is not in contact with the other electrodes. Height of the conductive member is smaller than depth of the well, and an area occupied by the conductive member in plan view of the well is smaller than the bottom area of the well.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a multiwell plate, an electrochemical measurement method, a measurement device, an automatic measurement system, and a manufacturing method. [Background technology]

[0002] In the field of materials science, the search for new materials with excellent properties has traditionally been carried out through the following cycle: In other words, the cycle includes the steps of (1) planning a new raw material formulation and synthesis method by experienced engineers, (2) evaluating the properties of samples prepared based on that formulation and method, and (3) improving the raw material formulation and synthesis method based on the results of the evaluation.

[0003] In the above cycle, each step has been performed manually, which naturally limits the number of samples that can be tested, and also limits the speed at which new materials can be discovered.

[0004] However, in recent years, with the rapid advancement of artificial intelligence technology and simulation technology, it has become possible to automatically design new raw material combinations and synthesis methods at a volume and speed incomparable to that of the past, using statistical analysis methods based on data described in published papers and vast amounts of actual measurement data, and / or computational science methods based on physical laws. Furthermore, advances in robotics have led to remarkable advances in the technology and devices that can automatically prepare samples according to planned raw material blends and synthesis methods.

[0005] As mentioned above, in an environment where a huge number of materials science samples are automatically generated, one of the steps that may limit the speed of new materials discovery is the sample characterization step. From the perspective of facilitating the overall flow of new materials discovery, there is a strong demand for the development of a measurement system that can rapidly evaluate a huge number of samples.

[0006] Among these technologies, in the field of electrochemical measurement, Patent Document 1 describes "an electrochemical measurement system comprising an insertion mechanism movably provided with respect to a plurality of reactors in which a plurality of types of solutions are respectively accommodated and arranged, and an electrode member attached to the insertion mechanism so as to be insertable into the plurality of types of solutions accommodated in the plurality of reactors, and connected to an electrochemical measurement device."

[0007] Furthermore, Patent Document 2 describes a multi-well plate having multiple wells arranged in a two-dimensional array and at least two electrodes arranged at the bottom of each well, which can be used to screen the electrochemical properties of multiple samples. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] International Publication No. 2019-510960 [Patent Document 2] Patent Publication No. 2021-036806 Summary of the Invention [Problem to be solved by the invention]

[0009] For example, when searching for new battery materials, the present inventors investigated whether electrochemical measurements of a wide variety of measurement targets could be carried out quickly using the techniques described in Patent Documents 1 and 2.

[0010] As a result, it was found that although the electrochemical measurement system described in Patent Document 1 can rapidly evaluate the properties of a wide variety of electrolyte solutions, it is difficult to evaluate the electrochemical properties of other battery materials, particularly solid materials (e.g., electrode materials, catalysts, etc.).

[0011] Furthermore, when using the multi-well plate described in Patent Document 2, although measurement itself is possible by placing various electrode materials on the bottom working electrode, there are cases where the placed electrode material comes into contact with the adjacent counter electrode and / or working electrode, causing a short circuit, etc. In this regard, there is room for improvement when attempting to apply a method of electrochemical measurement in which various types of measurement targets are placed on the working electrode.

[0012] Therefore, an object of the present invention is to provide a multi-well plate that allows rapid electrochemical measurement of a measurement target, as well as an electrochemical measurement method, a measurement device, an automatic measurement system, and a manufacturing method. [Means for solving the problem]

[0013] As a result of extensive research into achieving the above object, the present inventors have found that the above object can be achieved by the following configuration.

[0014] [1] A multi-well plate having a plurality of wells that open upward, at least two electrodes arranged at the bottom of the wells, and a columnar conductive member arranged so as to be in electrical contact with one of the electrodes but not in contact with the other electrodes, wherein the height of the conductive member is smaller than the depth of the wells, and the area occupied by the conductive member in a planar view of the wells is smaller than the bottom area of ​​the wells. [2] The multiwell plate according to [1], wherein the electrodes and the conductive member are made of different materials. [3] The multi-well plate according to [1] or [2], wherein the electrodes are three or more electrodes arranged at predetermined intervals from each other. [4] The multiwell plate according to any one of [1] to [3], wherein the object to be measured is placed on the top surface of the conductive member. [5] The multiwell plate according to [4], wherein at least one of the electrodes is a reference electrode. [6] The multiwell plate according to [5], wherein the electrodes comprise a working electrode, a counter electrode, and a reference electrode, and the conductive member is disposed on the working electrode. [7] The multiwell plate according to any one of [1] to [6], wherein the conductive member has a frustum shape. [8] The multi-well plate according to any one of [1] to [6], wherein the conductive member has a shape in which a plurality of pillars are stacked approximately coaxially, and the area of ​​the top surface is larger than the area of ​​the bottom surface. [9] The multi-well plate according to any one of [1] to [8], wherein the conductive member has a fluid leakage prevention mechanism disposed on the top surface.

[10] The multiwell plate according to any one of [1] to [9], wherein the electrode and the conductive member are in direct contact with each other.

[11] An electrochemical measurement method comprising: placing a measurement object on the conductive member of the multiwell plate described in any one of [1] to

[10] so that the measurement object is in electrical contact with the conductive member; and performing electrochemical measurement on the multiwell plate on which the measurement object is placed, according to predetermined conditions.

[12] An electrochemical measurement method according to

[11] , which includes, before the above-mentioned setting, performing a preliminary measurement under conditions similar to the above-mentioned specified conditions, and determining whether or not there is an electrochemical response resulting from deterioration of the conductive member based on predetermined criteria from the results of the preliminary measurement, and performing the above-mentioned setting if there is no electrochemical response resulting from the deterioration.

[13] A measuring device comprising: a reader device including a connector for electrically connecting to the electrodes of a multiwell plate described in any one of [1] to

[10] and an electrochemical measuring device for controlling the electrochemical reaction of the electrodes via the connector; and a control device, wherein the control device has a preliminary measurement analysis unit that determines, based on predetermined criteria, the presence or absence of an electrochemical response resulting from deterioration of the conductive member from the results of a preliminary measurement performed under conditions similar to the specified conditions for electrochemical measurement of the object to be measured before the object to be measured is placed on the conductive member so as to be in electrical contact with the conductive member.

[14] An automatic measurement system comprising: a sample preparation device that prepares a measurement object and places the measurement object on the conductive member of a multiwell plate described in any one of [1] to

[10] ; a reader device having a connector for electrically connecting to the electrodes of the multiwell plate and an electrochemical measurement device that controls the electrochemical reaction of the electrodes via the connector; a plate transport device that transports the multiwell plate between the sample preparation device and the reader device; and a control device, wherein the control device has a preliminary measurement analysis unit that determines, based on predetermined criteria, the presence or absence of an electrochemical response due to deterioration of the conductive member from the results of a preliminary measurement performed under conditions similar to the specified conditions for electrochemical measurement of the measurement object before the measurement object is placed on the conductive member so as to be in electrical contact with the conductive member.

[15] A manufacturing method for manufacturing a multiwell plate according to any one of [1] to

[10] , comprising: applying an electrode-forming composition onto a substrate to form at least two composition layers spaced apart from each other; placing the conductive member so that it is in direct contact with one of the composition layers but not in contact with the other composition layers; and hardening the composition layer to form the electrode and fix the conductive member to the electrode. [Effects of the Invention]

[0015] According to the present invention, a multi-well plate that allows rapid electrochemical measurement of a measurement target can be provided. The present invention also provides an electrochemical measurement method, a measurement device, an automatic measurement system, and a manufacturing method. [Brief explanation of the drawings]

