Well plate and base plate apparatus for implementing high-speed drug screening using a three-dimensional biological model

Abstract

Embodiments of the present invention relate to an apparatus for implementing high-speed drug screening using a three-dimensional biological model. The apparatus according to one aspect may include: a well plate; a base plate; and a probe provided on the base plate, wherein the well plate includes a well configured as a region in which at least a portion of the upper surface of the well plate is recessed along a first direction, the well being configured to accommodate the three-dimensional biological model.

Description

Well plate and base plate device for implementing high-speed drug screening based on 3D biological models

[0001] Embodiments of the present invention relate to a device for implementing high-speed drug screening based on a three-dimensional biological model.

[0002] Organoids are representative biological models of microphysiological systems (MPS) that mimic the intercellular interactions and biological microenvironments of tissues or organs in vitro. They are being widely studied as tools for efficient and accurate drug development, as well as for diagnostic research and regulatory reform. However, while decades of advancement in biomimicry have been achieved across various organs, standardization and the assurance of reproducibility remain insufficient.

[0003] Meanwhile, conventional 2D multiple electrode arrays (MEAs) are designed to analyze biological models, such as single-layer (2D) cultured neural networks, and have limitations in analyzing multi-layer (3D) cultured models due to structural limitations that result in an extremely limited contact area. Consequently, despite exhibiting high numerical specifications, there is a problem with low utility for analyzing 3D biological models. For instance, there are limitations in observing signals occurring deep within the body, and it is impossible to evaluate electrical characteristics, such as potential difference and impedance measurements inside and outside the biological model. These problems are not significantly improved even when electrodes are arranged on a curved surface to match the shape of the 3D biological model.

[0004] Three-dimensional biological models are high-cost research materials that require delicate management during long culture periods of approximately several months. Since they are small in size—ranging from several centimeters to typically less than 1 mm—and are prone to damage, performing sensitive analyses of the biological model's microenvironment requires more precise sample manipulation and appropriate control methods compared to general experimental environments. However, existing analytical devices or methods rely excessively on manual user operation, making it difficult to ensure the precision of the inspection process and resulting in low throughput due to reduced inspection efficiency.

[0005] According to one aspect of the present invention, an analysis device for a three-dimensional biological model, such as an organoid, can be provided to perform analysis of the three-dimensional biological model simply and accurately.

[0006] According to another aspect of the present invention, an analysis device for a three-dimensional biological model capable of multiple simultaneous analyses of a plurality of three-dimensional biological models can be provided.

[0007] An apparatus according to one embodiment of the present invention comprises a well plate; a base plate; and a probe provided on the base plate; wherein the well plate may include a well that accommodates the three-dimensional biological model, wherein at least a portion of the upper surface of the well plate is a region recessed along a first direction.

[0008] In an apparatus according to one embodiment, the three-dimensional biological model may include at least one selected from the group consisting of a heart organoid, a blood vessel organoid, a retinal organoid, a brain organoid, a spinal cord organoid, a tumor organoid, a neural organoid, an organoid containing cells subjected to optogenetic manipulation, a lung organoid, a stomach organoid, a small intestine organoid, a liver organoid, a pancreas organoid, a kidney organoid, a bladder organoid, a testis organoid, an ovary organoid, a bone marrow organoid, a thymus organoid, a skin organoid, a hair follicle organoid, an inner ear organoid, and an olfactory epithelial organoid.

[0009] In an apparatus according to one embodiment, the well plate may include a through hole penetrating at least a portion of the well plate and a well membrane covering the through hole.

[0010] In a device according to one embodiment, the through hole may penetrate at least a portion of the well plate along the first direction.

[0011] In a device according to one embodiment, the probe may be extended along the first direction.

[0012] In an apparatus according to one embodiment, the probe may include a plurality of electrodes arranged along the first direction.

[0013] In an apparatus according to one embodiment, the base plate comprises a bottom portion and a side wall portion extending along the first direction around the perimeter of the bottom portion, and the side wall portion may include a stepped portion forming a step so that at least a portion of the well plate is seated at one end of the side wall portion.

[0014] In a device according to one embodiment, the probe may be provided in the bottom portion.

[0015] In a device according to one embodiment, the first length, which is the length from the bottom portion along the first direction to the step portion, may be shorter than the second length, which is the length of the probe along the first direction.

