Well plate and manufacturing method therefor

Abstract

A well plate and a manufacturing method therefor are provided according to an example of the present disclosure. In particular, the well plate may comprise: a main body having multiple wells; and a sensor array which is configured to be mountable on a lower portion of the main body and in which multiple unit sensors are disposed to correspond to the multiple wells, respectively.

Description

Well plate and method of manufacturing the same

[0001] The present disclosure relates to a well plate and a method for manufacturing the same.

[0002] Target substances, such as hormones, proteins, and pathogens, which enable the prediction of human disease symptoms and progression, as well as the condition of food, can be analyzed using immunoassays based on antigen-antibody reactions. Meanwhile, the analysis of target substances based on immunoassays has generally been performed in clinical laboratories equipped with specialized instruments. However, with the recent increase in the need for testing in medical settings such as hospitals and emergency rooms, as well as for self-diagnosis at home, there has been a continuous demand for the development of immunoassay platforms that do not require specialized knowledge or complex procedures and offer short analysis times.

[0003] As a solution to this problem, biosensors capable of rapid and accurate analysis of target substances through electrochemical analysis have emerged. More specifically, biosensor-based electrochemical analysis methods enable qualitative and quantitative analysis of target substances within an analysis sample by analyzing the current generated by oxidation-reduction reactions resulting from the contact between the electrode equipped within the biosensor and the analysis sample.

[0004] Metals with excellent electrical properties and stability against external environmental changes (e.g., gold, platinum, palladium, etc.) can be used as electrode materials for biosensors. Electrodes made of such materials can be fabricated into thin film electrodes through sputtering or electroplating methods that maintain material characteristics while offering cost competitiveness.

[0005] There is a continuous demand for the development of technologies that enable more accurate and rapid electrochemical analysis based on such biosensors.

[0006] The background art is provided to facilitate understanding of the present disclosure. It should not be understood as an acknowledgment that the matters described in the background art exist as prior art.

[0007] The biosensor is configured to be guided to multiple electrodes through a channel, and detects the target substance by generating an electrochemical signal through the reaction of the multiple electrodes with the target substance contained in the analytical sample. In this case, the multiple electrodes are spaced apart from each other, and the closer the distance between them, the more rapid and accurate the detection of the target substance can be.

[0008] However, while biosensors have traditionally been produced based on semiconductor technology, this approach has limitations due to high manufacturing costs and complex processes. Therefore, by enabling the low-cost manufacturing of biosensors through a gold foil printing process, the manufacturing process is simplified, making commercialization possible and enhancing both time and economic efficiency in production.

[0009] Meanwhile, multiple electrodes of the biosensor have a nano-gap / micro-gap structure, and by measuring the electrical signal obtained from the reaction that occurs as a fluid flows through the gap and transmitting it to an external device, the user can verify information about the target substance.

[0010] Generally, most biosensors are formed with a single sensor structure, which not only made it difficult to perform analysis when examining various samples simultaneously but also resulted in the problem of requiring a long time for analysis.

[0011] Accordingly, the inventors of the present disclosure have invented a well plate equipped with a sensor array comprising a plurality of biosensors and a method for manufacturing the same.

[0012] Accordingly, the problem to be solved by the present disclosure is to provide a well plate and a method for manufacturing the same that can improve time and economic efficiency by shortening the time required for analysis by using a well plate equipped with a sensor array comprising a plurality of unit sensors (biosensors) in the lower part of a main body equipped with a plurality of wells, thereby enabling the simultaneous inspection of various analysis samples.

[0013] The problems that this disclosure aims to solve are not limited to those mentioned above, and other unmentioned problems will be clearly understood by a person skilled in the art from the description below.

[0014] To solve the problem described above, a well plate equipped with a sensor according to an example of the present disclosure is provided. The well plate may include a main body having a plurality of wells; and a sensor array configured to be mountable on the lower part of the main body, wherein a plurality of unit sensors are arranged to correspond to each of the plurality of wells.

[0015] According to the features of the present disclosure, each of the plurality of wells forms a receiving space having a certain width and depth to accommodate an analysis sample, and an opening may be formed in a part of the bottom surface of the receiving space to allow the analysis sample accommodated in the receiving space to flow in.

[0016] According to the features of the present disclosure, the opening may be formed in a shape that surrounds the plurality of electrodes so as to expose the sensors provided in the plurality of unit sensors and allow an analysis sample contained in the receiving space to come into contact with the plurality of electrodes formed in the sensors.

[0017] According to the features of the present disclosure, each of the plurality of unit sensors may include a substrate; and a sensor attached to one surface of the substrate by a conductive adhesive member and reacting with an analysis sample contained in a corresponding well.

[0018] According to the features of the present disclosure, the substrate may have a through hole formed therein to expose a plurality of electrodes formed in the sensor.

[0019] According to the features of the present disclosure, the sensor comprises a plurality of electrodes provided on one surface of the substrate and reacting with the analysis sample to generate an electrochemical signal, and each of the plurality of electrodes may be formed spaced apart by a predetermined distance.

[0020] According to the features of the present disclosure, the plurality of electrodes may include: a first electrode composed of a plurality of pillars and oxidizing with the target substance; a second electrode that is spaced at least a certain distance from the first electrode, forms a counter electrode with the first electrode, and oxidizes with the target substance; and a third electrode that maintains a constant operating voltage between the first electrode and the second electrode.

[0021] To solve the problem described above, a method for manufacturing a well plate equipped with a sensor according to an example of the present disclosure is provided. The manufacturing method may include the steps of: providing a main body having a plurality of wells; providing a sensor array in which a plurality of unit sensors are arranged to correspond to each of the plurality of wells; and mounting the sensor array on the lower part of the main body such that the plurality of unit sensors are each positioned in an opening formed on the bottom surface of each of the plurality of wells.

[0022] According to the features of the present disclosure, the step of providing the sensor array may include the step of stacking a substrate, a conductive adhesive member, and a sensor in that order to form each of the plurality of unit sensors.

[0023] According to the features of the present disclosure, the step of mounting the sensor array on the lower part of the main body may include the step of arranging each sensor of the plurality of unit sensors so as to be exposed through an opening formed on the bottom surface of each of the plurality of wells.

[0024] Specific details of other embodiments are included in the detailed description and drawings.

