Chipset and organ-on-chip thereof, and bionic device using same

Abstract

A chipset comprising a plurality of organs-on-chips, wherein each organ-on-chip comprises a first body, a second body, and a membrane layer. The first body and the second body are connected to each other, and the organs-on-chips are connected to each other by means of a plurality of connecting ports and connecting holes. The first body further is further provided with an accommodating hole, a first flow channel, a second flow channel, and a third flow channel. The accommodating hole is in communication with the upper surface and the lower surface of the first body, and the membrane layer is arranged between the first body and the second body and covers the accommodating hole. The first flow channel passes through the accommodating hole and opens at a side edge of the first body; the second flow channel opens at a side edge and the lower surface of the first body; and the third flow channel opens at the upper surface and the lower surface of the first body. The second body is provided with an accommodating recess, the second flow channel is in communication with the accommodating recess and a side edge of the first body, and the third flow channel is in communication with the accommodating recess and the upper surface of the first body.

Description

Chip set and organ chip thereof, and bionic device using the same Technical Field

[0001] The present invention relates to a bionic technology, and in particular to a chipset and a combinable organ chip. Background Art

[0002] Traditional cell culture models have been widely used in human physiology, pharmacology, and other physical studies, but these simple models cannot reflect the complex physiological functions of human tissues and organs. Animal experiments have disadvantages such as long cycles and high costs. In addition, animal models cannot always directly predict the true response of the human body. Organ-on-a-chips mimic the key functions of human organs in a microfluidic system, recreating the physiological environment of organ cells in the body to simulate the complex structure, microenvironment, and physiological functions of human organs. They can also accurately control parameters and have advantages such as miniaturization, integration, high efficiency, and reduced costs. Therefore, they can serve as a beneficial tool for research and development in fields such as biomedicine, food science, and environmental chemistry.

[0003] Summary of the Invention

[0004] The present invention provides a chipset and organ-on-a-chip thereof, wherein the chipset is composed of multiple organ-on-a-chips. Due to the combinability of the organ-on-a-chip, the chipset is scalable and flexible in form, allowing for changes to be made in response to R&D needs and experimental conditions.

[0005] The chipset provided by the present invention includes a plurality of organ chips, and each organ chip includes a first body, a second body, and a membrane layer. The membrane layer is disposed between the first body and the second body, and the first body and the second body are interconnected. The first body has a receiving hole, a plurality of connection ports, and a plurality of connection holes, as well as a first flow channel, a second flow channel, and a third flow channel, wherein the receiving hole is arranged in the center of the first body and connects the upper surface and the lower surface of the first body; the plurality of connection ports and the plurality of connection holes are arranged on the side of the first body, and the organ chips are connected to each other through the plurality of connection ports and the plurality of connection holes; the first flow channel passes through the receiving hole and extends from the receiving hole in two different directions and opens to the side of the first body; the second flow channel connects the side and the lower surface of the first body and opens to the side and the lower surface of the first body respectively; the third flow channel connects the upper surface and the lower surface of the first body and opens to the upper surface and the lower surface respectively. The membrane layer is connected to the lower surface of the first body and shields the receiving hole from the lower surface, and the upper surface of the second body faces the lower surface of the first body and is interconnected with the first body. The second body has a receiving groove which is arranged in the center of the second body. The second flow channel communicates with the receiving groove and the side of the first body. The third flow channel communicates with the receiving groove and the upper surface of the first body.

[0006] The present invention also provides an organ chip, comprising a first body, a second body and a membrane layer. The membrane layer is disposed between the first body and the second body, and the first body and the second body are interconnected. The first body has a receiving hole, a plurality of connection ports and a plurality of connection holes, as well as a first flow channel, a second flow channel and a third flow channel, wherein the receiving hole is arranged in the center of the first body and connects the upper surface and the lower surface of the first body; the plurality of connection ports and the plurality of connection holes are arranged on the side of the first body and are suitable for connecting multiple organ chips to each other; the first flow channel passes through the receiving hole and extends from the receiving hole in two different directions and opens at the side of the first body; the second flow channel connects the side and the lower surface of the first body and opens at the side and the lower surface of the first body respectively; the third flow channel connects the upper surface and the lower surface of the first body and opens at the upper surface and the lower surface respectively. The membrane layer is connected to the lower surface of the first body and shields the receiving hole from the lower surface, and the upper surface of the second body faces the lower surface of the first body and is interconnected with the first body. The second body has a receiving groove which is arranged in the center of the second body. The second flow channel communicates with the receiving groove and the side of the first body. The third flow channel communicates with the receiving groove and the upper surface of the first body.