[0016] In a device according to one embodiment, the difference between the second length and the first length may be 50 μm to 5 mm.

[0017] In a device according to one embodiment, the device further comprises a holder positioned spaced apart from the well plate; and the holder may be movable along the first direction within the well.

[0018] In a device according to one embodiment, the holder may include a rod extending along the first direction and a holder membrane located at one end of the rod.

[0019] In an apparatus according to one embodiment, the rod includes a stopper extending from the other end of the rod along the circumference of the rod in a direction perpendicular to the first direction, and a third length, which is the maximum length among the lengths connecting one point of the stopper and another point along the direction perpendicular to the first direction, may be longer than a fourth length, which is the maximum length among the lengths connecting one point of the well and another point along the direction perpendicular to the first direction.

[0020] In a device according to one embodiment, when the holder applies an external force to the well plate along the first direction, the well plate may be movable along the first direction.

[0021] In an apparatus according to one embodiment, the wells are provided in a plurality of numbers, and each of the holder and the probe may be provided in a plurality of numbers to correspond to each of the plurality of wells.

[0022] According to one aspect of the present invention, an analysis device for a three-dimensional biological model, such as an organoid, can be provided to perform analysis of the three-dimensional biological model simply and accurately.

[0023] According to another aspect of the present invention, an analysis device for a three-dimensional biological model capable of multiple simultaneous analyses of a plurality of three-dimensional biological models can be provided.

[0024] FIG. 1 is a drawing showing an example of a device according to one embodiment of the present invention.

[0025] Figure 2 is a diagram showing an example of a state in which a three-dimensional biological model is accommodated in the device illustrated in Figure 1.

[0026] FIG. 3 is a drawing showing an example of a probe according to one embodiment of the present invention.

[0027] Figure 4 is a diagram showing an example of performing an analysis on a three-dimensional biological model by manipulating a holder.

[0028] Since the embodiments described in this specification may be modified in various different forms, the technology according to one embodiment is not limited to the embodiments described below. Furthermore, throughout the specification, the terms "comprising," "having," "containing," or "having" any component do not exclude other components but may include additional components unless specifically stated otherwise, and do not exclude elements, materials, or processes not additionally listed.

[0029] In this specification, "identical or uniform" may mean that they are identical or uniform to one another within an acceptable margin of error, unless otherwise specified. For example, the statement that certain components or physical property measurements are identical may include not only that the two objects being compared are completely identical, but also that they are identical within a margin of error. Meanwhile, the statement that certain physical property measurements are identical may mean that the difference between the measurements between the objects is approximately less than 5%, specifically less than 3%, and more specifically less than 1%.

[0030] In this specification, the angle formed by two objects being perpendicular, or parallel or parallel to each other, may include not only geometrically perpendicular or parallel but also within a slight margin of error.

[0031] The numerical ranges used in this specification include lower and upper limits and all values ​​within the range, increments logically derived from the form and width of the defined range, all of which are limited values, and all possible combinations of upper and lower limits of numerical ranges limited in different forms.

[0032] Unless otherwise specifically defined in this specification, “about” may be considered to be a value within 30%, 25%, 20%, 15%, 10%, or 5% of the specified value.

[0033] In this specification, the use of terms such as "first," "second," or "third" preceding any component is intended solely to avoid confusion regarding the components being referred to, and is unrelated to the order, importance, or hierarchical relationship between the components. For example, an invention comprising only the second component without the first component is also possible.

[0034] In this specification, the term "electrically connected" may mean any method of connection in which a plurality of objects can be connected so as to be electrically connected to one another without limitation, and may be implemented in various ways, such as the plurality of objects being connected directly or being connected through a third object.

[0035] In this specification, a configuration defined as “…part” or “…unit” may, without limitation, mean a single component or a set of two or more identical or similar components that have commonalities in terms of function, and said set of components may be composed of a combination of hardware and / or software without limitation.

[0036] The present invention will be described in detail below. However, the following description is merely illustrative and does not imply that the present invention is limited to the exemplary embodiments described below.

[0037] FIG. 1 is a drawing showing an example of a device according to one embodiment of the present invention.

[0038] Figure 2 is a diagram showing an example of a state in which a three-dimensional biological model is accommodated in the device illustrated in Figure 1.

