Cell chip and manufacturing method therefor

Abstract

A disclosed cell chip comprises: a substrate on which a plurality of electrode pads are provided in pairs; a bonding wire which connects each pair of electrode pads in an arch shape having a height so that the electrode pads are electrically connected; and a resin layer stacked on the substrate such that a portion including the apex of the bonding wire is exposed.

Description

Cell chip and method of manufacturing the same

[0001] The present invention relates to a technology that enables the production of 2D cell chips and 3D cell chips using the same process, with low process costs for manufacturing cell chips.

[0002] Organoid / spheroid (hereinafter referred to simply as "organoid") and tissue analysis are currently being attempted for stem cell differentiation, drug screening, disease modeling, and in-depth analysis of gene screening, and various analysis techniques are required to respond to manufacturing forms that vary depending on the culture method.

[0003] Representative organoid culture methods include culture in a 3D suspension state using gel types such as hydrogel or Matrigel, culture in 2D / 3D structures using culture medium and extracellular matrix proteins (ECM), or fabrication and culture through various methods such as 3D bioprinting.

[0004] The fabricated organoids are being analyzed using various techniques, including optical microscopy analysis with fluorescent staining marker labeling, imaging analysis methods using tomography (micro-CT), 3D imaging analysis, analysis methods using an organ-on-a-chip platform made of a microfluidic flow device and a biocompatible polymer structure, and electrical analysis techniques using a cell chip combined with a 3D cultureware structure and an electrode plate.

[0005] To fabricate cell chips used for the electrical analysis of organoids, a process of forming electrodes on a substrate is required. Generally, semiconductor processes such as photolithography, deposition, and etching are used to fabricate electrode plates. However, since the process involves photolithography, an exposure mask is necessary; consequently, if the design of the electrode pattern, arrangement, or number changes, the entire process design must be modified. Furthermore, Indium Tin Oxide (ITO) and general metal materials, which are primarily used as electrode materials, are subject to significant limitations in terms of cytotoxicity, which consequently imposes many constraints on designing process conditions.

[0006] Therefore, it is necessary to develop technology that can flexibly respond to changes in cell chip design and reduce process costs.

[0007] The purpose of the present invention is to provide a cell chip technology that enables the manufacture of cell chips at a low process cost and allows for flexible response in the manufacture of cell chips suitable for the analysis of various types of organoids.

[0008] The technical problems of the present invention are not limited to those mentioned above, and other unmentioned technical problems will be clearly understood by a person skilled in the art from the description below.

[0009] A cell chip according to one embodiment of the present invention comprises a substrate having a plurality of electrode pads formed in pairs, a bonding wire connecting the pairs of electrode pads in an arch shape having height so as to be electrically connected, and a resin layer formed laminated on the substrate such that a portion including the apex of the bonding wire is exposed.

[0010] The bonding wire has an upward portion extending toward the apex from one of the pair of electrode pads and a downward portion extending toward the other electrode pad from the apex, and the slope of the downward portion may be greater than the slope of the upward portion.

[0011] The above pair of electrode pads can be arranged so that the lower portion faces the inside of the substrate.

[0012] In one embodiment, the other electrode pad connected to the lower portion may form a bottom electrode in which a portion of one end region facing the substrate is exposed to the outside with respect to the resin layer.

[0013] Alternatively, according to another embodiment, a separate bottom electrode is formed on the inside of the substrate for the other electrode pad to which the lowering portion is connected, the bottom electrode is exposed to the outside with respect to the resin layer, and the bottom electrode can be electrically connected to a conductive wiring formed on the substrate.

[0014] The above bottom electrodes can form a pair of two to form a 2D electrode.

[0015] In addition, the bottom electrode can have a conductive nanomaterial bonded to the surface exposed to the outside with respect to the resin layer.

[0016] Furthermore, depending on the embodiment, a fixing structure for restricting the movement and / or position of a 3D cell may be disposed above the inner region of the substrate toward which the lowering portion faces.

[0017] In one embodiment, three or more of the paired electrode pads may be provided and arranged radially on the substrate.

[0018] The bonding wire mentioned above may preferably be a gold wire.