[0007] The present invention further provides a bionic system, comprising the aforementioned chipset, at least one culture fluid, and at least one liquid delivery device, wherein the at least one liquid delivery device delivers the at least one culture fluid to the chipset.

[0008] Because the chipset of the present invention uses organ chips, the organ chips have multiple connection ports and multiple connection holes for connecting organ chips and producing combination changes, so the chipset has scalability and flexibility in terms of style. Because the organ chips of the present invention have multiple connection ports and multiple connection holes for connecting organ chips, the chipset can be provided with scalability and flexibility in terms of style, and can be used for stand-alone or open bionic system design. Because the bionic system of the present invention uses the aforementioned chipset and organ chips, it has scalability and flexibility in terms of style, and can be changed according to research and development needs and experimental conditions.

[0009] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention, which can be implemented in accordance with the contents of the specification, and to make the above and other purposes, features and advantages of the present invention more obvious and easy to understand, the following specifically cites preferred embodiments and describes them in detail with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] FIG1 is a schematic exploded perspective view of an organ chip according to an embodiment of the present invention.

[0011] FIG2 is a schematic cross-sectional view along AA in FIG1 .

[0012] FIG3 is a schematic cross-sectional view along line BB in FIG2 .

[0013] FIG4 is a schematic cross-sectional view of an organ chip according to an embodiment of the present invention.

[0014] FIG5 is a schematic exploded perspective view of an organ chip according to another embodiment of the present invention.

[0015] FIG. 6 is another schematic perspective view of the embodiment of FIG. 5 .

[0016] FIG. 7 is a schematic side view of a chipset according to an embodiment of the present invention.

[0017] FIG8 is a schematic top view of a chipset according to an embodiment of the present invention.

[0018] FIG9 is a schematic top view of a chipset according to an embodiment of the present invention.

[0019] FIG10 is a schematic side view of a bionic system according to an embodiment of the present invention.

[0020] FIG. 11 is a schematic top view of a bionic system according to an embodiment of the present invention.

[0021] FIG. 12 is a perspective schematic diagram of a support structure according to an embodiment of the present invention. DETAILED DESCRIPTION

[0022] FIG1 is a perspective exploded schematic diagram of an organ chip according to an embodiment of the present invention, and FIG2 and FIG3 are schematic cross-sectional views along lines AA and BB in FIG1 , respectively. As shown in FIG1-3 , the organ chip 100 according to an embodiment of the present invention comprises a first body 200, a second body 300, and a membrane layer 400. The first body 200 and the second body 300 are made of a light-transmissive material, preferably transparent, while the membrane layer 400 is made of a material suitable for cell attachment, preferably porous. The membrane layer 400 is disposed between the first body 200 and the second body 300, and the first body 200 and the second body 300 are interconnected. The first body 200 and the second body 300 are removably connected to each other, and the connection therebetween can be achieved by any known means, such as screws, snaps, mortise and tenon joints, magnetic attraction, or other means capable of achieving a removable connection. The membrane layer 400 is connected to either the first body 200 or the second body 300. In a preferred embodiment of the present invention, the membrane layer 400 can be bonded to the lower surface 202 of the first body 200. The bonding therebetween can be achieved by any known means, such as heat pressing, welding, gluing, or other means capable of achieving bonding.