[0039] Referring to FIGS. 1 and 2, an apparatus (10) according to one aspect of the present invention is an analysis apparatus (10) for a three-dimensional biological model (50), comprising a well plate (100); a base plate (200); and a probe (500) provided on the base plate (200). The well plate (100) may include a well (110) that accommodates the three-dimensional biological model (50), wherein at least a portion of the upper surface (100A) of the well plate (100) is recessed along a first direction (DR1).

[0040] In one embodiment, the device (10) may be a device (10) for analyzing a three-dimensional biological model (50). In an exemplary embodiment, the device (10) may be a device (10) for electrically or electrochemically analyzing the three-dimensional biological model (50). Meanwhile, the device (10) may be a device (10) capable of performing electrical or electrochemical analysis of the three-dimensional biological model (50) simply and accurately.

[0041] In one embodiment, the three-dimensional biological model (50) may be a plurality of units. As will be described later, the device (10) according to one aspect of the present disclosure may be a device (10) capable of simultaneously performing electrical or electrochemical analysis on a plurality of three-dimensional biological models (50) with a simple operation.

[0042] FIG. 2 shows an example of the three-dimensional biological model (50) being accommodated in the device (10). In an exemplary embodiment, the three-dimensional biological model (50) may float in the well (110) while immersed in the culture medium (20), or a portion of it may come into contact with the inner wall (112) of the well.

[0043] In an exemplary embodiment, the three-dimensional biological model (50) may be a tissue removed from a living organism or a cultured cell culture. For example, the cell culture may be a spheroid or an organoid.

[0044] In one embodiment, the three-dimensional biomodel (50) may include a biomodel capable of generating an electrical signal or a biomodel capable of generating a signal linked thereto in response to light stimulation.

[0045] In one embodiment, the three-dimensional biomodel (50) may include an organoid model that mimics human organs and tumors.

[0046] In one embodiment, the three-dimensional biological model (50) may include at least one selected from the group consisting of a heart organoid, a blood vessel organoid, a retinal organoid, a brain organoid, a spinal cord organoid, a tumor organoid, a neural organoid, an organoid containing cells subjected to optogenetic manipulation, a lung organoid, a stomach organoid, a small intestine organoid, a liver organoid, a pancreas organoid, a kidney organoid, a bladder organoid, a testicular organoid, an ovarian organoid, a bone marrow organoid, a thymus organoid, a skin organoid, a hair follicle organoid, an inner ear organoid, and an olfactory epithelial organoid.

[0047] In one embodiment, the three-dimensional biological model (50) may be a cardiac organoid (CO) or a retinal organoid (RO).

[0048] In one embodiment, the diameter of the three-dimensional biological model (50) may be 50 μm to 5 mm. In an exemplary embodiment, the diameter of the three-dimensional biological model (50) may be a diameter measured by a known image analysis method.

[0049] In one embodiment, the culture medium (20) may be an electrolyte solution based on a basic ionic buffer solution similar to PBS (phosphate-buffered saline), with various nutrients, growth factors, and signaling substances added to it so that the cells constituting the organoid form a three-dimensional structure and function similar to an internal organ.

[0050] Referring again to FIGS. 1 and FIGS. 2, a device (10) according to one aspect of the present invention may include a well plate (100).

[0051] In one embodiment, the well plate (100) may include a well (110).

[0052] In one embodiment, the well (110) may be an area in which at least a portion of the upper surface (100A) of the well plate (100) is recessed along the first direction (DR1).

[0053] In such an embodiment, the well plate (100) is a plate-shaped structure having an upper surface (100A) and a lower surface (100B) in general, provided that, in detail, at least a portion of the upper surface (100A) may be in a recessed shape. Furthermore, as will be described later, the well plate (100) may be a structure in which the upper surface (100A) is in a recessed shape in a plurality of areas spaced apart from each other.

[0054] Meanwhile, at least a portion of the upper surface (100A) of the well plate (100) may be sunken along the first direction (DR1). Referring to FIGS. 1 and 2, the first direction (DR1) may mean a direction parallel to the direction connecting the upper surface (100A) and the lower surface (100B) of the well plate (100) by the shortest distance, and may mean both directions among the parallel directions. If the upper surface (100A) of the well plate (100) undergoes a deformation of shape along the first direction (DR1), it may be assumed that it protrudes or is sunken along the first direction (DR1). Among these, the well (110) may be an area where at least a portion of the upper surface (100A) of the well plate (100) is sunken along the first direction (DR1).