[0025] According to one example of the present disclosure, various analysis samples can be examined at once using a well plate equipped with a sensor array comprising a plurality of unit sensors (biosensors) in the lower part of a main body having a plurality of wells, thereby shortening the time required for analysis and improving time and economic efficiency.

[0026] The effects of the present disclosure are not limited to those mentioned above, and other unmentioned effects will be clearly understood by a person skilled in the art from the description below.

[0027] FIG. 1 is a schematic diagram showing a well plate according to one embodiment of the present disclosure.

[0028] FIG. 2 is a schematic diagram showing a sensor array provided in a well plate according to one embodiment of the present disclosure.

[0029] FIG. 3 is a schematic diagram showing a unit sensor constituting a sensor array according to one embodiment of the present disclosure.

[0030] FIG. 4 is a perspective view showing a disassembled unit sensor constituting a sensor array according to one embodiment of the present disclosure.

[0031] FIG. 5 is a schematic diagram showing a sensor embedded in a unit sensor according to one embodiment of the present disclosure.

[0032] FIG. 6 is a diagram exemplarily showing the structure of a first electrode of a unit sensor according to one embodiment of the present disclosure.

[0033] FIG. 7 is a diagram illustrating, exemplarily, the structure of a pillar formed on a first electrode of a unit sensor according to one embodiment of the present disclosure.

[0034] FIG. 8 is a flowchart schematically illustrating a method for manufacturing a well plate according to one embodiment of the present disclosure.

[0035] FIG. 9 is a schematic diagram showing a single sensor according to another embodiment of the present disclosure.

[0036] FIGS. 10 and FIGS. 11 are drawings illustrating an example in which a single sensor according to another embodiment of the present disclosure is coupled to a measuring device.

[0037] The advantages and features of the present disclosure and the methods for achieving them will become clear by referring to the embodiments described below in detail together with the accompanying drawings. However, the present disclosure is not limited to the embodiments disclosed below but may be implemented in various different forms. These embodiments are provided merely to ensure that the disclosure is complete and to fully inform those skilled in the art of the scope of the invention, and the present disclosure is defined only by the scope of the claims. In connection with the description of the drawings, similar reference numerals may be used for similar components.

[0038] In this document, expressions such as "have," "can have," "include," or "can include" refer to the existence of the relevant feature (e.g., numerical values, functions, actions, or components, etc.) and do not exclude the existence of additional features.

[0039] In this document, expressions such as “A or B,” “at least one of A or / and B,” or “one or more of A or / and B” may include all possible combinations of items listed together. For example, “A or B,” “at least one of A and B,” or “at least one of A or B” may refer to cases including (1) at least one A, (2) at least one B, or (3) both at least one A and at least one B.

[0040] Expressions such as "first," "second," "first," or "second" used in this document may modify various components regardless of order and / or importance, and are used merely to distinguish one component from another without limiting such components. For example, the first user device and the second user device may represent different user devices regardless of order or importance. For example, without departing from the scope of rights set forth in this document, the first component may be named the second component, and similarly, the second component may be renamed the first component.

[0041] Where it is stated that a certain component (e.g., a first component) is "(operatively or communicatively) coupled with" or "connected to" another component (e.g., a second component), it should be understood that the said certain component may be directly connected to the said other component or connected through another component (e.g., a third component). On the other hand, where it is stated that a certain component (e.g., a first component) is "directly connected" or "directly connected" to another component (e.g., a second component), it may be understood that no other component (e.g., a third component) exists between the said certain component and the said other component.

[0042] As used in this document, the expression “configured to” may be replaced, depending on the context, with, for example, “suitable for,” “having the capacity to,” “designed to,” “adapted to,” “made to,” or “capable of.” The term “configured to” does not necessarily mean “specifically designed to” in hardware. Instead, in some situations, the expression “device configured to” may mean that the device is “capable of” in conjunction with other devices or components. For example, the phrase “processor configured to perform A, B, and C” may mean a dedicated processor for performing those operations (e.g., an embedded processor) or a generic-purpose processor (e.g., a CPU or application processor) capable of performing those operations by executing one or more software programs stored in a memory device.

[0043] The terms used in this document are used merely to describe specific embodiments and are not intended to limit the scope of other embodiments. Singular expressions may include plural expressions unless the context clearly indicates otherwise. Terms used herein, including technical or scientific terms, may have the same meaning as generally understood by those skilled in the art described in this document. Terms used in this document that are defined in general dictionaries may be interpreted as having the same or similar meaning as they have in the context of the relevant technology, and are not to be interpreted in an ideal or overly formal sense unless explicitly defined in this document. In some cases, even terms defined in this document may not be interpreted to exclude the embodiments of this document.

[0044] The features of each of the various embodiments of the present disclosure may be combined or combined with one another, either partially or wholly, and as will be fully understood by those skilled in the art, various technical interlocking and operation are possible, and each embodiment may be implemented independently of one another or together in an interlocking relationship.

[0045] For clarity in the interpretation of this specification, the terms used in this specification are defined below.

[0046] As used in this specification, the term "biosensor" may be an electrochemical biosensor capable of qualitative and quantitative analysis of a target substance by measuring the potential resulting from an oxidation-reduction reaction between the target substance and an electrode disposed on the biosensor.

[0047] As used herein, the term “analytical sample” may be a solution containing an electrolyte in a fluid. For example, it may be urine, cell lysate, whole blood, plasma, serum, saliva, ocular fluid, cerebrospinal fluid, sweat, milk, ascites fluid, synovial fluid, and peritoneal fluid. Preferably, the analytical sample may be tears or a tear film, but is not limited thereto. Furthermore, “analytical sample” may be defined as synonymous with the “fluid to be measured” of the electrical conductivity sensor of the present disclosure. Accordingly, the electrical conductivity measured in the present disclosure may represent the concentration of an electrolyte in the fluid to be measured.

[0048] As used in this specification, the term "substrate" may mean a plate that supports the entire structure as a lower support layer of the sensor. The substrate disclosed in this specification may be a flexible substrate.

[0049] For example, the substrate may be at least one of polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polyimide (PI), polystyrene (PS), polyethylene naphthalate (PEN), and polycarbonate (PC).

[0050] However, the material of the substrate is not limited to this and can be composed of various materials capable of supporting the entire biosensor.