[0023] As shown in Figures 1-3, the first body 200 has a receiving hole 210, a plurality of connection ports 230, and a plurality of connection holes 250. The receiving hole 210 is approximately located in the center of the first body 200 and passes through the first body 200 in the z-axis direction as shown in Figures 1-3 to connect its upper surface 201 and lower surface 202. The receiving hole 210 is preferably a circular hole with a diameter of, for example, 5-20 millimeters (mm), but the present invention is not limited to this. The plurality of connection ports 230 and the plurality of connection holes 250 are arranged on the side of the first body 200 and are suitable for interconnecting multiple organ chips 100. In other words, the organ chips 100 of the embodiment of the present invention can be interconnected (described in detail later). Multiple organ chips 100 can form a chip set through the plurality of connection ports 230 and the plurality of connection holes 250. In a preferred embodiment of the present invention, the organ chip 100 is preferably rectangular. The first body 200 is also rectangular and has four sides in the xy plane. The connection ports 230 can be disposed on two adjacent sides, and the connection holes 250 can be disposed on opposite sides of the connection ports 230. When multiple organ chips 100 are assembled, for example, each organ chip 100 can be arranged in the same direction as shown in Figures 1-3 and connected in two mutually perpendicular directions x and y.

[0024] The first body 200 also has a first flow channel 271, a second flow channel 272, and a third flow channel 273. As shown in Figure 2, the first flow channel 271 passes through the accommodating hole 210 and extends from the accommodating hole 210 in two different directions, such as direction y and its opposite direction, and opens at the side of the first body 200. The second flow channel 272 connects the side of the first body 200 and the lower surface 202, and opens at the side and lower surface 202 of the first body 200 respectively. The third flow channel 273 connects the upper surface 201 and the lower surface 202 of the first body 200, and opens at the upper surface 201 and the lower surface 202 respectively. The diameters of the first flow channel 271, the second flow channel 272, and the third flow channel 273 can be the same or different. In an embodiment of the present invention, the diameters of the flow channels are partially the same and partially the same. Some flow channels may have smaller diameters and are suitable for liquids to pass through by capillary action.

[0025] The plurality of connection ports 230 further include a first connection port 231 and a second connection port 232, while the plurality of connection holes 250 include a first connection hole 251 and a second connection hole 252. The first connection port 231 and the second connection port 232 are located on different sides of the first body 200, such as the first side S1 and the second side S2, respectively. The first connection hole 251 and the second connection hole 252 are located on different sides of the first body 200, such as the third side S3 relative to the first side S1 and the fourth side S4 relative to the second side S2, respectively. In a preferred embodiment of the present invention, the first connection hole 251 and the first connection port 231 are located at opposite ends of the first flow channel 271 in the direction in which it extends. The first flow channel 271 further forms an opening 271a on the first side S1 through the first connection port 231, and an opening 271b is formed within the first connection hole 251 on the third side S3. The openings 271a and 271b are located at opposite ends of the first flow channel 271 in the direction in which it extends. Based on this, when multiple organ chips 100 are connected in direction y at an angle as shown in Figures 1-3, they are not only connected through the connection port 230 and the communication hole 250, but also interconnected through the first communication port 231 and the first communication hole 251, and the multiple first flow channels 271 are interconnected. The receiving holes 210 of the multiple organ chips 100 are also interconnected through the first flow channels 271. An elastic body, such as an elastic sheath, can be placed between the first communication port 231 and the first communication hole 251 to enhance the adhesion between them.

[0026] In a preferred embodiment of the present invention, the second flow channel 272 and the first flow channel 271 open on different sides of the first body 200. For example, when the openings 271a and 271b of the first flow channel 271 are located on the first side S1 and the third side S3, the second flow channel 272 opens on the second side S2 or the fourth side S4. More preferably, the second flow channel 272 further forms an opening 272a on the second side S2 through the second connecting port 232, and an opening 272b on the lower surface 202. As shown in Figure 3, the second flow channel 272 may include a horizontal section 2721 extending substantially along the direction x and a vertical section 2722 extending substantially along the direction z, wherein the horizontal section 2721 leads to the side of the first body 200, and the vertical section 2722 leads to the lower surface 202 of the first body 300. The second flow channel 272 of this embodiment of the present invention does not pass through the accommodating hole 210.