[0016] [Figure 1] FIG. 1 is an exploded perspective view of an embodiment of a well plate of the present invention. [Figure 2] FIG. 2 is a plan view of a well of the well plate of the present invention. [Figure 3] FIG. [Figure 4] FIG. 1 is a bottom view of the well plate (the back surface of the lower substrate). [Figure 5] FIG. 1 is a hardware configuration diagram of an embodiment of a measurement device for performing electrochemical measurements using a well plate. [Figure 6] FIG. 1 is a schematic diagram of a reader device, which is one of the devices that make up the measurement device. [Figure 7] FIG. 2 is a functional block diagram of the measurement device. [Figure 8] FIG. 1 is a flow diagram of electrochemical measurement using a well plate and a measurement device. [Figure 9] FIG. 1 is an explanatory diagram showing a state in which a sheet-like measurement object is placed in a well of a well plate. [Figure 10] 10A and 10B are schematic diagrams of other forms of conductive members. [Figure 11] FIG. 1 is a flow diagram of a method for manufacturing a well plate of the present invention. [Figure 12] FIG. 1 is a flow diagram of electrochemical measurement according to the present invention. [Figure 13] FIG. 1 shows the electrochemical response when aluminum foil is used as the working electrode and the experimental conditions are linear sweep voltammetry. [Figure 14] FIG. 2 is a hardware configuration diagram of the measurement device of the present invention. [Figure 15] FIG. 2 is a functional block diagram of the measuring device. [Figure 16] FIG. 4 is an operation flow diagram of a control device of the measuring device. [Figure 17] FIG. 1 is a hardware configuration diagram of an automatic measurement system according to the present invention. [Figure 18] FIG. 2 is a functional block diagram of the automatic measurement system. [Figure 19] FIG. 10 is an operational flow diagram of the control device (processor 52) of the automatic measurement system. [Figure 20] These are the results of a cyclic voltammetry test using a highly concentrated aqueous solution of 21M LiTFSA / H2O (TFSA: bis (trifluoromethanesulfonyl) amide) as the electrolyte. DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention will be described in detail below. The following description of the components may be based on a representative embodiment of the present invention, but the present invention is not limited to such an embodiment. In this specification, a numerical range expressed using "to" means a range that includes the numerical values ​​before and after "to" as the lower and upper limits. Furthermore, in this specification and drawings, substantially the same components may be denoted by the same reference numerals, and redundant explanations may be omitted.

[0018] [Multi-well plate] The multi-well plate of the present invention (hereinafter also referred to simply as "well plate") has a plurality of wells that open upward, at least two electrodes arranged at the bottom of the wells, and a columnar conductive member arranged so as to be in electrical contact with one of the electrodes but not in contact with the other electrodes, wherein the height of the conductive member is smaller than the depth of the wells, and the area occupied by the conductive member in a planar view is smaller than the bottom area of ​​the wells.

[0019] The well plate will be described with reference to the drawings, in which: Figure 1 is an exploded perspective view of an embodiment of the well plate of the present invention (hereinafter also referred to as "this embodiment").

[0020] The well plate 10 is composed of an upper substrate 16 and a lower substrate 12 joined to the bottom side of the upper substrate 16 . Of these, the upper substrate 16 has cylindrical tubes 13 that are open in both the vertical and horizontal directions, and a skirt 11 that supports the multiple tubes 13. The cylindrical tubes 13 are combined with the top surface of the lower substrate 12 to form wells (recesses) that have a bottom that opens upward.

[0021] On the lower substrate 12, a plurality of electrode sets 15 consisting of three electrodes, which will be described later, and a cylindrical conductive member 14 placed on the working electrode 20 of the electrode sets 15 are arranged in a two-dimensional matrix. The region 17 on the top surface of the lower substrate 12 becomes the bottom of the well when combined with the tube 13 .

[0022] As described above, by joining the upper substrate 16 and the lower substrate 12, a well plate 10 is formed in which multiple wells opening upward, electrode sets 15 placed at the bottom of the wells, and cylindrical conductive members 14 placed on one of the electrodes (the working electrode 20 described below) are arranged two-dimensionally (planarly).

[0023] Fig. 2 is a plan view of the well, and Fig. 3 is a perspective view of the well, in which tube 13 is omitted. The electrode set 15 is composed of a working electrode 20, a counter electrode 22, and a reference electrode 24, all of which are thin film electrodes. The electrode set 15 is typically formed on a lower substrate 12, which is a wiring board, using a printing technique.

[0024] In the well, the electrodes constituting the electrode set 15 are arranged at a predetermined interval, with the working electrode 20 at the center, and the counter electrode 22 and reference electrode 24 arranged around it.

[0025] A cylindrical conductive member 14 is placed on the working electrode 20. In the well plate 10, the conductive member 14 is in direct contact with the working electrode 20. When the conductive member 14 and the working electrode 20 are in direct contact, more accurate measurement results are likely to be obtained.

[0026] The working electrode and the conductive member do not need to be in direct contact as long as they are in electrical contact with each other. For example, a conductive adhesive layer may be disposed between the working electrode and the conductive member.

[0027] The diameter of the conductive member 14 is approximately the same as that of the working electrode 20. The bottom surface of the conductive member 14 is disposed so as to cover approximately the entire working electrode 20.

[0028] In the well plate of the present invention, the bottom area of ​​the conductive member is not limited to the above and may be larger or smaller than the area of ​​the working electrode as long as it is in electrical contact with the working electrode. When the bottom area of ​​the conductive member is larger than the area of ​​the working electrode, the conductive member is adjusted in shape and size so as not to come into contact with other electrodes (counter electrode, reference electrode).

[0029] As shown in Figure 2, the area occupied by the conductive member 14 in a plan view of the well is smaller than the bottom area of ​​the well. When electrochemical measurements are performed using this well plate, the wells are filled with an electrolyte. If the area occupied by the conductive member 14 were the same as the bottom area of ​​the well, the flow of the electrolyte within the well would be hindered, making electrochemical measurements difficult.

[0030] Furthermore, the height of the conductive member 14 is smaller than the depth of the well (the height of the tube 13). As will be described later, an object to be measured is placed on the top surface of the conductive member 14 and electrochemical measurement is performed. If the height of the conductive member 14 is greater than the depth of the well, it will be difficult to bring the measurement object into contact with the electrolyte (immerse it in the electrolyte), making electrochemical measurement difficult. The height of the conductive member is not particularly limited as long as it is a height that does not allow the object to be measured to come into contact with the counter electrode and / or reference electrode, depending on the rigidity of the object to be measured placed on the top surface, but generally, 1 to 70% of the depth of the well is preferred.

[0031] FIG. 4 is a bottom view of the well plate 10 (the back surface of the lower substrate 12). The working electrode 20 and the wiring 21 of the lower substrate 12 connected thereto are led to the back surface of the lower substrate 12 through via holes 30 and are electrically connected to a connection pad 31. Similarly, the counter electrode 22 and the wiring 23 connected thereto are connected to a connection pad 33 through via holes 32, and the reference electrode 24 and the wiring 25 connected thereto are connected to a connection pad 35 through via holes 34.

[0032] As described above, the working electrode 20, the counter electrode 22, and the reference electrode 24 are each drawn out to the back surface of the lower substrate 12. Therefore, electrochemical measurements can be performed by connecting an electrochemical measurement device (e.g., a potentiostat and / or a galvanostat) for controlling the electrochemical reaction of the electrodes to the corresponding connection pads 31, 33, and 35 from the back surface of the lower substrate 12.

[0033] The material of the well plate 10 is not particularly limited, but insulating materials are preferred for the upper substrate 16 and the lower substrate 12. Specifically, glass, resin, and the like are preferred. The resin is not particularly limited, but examples thereof include polyolefin resins such as polypropylene resin, polyethylene resin, and ethylene-propylene copolymer, or cyclic polyolefin resins; polystyrene resins such as polystyrene and acrylonitrile-butadiene-styrene resin; polycarbonate resin; polyethylene terephthalate resin; methacrylic resins such as polymethyl methacrylate resin; vinyl chloride resin; polybutylene terephthalate resin; polyarylate resin; polysulfone resin; polyethersulfone resin; polyetheretherketone resin; polyetherimide resin; fluorine-based resins such as polytetrafluoroethylene; polymethylpentene resin; acrylic resins such as polyacrylonitrile; and cellulose-based resins such as propionate resin.

[0034] The material of the working electrode 20 can be selected appropriately depending on the object to be measured. Specific examples include precious metals such as gold and platinum. Silver, copper, carbon (glassy carbon), and boron (B)-doped diamond can also be used. The counter electrode 22 can be selected from the same materials as above. A silver / silver chloride (Ag / AgCl) electrode or the like can be used as the reference electrode 24. The wiring and connection pads of the lower substrate 12 can also be selected from the same materials as the electrodes.