[0019] The surface of the resin layer forms a cell culture area, and it is preferable that the resin layer be made of a non-toxic resin material.

[0020] Meanwhile, the present invention provides a method for manufacturing a cell chip comprising: a first step of forming a plurality of electrode pads, each forming a pair, on a substrate; a second step of connecting the pair of electrode pads with a bonding wire having a height so as to be electrically connected; and a third step of forming a resin layer laminated on the substrate such that a portion including the apex of the bonding wire is exposed.

[0021] In the third step above, the exposure height of the bonding wire can be changed by adjusting the height of the resin layer stacked on the substrate.

[0022] In the second step above, the bonding wire has an upward portion extending toward the apex from one of the pair of electrode pads and a downward portion extending toward the other electrode pad from the apex, and the slope of the downward portion may be greater than the slope of the upward portion.

[0023] In the second step above, the bonding wire can be connected so that the lowering portion faces the inside of the substrate.

[0024] The cell chip of the present invention, having the above-described configuration, can control the protrusion amount of the bonding wire by changing the height of the resin layer formed by stacking on the substrate, and thereby can provide electrode plates suitable for various types of organoids with the same structure, differing only in the height of the resin layer.

[0025] Cell chips of various specifications can be manufactured using the same process, and by eliminating complex semiconductor processes such as photolithography, deposition, and etching that were previously used and implementing cell chips using wire bonding technology, process costs can be reduced and the defect rate can be significantly lowered.

[0026] The effects of the present invention 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] Figure 1 is a diagram illustrating an example of a cell chip.

[0028] FIG. 2 is a drawing illustrating an electrode plate according to one embodiment of the present invention.

[0029] Figure 3 is a drawing of an electrode plate with different heights of resin layers.

[0030] Figure 4 is a schematic diagram illustrating the state in which an organoid is cultured on the electrode plate of Figure 3.

[0031] Figure 5 is a diagram illustrating various arrangement forms of electrode pads formed on an electrode plate.

[0032] FIG. 6 is a drawing illustrating one embodiment of an electrode plate that arranges bonding wires in a double arrangement.

[0033] FIGS. 7 and FIGS. 8 are drawings illustrating different embodiments of an electrode plate including a bottom electrode, respectively.

[0034] FIG. 9 is a drawing illustrating one embodiment of a cell chip in which a fixing structure is placed to restrict the movement and / or position of a 3D cell.

[0035] FIG. 10 is a flowchart of a method for manufacturing a cell chip according to one embodiment of the present invention.

[0036] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the attached drawings. The advantages and features of the present invention and the methods for achieving them will become clear by referring to the embodiments described below in detail together with the attached drawings. However, the present invention is not limited to the embodiments disclosed below but can be implemented in various different forms. These embodiments are provided merely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims. Throughout the specification, the same reference numerals refer to the same components.

[0037] Unless otherwise defined, all terms used herein (including technical and scientific terms) may be used in a meaning commonly understood by those skilled in the art to which the present invention pertains. Furthermore, terms defined in commonly used dictionaries are not to be interpreted ideally or excessively unless explicitly and specifically defined otherwise. The terms used herein are for describing embodiments and are not intended to limit the present invention. In this specification, the singular form includes the plural form unless specifically stated otherwise in the text.

[0038] As used in the specification, "comprises" and / or "comprising" do not exclude the presence or addition of one or more other components, steps, actions, and / or elements to the mentioned components, steps, actions, and / or elements.

[0039]

[0040] FIG. 1 is a drawing illustrating an example of a cell chip (10). The illustrated cell chip (10) includes a cell culture ware (20) having wells (22) for culturing cells or processing cultured cells, and an electrode plate (30) having a plurality of electrodes formed to correspond to the wells (22) of the cell culture ware (20). The electrode plate (30) is replaceable so as to correspond to the contents of various electrical analysis techniques performed on organoids.

[0041] Various electrical analyses are performed on organoids, and the electrode arrangement structures required for each analysis also vary. For example, in the case of impedance measurement, multiple electrodes may consist of a working electrode and a counter electrode. Impedance can be measured by the working electrode and the counter electrode coming into contact with the cell.