[0027] In an embodiment of the present invention, the third flow channel 273 communicates with the second connecting hole 252. Preferably, the third flow channel 273 is disposed proximate to the second connecting hole 252, for example, proximate to the fourth side S4. As shown in FIG3 , the third flow channel 273 may extend substantially along direction z, with openings 273a and 273b formed on the upper surface 201 and the lower surface 202, respectively. The third flow channel 273 may also have an opening 273c formed on its inner wall, with the opening 273c connecting the third flow channel 273 with the second connecting hole 252. When multiple organ chips 100 are connected in direction x at an angle as shown in FIG1-3 , the connection port 230 and the connecting hole 250 cooperate to connect, and the second flow channel 272 or the third flow channel 273 communicates with the second flow channel 272 or the third flow channel 273 of an adjacent organ chip 100 through the cooperation of the second connecting port 232 or the second connecting hole 252. The multiple organ chips 100 may further include an elastic body such as an O-ring disposed between the second communication port 232 and the second communication hole 252 to enhance the close contact therebetween.

[0028] As shown in Figures 1-3, the second body 300 has a receiving groove 320 located approximately in the center of the second body 300 and opening at the upper surface 301 of the second body 300. The second body 300 is connected to the first body 200 with the upper surface 301 facing the lower surface 202 of the first body 200. In this embodiment of the present invention, the opening of the receiving groove 320 is preferably larger than the diameter of the receiving hole 210. As shown in Figures 2-3, the projection of the receiving hole 210 on the second body 300 is contained within the range of the receiving groove 320. More preferably, the openings 272b and 273b of the second and third flow channels 272 and 273 on the lower surface 202 can fall within the range of the receiving groove 320, thereby connecting the second and third flow channels 272 and 273 to the receiving groove 320. The second flow channel 272 connects the receiving groove 320 to the side of the first body 200, and the third flow channel 273 connects the receiving groove 320 to the upper surface 201 of the first body 200. Furthermore, through the second connecting hole 252, the third flow channel 273 also connects the receiving groove 320 to the side of the first body 200 (S2). When the second connecting ports 232 and the second connecting holes 252 are mated and connected between multiple organ chips 100, the receiving grooves 320 of the multiple organ chips 100 can be interconnected via the second and third flow channels 272 and 273, and the multiple second flow channels 272 and the multiple third flow channels 273 are also indirectly connected to each other.

[0029] FIG4 is a schematic cross-sectional view of an organ chip according to one embodiment of the present invention. In a preferred embodiment of the present invention, as shown in FIG4 , a membrane layer 400 is connected to the lower surface 202 of the first body 200, shielding the receiving hole 210 from the lower surface 202 and separating the receiving hole 210 and the receiving tank 320 of the organ chip 100. The membrane layer 400 further has a first surface 401 and a second surface 402. The first surface 401 and the second surface 402 are suitable for cell attachment and face the receiving hole 210 and the receiving tank 320, respectively. When cells are attached to the first surface 401 and / or the second surface 402, the receiving hole 210 and / or the receiving tank 320 can contain an appropriate cell culture medium.

[0030] FIG5 is a perspective exploded schematic diagram of an organ chip according to another embodiment of the present invention. As shown in FIG5 , the difference from the aforementioned embodiment is that the organ chip 100′ includes an elastomer. The elastomer includes a first elastomer 510, which is disposed between the first body 200 and the second body 300. The first elastomer 510 can be, for example, a rubber ring, which can be used to strengthen the tightness between the first body 200 and the second body 300. The elastomer also includes a second elastomer 520, which can be disposed on the connection port 230. When multiple organ chips 100′ are connected to each other, the second elastomer 520 is equivalent to being disposed between the connection port 230 and the connection hole 250 of adjacent organ chips 100′. In a preferred embodiment of the present invention, the second elastomer 520 is disposed on the first connecting port 231 and the second connecting port 232, respectively.