[0055] Accordingly, in the above embodiment, with reference to FIGS. 1 and FIGS. 2, the well (110) may refer to an area in which at least a portion of the upper surface (100A) of the well plate (100) is recessed. Meanwhile, it is sufficient that the well (110) is formed as described above, and its detailed shape may not be particularly limited. For example, with reference to FIGS. 1 and FIGS. 2, the well (110) is depicted as a cylindrical area including a rounded shape on one side, but it is not necessarily limited thereto, and it is understood that it may have various shapes as long as it does not impair the scope defined in the present invention.

[0056] Meanwhile, in one embodiment, a separate member corresponding to the shape of the well (110) may be provided in the well (110). In this case, the member may be a detachable member within the well (110). In this case, the inner wall of the well (110) (inner wall (112) to be described later) may come into contact with the member, and the three-dimensional biological model (50) and the culture medium (20) to be described later may be contained within the member. In this case, the details regarding the opening (111) described below may be understood as a description of the opening of the member, and the details regarding the inner wall (112) may be understood as a description of the inner wall of the member. However, this is an example provided as necessary, and it goes without saying that the present invention is not necessarily limited thereto.

[0057] In one embodiment, the well (110) can accommodate the three-dimensional biomodel (50).

[0058] As described above, since the well (110) is a recessed area of ​​at least a portion of the upper surface (100A) of the well plate (100), the well (110) formed in the well plate (100) can accommodate the three-dimensional biological model (50) to be analyzed.

[0059] For example, one of the above three-dimensional biological models (50) may be accommodated, but it is not necessarily limited thereto, and it is of course possible to accommodate multiple of the above three-dimensional biological models (50) in one well (110) as needed.

[0060] In one embodiment, the well (110) may include an opening (111) and an inner wall (112).

[0061] In one embodiment, the well (110) may include an opening (111).

[0062] The opening (111) may refer to an area that serves as a boundary between the well (110) and the external space. Thus, the well (110) and the external space may be connected through the opening (111).

[0063] In one embodiment, the well (110) may include an inner wall (112).

[0064] Although this is a non-limiting example, in terms of process, the well (110) may be formed by recessing at least a portion of the upper surface (100A) of the well plate (100). In this case, the inner wall (112) can be understood as a portion that originally constituted the upper surface (100A) of the well plate (100), but whose shape and position have been altered as a result of recessing at least a portion of the upper surface (100A) as described above. However, this is merely an example for convenience of explanation, and the present invention is not limited thereto.

[0065] Referring again to FIGS. 1 and FIGS. 2, in one embodiment, the well plate (100) may include a through hole (not shown) penetrating at least a portion of the well plate (100) and a well membrane (120) covering the through hole (not shown).

[0066] In one embodiment, the well plate (100) may include a through hole (not shown). The through hole (not shown) may penetrate at least a portion of the well plate (100).

[0067] As will be described later, if the presence of at least the well membrane (120) is excluded, the through hole (not shown) penetrates at least a part of the well plate (100), and the well (110) and the external space may be additionally connected through the through hole (not shown). In this case, the well (110) may be connected to the external space through the opening (111) and simultaneously to the external space through the through hole (not shown).

[0068] However, as described below, the through hole (not shown) may be covered by the well membrane (120). Therefore, in the configuration of the device (10) according to the embodiment of the present invention, the well (110) and the external space cannot be communicated at least through the through hole (not shown).

[0069] In this regard, the existence of the through hole (not shown) is not shown in FIG. 1 and FIG. 2 and in the drawings to be described later. However, since the through hole (not shown) is covered by the well membrane (120), at least the area spatially occupied by the well membrane (120) may be substantially the same as the area of ​​the through hole (not shown).

[0070] Referring again to FIGS. 1 and FIGS. 2, in one embodiment, the through hole (not shown) may penetrate at least a portion of the well plate (100) along the first direction (DR1).

[0071] Referring again to the description of the through hole (not shown) above, when the presence of at least the well membrane (120) is excluded, the well (110) can be connected to the external space along the first direction (DR1) through the through hole (not shown).

[0072] In an exemplary embodiment, the through hole (not shown) may be formed such that the area in contact with the deepest part of the well (110) in the well plate (100) is penetrated along the first direction (DR1).