[0035] The material of the conductive member 14 may be the same as that of the working electrode and the counter electrode, or may be a conductive material other than those mentioned above. In particular, the material of the conductive member 14 is preferably different from the material of each electrode.

[0036] For example, when the working electrode 20 and the counter electrode 22 are made of a noble metal, the conductive member 14 may be made of a metal having a higher ionization tendency than the materials of the electrodes, such as iron, copper, nickel, aluminum, lead, zinc, tin, tungsten, titanium, and chromium. Conductive member 14 is thicker and uses more material than each electrode that makes up electrode set 15. Metals with a higher ionization tendency, such as those described above, are often inexpensive, and using such metals for conductive member 14 further reduces the manufacturing cost of the multiwell plate.

[0037] On the other hand, if the conductive member 14 is made of the same material as the working electrode 20 and the counter electrode 22, electrochemical measurements can be performed more stably.

[0038] The shape and size of the well plate are not particularly limited, but one form may be a shape and size that conforms to the standards established mainly by the Society for Biomolecular Screening (SBS) in 2004. The number of wells in well plate 10 is 96, but the number of wells in the well plate of the present invention is not limited to the above and may be any number such as 6, 12, 24, 48, 384, and 1536, with 96 or more being preferred, and 96 being more preferred from the standpoint of excellent handleability.

[0039] FIG. 5 is a hardware configuration diagram of one embodiment of a measurement device for performing electrochemical measurements using a well plate 10, and FIG. 6 is a schematic diagram of a reader device, which is one of the devices that make up the measurement device.

[0040] The measuring device 50 includes a reader device 40 for performing electrochemical measurements using the well plate 10 and a control device 51 for the reader device, and each device is configured to be able to exchange data with each other via a bus.

[0041] The reader device 40 has a main body 42 , a tray 47 disposed on the main body 42 , and a cover 44 that houses the tray 47 . The well plate 10 is fitted into a tray 47. The tray 47 has on its surface a plurality of connection terminals 41, 43, 45 (collectively referred to as connectors 46) for electrical contact with the connection pads 35 formed on the bottom surface of the well plate 10. The number of connectors 46 provided is equal to the number of wells in the well plate 10.

[0042] When the well plate 10 is fitted into the tray 47, the tray 47 slides into the cover 44 and is connected to the electrochemical measurement device 48 arranged in the main body 42 via wiring (not shown) provided inside the cover 44.

[0043] The electrochemical measurement device 48 is typically a device including a potentiostat, a galvanostat, or a combination thereof, and is a hardware device for controlling the electrochemical reaction of the electrodes in each well connected via the connector 46 and measuring the electrochemical response. Specifically, it has the function of applying a voltage between the working electrode 20 and the counter electrode 22, controlling the potential between the working electrode 20 and the reference electrode 24 to measure the current value, or controlling the current between the working electrode 20 and the counter electrode 22 to measure the potential between the working electrode 20 and the reference electrode 24, and can perform the above operations independently for each well.

[0044] In addition to the above, the reader device 40 may also have a frequency analyzer for measuring impedance, an amplifier for amplifying the response current, and an atmosphere adjusting device for adjusting the atmosphere (particularly, for maintaining an anaerobic state or removing moisture from the atmosphere). Any of the above devices may be incorporated into the reader device 40.

[0045] The control device 51 is a computer that includes a processor 52, a storage device 53, a display device 54, an input device 55, and a communication device 56.

[0046] The processor 52 is, for example, a microprocessor, a processor core, a multiprocessor, an application-specific integrated circuit (ASIC), a field programmable gate array (FPGA), or a general-purpose computing on graphics processing unit (GPGPU).

[0047] The storage device 53 has the function of temporarily and / or non-temporarily storing various programs and data, and provides a working area for the processor 52. The storage device 53 is, for example, a read only memory (ROM), a random access memory (RAM), a hard disk drive (HDD), a flash memory, or a solid state drive (SSD).

[0048] The display device 54 can display analysis results, operation procedures, etc. The display device 54 may be a liquid crystal display, an organic EL (Electro Luminescence) display, or the like. Furthermore, the display device 54 may be configured integrally with the input device 55. In this case, the display device 54 may be a touch panel display that provides a GUI (Graphical User Interface).

[0049] The input device 55 can receive input of measurement conditions, the name of the object to be measured, etc., and can also receive input of instructions to start and end measurement. The input device 55 may be a keyboard, a mouse, a scanner, a touch panel, etc.

[0050] The communication device 56 is connected to a communication network and can receive instructions such as measurement conditions from a client terminal etc. and transmit measurement and analysis results to the client terminal etc. The communication device 56 may be a wired or wireless LAN (Local Area Network), a Bluetooth (registered trademark) communication card, a router for optical communication, or the like.

[0051] The communication device 56 transmits and receives signals between the Internet and other communication devices using a predetermined protocol such as TCP / IP. The communication network connected to the communication device 56 is a wired or wireless network, such as the Internet, a home LAN, infrared communication, radio wave communication, or satellite communication.

[0052] 7 is a functional block diagram of the measurement device 50. The measurement device 50 includes a reader device 40 and a control device 51, the reader device 40 includes a connector 46 and an electrochemical measurement device 48, and the measurement device 50 includes a measurement unit 60 and an analysis unit 61.

[0053] The measurement unit 60 has a function in which the processor 52 of the control device 51 executes a program stored in the memory device 53, and controls the electrochemical reaction of the electrodes of the well plate 10, which is connected to the reader device 40 via a connector 46 also provided in the reader device 40, using an electrochemical measurement device 48 provided in the reader device 40. Measurement conditions are input 62 to the measurement unit 60 via an input device 55 or a communication device 56 .

[0054] The analysis unit 61 is a function realized by the processor 52 of the control device 51 executing a program stored in the storage device 53. The analysis unit 61 analyzes the electrochemical response (measurement data) acquired by the measurement unit 60 and outputs 63 the results to the display device 54 and / or via the communication device 56.

[0055] Although the measuring device 50 has an analysis unit 61, the measuring device of the present invention does not have to have an analysis unit. When the measuring device does not have an analysis unit, it may be configured to output 63 the measurement data (electrochemical response) acquired by the measuring unit 60 as is.

[0056] FIG. 8 is a flow diagram of electrochemical measurement performed using the well plate 10 and the measurement device 50. First, in step S10, the measurement object is placed on the conductive member 14 of the well plate 10 so that the measurement object is in electrical contact with the conductive member 14.

[0057] FIG. 9 is an explanatory diagram showing a state in which a sheet-like measurement object 70 is placed in the well of the well plate 10. As shown in FIG. The measurement object 70 is placed on the top surface of the conductive member 14. The conductive member 14 is in electrical contact with the working electrode 20 on the bottom surface, which allows electrochemical measurement of the measurement object 70 to be performed.

[0058] There are no particular limitations on the shape of the measurement object 70, but a sheet (thin film) is preferred. In a sheet shape, electrochemical reactions tend to occur more uniformly, and more accurate measurement results can be obtained. Although the size of the measurement object 70 is not particularly limited, it is preferable that the area occupied by the measurement object in a plan view of the well be smaller than the bottom area of ​​the well. When the measurement object 70 has the above-described shape, the electrolyte can easily spread throughout the measurement object 70, allowing for more accurate measurement.

[0059] Furthermore, the thickness of the object to be measured 70 is not particularly limited, but is generally preferably 0.001 μm to 5 mm. If the object to be measured 70 is thin and / or has low rigidity, the object to be measured 70 placed on the top surface of the conductive member 14 may bend and come into contact with the counter electrode 22 and / or the reference electrode 24. In this case, the object to be measured 70 may be laminated on another conductive member (preferably in a sheet form) as a support to form a composite, and then placed on the conductive member 14.

[0060] The object to be measured 70 may be placed on the conductive member 14, but a conductive adhesive layer or the like may be placed between the two to prevent misalignment when, for example, an electrolyte is injected into the well, and / or to ensure more reliable electrical contact between the conductive member 14 and the object to be measured 70.

[0061] The shape of the measurement object 70 is not particularly limited, and may be any shape such as a polygon having vertices, an ellipse, a circle, etc. Among these, a shape without vertices is preferred from the viewpoint that more uniform ion conduction is likely to be induced and more accurate measurement results are likely to be obtained.