[0042] Alternatively, in the case of LFP (Local Field Potential) measurement used to analyze signal excitation and synapse block according to electrical / drug stimulation of brain organoids, analyze cardiovascular pharmacological evaluation according to drug response of cardiac organoids, or analyze the degree of connectivity of auditory neurons according to electrical / chemical stimulation, the multiple electrodes may consist of three electrodes: a reference electrode, a stimulating electrode, and a recording electrode.

[0043] Alternatively, the classification of damage levels and the determination of inflammation levels due to epithelial barrier damage in intestinal organoids can be analyzed using an impedance method that includes a TEER (Trans Epithelial Electrical Resistance) measurement function, and the electrode configuration for this can be composed of a 2-electrode or 4-electrode (V+, V-, I+, I-) configuration consisting of a counter electrode and an operating electrode.

[0044] Alternatively, in DPV (Differential Pulse Voltametry) measurements, which allow for the identification of protein concentrations and organoid types for metabolites through electrochemical redox signal analysis, as well as the analysis of tumor and cancer cell activity, target protein concentrations, and anticancer drug effects, the multiple electrodes may be composed of three electrodes: a reference electrode, an operating electrode, and a counter electrode.

[0045] As such, since the electrode structure varies depending on the content of the electrical analysis, the electrode plate (30) must also be prepared in various ways. Conventionally, semiconductor processes such as photolithography, deposition, and etching were used to manufacture the electrode plate (30), but if the design of the electrode pattern, arrangement, number, etc., was changed, the process design had to be completely modified, and as a result, the manufacturing cost of the cell chip (10) increased. The present invention proposes a new process that can solve this problem, and thereby the price of the cell chip (10) can be lowered.

[0046] FIG. 2 is a drawing showing an electrode plate (30) according to an embodiment of the present invention, where (a) is a plan view and (b) is a cross-sectional view.

[0047] Referring to FIG. 2, the electrode plate (30) includes a substrate (100) having a plurality of electrode pads (110) formed thereon, a bonding wire (120) electrically connecting the electrode pads (110), and a resin layer (130) laminated on the substrate (100). Wiring (102) for connecting the plurality of electrode pads (110) to an external device is formed on the substrate (100) (see FIG. 1). In FIG. 2 to FIG. 5, the wiring (102) is omitted for the clear explanation of the invention, and an electrode structure corresponding to one well (22) is also shown.

[0048] Two electrode pads (110) form a pair, and the two paired electrode pads (110) form a single electrode. For example, if two electrodes are placed in each of the multiple wells (22) provided in the cell culture ware (20) of the cell chip (10) exemplified in FIG. 1, a total of four electrode pads (110) will be located in one well (22). FIG. 2 illustrates an example where two electrode pads (110) form two pairs to form two electrodes.

[0049] A bonding wire (120) electrically connects a pair of electrode pads (110), and the bonding wire (120) may not lie flat on the substrate (100) but may be in the shape of an arch with height. The bonding wire (120) is bonded to a pair of electrode pads (110) by wire bonding technology widely used in semiconductor processes. Since it does not undergo complex multi-stage processes such as photolithography and etching, and because a general-purpose wire bonding device is used, bonding the bonding wire (120) to the electrode pads (110) on the substrate (100) is inexpensive. In addition, the fast process speed is also advantageous for increasing productivity.

[0050] A resin layer (130) is formed by laminating it over a substrate (100) such that a portion including the apex (122) of the bonding wire (120) is exposed. For example, the resin layer (130) can be formed by applying a fluid resin onto the substrate (100) and allowing it to solidify over time.

[0051] As illustrated in FIG. 2(b), only a portion including the apex (122) of the bonding wire (120) is exposed above the resin layer (130). This exposed portion of the apex (122) of the bonding wire (120) forms an electrode on the electrode plate (30). Furthermore, it is preferable that the apex (122) of the bonding wire (120) be in the shape of a smooth curve rather than a sharp point. This prevents stress from being concentrated at the apex (122) structurally and is also more suitable for an automated wire bonding process.