[0051] At this time, the electrodes may be formed on a support plate by screen printing, inkjet, and photolithography techniques. However, if necessary, the electrodes may be placed in various ways on a portion of the surface of the support plate or substrate.

[0052] Unless otherwise specifically stated in this specification, the electrode pattern is typically formed on a support plate, and the substrate functions as a support configuration for aligning the lower support layer and opening of the sensor.

[0053] As used in this specification, the term "electrode" means a conductive electrode having electrical conductivity.

[0054] At this time, the electrode disclosed in this specification may include an electrode pattern formed by printing a conductive material on a support plate (or a part of the surface of a substrate) in various ways.

[0055] For example, the electrode may be a conductive electrode formed by printing at least one organic material selected from carbon black, carbon graphite, graphene, fullerene, and carbides onto a support plate. Additionally, the electrode may be a conductive electrode formed by printing at least one metal selected from Au, Ni, Cu, Zn, Fe, Al, Ti, Pt, Hg, Ag, Pb, and alloys thereof onto a support plate (or a portion of the surface of a substrate).

[0056] As used herein, the term “support plate” may refer to a supporting substrate on which electrodes for measuring the electrical conductivity of an analysis sample are formed. For example, the support plate may be a metal plate (e.g., copper, gold, platinum, etc.) or a material suitable for depositing or printing a conductive material.

[0057] However, the material of the support plate is not limited to this, and can be made of various materials in which electrodes generating a potential difference according to changes in the level of the target substance in the analysis sample can be placed.

[0058] The electrodes are generally formed on a support plate, and in other embodiments, they may be formed on a substrate.

[0059] As used herein, the term "first electrode" may refer to a working electrode for measuring the electrical conductivity of an analytical sample. Furthermore, it may refer to a working electrode for qualitatively and / or quantitatively sensing (detecting) a specific target substance of an analytical sample.

[0060] In this case, the first electrode may be an electrode containing an ion-selective ionophore whose potential changes depending on the ion level, or an electrode composed of a sensitive material sensitive to lactic acid, glucose, heavy metals, or pH. Accordingly, the first electrode may refer to an area formed on a support plate for sensing a target substance within the analytical sample.

[0061] For example, the first electrode may be made of a sensitive material to react with an analysis sample. Alternatively, the first electrode may be formed by coating the sensitive material on the electrode or by printing the sensitive material on a support plate. In this case, the sensitive material may exist in a partial area, such as one end of the electrode, but is not limited thereto. Furthermore, the first electrode may be electrically connected to wiring.

[0062] Meanwhile, the sensitive material layer can be immobilized on a conductive layer disposed on a support plate by means of adsorption, entrapment, covalent bonding, or ionic bonding.

[0063] As used in this specification, the term "second electrode" may refer to a counter electrode that provides a current return path opposite to the first electrode on the biosensor. For example, if oxidation occurs at the first electrode due to a reaction with a target substance, reduction may occur at the second electrode.

[0064] In this case, the second electrode may refer to a pattern formed by printing a conductive material on a support plate. Accordingly, the second electrode may refer to a current return region formed on the support plate.

[0065] This second electrode can be formed from conductive materials such as graphene, carbon-based ink, gold (Au), or platinum (Pt). If necessary, a structure (nanopilla) in which a conductive layer is deposited on a pillar-shaped polymer structure can be added to the surface of the second electrode to expand the reaction surface area and improve the stability of current transmission.

[0066] According to the features of the present disclosure, a pillar having a conductive layer deposited thereon may be disposed on the second electrode.

[0067] As used in this specification, the term "third electrode" may refer to a reference electrode composed of a half-cell reactive material that has a stable potential even in contact with a target material and high reproducibility.

[0068] In this case, the third electrode may refer to a pattern formed by printing a conductive material, preferably a half-cell reactive material, on a support plate. Accordingly, the third electrode may refer to an area formed on the support plate.

[0069] Meanwhile, as the potential of the third electrode may be predetermined, it can be used as a reference electrode to serve as a reference when measuring the electromotive force or electrode potential of the analysis sample through the first electrode.

[0070] Meanwhile, it is preferable that this third electrode be formed by a half-cell reaction layer (e.g., Ag / AgCl, etc.). If necessary, conductive wiring or pads for electrical connection to the reference electrode may be formed on the support plate, but it is preferable that the exposed surface of the reference electrode be maintained by the half-cell reaction layer. In this case, the conductive wiring / pads may be formed at the outer edge (e.g., one end) of the exposed area of ​​the reference electrode.

[0071] Accordingly, the third electrode provides a stable reference potential based on the half-cell potential in accordance with the electrical conductivity of the analysis sample of the first electrode, and does not substantially participate in the electrochemical reaction. As a result, the potential of the first electrode can be stably referenced and measured.

[0072] Meanwhile, the "conductive material" placed on the third electrode may be a reversible oxidation or reduction material, and may be a stable material with low reactivity to changes in temperature or ion concentration and a constant potential difference. Such a conductive material may have high reproducibility (or stability) in terms of potential, be stable in acidic or salt solutions, and be easy to handle.

[0073] For example, conductive materials include not only conductive graphene but also Ag / AgCl, Ag, Hg2SO4, and Ag / Ag + The potential difference between the saturated calomel half-cell (SCE) and the salt bridge platinum, , Hg / Hg2SO4, RE-6H, Hg / HgO, Hg / Hg2Cl2, Ag / Ag2SO4, Cu / CuSO4, and KCl may be a known material. Preferably, the conductive material may be Ag / AgCl, but is not limited thereto and may be composed of a wider variety of materials.

[0074] However, not limited thereto, the third electrode may be composed of a wider variety of materials as long as it provides a stable potential as a reference electrode.

[0075] As used in this specification, the term "pillar" may be a nano-sized polymer structure formed on an electrode. In this case, "pillar" may be interpreted within this specification as having the same meaning as "nanophila array" or "pillar-shaped polymer structure."

[0076] According to the features of the present disclosure, the pillar may be composed of a blend (PUNO) of polyurethane (PU) and a NOA-based adhesive (e.g., trade name NOA 68). In this case, the content of each of the PU and the NOA-based adhesive in the blend may be 20 to 80 weight%, preferably 30 to 70 weight%, and more preferably 40 to 60 weight%.