[0062] The method of placing a sample to be measured on the working electrode using an electrode-equipped well plate as described in Patent Document 2 and measuring its electrochemical properties has rarely been practiced in the past. The present inventor, without being bound by the above-mentioned common technical knowledge, attempted to perform electrochemical measurements by placing a sample to be measured on the working electrode of the electrode-equipped well plate described in Patent Document 2. However, when attempting to place the sample to be measured on the working electrode, the location where the sample is placed may shift from the intended location, resulting in contact with the counter electrode or reference electrode.

[0063] This leads to a decrease in handling ability when an experiment is carried out manually, and also leads to a decrease in the operational margin when placing an object to be measured when automation is taken into consideration. Furthermore, when measurements are made using a well plate that does not have the conductive member 14, the size of the measurement object 70 is limited to a size that does not come into contact with the counter electrode 22 and the reference electrode 24 (substantially the same size as the working electrode 20), and it cannot be made any larger. The more wells a well plate has (the more samples are measured), the smaller the wells become, and therefore the measurement object must be made smaller.

[0064] On the other hand, the present inventors have confirmed that, as in the Reference Example described below, a single-cell plate provides sufficient space for placing the measurement targets and allows measurement, but in this case, unlike with a well plate, it is not possible to perform electrochemical measurements on a large number of measurement targets at once.

[0065] The well plate 10 solves all of the above problems. One of its features is that a conductive member 14 is placed on the working electrode 20, so that the working electrode 20 is three-dimensionally (in the height direction of the well) spaced apart from the counter electrode 22 and the reference electrode 24. Therefore, when the measurement object 70 is placed on the top surface of the conductive member 14, there is no risk of short-circuiting with the counter electrode 22 and the reference electrode 24, and as a secondary effect, the area of ​​the measurement object 70 can be increased. Increasing the area of ​​the measurement object 70 is advantageous when subjecting the measurement object to other evaluation tests after electrochemical measurement. A gap is provided between the measurement object 70 and the inner wall surface 71 of the tube 13 to allow the electrolyte to flow.

[0066] Next, in step S11, electrochemical measurement is performed on the well plate 10 on which the measurement object 70 is placed under predetermined conditions. The predetermined conditions refer to the conditions of the electrochemical reaction of the electrodes (electrode potential), the measurement format, the type of electrolyte, etc. These conditions are input 62 to the measurement unit 60.

[0067] The measurement format of the electrochemical measurement is not particularly limited, and examples thereof include cyclic voltammetry, chronoamperometry, chronopotentiometry, linear sweep voltammetry, differential pulse voltammetry, and impedance measurement, and may be appropriately selected depending on the purpose.

[0068] The electrochemical measurement is typically performed after injecting an electrolyte into the well so that the electrode set 15 and the object to be measured 70 in the well come into contact with the electrolyte. The method may further include a step of analyzing the obtained electrochemical response, if necessary.

[0069] The above electrochemical measurement method uses the well plate 10, which makes it easy to set the measurement object 70 and provides excellent handling. Also, the surface area of ​​the measurement object 70 can be made larger than before.

[0070] (Other forms of conductive members) Next, we will explain modified examples of the conductive member 14 in the well plate 10. In the well plate 10, the conductive member 14 is cylindrical, but the shape of the conductive member is not limited to the above as long as it is columnar. The conductive member may have a shape such as a cylinder or a rectangular pillar, a truncated cone or a truncated pyramid, or a combination of these shapes.

[0071] FIG. 10 is a schematic diagram of another embodiment of the conductive member. The conductive member 80 in Fig. 10(A) is a truncated cone (frustum cone) with a top surface 80b larger than a bottom surface 80a and tapered side surfaces 80c. The conductive member 81 in Fig. 10(B) is a modified example of the above, and is similar in that the top surface 81b is larger than the bottom surface 81a, but differs in that the side surfaces 81c are curved. The conductive member 82 of FIG. 10(C) has a T-shape in side view, with a cylinder 82a and a cylinder 82b stacked on top of each other on a substantially coaxial line.

[0072] 10(A) to 10(C) have a larger top surface area than the bottom surface, so even if the bottom surface area is approximately the same as the working electrode, the top surface area on which the object to be measured is placed can be made larger. Therefore, even if the object to be measured has low rigidity, the object to be measured is more prevented from bending and coming into contact with the counter electrode 22 and the reference electrode 24. In other words, even if the object to be measured has low rigidity, electrochemical measurement can be more easily performed without the object being complexed with a support.

[0073] 10(D) and 10(E) are modified examples of the conductive member of FIG. 10(C). Similar to conductive member 82, conductive member 83 has a shape in which a cylinder 83a and a cylinder 83b are stacked approximately coaxially. Furthermore, a groove 83c is formed on the top surface of conductive member 83 along the circumferential direction of the circular top surface.

[0074] The conductive member 83 is particularly useful when a composition that is a precursor of the object to be measured is applied to the top surface of the conductive member 83 and formed into a sheet to obtain the object to be measured. Conductive member 83 has groove 83c on the top surface, which can prevent the composition from leaking (overflowing) from conductive member 83. This is because groove 83c functions as a buffer to store excess composition. Groove 83c is an example of a fluid leakage prevention mechanism. Although groove 83c is formed along the entire circumferential direction of the top surface, the form of the fluid leakage prevention mechanism that is a groove is not limited to the above. The number and shape of the groove can be changed as appropriate depending on the properties of the composition that is the precursor of the object to be measured.

[0075] FIG. 10(E) shows another form of conductive member having a fluid leakage prevention mechanism. Similar to conductive member 82, conductive member 84 has a shape in which cylinders 84a and 84b are stacked approximately coaxially. Furthermore, a frame 84c is disposed on the peripheral edge of the top surface of conductive member 84. Frame 84c makes it more difficult for the applied composition to leak out of conductive member 84. The height of the frame can be changed as appropriate depending on the properties of the composition, which is the precursor of the object to be measured.

[0076] [Well plate manufacturing method] The well plate of the present invention can typically be produced by patterning electrodes at predetermined positions on a lower substrate on which lead wiring to the back surface and the like have been previously formed, placing a conductive member on the working electrode, and then bonding the upper substrate to it. Alternatively, a method can be applied in which the lower substrate on which the electrodes have been formed and the upper substrate are bonded together, and then a conductive member is placed in each cell.

[0077] The electrode can be patterned by vapor deposition, sputtering, photolithography, printing, etc. Among these, the printing method is preferred because it is more efficient and allows for inexpensive production.

[0078] The printing of the electrodes can be carried out by a known method, and the type is not particularly limited, and screen printing, inkjet printing, gravure printing, a knife coater, a bar coater, a blade coater, a spray, a dip coater, a spin coater, a roll coater, a die coater, a curtain coater, and the like can be used.

[0079] The electrode-forming composition used for printing can be, for example, a composition containing conductive particles, a binder, and a solvent for forming each electrode. The conductive particles may be selected according to the function of each electrode. For the working electrode and counter electrode, carbon and / or precious metal powder can be used, and for the reference electrode, silver chloride particles can be used.

[0080] From the viewpoint of more efficient well plate production, the method for producing a well plate of the present invention preferably includes applying an electrode-forming composition onto a substrate to form at least two mutually spaced composition layers, placing a conductive member in direct contact with one of the composition layers but not in contact with the other composition layers, and hardening the composition layer to form an electrode and fix the conductive member to the electrode.

[0081] FIG. 11 is a flow chart of the above manufacturing method. In step S50, an electrode-forming composition is applied to the lower substrate 12 to form at least two spaced-apart composition layers. The composition layers formed at this time preferably include a composition layer that will become the working electrode 20 after curing. The composition layers are spaced apart from one another to form separate electrodes, and a number of sets of composition layers that will form an electrode set after curing are formed on the substrate, the number of which corresponds to the number of wells.

[0082] The electrode-forming composition is not particularly limited, but when producing a well plate having a working electrode 20, a counter electrode 22, and a reference electrode 24 at the bottom of each well, the composition for forming the reference electrode 24 may contain different conductive particles than the composition for forming the working electrode 20 and / or the counter electrode 22. For example, the electrode-forming composition for forming the working electrode 20 and the counter electrode 22 may contain carbon particles, and the electrode-forming composition for forming the reference electrode 24 may contain silver chloride particles.