[0052] Referring again to FIG. 2(b), the arch shape of the bonding wire (120) may be asymmetric. That is, the bonding wire (120) may be divided into two parts: an upward section (124) extending from one electrode pad (110) of a pair of electrode pads (110) toward a apex (122), and a downward section (126) extending from the apex (122) toward the other electrode pad (110), wherein the slope of the downward section (126) may be greater than the slope of the upward section (124). Here, the magnitude of the slopes of the upward section (124) and the downward section (126) is a comparison of absolute values, and the direction of the slope (+, -) is not taken into account. In other words, the slopes of the upward section (124) and the downward section (126) may be in the same direction or different directions. And, a pair of electrode pads (110) are arranged so that the lower portion (126) faces the inside of the substrate (100). By making the inclination of the lower portion (126) located inside the substrate (100) larger, the contact state of the cell with the bonding wire (120) is improved when the cell is located in the central region of the substrate (100).

[0053] FIG. 3 is a drawing of an electrode plate (30) having a different height of resin layer (130).

[0054] Referring to FIG. 3, the height of the resin layer (130) can be easily changed by adjusting the amount of resin applied to the substrate (100). FIG. 3(a) shows the height of the resin layer (130) so that only a very small part of the apex (122) of the bonding wire (120) is slightly exposed, whereas FIG. 3(b) shows the resin layer (130) formed lower so that more of the bonding wire (120) is exposed. By simply changing the height of the resin layer (130), the amount of protrusion of the bonding wire (120) can be controlled, and thereby, electrode plates (30) suitable for various organoids can be provided with the same structure, differing only in the height of the resin layer (130).

[0055] FIG. 4 is a schematic diagram illustrating the state in which an organoid is cultured on the electrode plate (30) of FIG. 3. FIG. 4(a) shows an example of application to an organoid with a wide width and low height (hereinafter referred to as '2D organoid' or '2D-Org'), and FIG. 4(b) shows an example of application to an organoid with a narrow width and high height (hereinafter referred to as '3D organoid' or '3D-Org').

[0056] Referring to FIG. 4(a), the cell chip (10) for a 2D organoid (2D-Org) has only a portion of the apex (122) of the bonding wire (120) slightly protruding. Also, referring to FIG. 4(b), the cell chip (10) for a 3D organoid (3D-Org) has a much larger exposed area of ​​the bonding wire (120). In the cell chip (10) of the present invention, since the bonding wire (120) acts as an electrode that contacts the cell, the exposed area of ​​the bonding wire (120) is made larger in the case of a 3D organoid (3D-Org) because the surface area in contact with the cell must be larger.

[0057] Also, referring to FIG. 4(b), in making stable contact with the 3D organoid (3D-Org), it is advantageous for the downward slope (126) of the bonding wire (120) to be large. Since the multiple bonding wires (120) are arranged so that all downward slopes (126) face inward toward the substrate (100), not only is cell contact with the 3D organoid (3D-Org) placed in the center improved, but the effect of stably fixing the position of the cell can also be obtained.

[0058] Referring again to FIG. 4, the portion that contacts the organoid on the electrode plate (30) is the surface of the bonding wire (120) and the resin layer (130). Therefore, it is preferable that the bonding wire (120) and the resin layer (130) be made of non-toxic materials that do not harm the cells. For example, it is preferable that the bonding wire (120) be a non-toxic gold wire. Also, since the surface of the resin layer (130) forms a cell culture area (CA), it is preferable that the resin layer (130) be made of a non-toxic resin material. For example, non-toxic resin materials that form the resin layer (130) include PDMS (Polydimethylsiloxane). Also, since the toxicity of the substrate (100) and the electrode pad (110) is blocked by the resin layer (130), the substrate (100) and the electrode pad (110) may have a relatively high degree of freedom in material selection.

[0059] FIG. 5 is a drawing illustrating various arrangement forms of electrode pads (110) formed on an electrode plate (30).

[0060] Referring to FIG. 5(a), a cell chip (10) according to one embodiment of the present invention may have two bonding wires (120) arranged opposite each other in a straight line, and in this case, it may be applied to impedance measurement requiring two electrodes.

[0061] Referring to FIG. 5(b), a cell chip (10) according to another embodiment of the present invention may have three bonding wires (120) arranged radially from the center, and in this case, it may be applied to local field potential (LFP) measurement requiring three electrodes.