[0073] In an exemplary embodiment, the inner wall (112) may be partially discontinuous by the through hole (not shown) in the portion in contact with the deepest part of the well (110).

[0074] Although this is a non-limiting example, in terms of process, the through hole (not shown) may be formed by penetrating at least a portion of the inner wall (112), and more specifically, it may be formed by penetrating the portion of the inner wall (112) that contacts the deepest part of the well (110) in the first direction (DR1). However, this is merely an example for convenience of explanation, and it goes without saying that the present invention is not limited thereto.

[0075] Referring again to FIGS. 1 and FIGS. 2, in one embodiment, the well plate (100) may include a well membrane (120). The well membrane (120) may cover the through hole (not shown).

[0076] As explained above, since the well membrane (120) covers the through hole (not shown), the well (110) and the external space in the area where the through hole (not shown) is located can be spatially separated by the well membrane (120).

[0077] In one embodiment, the well membrane (120) may include a flexible material.

[0078] In an exemplary embodiment, the well membrane (120) can be easily penetrated by the invasive structure when subjected to an external force by the invasive structure.

[0079] In one embodiment, the well membrane (120) may comprise a synthetic polymer material comprising at least one of polyethylene terephthalate, polycarbonate, polytetrafluoroethylene, cellulose nitrate, and cellulose acetate, and / or a natural polymer comprising at least one of collagen, gelatin, and extracellular matrix-coated membranes (ECM coated membranes).

[0080] As described below, the probe (500) may be provided on the base plate (200). The probe (500) may be provided in a form that extends along the first direction (DR1) from the base plate (200).

[0081] In this case, if the well plate (100) is operated to move along the first direction (DR1) to the part where the base plate (200) is located, the end of the probe (500) may come into contact with the well membrane (120). If such operation is continuously performed even after contact, the well membrane (120) receives an external force from the probe (500) along the first direction (DR1), and if an external force exceeding a certain level is applied, the well membrane (120) may be penetrated by the probe (500). When penetration is completed, the probe (500) passes through the well membrane (120), and at least a portion thereof may be located within the well (110).

[0082] It is not necessary, but at least the length having the maximum value among the lengths connecting one point and another point of the stopper (311) according to some direction may be the third length (L3).

[0083] As a non-limiting example for explanation, if the rod (310) is provided in a cylindrical shape as described above, the outer diameter of the stopper (311) can eventually become the third length (L3).

[0084] In one embodiment, the fourth length (L4) may mean the maximum length among the lengths connecting one point of the well (110) and another point along a direction perpendicular to the first direction (DR1) in the well (110). This can be defined similarly to the third length (L3), but based on the well (110).

[0085] Meanwhile, the above-mentioned fourth length (L4) may be the same as the distance between the upper surfaces of any two well plates (100) that are spaced apart in a direction perpendicular to the first direction (DR1) with the well (110) in between.

[0086] In one embodiment, the stopper (311) can restrict the holder (300) from moving below a preset depth when it moves along the first direction (DR1) within the well (110).

[0087] As previously explained, the third length (L3) may be larger than the fourth length (L4). In this embodiment, when looking at the positional relationship between the holder (300) and the well plate (100), if both the holder (300) and the well plate (100) are projected onto a virtual plane perpendicular to the first direction (DR1), at least a portion of the stopper (311) and at least a portion of the upper surface (100A) of the well plate (100) may overlap each other.

[0088] Accordingly, when the holder (300) moves along the first direction (DR1) within the well (110) and approaches the well membrane (120), at least a portion of the stopper (311) also approaches at least a portion of the upper surface (100A) along the first direction (DR1). If it moves to a preset depth, due to the relationship between the third length (L3) and the fourth length (L4) described above and the positional relationship between the holder (300) and the well plate (100), at least a portion of the stopper (311) and at least a portion of the upper surface (100A) of the well plate (100) come into contact. From this point on, even if an external force is continuously applied to cause the holder (300) to approach the well membrane (120), further movement of the holder (300) is restricted by contact between the stopper (311) and the upper surface (100A) of the well plate (100), so the holder (300) cannot move in the first direction (DR1) within the well (110).

[0089] Meanwhile, the above-mentioned depth may be related to the length of the rod (310).