[0083] In this case, it is preferable that the manufacturing method further includes, before step S50, a step of forming a reference electrode 24 on the lower substrate 12. More specifically, the step of forming the reference electrode 24 includes the steps of applying a composition for forming a reference electrode on the lower substrate 12 to form a composition layer for forming a reference electrode, and curing the composition layer for forming a reference electrode to form the reference electrode 24.

[0084] According to the present manufacturing method including the above steps, the reference electrode 24 is formed first, and therefore there is no need to further form an electrode (form the reference electrode 24) after placing the conductive member 14 in the subsequent step. Compared to forming the reference electrode 24 after placing the conductive member 14 on the working electrode 20, forming the reference electrode 24 before placing the conductive member 14 is easier to apply printing methods and is more efficient.

[0085] Next, in step S51, the conductive member 14 is placed so as to be in contact with one of the composition layers (typically the composition layer for forming the working electrode) but not in contact with the other composition layer (typically the composition layer for forming the counter electrode). By placing the conductive member 14 on the composition layer for forming the working electrode, after the composition layer is hardened to form the electrode, the conductive member 14 prevents the electrodes from shorting out. Moreover, "direct contact" means that the electrode-forming composition and the conductive member 14 are in contact with each other without any other layer interposed therebetween.

[0086] Next, in step S52, the composition layer is hardened to form an electrode, and the conductive member 14 that was placed so as to be in direct contact with the composition layer is fixed onto the electrode formed by the electrode-forming composition layer.

[0087] Methods for curing the composition layer include methods of removing the solvent by heating, and methods of reactively curing the binder by heating, and may be selected as appropriate depending on the type and components of the electrode-forming composition used.

[0088] In the manufacturing method of the present invention, the conductive member 14 is placed before the electrode-forming composition layer is cured, and therefore the conductive member 14 is also fixed by the curing of the electrode-forming composition layer. Therefore, there is no need to use an additional binder or adhesive to fix the conductive member 14, and this method is highly efficient.

[0089] In step S53, the lower substrate 12 and the upper substrate 16 are bonded together. There are no particular limitations on the method for bonding the lower substrate 12 and the upper substrate 16, but examples include a method of bonding them together using an insulating adhesive.

[0090] [Electrochemical measurement method] The electrochemical measurement method of the present invention includes the steps of: performing a preliminary measurement under conditions similar to those of the measurement (main measurement) to be performed after placing the object to be measured on a conductive member of a multi-well plate; determining whether or not there is an electrochemical response due to deterioration of the conductive member based on predetermined criteria from the results of the preliminary measurement; placing the object to be measured on the conductive member of the multi-well plate if there is no electrochemical response due to the deterioration; and performing electrochemical measurement on the well plate on which the object to be measured is placed, according to predetermined conditions.

[0091] FIG. 12 is a flow diagram of the electrochemical measurement. Step S20 is a step in which a preliminary measurement is performed under the same conditions as those of the main measurement before the measurement object is placed on the conductive member of the multiwell plate (without the measurement object being placed thereon).

[0092] The preliminary measurement is a test to confirm whether the conductive material will deteriorate under the measurement conditions of the main measurement, which is a combination of the conditions of the electrode's electrochemical reaction (potential, current, etc.), the measurement method, and the electrolyte used in the measurement. The present inventors have found that the conductive member may be dissolved or otherwise deteriorated depending on the conditions of this measurement.

[0093] Generally, the materials of electrodes used in electrochemical measurements are stable under various conditions (e.g., noble metals and glassy carbon), but such materials are generally expensive.

[0094] The conductive members of the multiwell plate of the present invention are columnar, and therefore generally require more material for manufacturing than thin-film electrodes. While the well plate exhibits excellent stability under various conditions when the conductive members are made of a precious metal or the like, the cost of the material tends to significantly affect the overall cost of the well plate. From this perspective, it is preferable to use a less expensive material for the conductive members.

[0095] In other words, as for the conductive member, which tends to require more material for manufacturing than the electrodes, it is preferable in one embodiment to use a cheaper material (generally with a higher ionization tendency) different from the material of the electrodes.

[0096] The preliminary measurement step is more effective when the material of the conductive member is different from that of the electrode, particularly when the material is less stable. In other words, by performing the preliminary measurement under the same conditions as the main measurement except that no measurement object is placed on the conductive member, the main measurement can be performed after confirming that the conductive member will not deteriorate during the main measurement, thereby obtaining more accurate measurement results.

[0097] Step S21 is a step of determining whether or not an electrochemical response resulting from the deterioration of the conductive member occurs based on a predetermined criterion in the results of the preliminary measurement. Typical forms of deterioration of the conductive member include dissolution of the conductive member. Since such deterioration of the conductive member can be observed as a specific electrochemical response, it is possible to determine whether or not an electrochemical response resulting from the deterioration of the conductive member occurs based on a predetermined criterion.

[0098] An example of a specific criterion set for determining whether or not there is an electrochemical response resulting from deterioration of the conductive member will be described below. FIG. 13 shows the electrochemical response when aluminum foil was used as the working electrode and the experimental conditions were linear sweep voltammetry.

[0099] The experimental conditions are explained in detail below. First, two types of aqueous solutions were used as electrolytes: (1) 1 M LiCl / H2O and (2) 21 M LiTFSA / H2O.

[0100] The experiment was carried out at room temperature using a three-electrode beaker cell with a Pt mesh counter electrode and an Ag / AgCl reference electrode. The surface area of ​​the aluminum foil immersed in the electrolyte was approximately 2 cm2 in both experiments. 2 It was made to be like this.

[0101] Linear sweep voltammetry was performed from each open circuit potential (near -1.0 V vs. Ag / AgCl) to a higher potential at a scan rate of 5 mV / s.

[0102] As shown in Figure 13, in 1 M LiCl / H2O, a large current of several mA was observed from around -0.5 V vs. Ag / AgCl. This is an increase in the current value associated with the dissolution of the aluminum foil.

[0103] On the other hand, in 21 M LiTFSA / HO, no increase in the current value was observed even when the potential was swept to a level higher than 1.0 V vs. Ag / AgCl, suggesting that the aluminum surface was passivated in 21 M LiTFSA / HO, suppressing dissolution.

[0104] As described above, if the change in the measured value (increase in the current value) due to dissolution is used as a criterion (index) for the deterioration of the conductive member, the deterioration of the conductive member can be determined.

[0105] Returning to FIG. 12, if the result of the above determination is that there is no electrochemical response due to deterioration of the conductive member (step S22: NO), the object to be measured is placed on the conductive member (step S10), and electrochemical measurement is performed on the well plate on which the object to be measured is placed (step S11). Note that steps S10 and S11 have already been explained with reference to FIG. 8, and therefore will not be explained here.

[0106] Furthermore, the present electrochemical measurement method may further include, before step S10, a step of discarding the electrolyte used in the preliminary measurement from each well of the well plate 10 and / or a step of washing each well. The method may further include a step of using the result of the preliminary measurement as a background measurement result, and analyzing the measurement result in the corresponding well during the main measurement, taking the background measurement result into consideration. Specifically, taking the background measurement result into consideration includes removing the result of the preliminary measurement as noise from the main measurement result.

[0107] If the result of the preliminary measurement (step S21) indicates that there is an electrochemical response due to deterioration of the conductive member (step S22: YES), the well plate is discarded and the measurement ends.

[0108] According to the electrochemical measurement method, more accurate measurement results can be obtained by performing a preliminary measurement. In particular, when the working electrode and the conductive member are made of different materials, the electrochemical measurement method including the preliminary measurement is particularly useful.

[0109] [Measuring equipment] The measuring device of the present invention comprises a reader device including a connector for electrically connecting to the electrodes of a multiwell plate and an electrochemical measuring device that controls the electrochemical reaction of the electrodes via the connector, and a control device, and the control device has a preliminary measurement analysis unit that determines, based on predetermined criteria, the presence or absence of an electrochemical response due to deterioration of the conductive member from the results of a preliminary measurement conducted under conditions similar to the specified conditions for electrochemical measurement of the object to be measured before the object to be measured is placed so as to be in electrical contact with the conductive member of the multiwell plate.