[0062] Referring to FIG. 5(c), a cell chip (10) according to another embodiment of the present invention can have a plurality of electrodes easily arranged in a dense manner by applying wire bonding technology. In the embodiment of FIG. 5(c), there are a total of 12 bonding wires (120), and in arranging a plurality of electrodes in this way, a total of 24 electrode pads (110) are formed radially on the substrate (100), and then the electrode plate (30) can be simply manufactured by connecting the bonding wires (120).

[0063] FIG. 6 is a drawing illustrating an embodiment of an electrode plate (30) that arranges bonding wires (120) in a double arrangement. The illustrated electrode plate (30) has two pairs of electrode pads (110) spaced apart in the radial direction, and these pairs of electrode pads (110) are arranged circumferentially.

[0064] In particular, looking at FIG. 6(b), the bonding wire (120) electrically connecting the two paired electrode pads (110) is distinguished into two types of groups with different heights. And, for each group of bonding wires (120), the apex (122) of the bonding wire (120) of the lower height group is positioned closer to the center of the electrode plate (30) than the apex (122) of the bonding wire (120) of the higher height group.

[0065] This double arrangement of bonding wires (120) forms a better contact state of the bonding wires (120) with the cultured organoid, particularly the 3D organoid (3D-Org). As illustrated exemplarily in FIG. 6 (b), the 3D organoid (3D-Org) with a narrow width and high height has a curved surface (the drawing is for illustrative purposes, and the actual surface of the 3D organoid is generally irregularly curved), so that the vertices (122) of the two types of bonding wires (120) of different heights naturally support the 3D organoid (3D-Org) radially inward and outward. As a result, the contact state between the organoid and the bonding wires (120) becomes more robust and better compared to the embodiment of FIG. 4.

[0066] Each group of bonding wires (120), having different heights and positions of the vertices (122), is appropriately distributed along the circumferential direction. For example, as shown in FIG. 6 (a), each group of bonding wires (120) may be arranged alternately along the circumferential direction, or each group of bonding wires (120) may be arranged to face each other while looking toward the center of the electrode plate (30). Additionally, each group of bonding wires (120) may be configured differently, such as the curvature at the vertex (122) where the rising portion (124) and the falling portion (126) meet, and the slope of the rising portion (124) and the falling portion (126). That is, the electrode plate according to the embodiment of FIG. 6 can vary various design elements such as height, arrangement, curvature, slope, length, and thickness of the bonding wire (120) for each group of bonding wires (120), and can optimize the contact state between the organoid and the bonding wire (120) through various combinations of these design elements.

[0067] FIGS. 7 and FIGS. 8 are drawings illustrating different embodiments of an electrode plate (30) including a bottom electrode (112). According to the embodiment of FIG. 7, among a pair of electrode pads (110), the electrode pad (110) connected to the lowering portion (126) forms a bottom electrode (112) in which a portion of one end region facing the substrate (100) is exposed to the outside with respect to the resin layer (130). To form the bottom electrode (112), the electrode pad (110) connected to the lowering portion (126) may be formed to be relatively longer or larger. The bottom electrode (112) may form a structure exposed in the resin layer (130) by, for example, by a method such as masking a portion of the electrode pad (110) before forming the resin layer (130) and removing the masking after forming (solidifying) the resin layer (130).

[0068] FIG. 8 illustrates an embodiment in which a bottom electrode (112) is formed separately from the electrode pad (110). Referring to FIG. 8, a separate bottom electrode (112) is formed inside the substrate (100) relative to the electrode pad (110) to which the lowering portion (126) is connected. In the embodiment of FIG. 8, the bottom electrode (112) is also exposed to the outside with respect to the resin layer (130). Furthermore, the bottom electrode (112) is electrically connected to a conductive wiring (114) formed on the substrate (100). The conductive wiring (114) is provided to output a signal from the bottom electrode (112) to the outside of the substrate (100). Although the bottom electrode (112) is exposed to the resin layer (130), the conductive wiring (114) is covered by the resin layer (130). The electrode pad (110), the bottom electrode (112), and the conductive wiring (114) can be formed simultaneously on the substrate (100) in a single process.