[0090] In one embodiment, the length from one end to the other end of the rod (310) along the first direction (DR1) may be shorter than the maximum length of the well (110) along the first direction (DR1).

[0091] Referring again to FIGS. 1 and FIGS. 2, in one embodiment, the holder (300) may include a holder membrane (320).

[0092] In one embodiment, the holder membrane (320) may be located at one end of the rod (310).

[0093] Meanwhile, the upper end of the rod (310) may be the upper end intended to be closest to the three-dimensional biological model (50) when the holder (300) is operated. Accordingly, the holder membrane (320) located at the upper end of the rod (310) may be located at a position intended to come into contact with the three-dimensional biological model (50) when the holder (300) is operated.

[0094] In one embodiment, the holder membrane (320) may include a material that is relatively soft and chemically stable. In such an embodiment, the holder membrane (320) may be soft overall and may not cause a significant chemical reaction even when in contact with the culture medium (20) and / or the three-dimensional biological model (50) contained within the well (110).

[0095] Meanwhile, the holder membrane (320) is positioned at a location intended to contact the three-dimensional biological model (50), so that the holder membrane (320) can come into contact with the three-dimensional biological model (50) when the holder (300) is operated. At this time, as described above, the holder membrane (320) can have flexibility, so the impact that may be applied to the three-dimensional biological model (50) when in contact with the three-dimensional biological model (50) can be minimized.

[0096] In one embodiment, the holder membrane (320) may use the same material as the well membrane (120) or a different material as its material.

[0097] In one embodiment, the holder membrane (320) may include at least one of an elastic synthetic polymer (Polydimethylsiloxane, Polyethylene-co-vinyl acetate, Polyurethane, Hydrogel, etc.) and a natural polymer (Collagen, Gelatin, Silk fibroin, Chitosan, etc.) based porous structure as its material, which is harmless to cell viability, has mechanical support and appropriate permeability, and has chemical stability and biocompatibility.

[0098] In one embodiment, the holder membrane (320) may be flexible compared to the well membrane (120).

[0099] Accordingly, the holder membrane (320) can apply pressure to fix the three-dimensional biomodel (50) without damaging the well membrane (120).

[0100] In one embodiment, the holder membrane (320) may have a concave shape in the direction toward the other end of the rod (310).

[0101] In such an embodiment, by manipulating the holder (300), the positional movement of the three-dimensional biological model (50) can be controlled with simple and precise movements without damaging the three-dimensional biological model (50). Additionally, the position of the three-dimensional biological model (50) can be aligned with the position of the probe (500) by having a concave shape at the part where the holder membrane (320) contacts the three-dimensional biological model (50). In particular, by the structure described above, the three-dimensional biological model (50) can be controlled to maintain a fixed state on the well membrane (120) to a certain extent without damaging the three-dimensional biological model (50). This aspect may be illustrated in FIG. 4, which will be described later.

[0102] Referring again to FIGS. 1 and FIGS. 2, in one embodiment, the device (10) further includes a cover (400) for opening and closing the well plate (100); and the holder (300) can be coupled with the cover (400) at the other end of the rod (310).

[0103] In one embodiment, the device (10) may further include a cover (400). The cover (400) can open and close the well plate (100).

[0104] The cover (400) may seal the well plate (100) if necessary. In a specific embodiment, the cover (400) may seal the well (110) of the well plate (100) from the outside. In such an embodiment, the upper surface (100A) of the well plate (100) may be adjacent to the cover (400). Although not necessarily limited thereto, the lower surface (100B) of the well plate (100) may not be covered by the cover (400).

[0105] In one embodiment, the cover (400) may be configured to be separate from the well plate (100). In another embodiment, the cover (400) may be configured to be connected to the well plate (100) via a hinge connection or the like, and various other embodiments may be envisioned.

[0106] Furthermore, the cover (400) may be configured to be provided separately from the base plate (200). In another embodiment, the cover (400), well plate (100), and base plate (200) may be configured to be connected by means such as a hinge connection, or various other embodiments may be envisioned.

[0107] In one embodiment, the holder (300) can be coupled with the cover (400) at the other end of the rod (310).

[0108] As described above, the holder membrane (320) is positioned at one end of the rod (310). In this embodiment, the other end can be combined with the cover (400).