[0110] 14 is a diagram showing the hardware configuration of the measurement device 90. The measurement device 90 includes a reader device 40 and a control device 51. The hardware configuration of the measurement device 90 is similar to that of the measurement device 50 already described, and therefore the following description will be omitted.

[0111] 15 is a functional block diagram of the measurement device 90. The measurement device 90 includes a reader device 40 and a control device 51, and also includes a connector 46, an electrochemical measurement device 48, a measurement unit 60, an analysis unit 61, and a preliminary measurement analysis unit 91.

[0112] The preliminary measurement analysis unit 91 is a function realized by the processor 52 of the control device 51 executing a program stored in the storage device 53. The preliminary measurement analysis unit 91 is a function that determines, based on predetermined criteria, the presence or absence of an electrochemical response resulting from deterioration of the conductive member, from the results of a preliminary measurement that is performed under conditions similar to the predetermined conditions for electrochemical measurement of the object to be measured, before the object to be measured is placed on the conductive member so as to be in electrical contact with the conductive member.

[0113] FIG. 16 is a flow chart showing the operation of the control device of the measuring device. In step S30, the control device 51 (the processor 52 thereof) controls the measurement unit 60 to perform a preliminary measurement without placing the measurement object on the conductive member.

[0114] As already explained, except that the preliminary measurement does not involve placing an object to be measured, the conditions of the electrochemical reaction of the electrodes (potential, current, etc.), the measurement method, the electrolyte used, etc. are preferably the same as those of the main test. However, for example, in a potential sweep test, if the conductive member is dissolved or deteriorated before the entire range of specified conditions is performed, the conditions of the preliminary test and the main test do not necessarily have to be the same.

[0115] Next, in step S31, the preliminary measurement analysis unit 91 is controlled to determine the presence or absence of an electrochemical response resulting from deterioration of the conductive member based on a predetermined criterion from the results of the preliminary measurement.

[0116] In this step, a preliminary measurement is performed to determine whether or not there is an electrochemical response due to deterioration of the conductive member, but the criteria for this determination are as described in the explanation of the electrochemical measurement method of the present invention, and therefore will not be explained here.

[0117] If the result of the above determination is that there is no electrochemical response due to deterioration of the conductive member (step S32: NO), a notification is made that the measurement object can be placed on the conductive member (step S33). The notification may be made by displaying the notification on the display device 54 or by outputting the notification to a device (client) outside the measuring apparatus 90 via the communication device 56. The information to be notified is not particularly limited, but may be the result of the preliminary measurement itself or the result of the determination. On the other hand, if there is an electrochemical response resulting from deterioration of the conductive member (step S32: YES), the measurement ends.

[0118] Next, in step S34, the measurement unit 60 is controlled to perform the main measurement on the well plate in which the measurement object is placed on the conductive member. At this time, it is preferable that an electrolyte solution is injected into each well according to predetermined conditions. The conditions for the main measurement are the same as those for the preliminary measurement. These conditions may be information from an external input 62 received by the measurement unit 60 and stored in the storage device 53.

[0119] Next, in step S35, the results of this measurement are analyzed and notified by analysis unit 61. The notification method may be a display on display device 54 or an output to a device external to measurement apparatus 90 via communication device 56.

[0120] Since the measuring device 90 has a preliminary measurement analysis unit 91, the actual measurement can be carried out after confirming that the conductive material has not deteriorated under specified conditions, thereby obtaining more accurate measurement results.

[0121] [Automatic measurement system] The automatic measurement system of the present invention comprises a sample preparation device that prepares the object to be measured and places it on a conductive member of a multiwell plate; a reader device that includes a connector for electrically connecting it to the electrodes of the multiwell plate and an electrochemical measurement device that controls the electrochemical reaction of the electrodes via the connector; a plate transport device that transports the multiwell plate between the sample preparation device and the reader device; and a control device.The control device has a preliminary measurement analysis unit that determines, based on predetermined criteria, the presence or absence of an electrochemical response due to deterioration of the conductive member from the results of a preliminary measurement conducted under conditions similar to the specified conditions for electrochemical measurement of the object to be measured before the object to be measured is placed on the conductive member so as to be in electrical contact with the conductive member.

[0122] FIG. 17 is a hardware configuration diagram of the above-mentioned automatic measurement system, and FIG. 18 is a functional block diagram. The automatic measurement system 100 comprises a sample preparation device 101, a plate transport device 102, a reader device 40, and a control device 51, and each device is configured to be able to exchange data with each other via a bus.

[0123] The sample preparation device 101 is an apparatus for preparing a measurement object (preferably in a sheet form) and placing the measurement object on a conductive member of a multiwell plate. The sample preparation device 101 includes an automated synthesizer 103 for synthesizing the measurement object and forming it into a predetermined shape as necessary, and a placement device 104 for placing the measurement object synthesized by the automated synthesizer 103 on the conductive member of the multiwell plate.

[0124] The automated synthesis device 103 and the mounting device 104 are both controlled by the control device 51, and typically synthesize the measurement object based on a recipe input or acquired by the input device 55 or the communication device 56.

[0125] Examples of the automated synthesis device 103 include the automated synthesis device described in Japanese Patent Application Laid-Open No. 2002-166160, the mixed liquid droplet formation device described in International Publication No. 2003-020418, the automated synthesis device described in Japanese Patent Application Laid-Open No. 2003-135977, the multiple simultaneous synthesis device described in Japanese Patent Application Laid-Open No. 11-236339, the rapid preparation device described in Japanese Patent Application Laid-Open No. 2003-230839, the synthesis reaction device described in Japanese Patent Application Laid-Open No. 11-137990, Examples of devices that can be used include the metal oxide thin film library manufacturing apparatus described in JP 2003-083855 A, the inorganic compound synthesis apparatus described in JP 2002-011343 A, the apparatus described in JP 2002-537544 A, the multi-component alloy film preparation apparatus described in JP 2020-504228 A, the continuous automatic casting system described in JP 2002-079367 A, and the apparatus described in JP 01-286255 A. These known devices can be selected appropriately depending on the purpose of measurement and / or the type of object.

[0126] The automated synthesizer 103 may not only synthesize the measurement target, but also inject an electrolyte into the wells, discard the used electrolyte, and clean the wells, etc. These operations can be performed by combining the above-mentioned known device with the mounting device 104 described below.

[0127] Furthermore, if the synthesized measurement object needs to be formed into a predetermined shape, a known processing device such as that described in JP 2020-009557 A can be incorporated into the automated synthesis device 103.

[0128] A known device such as an articulated robot system can be used as the mounting device 104. An example of such a device is that described in Japanese Patent Application Laid-Open No. 2015-167645. Note that the mounting device 104 may be configured as a functionally integrated unit with the plate transport device 102 described below.

[0129] If there is no electrochemical response due to deterioration of the conductive material by the preliminary measurement analysis unit 91, the sample preparation device 101 prepares the measurement object under the control of the control device 51, and sequentially places the measurement object on the conductive material of the well plate.

[0130] The plate transport device 102 is a device that transports well plates between the sample preparation device 101 and the reader device 40 under the control of the control device 51. Note that the plate transport device 102 may transport the well plate to another position as long as it transports the well plate between the sample preparation device 101 and the reader device 40.

[0131] Transporting between the sample preparation device 101 and the reader device 40 means, for example, transporting the well plate to a position (loading position) of the well plate suitable for placing the object to be measured on the conductive member, and to the tray 47 (measurement position) of the reader device 40, etc.

[0132] Furthermore, the plate transport device 102 may transport the well plate to a position other than the above. Examples of such positions include a stack position when the automated measurement system has a function for stacking unused well plates, and a disposal position when used well plates are to be discarded.

[0133] An example of a transport path of the plate transport device 102 will be described. First, the well plate is picked up by the plate transport device 102 at the stack position and transported to the placement position. After the electrolyte is poured into each well at the placement position, the well plate is transported by the plate transport device 102 to the measurement position. Next, after preliminary measurement is performed by the reader device 40, the well plate is transported to the mounting position by the plate transport device 102. Next, after the wells are cleaned as necessary at the placement position, the measurement object is placed on each conductive member, and an electrolyte is poured into each well. Thereafter, the well plate is transported again to the measurement position by the plate transport device 102. Furthermore, after the measurement is completed, the well plate is transported to a disposal position by the plate transport device 102.