[0069] FIGS. 7 (b) and FIGS. 8 (b) illustrate the advantages of forming bottom electrodes (112). Two bottom electrodes (112) form a pair to form additional 2D electrodes. The position of the bottom electrodes (112) is located further inside the substrate (100) than the electrode pad (110) to which the lower portion (126) is connected among the pair of electrode pads (110). According to this arrangement of bottom electrodes (112), the two bottom electrodes (112) form a pair and face each other toward the inside (central region) of the substrate (100).

[0070] For example, if a 3D organoid (3D-Org) with a narrow width and high height is used, the 3D organoid (3D-Org) placed in the center of the substrate (100) comes into contact with a plurality of bonding wires (120) on the side, and the lower center of the 3D organoid (3D-Org) comes into contact with a bottom electrode (112) exposed to the resin layer (130). Thus, the bottom electrodes (112), which form a pair of two, provide additional 2D electrodes for the electrical analysis performed on the organoid, thereby allowing the electrical analysis of the organoid to be performed more accurately.

[0071] The bottom electrode (112) can improve the sensitivity and / or accuracy of the electrical analysis through surface modification. For example, the bottom electrode (112) may have a conductive nanomaterial bonded (deposited) to the surface exposed to the resin layer (130). The conductive nanomaterial is non-toxic and may include any one of gold nanoparticles (Au nanoparticles, AuNPs), quantum dots (QD), reduced graphene oxide (rGO), poly(3,4-ethylenedixoythiophene)-polystyrene sulfonate (PEDOT: PSS), polyaniline (PANI), carbon nanotubes (CNT), multi-walled carbon nanotubes (MWCNT), and combinations thereof.

[0072] Meanwhile, FIGS. 7 and 8 illustrate an embodiment in which a bottom electrode (112) is added, using the arrangement of the electrode pad (110) corresponding to FIG. 5 (a) as an example. However, this uses the simplest arrangement of the electrode pad (110) as an example to aid in understanding the invention, and it is obvious that the same principle can be extended and applied to arrangements of the electrode pad (110) such as FIG. 5 (b) and (c).

[0073] FIG. 9 illustrates an embodiment of a cell chip (10) in which a fixing structure (140) for restricting the movement and / or position of 3D cells is disposed. In the cell chip (10) provided by the present invention, a fixing structure (140) for restricting the movement and / or position of 3D cells may be disposed above the inner region of the substrate (100) toward which the lower portion (126) of the bonding wire (120) faces. For example, the fixing structure (140) may be installed in a well (22) of a cell culture ware (20). The fixing structure (140) may be made of a non-toxic silicone material or the like, and may be made in the form of a flexible net structure that allows good contact with the culture medium and prevents excessive pressure from being applied so as not to have an adverse effect on the life activities of the organoid. The organoid is in good contact with the bonding wire (120) and further the bottom electrode (112) by the fixed structure (140) and its position is maintained, thereby allowing the electrical analysis of the organoid to be performed more accurately and stably.

[0074] FIG. 10 is a flowchart of a method for manufacturing a cell chip (10) according to an embodiment of the present invention. The basic structure of the cell chip (10) provided by the present invention has been described with reference to FIG. 1 to 6, and the method for manufacturing thereof will be described briefly to avoid duplication for the sake of brevity of the specification.

[0075] The method for manufacturing a cell chip (10) provided by the present invention comprises a first step of forming a plurality of electrode pads (110) that form a pair on a substrate (100), a second step of connecting the pair of electrode pads (110) with an arch-shaped bonding wire (120) having height so as to electrically connect them, and a third step of forming a resin layer (130) laminated on the substrate (100) such that a portion including the apex (122) of the bonding wire (120) is exposed.

[0076] In the third step, the exposure height of the bonding wire (120) can be changed by adjusting the height of the resin layer (130) stacked over the substrate (100). Through this, an electrode plate (30) suitable for each of the 2D organoid and 3D organoid can be provided.

[0077] And, in the second step, the bonding wire (120) is provided with an upward section (124) extending from one of the pair of electrode pads (110) toward a peak (122) and a downward section (126) extending from the peak (122) toward another electrode pad (110), and the downward section (126) may be made to have a greater slope than the slope of the upward section (124).