[0109] Meanwhile, as described above, the stopper (311) may be formed at the other end of the rod (310). In such an embodiment, the rod (310) can be fixed to the cover (400) by combining the stopper (311) and the cover (400).

[0110] As described above, when the holder (300) moves to a preset depth within the well (110), at least a portion of the stopper (311) and at least a portion of the upper surface (100A) of the well plate (100) come into contact. At this time, either side of the stopper (311) comes into contact with the upper surface (100A) of the well plate (100). At this time, the other side of the stopper (311) may be in a state where it is combined with the cover (400).

[0111] In this embodiment, the position control operation of the three-dimensional biological model (50) can be performed simply and accurately by means of the holder (300) fixed to the cover (400) by only the simple operation of sealing the well plate (100) with the cover (400). In this case, the wells (110) can also be sealed by the cover (400), thereby providing an environment for analyzing the three-dimensional biological model (50), so that more accurate and convenient analysis can be performed.

[0112] Figure 4 is a diagram showing an example of performing an analysis on a three-dimensional biological model by manipulating a holder.

[0113] As previously explained, the holder (300) can be moved along the first direction (DR1) within the well (110) to maintain the state in which the three-dimensional biomodel (50) is positioned on the well membrane (120).

[0114] In one embodiment, when the holder (300) applies an external force to the well plate (100) along the first direction (DR1), the well plate (100) may be movable along the first direction (DR1).

[0115] As described above, when the holder (300) moves to a preset depth within the well (110), at least a part of the stopper (311) and at least a part of the upper surface (100A) of the well plate (100) come into contact. Even after such contact is made, if an external force according to the first direction (DR1) is continuously applied to the holder (300), the external force according to the first direction (DR1) can be transmitted to the well plate (100) that is in contact with the part of the stopper (311), and accordingly, the well plate (100) can also move along the first direction (DR1).

[0116] In this case, while the holder (300) is still regulating the position of the three-dimensional biomodel (50), the well plate (100) can move along the first direction (DR1), specifically to move to approach the base space (250) and / or the probe (500).

[0117] Referring to the embodiments described above, the well plate (100), which moves along the first direction (DR1) to approach the base space (250) and / or the probe (500), may be placed on the side wall (220) after entering the base space (250). Even at this time, the position of the three-dimensional biomodel (50) on the well membrane (120) is still restricted by the holder (300), and as previously described, the well membrane (120) may be invaded by the probe (500) before the well plate (100) is fully placed. Accordingly, the three-dimensional biomodel (50), whose position was restricted on the well membrane (120) before the well plate (100) is placed, or simultaneously with the placement, may also be invaded by the probe (500). Such an aspect is illustrated in FIG. 4.

[0118] Meanwhile, the base plate (200) and the well plate (100) are configured separately, and have a structure in which at least a portion of the probe (500) enters the well (110) only during the analysis process by user operation. Additionally, the same well plate (100) can be applied to various analyses by replacing the base plate (200) with one having a different probe (500) configuration. Similarly, by replacing the well plate (100), analyses of different biological models (50) can be performed continuously. In such an embodiment, the base plate (200) can be reused multiple times after undergoing only a slight cleaning process.

[0119] In one embodiment, the wells (110) are provided in a plurality, and each of the holder (300) and the probe (500) may be provided in a plurality so as to correspond to each of the plurality of wells (110).

[0120] In one embodiment, the well (110) in the well plate (100) may be provided in multiple numbers. Since the details regarding each individual well (110) can be applied in the same way as the details described above with reference to FIG. 1 and FIG. 2, etc., redundant descriptions will be omitted below.

[0121] The number of wells (110) provided in the well plate (100) may not be particularly limited. For example, it may be a 12-well plate with 12 wells, but it is not necessarily limited to this, and may be configured in various ways as needed, such as a 6-well plate, a 24-well plate, a 48-well plate, a 72-well plate, a 96-well plate, a 384-well plate, etc.

[0122] In one embodiment, the probe (500) may be provided in multiple numbers on the base plate (200).

[0123] In the above embodiment, the base space (250) may be provided so that one is located at a position corresponding to each of the wells (110).

[0124] In such an embodiment, the number of base spaces (250) may be the same as the number of wells (110).

[0125] Meanwhile, in the above embodiment, the probe (500) may be provided to be positioned one by one in each of the base spaces (250).