[0077] However, the filament is not limited to this and can be made of a wider variety of polymer materials (e.g., PDMS, PEG, PMMA, etc.) as long as they are flexible.

[0078] Meanwhile, multiple pillars formed on the surface of the electrode are formed of a polymer of a material different from that of the electrode, but can play a role in increasing the mechanical flexibility of the entire sensor.

[0079] Accordingly, the biosensor of the present disclosure can have improved durability against mechanical deformation (bending, folding) compared to a sensor having a flat electrode surface.

[0080] In addition, the material of the support plate (or substrate) is not limited thereto and can be formed from various insulating materials (e.g., PET, PI, PDMS, etc.) as long as it can stably support electrodes that generate a potential difference due to reaction with a target substance and provide flexibility for the entire sensor.

[0081] As used herein, the term "conductive layer" may refer to a layer composed of a conductive material. In this specification, the conductive layer may be composed of at least one of Ni, Zn, Pd, Ag, Cd, Pt, Ga, In, and Au. Preferably, the conductive layer may be Au, which has oxidation resistance and corrosion resistance, can provide an inert surface, has good electrical and thermal conductivity, has high optical reflectivity, and can provide a smooth surface, but is not limited thereto.

[0082] According to the features of the present disclosure, the first electrode and the second electrode on the biosensor may be configured to allow current to flow by depositing a conductive layer on a pillar-shaped polymer structure.

[0083] As used in this specification, the term "intermediate layer" may be a layer disposed between a pillar-shaped polymer structure and a conductive layer. More specifically, the intermediate layer may be configured to form chemical bonds with polar atoms on the surface of the pillar-shaped polymer structure so that the conductive layer on the upper surface and the structure on the lower surface can be firmly attached. Meanwhile, the intermediate layer may be composed of at least one of Ti, V, Cr, Sc, Nb, Mo, and W.

[0084] According to the features of the present disclosure, the first electrode and the second electrode on the biosensor may be configured such that an intermediate layer is formed on a pillar-shaped polymer structure, and a conductive layer is deposited on the intermediate layer to allow current to flow.

[0085] As used herein, the term "half-cell reaction layer" may be a layer composed of a stable material having a constant potential even in contact with a target material. More specifically, the half-cell reaction layer may be Ag / AgCl, Ag, Hg2SO4, Ag / Ag + , Hg / Hg2SO4, RE-6H, Hg / HgO, Hg / Hg2Cl2, Ag / Ag2SO4, Cu / CuSO4, KCl saturated calomel half-cell (SCE) and salt bridge platinum can be made of materials with a known potential difference.

[0086] According to the features of the present disclosure, a half-cell reaction layer may be formed on the third electrode.

[0087] The term "mask" as used in this specification may mean a plate for covering unnecessary parts and exposing only necessary parts.

[0088] In the present specification, the mask may include a plurality of masks predetermined for the shape, size, and spacing of each of the first electrode, the second electrode, and the third electrode.

[0089] Accordingly, the first electrode, the second electrode, and the third electrode can be formed on the support plate by a plurality of predetermined masks.

[0090] For example, a first electrode with a conductive layer formed on a support plate can be obtained by placing a mask, which is configured to mask a specific area and has a predetermined shape and size, on a support plate, and then depositing, printing, or plating a conductive material so that a conductive layer is deposited only in the area where a pillar exists on the support plate.

[0091] Furthermore, a second electrode can be formed on a support plate by placing a mask on the support plate that is configured to mask the formed first electrode and has an open area separated from the first electrode by a certain distance, and then depositing a conductive material.

[0092] Furthermore, a third electrode can be formed on a support plate by placing a mask on the support plate that is configured to mask the first electrode and the second electrode, with an open area separated from the second electrode by a certain distance, and then depositing a half-cell reactive material.

[0093] As used in this specification, the term "potential measuring unit" may be a unit configured to control or maintain a constant potential of a first electrode (working electrode) and a third electrode (reference electrode).

[0094] This potential measuring unit enables stable measurement of a signal resulting from an electrochemical reaction occurring between the first electrode and the second electrode (counter electrode) while maintaining a constant potential between the first electrode and the third electrode.

[0095] As used herein, the term "output unit" may be a unit configured to convert the amount (or concentration) of a target substance based on a measured electrochemical signal (e.g., current, voltage, or current-voltage characteristics). In this case, the output unit may be connected to a potential measuring unit and configured to provide the concentration of the target substance, i.e., a quantitative analysis value, based on the potential difference of the analysis sample measured by the potential measuring unit.

[0096] More specifically, the output unit may be a display device including a liquid crystal display, an organic light-emitting display, etc., but is not limited thereto, and may be provided in various forms as long as it provides quantitative analysis results for a target substance. In this case, the output unit may further include a processor configured to convert the potential difference resulting from the electrochemical reaction of the analysis sample into a concentration value.

[0097] Hereinafter, the present disclosure will be described in detail by explaining preferred embodiments of the present disclosure with reference to the attached drawings.

[0098] FIG. 1 is a schematic diagram showing a well plate according to one embodiment of the present disclosure, and FIG. 2 is a schematic diagram showing a sensor array provided in a well plate according to one embodiment of the present disclosure.

[0099] Referring to FIGS. 1 and FIGS. 2, a well plate (10000) according to one embodiment of the present disclosure may be configured to include a main body (1000) and a sensor array (1200).

[0100] Specifically, the main body (1000) may be formed with a plurality of wells (1100) spaced apart at regular intervals. At this time, each of the plurality of wells (1100) may form a receiving space (1110) having a certain width and depth to accommodate an analysis sample. Here, the number of the plurality of wells (1100), as well as the width and depth of the receiving space (1110), are not limited.

[0101] Additionally, an opening (1120) may be formed in a part of the bottom surface of the receiving space (1110) to allow the analysis sample contained within the receiving space (1110) to flow in. At this time, the opening (1120) may be formed in the center of the bottom surface, but may also be formed in other areas within the bottom surface of the receiving space (1110), and its location is not limited. Furthermore, the bottom surface of the receiving space (1110) may be formed to have a slope at a certain angle so that the analysis sample can flow more smoothly toward the opening (1120). Here, the angle may be designed to be changed according to the design dimensions of the opening (1120) and / or the plurality of electrodes (1310, 1320, 1330), and is not limited thereto. Also, the opening (1120) does not necessarily have to be circular and may be formed in a specific shape, and the shape may be changed during design (manufacturing).