[0134] Such a plate transport device 102 can be a known device, and devices described in Patent Publication No. 2020-153733, Patent Publication No. 2020-183885, Patent Publication No. 2021-519220, Patent Publication No. 2005-502479, Patent Publication No. 2000-040728, and Patent Publication No. 2010-169497, etc., can be appropriately incorporated.

[0135] The hardware configurations of the reader device 40 and the control device 51 included in the automatic measurement system 100 are the same as those of the measurement device 50 already described, and therefore will not be described again.

[0136] FIG. 19 is an operational flow diagram of the control device 51 (processor 52 thereof) of the automatic measurement system 100. First, in step S40, the control device 51 controls the plate transport device 102 to set the well plate in the reader device 40. That is, before the measurement object is placed on the conductive member so as to be in electrical contact with the plate, the plate transport device 102 transports the well plate to the measurement position of the reader device 40, and makes it ready for measurement.

[0137] Next, in step S41, the control device 51 controls the preliminary measurement and analysis unit 91 to cause the measurement unit 60 to perform a preliminary measurement without placing the measurement object thereon.

[0138] As already explained, the preliminary measurement is preferably performed in the same manner as the main test in terms of the conditions for the electrochemical reaction of the electrodes (potential, current, etc.), the measurement method, the electrolyte solution used, etc., except that no object to be measured is placed on the preliminary measurement. The above measurement conditions are input 62 to the measurement unit 60 from outside.

[0139] Next, in step S42, the preliminary measurement analysis unit 91 is controlled to determine the presence or absence of an electrochemical response resulting from deterioration of the conductive member based on a predetermined criterion from the results of the preliminary measurement.

[0140] The criteria for judgment in this step are as described in the description of the electrochemical measurement method of the present invention, and therefore a description thereof will be omitted here.

[0141] If the result of the above determination is that there is no electrochemical response due to deterioration of the conductive material (step S43: NO), the plate transport device 102 is controlled to return the well plate from the measurement position to the loading position, and the sample preparation device 101 is controlled to start preparation of the object to be measured (step S44).

[0142] At this time, the sample preparation device 101 may also discard the electrolyte used in the preliminary measurement and wash the wells at the same time.

[0143] In this flow, after it is confirmed that there is no electrochemical response due to deterioration of the conductive material, the sample preparation device 101 is controlled and preparation of the object to be measured is started, but the timing for starting preparation of the object to be measured in a measurement method using this automatic measurement system is not limited to the above. Preparation of the measurement object may be started without waiting for the determination result (for example, during the execution of the preliminary measurement).

[0144] In this case, after confirming that there is no electrochemical response due to deterioration of the conductive member, the control device 51 may control the plate transporting device 102 to transport the well plate from the measurement position to the loading position, and further control the sample preparation device 101 to discard the electrolyte used in the preliminary measurement and wash the wells.

[0145] On the other hand, if an electrochemical response resulting from deterioration of the conductive member is obtained (step S43: YES), the control device 51 ends the measurement.

[0146] Next, in step S45, the control device 51 controls the sample preparation device 101 to place the measurement object on the conductive member of the well plate. At this time, it is preferable that an electrolyte solution is also injected into each well. Next, in step S46, the control device 51 controls the plate transport device 102 to set the well plate, on which the measurement object is placed on the conductive member, at the measurement position of the reader device 40.

[0147] Next, in step S47, the measurement unit 60 is controlled to perform the main measurement on the well plate in which the measurement object is placed on the conductive member. The conditions for the main measurement are the same as the conditions for the preliminary measurement, and are typically information from the external input 62 received by the measurement unit 60 and stored in the storage device 53.

[0148] Next, in step S48, the results of this measurement are analyzed and notified by the analysis unit 61. The notification method may be a form in which the results are displayed on the display device 54, or a form in which the results are output to a device outside the automatic measurement system via the communication device 56, etc.

[0149] This automated measurement system includes a sample preparation device, a plate transport device, and a reader device, allowing for the automatic synthesis, shaping, placement, and measurement of the measurement object. Furthermore, because the control device includes a preliminary measurement and analysis unit, even when a well plate with a conductive material is used, the conductive material is less likely to deteriorate, making it easier to obtain more accurate measurement results. [Example]

[0150] The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0151] [Preparation of well plates with electrodes] A circuit pattern (a laminate of Ni / Au plating and Ag paste on a Cu circuit) corresponding to 96 (8 x 12) sets of three electrodes (WE, CE, RE) was formed on one side of a rigid substrate, and each electrode circuit was connected to a connection pad formed on the other side by an inner layer circuit and via holes.A substrate was then prepared, and each electrode was formed by screen printing.

[0152] The WE and CE were formed using the conductive carbon paste "JELCON CH-8" (one-component curing type) manufactured by Jujo Chemical Co., Ltd., and the RE was formed using "Silver-silver chloride ink for reference electrodes" (one-component curing type) manufactured by BAS Co., Ltd.

[0153] Specifically, the silver-silver chloride ink was applied 1 to 3 times at predetermined positions corresponding to the RE of the circuit pattern, with a film thickness of 15 to 40 μm per application, to form a silver-silver chloride ink layer. Next, the entire substrate was heated in an oven at 120°C for 5 minutes to dry and harden the silver-silver chloride ink layer, forming the RE.

[0154] Next, the carbon paste was applied to predetermined positions corresponding to WE and CE of the circuit pattern so that the film thickness was approximately the same as that of the silver-silver chloride ink layer, to form a carbon paste layer.

[0155] Next, an aluminum cylindrical member (φ=3 mm, approximately the same size as the WE) was placed on the carbon paste layer, which would become the WE after drying. Next, with the cylindrical member still in place, the entire structure, including the substrate, was heated in an oven at 120°C for 15 minutes to dry and harden the carbon paste layer, thereby forming the WE and CE and fixing the cylindrical member placed on the WE.

[0156] A base plate with 96 cylinders arranged in a two-dimensional matrix and coated with adhesive on the bottom was stacked on the bottom substrate formed as described above, and the adhesive was dried and hardened to produce a well plate with electrodes having 96 wells and electrode sets formed on the bottom of the wells.

[0157] [Reference example] LiMn2O4 powder, which is used as the positive electrode of Li-ion batteries, was prepared as follows: A solution of a predetermined amount of lithium nitrate, manganese nitrate hexahydrate, and citric acid was prepared in a beaker and heated on a hot plate.

[0158] The hotplate temperature was started at 400°C and then lowered to 200°C as the water evaporated. The mixture remaining in the beaker was then ignited by raising the temperature to 400°C again, synthesizing the LiMn2O4 precursor with gas evolution. The resulting powder was placed in an electric furnace and heat-treated at 600°C for 10 hours to obtain LiMn2O4 powder.

[0159] (Coating on Al foil) A slurry was prepared by dispersing a predetermined amount of LiMn2O4 powder, a conductive additive, and a binder in NMP (N-methyl-2-pyrrolidone), and the slurry was applied to an Al foil using a hand coater. The NMP was then evaporated by vacuum drying at 120°C for 12 hours to obtain a coated electrode.

[0160] (electrode punching) The resulting coated electrode was cut into a diameter of 5 mm using a trimming cutter.

[0161] (Attaching to printed electrodes) A conductive double-sided tape was attached to the working electrode of the single-cell printed electrode, and a φ5 mm coated electrode was placed on top of it to adhere it.