[0126] In another embodiment, the number of probes (500) may be greater than the number of wells (110).

[0127] Meanwhile, in the above embodiment, a plurality of probes (500) may be provided to be located in at least a portion of each of the base spaces (250). That is, in some base spaces (250), a plurality of probes (500) may be located in one base space (250).

[0128] In one embodiment, the holder (300) in the cover (400) may be provided in multiple numbers.

[0129] In such an embodiment, the number of holders (300) may be the same as the number of wells (110).

[0130] Meanwhile, in the above embodiment, the holder (300) may be provided to be coupled to each position corresponding to each well (110) in the cover (400). Since the aspects such as the positional relationship between the well (110) and the holder (300) can be applied in the same way as described with reference to FIG. 1 and FIG. 2, redundant descriptions will be omitted below.

[0131] In such an embodiment, the above analysis can be performed simultaneously in a plurality of wells (110). Meanwhile, a different three-dimensional biological model (50) may be contained in each of the plurality of wells (110), or the analysis conditions may be set differently for each. In such an embodiment, the device (10) can accurately perform electrochemical analysis on various types of three-dimensional biological models (50) under various analysis conditions with just a single simple operation.

[0132] Although the present invention has been described above by way of embodiments, this is provided only to aid in a more comprehensive understanding of the invention, and the invention is not limited to the above examples. Those skilled in the art can make various modifications and variations from this description.

[0133] Accordingly, the scope of the concept of the present invention shall be considered to include not only the claims set forth below but also all things equivalent to or having equivalent variations thereof.

Claims

1. As an analysis device for a three-dimensional biological model, Well plate; base plate; and A probe provided on the base plate; comprising, The above well plate is, A device comprising a well that accommodates the three-dimensional biological model, wherein at least a portion of the upper surface of the well plate is a region recessed along a first direction.

2. In Paragraph 1, The above 3D biological model is, A device comprising at least one selected from the group consisting of cardiac organoids, vascular organoids, retinal organoids, brain organoids, spinal cord organoids, tumor organoids, neural organoids, organoids containing cells subjected to optogenetic manipulation, lung organoids, gastric organoids, small intestine organoids, liver organoids, pancreatic organoids, kidney organoids, bladder organoids, testicular organoids, ovarian organoids, bone marrow organoids, thymus organoids, skin organoids, hair follicle organoids, inner ear organoids, and olfactory epithelial organoids.

3. In Paragraph 1, The above well plate is, A device comprising a through hole penetrating at least a portion of the well plate and a well membrane covering the through hole.

4. In Paragraph 3, A device in which the through hole penetrates at least a portion of the well plate along the first direction.

5. In Paragraph 1, The above probe is a device extending along the first direction.

6. In Paragraph 5, The above probe is, A device comprising a plurality of electrodes arranged along the first direction.

7. In Paragraph 5, The above base plate is, It includes a bottom portion and a side wall portion extending along the first direction around the perimeter of the bottom portion, The above side wall portion is, A device comprising a stepped portion that forms a step so that at least a portion of the well plate is seated at one end of the side wall portion.

8. In Paragraph 7, The above probe is a device provided in the bottom portion.

9. In Paragraph 8, A device in which the first length, which is the length from the bottom portion along the first direction to the step portion, is shorter than the second length, which is the length of the probe along the first direction.

10. In Paragraph 9, A device in which the difference between the second length and the first length is 50 μm to 5 mm.

11. In Paragraph 1, The above device is, It further includes a holder positioned spaced apart from the well plate; The above holder is a device movable along the first direction within the well.

12. In Paragraph 11, The device comprises a holder extending along the first direction and a holder membrane located at one end of the rod.

13. In Paragraph 12, The rod includes a stopper extending from the other end of the rod along the circumference of the rod in a direction perpendicular to the first direction, and A device in which a third length, which is the maximum length among the lengths connecting one point of the stopper and another point along a direction perpendicular to the first direction, is longer than a fourth length, which is the maximum length among the lengths connecting one point of the well and another point along a direction perpendicular to the first direction.

14. In Paragraph 13, A device in which, when the holder applies an external force to the well plate along the first direction, the well plate is movable along the first direction.

15. In Paragraph 11, The above well is provided in multiple numbers, A device comprising a plurality of holders and probes, each of which is provided to correspond to a plurality of wells.

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