[0102] Meanwhile, the sensor array (1200) is configured to be mounted on the lower part of the main body (1000).

[0103] At this time, a plurality of unit sensors (100) may be formed on the sensor array (1200) at regular intervals, and a plurality of electrodes (1310, 1320, 1330) formed on the sensor (130) provided in each unit sensor (100) may be disposed within an opening (1120) and exposed to the outside. To this end, the opening (1120) may be formed in an annular (or circular) shape surrounding the plurality of electrodes (1310, 1320, 1330). To this end, the diameter of the opening (1120) may be formed to correspond to or larger than the number of electrodes (1310, 1320, 1330) so that the plurality of electrodes can be sufficiently exposed. In addition, the spacing between the plurality of unit sensors (100) may also be determined according to the spacing between the openings (1120) formed in each of the plurality of wells (1100).

[0104] As illustrated in FIGS. 1 and 2, the plurality of unit sensors (100) constituting this sensor array (1200) may be arranged regularly in an n×m array, but may also be arranged in other forms. In addition, it is not necessary to have a plurality of unit sensors (100), and it is also possible to configure it as a single unit sensor (100), that is, a single sensor, as needed. Here, the unit sensor (100) may represent a "biosensor".

[0105] Meanwhile, the sensor array (1200) can be mounted on the main body (1000) in various ways, and is not limited thereto.

[0106] As one embodiment, as shown in FIGS. 1 and 2, the sensor array (1200) can be mounted on the main body (1000) by being inserted into a space formed in the lower part of the main body (1000) so that the sensor array (1200) can be embedded therein.

[0107] In addition, as another embodiment, the sensor array (1200) itself may be formed to constitute the lower bottom surface of the main body (1000), and the sensor array (1200) may be mounted by coupling it to the lower part of the main body (1000).

[0108] At this time, as shown in Fig. 2(b), a plurality of electrodes (1310, 1320, 1330) formed on the sensor (130) of each unit sensor (100) can be arranged so as to face upward, and the sensor array (1200) can be mounted on the main body (1000).

[0109] Thus, as the analysis sample contained in the receiving space (1110) of the main body (1000) flows into the opening (1120) and comes into contact with a plurality of electrodes (1310, 1320, 1330) facing upward, the plurality of electrodes (1310, 1320, 1330) react with the target substance contained in the analysis sample to generate an electrochemical signal (electrical signal).

[0110] FIG. 3 is a schematic diagram showing a unit sensor constituting a sensor array according to one embodiment of the present disclosure, and FIG. 4 is an exploded perspective view showing a unit sensor constituting a sensor array according to one embodiment of the present disclosure.

[0111] Referring to FIGS. 3 and 4, a unit sensor (100) constituting a sensor array according to one embodiment of the present disclosure may be configured to include a substrate (110), a conductive adhesive member (120), and a sensor (130).

[0112] At this time, each unit sensor (100) can be formed by stacking a substrate (110), a conductive adhesive member (120), and a sensor (130) in the order as shown in (a).

[0113] The substrate (110) may have a preset size. Additionally, the substrate (110) may be made of a flexible and bendable material. A through hole (111) may be formed in the substrate (110) to expose a plurality of electrodes (1310, 1320, 1330) formed in the sensor (130). That is, as the sensor array (1200) is mounted on the main body (1000), the through hole (111) formed in the substrate (110) constituting the unit sensor (100) and the opening (1120) formed in the receiving space (1110) of the main body (1000) are aligned in a line, and the connection can be made in that state.

[0114] In addition, although not shown in FIGS. 3 and 4, at least one hole is formed on one side of the substrate to allow air contained within the channel to be discharged to the outside while guiding the fluid, and at least one hole may be arranged in a pre-set shape.

[0115] Meanwhile, the conductive adhesive member (120) may be composed of at least one of an anisotropic conductive film (ACF), an isotropic conductive adhesive (ICA), anisotropic conductive paste (ACP), or an electrically conductive adhesive (ECA).

[0116] This conductive adhesive member (120) is a product made by uniformly dispersing conductive particles, which are responsible for conducting electricity, within an insulating adhesive organic material. The conductive adhesive member (120) is a polymer adhesive material that simultaneously possesses the functions of conductivity in the thickness direction and insulation in the plane direction. Here, anisotropy means that electricity flows at one point but is in an insulating state at another point, that is, electricity flows only in one direction, and this result is obtained because the content of conductive particles is very low so that direct contact between particles does not occur. On the other hand, isotropy refers to a state in which the important characteristics of a material at one point are all the same regardless of direction, meaning that the physical properties are the same in all directions.

[0117] For example, the conductive adhesive member (120) may be in the form of a film or an adhesive, and may be formed in a shape that surrounds the through hole (111) of the substrate (110) so that the sensor (130) can be attached to one side of the substrate (110). At this time, the shape may be a square shape as shown in FIG. 4, but this is only one example and may be formed in other shapes and is not limited thereto.

[0118] Meanwhile, the sensor (130) is attached to one side of the substrate (110) by means of a conductive adhesive member (120) and reacts with the analysis sample contained in the corresponding well. Thus, the sensor (130) can detect a target substance from the contacted analysis sample and react with the target substance to generate an electrochemical signal.

[0119] This sensor (130) may be provided with a sensing material (e.g., an enzyme) that reacts with the target material contained in the analysis sample to detect the target material. When the sensor (130) comes into contact with the analysis sample, it interacts with the target material contained in the analysis sample to generate an electrochemical signal. However, the sensor (130) is not necessarily limited to this and may be configured to allow for the movement, stopping, filtration, purification, reaction, and mixing of the analysis sample.

[0120] Meanwhile, although a conductive adhesive member (120) is illustrated in FIGS. 3 and 4, this is a configuration that can be excluded or modified, and other configurations for attaching or bonding the sensor (130) to the substrate (110) without having this conductive adhesive member (120) may be added (replaced). The conductive adhesive member (120) can perform the function of preventing leakage of the sample while simultaneously providing an electrical connection between the sensor (130) and the substrate (110).