[0162] (Electrochemical measurements and results) FIG. 20 shows the results of a cyclic voltammetry test using a highly concentrated aqueous solution, 21 M LiTFSA / H 2 O (TFSA: bis(trifluoromethanesulfonyl)amide), as the electrolyte. The printed electrode used had a Pt counter electrode and an Ag / AgCl reference electrode, and measurements were performed at room temperature. The scan rate was 5 mV / s, and the potential was scanned in the range of 0.2 to 1.2 V vs. Ag / AgCl. The results were consistent with the typical profile of LiMn2O4. The oxidation current observed at high potentials above approximately 1.0 V vs. Ag / AgCl is thought to correspond to Li desorption from LiMn2O4, and the reduction current observed at potentials below approximately 1.0 V vs. Ag / AgCl is thought to correspond to Li ion insertion. These results demonstrate that printed electrodes can be used to evaluate battery materials. [Industrial Applicability]

[0163] The multiwell plate of the present invention enables rapid electrochemical measurement of a large amount of analyte. In one embodiment of the multiwell plate of the present invention, a conductive member is disposed on the working electrode, and the analyte is placed on the conductive member.

[0164] In other words, the counter electrode and reference electrode arranged at the bottom of the well are three-dimensionally spaced apart in the height direction of the well from the top surface of the conductive member (where the object to be measured is placed). This prevents the object to be measured from coming into contact with the counter electrode and / or the reference electrode, resulting in a short circuit. Furthermore, it is possible to increase the surface area (size) of the object to be measured, which is advantageous when subjecting the object to another measurement after electrochemical measurement.

[0165] The multiwell plate of the present invention enables rapid electrochemical measurements of many sheet-like measurement targets. Furthermore, by changing the measurement conditions (potential, current, measurement method, type of electrolyte, etc.) for each well, various measurements can be performed simultaneously on a single plate.

[0166] The multi-well plate of the present invention can be widely used for electrochemical measurements of solid, sheet-like objects, such as for evaluating materials used in batteries, such as electrode materials and catalysts, and for evaluating the corrosion process of metal materials. [Explanation of symbols]

[0167] 10: well plate, 11: skirt, 12: lower substrate, 13: tube, 14: conductive member, 15: electrode set, 16: upper substrate, 17: area, 20: working electrode, 21, 23, 25: wiring, 22: counter electrode, 24: reference electrode, 30, 32, 34: via hole, 31, 33, 35: connection pad, 40: reader device, 41, 43, 45: connection terminal, 42: main body, 44: cover, 46: connector, 47: tray, 48: electrochemical measurement device, 50, 90: measurement device, 51: control device, 52: processor, 53: Storage device, 54: display device, 55: input device, 56: communication device, 60: measurement unit, 61: analysis unit, 70: measurement object, 71: inner wall surface, 80, 81, 83, 84: conductive members, 80a, 81a: bottom surface, 80b, 81b: top surface, 80c, 81c: side surface, 82a, 82b, 83a, 83b, 84a, 84b: cylinder, 83c: groove, 84c: frame, 91: preliminary measurement analysis unit, 100: automatic measurement system, 101: sample preparation device, 102: plate transport device, 103: automatic synthesis device, 104: placement device

Claims

1. a plurality of upwardly opening wells; at least two electrodes disposed at the bottom of the well; a columnar conductive member disposed so as to be in electrical contact with one of the electrodes and not in contact with the other of the electrodes; the height of the conductive member is less than the depth of the well; an area occupied by the conductive member in a plan view of the well is smaller than a bottom area of ​​the well; the conductive member has a frustum shape, The frustum has a bottom surface and a top surface, and the area of ​​the top surface on the opening side is larger than that of the bottom surface on the bottom side.

2. a plurality of upwardly opening wells; At least two electrodes, including a working electrode, independently disposed at the bottom of the well; a columnar conductive member disposed so as to be in electrical contact with the working electrode but not in contact with the other electrodes; the height of the conductive member is less than the depth of the well; the conductive member is formed so that when an electrolyte solution is injected into the well, the side surface of the conductive member comes into contact with the electrolyte solution; A multi-well plate in which the area occupied by the conductive member in a planar view of the well is smaller than the bottom area of ​​the well, the conductive member has a shape in which multiple pillars are stacked approximately coaxially, and the area of ​​the top surface is larger than the area of ​​the bottom surface.

3. a plurality of upwardly opening wells; at least two electrodes disposed at the bottom of the well; a columnar conductive member disposed so as to be in electrical contact with one of the electrodes and not in contact with the other of the electrodes; the height of the conductive member is less than the depth of the well; an area occupied by the conductive member in a plan view of the well is smaller than a bottom area of ​​the well; A multi-well plate, wherein the conductive member has a fluid leakage prevention mechanism disposed on the top surface.

4. The multiwell plate according to any one of claims 1 to 3, wherein the electrodes and the conductive member are made of different materials.

5. The multi-well plate according to any one of claims 1 to 3, wherein the electrodes are three or more electrodes arranged at predetermined intervals from each other.

6. The multiwell plate according to any one of claims 1 to 3, wherein a measurement object is placed on the top surface of the conductive member.

7. 7. The multi-well plate of claim 6, wherein at least one of said electrodes is a reference electrode.

8. 8. The multi-well plate of claim 7, wherein the electrodes comprise a working electrode, a counter electrode, and a reference electrode, and the conductive member is disposed on the working electrode.

9. The multiwell plate according to any one of claims 1 to 3, wherein the electrodes and the conductive members are in direct contact with each other.

10. Placing a measurement object on the conductive member of the multiwell plate according to any one of claims 1 to 3 so as to be in electrical contact with the conductive member; and performing electrochemical measurement on the multiwell plate on which the object to be measured is placed under predetermined conditions.

11. A plurality of wells opening upward; at least two electrodes disposed at the bottom of the well; a columnar conductive member disposed so as to be in electrical contact with one of the electrodes and not in contact with the other of the electrodes; the height of the conductive member is less than the depth of the well; a multi-well plate in which the area occupied by the conductive member in a plan view of the well is smaller than the bottom area of ​​the well; placing a measurement object on the conductive member of the multiwell plate so as to be in electrical contact with the conductive member; performing electrochemical measurement on the multiwell plate on which the measurement object is placed under predetermined conditions; Before the placing, a preliminary measurement is performed under the same conditions as the predetermined conditions; and determining whether or not an electrochemical response resulting from deterioration of the conductive member occurs based on a predetermined criterion for the result of the preliminary measurement; An electrochemical measurement method, wherein the above-described step is carried out when there is no electrochemical response resulting from the deterioration.

12. A plurality of wells opening upward; at least two electrodes disposed at the bottom of the well; a columnar conductive member disposed so as to be in electrical contact with one of the electrodes and not in contact with the other of the electrodes; the height of the conductive member is less than the depth of the well; a reader device including a connector for electrically connecting to the electrodes of a multi-well plate, the area of ​​which, in a plan view of the wells, is smaller than the bottom area of ​​the wells, and an electrochemical measurement device for controlling the electrochemical reaction of the electrodes via the connector; a control device; The control device is a measuring device having a preliminary measurement analysis unit that determines, based on predetermined criteria, whether or not there is an electrochemical response due to deterioration of the conductive member from the results of a preliminary measurement conducted under conditions similar to the specified conditions for electrochemical measurement of the object to be measured before the object to be measured is placed on the conductive member so that it is in electrical contact with the conductive member.

13. A measurement object is prepared, a plurality of upwardly opening wells; at least two electrodes disposed at the bottom of the well; a columnar conductive member disposed so as to be in electrical contact with one of the electrodes and not in contact with the other of the electrodes; the height of the conductive member is less than the depth of the well; a sample preparation device in which the measurement object is placed on the conductive member of a multi-well plate, the conductive member having an area smaller than the bottom area of ​​the well in a plan view of the well; a reader device having a connector for electrically connecting to the electrodes of the multiwell plate and an electrochemical measurement device for controlling the electrochemical reaction of the electrodes via the connector; a plate transport device that transports the multiwell plate between the sample preparation device and the reader device; a control device; The control device is an automatic measurement system having a preliminary measurement analysis unit that determines, based on predetermined criteria, whether or not there is an electrochemical response due to deterioration of the conductive member from the results of a preliminary measurement conducted under conditions similar to the specified conditions for electrochemical measurement of the object to be measured before the object to be measured is placed on the conductive member so that it is in electrical contact with the conductive member.

14. A method for producing the multiwell plate according to any one of claims 1 to 3, comprising: applying an electrode-forming composition onto a substrate to form at least two spaced apart composition layers; placing the conductive member so as to be in direct contact with one of the composition layers and not in contact with the other of the composition layers; and curing the composition layer to form the electrode and fix the conductive member to the electrode.

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