[0078] And, in the second step, the bonding wire (120) can be connected so that the lower portion (126) faces the inside of the substrate (100). This improves the contact of the bonding wire (120) with the cell and allows the cell's position on the cell chip (10) to be maintained well.

[0079]

[0080] Although embodiments of the present invention have been described above with reference to the attached drawings, those skilled in the art will understand that the present invention may be implemented in other specific forms without changing its technical concept or essential features. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

[0081] 10: Cell Chip

[0082] 20: Cell Culture Cultureware

[0083] 22: Well

[0084] 30: Electrode plate

[0085] 100: Substrate

[0086] 102: Wiring

[0087] 110: Electrode pad

[0088] 112: Bottom electrode

[0089] 114: Challenge Wiring

[0090] 120: Bonding wire

[0091] 122: Peak

[0092] 124: Ascension

[0093] 126: Descent

[0094] 130: Resin layer

[0095] 140: Fixed structures

[0096] CA: Cell culture area

[0097] 2D-Org: 2D organoid

[0098] 3D-Org: 3D Organoid

Claims

1. A substrate having multiple electrode pads formed thereon, each forming a pair; Bonding wires connecting the above pair of electrode pads in an arched shape with height so as to electrically connect them; and A resin layer formed by lamination over the substrate such that a portion including the vertex of the bonding wire is exposed; A cell chip containing 2. In Paragraph 1, The bonding wire mentioned above is, It has an ascending portion extending toward the apex from one of the electrode pads forming the pair above, and a descending portion extending toward the other electrode pad from the apex. A cell chip in which the slope of the descending portion is greater than the slope of the ascending portion.

3. In Paragraph 2, The above-mentioned pair of electrode pads are, A cell chip in which the above-mentioned downward portion is positioned to face the inside of the substrate.

4. In Paragraph 3, The other electrode pad connected to the above-mentioned descending part is, A cell chip in which a portion of one end region facing the substrate forms a bottom electrode exposed to the outside with respect to the resin layer.

5. In Paragraph 3, A separate bottom electrode is formed on the inside of the substrate for the other electrode pad connected to the lowering part, and The above bottom electrode is exposed to the outside with respect to the resin layer, and A cell chip in which the bottom electrode is electrically connected to conductive wiring formed on the substrate.

6. In Paragraph 4 or 5, The above bottom electrode is, A cell chip in which two pieces form a pair to form a 2D electrode.

7. In Paragraph 4 or 5, The above bottom electrode is, A cell chip having a conductive nanomaterial bonded to a surface exposed to the outside with respect to the above resin layer.

8. In any one of paragraphs 3 through 5, Above the inner region of the substrate toward which the above-mentioned descending part faces, A cell chip on which a fixation structure is placed to restrict the movement and / or position of 3D cells.

9. In Paragraph 3, A cell chip having three or more of the above-mentioned pair of electrode pads arranged radially on the substrate.

10. In Paragraph 1, The bonding wire mentioned above is a gold wire, cell chip, 11. In Paragraph 1 or Paragraph 10, The surface of the above resin layer forms a cell culture area, and The above resin layer is a cell chip made of a non-toxic resin material.

12. A first step of forming a plurality of electrode pads, each forming a pair, on a substrate; A second step of connecting the above pair of electrode pads with a bonding wire in the shape of an arch having height so that they are electrically connected; and A third step of forming a resin layer laminated over the substrate such that a portion including the vertex of the bonding wire is exposed; A method for manufacturing a cell chip comprising 13. In Paragraph 12, In the third step above, A method for manufacturing a cell chip, wherein the height of the resin layer stacked on the substrate is adjusted to change the exposure height of the bonding wire.

14. In Paragraph 12, In the second step above, The bonding wire comprises an ascending portion extending toward the apex from one of the pair of electrode pads and a descending portion extending toward the other electrode pad from the apex. A method for manufacturing a cell chip in which the slope of the descending portion is greater than the slope of the ascending portion.

15. In Paragraph 14, In the second step above, A method for manufacturing a cell chip, wherein the bonding wire is connected such that the lower portion faces the inside of the substrate.

Images