[0121] Additionally, although not shown in FIGS. 1 to 4, a leak prevention member may be further provided between the substrate (110) and the sensor (130) or between the opening (1120) and the unit sensor (100) to prevent leakage.

[0122] FIG. 5 is a schematic diagram showing a sensor embedded in a unit sensor according to one embodiment of the present disclosure.

[0123] Referring to FIG. 5, a sensor (130) according to one embodiment may be configured on a support plate (1300) including a plurality of electrodes (1310, 1320, 1330).

[0124] Multiple electrodes (1310, 1320, 1330) can react with a target substance contained in an analysis sample to generate an electrochemical signal.

[0125] Specifically, the plurality of electrodes (1310, 1320, 1330) may further include a first electrode (1310) that reacts with an oxidation or reduction reaction with a target substance and a second electrode (1320) that reacts with an oxidation or reduction reaction with a target substance in opposition to the reaction of the first electrode (1310), and may further include a third electrode (1330) configured to maintain a constant operating voltage between the first electrode (1310) and the second electrode (1320). At this time, the second electrode (1320) and the third electrode (1330) may be arranged to be spaced apart from the first electrode (1310) and surround it.

[0126] Here, the first electrode (1310) may refer to a working electrode that performs an oxidation or reduction reaction by reacting with a target substance or an analysis sample containing a target substance on a support plate (1300), and the second electrode (1320) may refer to a counter electrode facing the first electrode (1310) on the support plate (1300). Additionally, the third electrode (1330) may refer to a reference electrode whose potential is stably maintained even when in contact with a target substance. Therefore, if an oxidation reaction occurs at the first electrode (1310) by reacting with a target substance, a reduction reaction may occur at the second electrode (1320).

[0127] First, the first electrode (1310) includes a first base (1311) in a circular shape and a first wire (1312) extending vertically from one end of the first base (1311). The second electrode (1320) includes a second base (1321) in a strip shape that is concentric with the first base (1311) of the first electrode (1310) and spaced apart from the circumference of the first base (1311) at a predetermined interval, and a second wire (1322) extending vertically from one end of the second base (1321). At this time, the first wire (1312) and the second wire (1322) may be arranged horizontally. Here, the first wire (1312) and the second wire (1322) correspond to a conductive extension layer, which is a conductive material extended for each electrode. Additionally, a material layer identical to the conductive layer may be disposed on each of the first base (1311) and the second base (1321).

[0128] Additionally, the third electrode (1330) includes a strip-shaped third base (1331) spaced apart from the other end of the second base (1321) at a predetermined interval, and a third wire (1332) extending vertically from one end of the third base (1331). At this time, the third wire (1332) may be arranged horizontally together with the first wire (1312) and the second wire (1322). Accordingly, by measuring electrochemical signals, such as the current flowing between the first electrode (1310) and the second electrode (1320), while maintaining a constant potential between the first electrode (1310) and the third electrode (1330) of the sensor (130), information regarding the target substance (information on at least one of the presence, amount, or concentration) can be derived.

[0129] Meanwhile, the support plate (1300) may be made of copper material and may be mounted on one side of the substrate (110).

[0130] As previously explained through FIG. 5, the first electrode (1310), the second electrode (1320), and the third electrode (1330) according to one embodiment are all formed apart by a predetermined distance. At this time, the predetermined distance corresponds to a nanogap, and the present disclosure makes it easier to detect a target substance by forming a metal layer on each of the plurality of electrodes (1310, 1320, 1330) to make the width (gap) of the nanogap smaller.

[0131] However, the shape and arrangement of each of the plurality of electrodes (1310, 1320, 1330) are not limited to the shape and arrangement shown in FIG. 5, and are not restricted therefrom. According to another embodiment, the sensor (130) may include only the first electrode (1310) and the second electrode (1320), and may not include the third electrode (1330).

[0132] FIG. 6 is a diagram exemplarily showing the structure of a first electrode of a unit sensor according to one embodiment of the present disclosure.

[0133] Referring to FIG. 6, a pillar (1313) having a conductive layer deposited thereon may be disposed on the first electrode (1310) of the sensor (130). In this case, the pillar (1313) may have a nano size and may be composed of multiple pillars.

[0134] According to the first embodiment, the diameter of the pillar (1313) may be 400 nm to 600 nm, and the height of the pillar (1313) may be 1300 to 1700 nm. Furthermore, the pillars (1313) may be spaced 100 nm to 700 nm apart and arranged on the support plate (1300). Additionally, the aspect ratio of the pillar (1313) may be 1:3.

[0135] According to the second embodiment, the diameter of the pillar (1313) may be 100 nm to 1000 nm, and the height of the pillar (1313) may be 200 nm to 2000 nm. Furthermore, the pillars (1313) may be spaced 500 nm to 2000 nm apart and arranged on the support plate (1300).

[0136] However, the size of the pillars (1313) and their spacing are not limited to those described above.

[0137] Through this pillar (1313), the reaction area with the target substance is widened, so that highly sensitive qualitative and quantitative analysis results can be provided even for small amounts of the target substance.

[0138] Meanwhile, this pillar can be placed on the first electrode (1310) as well as on the second electrode (1320), and is not limited to a configuration placed only on the first electrode (1310).

[0139] FIG. 7 is a diagram illustrating, exemplarily, the structure of a pillar formed on a first electrode of a unit sensor according to one embodiment of the present disclosure.

[0140] Referring to FIG. 7, the pillar (1313) may be composed of a plurality of pillar-shaped polymer structures (1313a), an intermediate layer (1313b) disposed on the surface of the polymer structures (1313a), and a conductive layer (1313c) disposed on the surface of the intermediate layer (1313b).

[0141] According to one embodiment of the present disclosure, the polymer structure (1313a) may be composed of at least one of polyurethane (PU), polydimethylsiloxane (PDMS), NOA (Norland Optical Adhesive), epoxy, polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polyimide (PI), polystyrene (PS), polyethylene naphthalate (PEN), and polycarbonate (PC).

[0142] According to another embodiment of the present disclosure, the intermediate layer (1313b) may be composed of at least one of Ti, V, Cr, Sc, Nb, Mo, and W, and the conductive layer (1313c) may be composed of at least one of Au, Ni, Zn, Pd, Ag, Cd, Pt, Ga, and In. However, it is not limited thereto.

[0143] Due to the structural features described above, the sensor (130) according to various embodiments of the present disclosure provides improved flexibility compared to a sensor having a flat array and can be easily handled. Furthermore, electrochemical quantitative analysis of a target substance can be performed with high sensitivity and accuracy.

[0144] FIG. 8 is a flowchart schematically illustrating a method for manufacturing a well plate according to one embodiment of the present disclosure. In this case, the method for manufacturing a well plate may be performed through a separate manufacturing device or a computing device.

[0145] Referring to FIG. 8, the manufacturing device has a main body (1000) equipped with a plurality of wells (1100) (S110).

[0146] At this time, the manufacturing device forms a receiving space (1110) having a certain width and depth so as to be able to receive an analysis sample in each of the plurality of wells (1100), and forms an opening (1120) in a part of the bottom surface of the receiving space (1110) so that the analysis sample received in the receiving space (1110) can be introduced.

[0147] Next, the manufacturing device has a sensor array (1200) arranged such that a plurality of unit sensors (100) correspond to each of a plurality of wells (1100) of the main body (1000) provided by step S110 (S120).

[0148] At this time, the manufacturing device may form each unit sensor (100) by stacking a substrate (110), a conductive adhesive member (120), and a sensor (130) in that order, thereby providing a sensor array (1200).

[0149] For example, a single sensor array (1200) may be provided by combining each individually formed unit sensor (100), but a single sensor array (1200) may also be provided by partitioning an area for forming each unit sensor (100) on a single substrate (110) and attaching a conductive adhesive member (120) and a sensor (130) to each partition.

[0150] Next, the manufacturing device mounts a sensor array (1200) on the lower part of the main body (1000) so that a plurality of unit sensors (100) are each positioned in an opening (1120) formed on the bottom surface of each of the plurality of wells (1100) (S130).

[0151] At this time, the manufacturing device is arranged so that each sensor (130) of a plurality of unit sensors (100) is exposed through an opening (1120) formed on the bottom surface of each of the plurality of wells (1100).

[0152] FIG. 9 is a schematic diagram showing a single sensor according to another embodiment of the present disclosure.

[0153] As previously explained, a single sensor (10000') can be configured using the unit sensor (100) that constitutes the sensor array (1200) described above.

[0154] As illustrated in FIG. 9, a single sensor (10000') can be configured by embedding the unit sensor (100) within a main body (1000') that is formed to have a certain length and width and has an embedded space capable of embedding the unit sensor (100).

[0155] At this time, as shown in FIG. 9 (a), a first opening (1110') may be formed on one side of the main body (1000') so as to expose one side of the substrate (110) of the unit sensor (100).

[0156] Meanwhile, as shown in FIG. 9 (b), a second opening (1120') may be formed on the other side of the main body (1000') to expose a plurality of electrodes (1310, 1320, 1330) formed on the sensor (130) of the unit sensor (100).

[0157] Here, the first opening (1110') is for measuring an electrochemical signal generated from this unit sensor (100) through a measuring device, and the second opening (1120') is for guiding an analysis sample toward a plurality of electrodes (1310, 1320, 1330). The first opening (1110') and the second opening (1120') may be formed to have a specific shape or angle, and their shape and structure are not limited.

[0158] FIGS. 10 and FIGS. 11 are drawings illustrating an example in which a single sensor according to another embodiment of the present disclosure is coupled to a measuring device.

[0159] First, referring to FIG. 10, the unit sensor (100) can be detached from the main body (1000') of the single sensor (10000') and mounted on the measuring device (200). To this end, the measuring device (200) may form a receiving portion on the lower plate (210) on which the unit sensor (100) can be mounted.

[0160] However, this is merely one embodiment, and a single sensor (10000') may be mounted directly on the lower plate (210) of the measuring device (200). In this case, the mounting space in the receiving portion where the single sensor (10000') or the unit sensor (100) is mounted may be formed in a shape corresponding to the shape so that they can be stably mounted, or it may be formed in a shape having a separate fixing member that allows for positional movement.

[0161] Through this structure, a single sensor (10000') or a unit sensor (100) is introduced and accommodated within the mounting space, and is configured to be detachable, so that a different single sensor (10000') or a different unit sensor (100) can be replaced and mounted using a measuring device (200) to perform a continuous and rapid inspection.

[0162] Meanwhile, on the upper plate (220) connected by a jig to the lower plate (210) of the measuring device (200), a pogo pin (300) for measuring an electrochemical signal by contacting the substrate (110) may be provided at a position corresponding to a single sensor (10000') or a unit sensor (100).

[0163] That is, the pogo pin (300) can electrically connect the tester and the substrate (110).

[0164] Thus, when the upper plate (220) of the measuring device (200) descends along the jig toward the lower plate (210), the pogo pin (300) comes into contact with the substrate (110), thereby enabling the measurement of an electrochemical signal.

[0165] Meanwhile, FIGS. 10 and 11 described above illustrate a case in which an electrochemical signal is measured from a unit sensor (100) embedded in a single sensor (10000') according to another embodiment of the present disclosure. The measuring device (200) may be configured in a different shape or form to measure an electrochemical signal from a unit sensor (100) that constitutes a sensor array (1200) mounted on a well plate (10000) described above based on FIGS. 1 to 8.

[0166] For example, the sensor array (1200) mounted on the main body (1000) of the well plate (10000) may be removed and mounted on the measuring device (200). To this end, a plurality of fixing holes (1210) may be formed in the sensor array (1200) so that it can be stably fixed to the lower plate (210). In this case, the pogo pin (300) may be configured to be movable in the X-axis and / or Y-axis direction on the upper plate (220), or only the pogo pin (300) movable in the X-axis and / or Y-axis direction without the upper plate (220) may be provided, so that the pogo pin (300) moves to each unit sensor (100) constituting the sensor array (1200) while the sensor array (1200) is fixed, and an electrochemical signal can be measured by contacting each substrate (110) with the pogo pin (300).

[0167] As described above, according to the present disclosure, by using a well plate equipped with a sensor array comprising a plurality of unit sensors (biosensors) in the lower part of a main body having a plurality of wells, various analysis samples can be examined at once, thereby shortening the time required for analysis and improving time and economic efficiency.

[0168] The examples of the present disclosure disclosed in this specification and drawings are provided merely to facilitate the explanation of the technical content of the present disclosure and to aid in understanding the present disclosure, and are not intended to limit the scope of the present name. It is obvious to those skilled in the art that other variations based on the technical concept of the invention are possible in addition to the examples disclosed herein.

[0169] [National R&D projects that supported this invention]

[0170] [Project ID] 2410005358

[0171] [Project No.] PIC24037M

[0172] [Ministry Name] Ministry of Trade, Industry and Energy

[0173] [Project Management (Specialized) Agency Name] Korea Institute of Industrial Technology Planning and Evaluation

[0174] [Research Project Name] 2024 Materials and Components Technology Development Project (3rd)

[0175] [Project Title] Development of Key Components for Real-time Process Analysis of Freeze-Drying Nucleic Acid Therapeutics

[0176] [Name of Project Implementing Organization] Osong Advanced Medical Industry Promotion Foundation

[0177] [Research Period] July 1, 2024 ~ December 31, 2024

[0178] [National R&D projects that supported this invention]

[0179] [Project ID] 2710017897

[0180] [Assignment No.] PSD24019M

[0181] [Ministry Name] Ministry of Science and ICT

[0182] [Name of Project Management (Specialized) Agency] National Research Foundation of Korea

[0183] [Research Project Name] Nano and Materials Source Technology Development Project

[0184] [Project Title] Development of Molecular Recognition Materials That Overcome Avoidance Variants Based on Target-Oriented Generative Molecular Design Technology

[0185] [Name of Project Performing Organization] Sungkyunkwan University

[0186] [Research Period] July 1, 2024 ~ December 31, 2024

[0187] [National R&D projects that supported this invention]

[0188] [Project ID] 2710018369

[0189] [Assignment No.] PSD24024M

[0190] [Ministry Name] Ministry of Science and ICT

[0191] [Name of Project Management (Specialized) Agency] National Research Foundation of Korea

[0192] [Research Project Name] Bio-Medical Technology Development (R&D) (Technology Development for Responding to Future Medical Innovation)

[0193] [Project Title] Development of Full-Cycle Diagnostic Platform Technology for Diffuse Molecular Subtype Gastric Cancer

[0194] [Name of Project Performing Organization] Korea Research Institute of Bioscience and Biotechnology

[0195] [Research Period] July 1, 2024 ~ December 31, 2024

[0196] [National R&D projects that supported this invention]

[0197] [Project ID] 2710018552

[0198] [Assignment No.] PSD24023M

[0199] [Ministry Name] Ministry of Science and ICT

[0200] [Name of Project Management (Specialized) Agency] National Research Foundation of Korea

[0201] [Research Project Name] Bio-Medical Technology Development (R&D) (Advanced GW Bio)

[0202] [Project Title] Development of a Cell-Free Biosensor System for On-Site Analysis of GW Biomaterials and Hazardous Substances

[0203] [Name of Project Performing Organization] Chungnam National University

[0204] [Research Period] July 1, 2024 ~ December 31, 2024

[0205] [National R&D projects that supported this invention]

[0206] [Project Unique ID] Not Assigned

[0207] [Project No.] RS-2024-00508418

[0208] [Ministry Name] Ministry of Trade, Industry and Energy

[0209] [Project Management (Specialized) Agency Name] Korea Institute of Industrial Technology Planning and Evaluation

[0210] [Research Project Name] Materials and Components Technology Development (R&D)

[0211] [Project Title] (Sub-project 3) Development of High-Quality Antibody-Drug Conjugate (ADC) Smart Production Components and Equipment

[0212] [Name of Project Performing Organization] Nexa Co., Ltd.

[0213] [Research Period] 2024.10.01 ~ 2028.12.31

Claims

In the case of a well plate, A main body equipped with a plurality of wells; and A sensor array configured to be mountable to the lower part of the above main body, comprising a plurality of unit sensors arranged to correspond to each of the plurality of wells, Well plate. In paragraph 1, Each of the above plurality of wells is, A receiving space having a certain width and depth is formed to accommodate an analysis sample, wherein an opening is formed in a part of the bottom surface of the receiving space to allow the analysis sample accommodated in the receiving space to flow in. Well plate. In paragraph 2, The above opening is, Formed in a shape that surrounds the plurality of electrodes so that the sensors provided in the plurality of unit sensors are exposed, allowing the analysis sample contained in the receiving space to come into contact with the plurality of electrodes formed on the sensors. Well plate. In paragraph 1, Each of the above plurality of unit sensors is, Substrate; and A sensor comprising a sensor attached to one surface of the substrate by a conductive adhesive member and reacting with an analysis sample contained in a corresponding well. Well plate. In paragraph 4, The above substrate is, A through hole is formed to expose a plurality of electrodes formed in the sensor above. Well plate. In paragraph 4, The above sensor is, It includes a plurality of electrodes provided on one surface of the above substrate and reacting with the analysis sample to generate an electrochemical signal, Each of the above plurality of electrodes is formed spaced apart by a preset distance, Well plate. In paragraph 6, The above plurality of electrodes are, A first electrode composed of multiple pillars and oxidizing with the target substance; A second electrode that is spaced apart from the first electrode by at least a certain distance, forms a counter electrode with the first electrode, and reacts with the target substance in a reduction reaction; and A third electrode comprising a constant operating voltage maintained between the first electrode and the second electrode, Well plate. In a method for manufacturing a well plate, performed by a device, A step of providing a main body equipped with a plurality of wells; A step of having a sensor array in which a plurality of unit sensors are arranged to correspond to each of the plurality of wells; and The method includes the step of mounting the sensor array on the lower part of the main body such that the plurality of unit sensors are each positioned in an opening formed on the bottom surface of each of the plurality of wells. Well plate manufacturing method. In paragraph 8, The step of providing the above sensor array is, A method comprising the step of forming each of the plurality of unit sensors by stacking a substrate, a conductive adhesive member, and a sensor in that order. Well plate manufacturing method. In Paragraph 9, The step of mounting the sensor array on the lower part of the main body is, A step comprising arranging each sensor of the plurality of unit sensors so as to be exposed through an opening formed on the bottom surface of each of the plurality of wells. Well plate manufacturing method.

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