[0031] As shown in Figure 5 , the second body 300, the first body 200, or a combination thereof may further include a receiving groove 330 for accommodating the first elastic body 510, while the first and second communicating ports 231 and 232 may respectively include receiving grooves 2310 and 2320 for accommodating the second elastic body 520. Figure 6 shows a perspective view of the first elastic body 510 assembled with the second body 300. As shown in Figure 6 , the first elastic body 510 may further surround the receiving groove 320 and separate it into an inner side 511 and an outer side 512. The projections of the receiving groove 210 of the first body 200 and the openings 272b and 273b of the second and third flow channels 272 and 273 on the second body 300 are located on the inner side 511 of the first elastic body 510. Because the first body 200 and the second body 300 are tightly sealed by the first elastic body 510, the liquid within the receiving groove 320 and the flow channels is confined to the inner side 511 of the first elastic body 510 and does not leak out.

[0032] The present invention also provides a chipset. Figure 7 shows a schematic side view of a chipset according to one embodiment of the present invention. As shown in Figure 7, the chipset 10 includes multiple organ chips 100'. The structure of the organ chips 100' is as described above for the organ chip 100. In addition, the chipset 10 can also be composed of organ chips 100.

[0033] As shown in FIG7 , multiple organ chips 100′ are arranged along a direction x, which is parallel to the first side S1. The connection ports 230 and communication holes 250 of adjacent organ chips 100′ are interconnected, and their second flow channels 272 and third flow channels 273 are interconnected via the second communication ports 232 and second communication holes 252. In this embodiment of the present invention, the opening 273a of the third flow channel 273 is located on the upper surface 201 of the first body 200 and is preferably exposed, suitable for serving as an inlet for a liquid 70, such as a culture medium. Furthermore, as shown in FIG7 , the opening 273a can be further connected to a connector 650 for injection of the liquid 70. The opening 273a of any organ chip 100′ allows the liquid 70 to enter, thereby allowing the liquid 70 to flow through the flow channel system including the second flow channel 272 and the third flow channel 273 and throughout the chipset 10. Liquid 70 is contained in each reservoir 320 of the chipset 10. In addition to that shown in FIG. 7 , the organ chips 100 ′ in the chip set 10 may also be combined into different patterns. For example, some of the organ chips 100 ′ are combined to be arranged along the direction y.

[0034] FIG8 is a schematic top view of a chipset according to another embodiment of the present invention. The difference from the embodiment of FIG7 is that the multiple organ chips 100' of the chipset 10a are arranged along direction y, which is parallel to the second side S2. The number of organ chips 100' is not limited to that shown in the figure. As shown in FIG8, the connection ports 230 and the connecting holes 250 of adjacent organ chips 100' are connected by cooperation, and their first flow channels 271 are interconnected through the first connecting ports 231 and the first connecting holes 251. In this embodiment of the present invention, the openings 271a and 271b of the first flow channel 271 can be exposed and configured on the side of the first body 200. Preferably, the opening 271b located in the first connecting hole 251 is suitable for serving as an inlet for the liquid 70'. As shown in FIG8, the opening 271b of the organ chip 100' at one end can be further connected to the connector 650 for injection of the liquid 70'. Liquid 70' flows through the flow channel system comprising the first flow channel 271 and the receiving holes 210, flowing throughout the chipset 10a. Liquid 70' is present in each receiving hole 210 in the chipset 10a. In addition to that shown in FIG8 , the organ chips 100' in the chipset 10a can be arranged in various configurations. For example, some organ chips 100' are arranged along the direction x.

[0035] FIG9 shows another schematic top view of the chipset 10a. The multiple organ chips 100′ of the chipset 10a are arranged along the x and y directions. The first communication ports 231 and / or first communication holes 251 of an organ chip 100′ communicate with the first communication ports 231 and / or first communication holes 251 of an adjacent organ chip 100′, and the second communication ports 232 and / or second communication holes 252 communicate with the second communication ports 232 and / or second communication holes 252 of an adjacent organ chip 100′. The openings 273a of any organ chip 100′ in each column allow liquid 70 to enter, while the openings 271b of the organ chips 100′ at the ends of each row allow liquid 70′ to enter. Thus, liquids 70 and 70′ flow through the chipset 10a and contact the first surface 401 and second surface 402 of the membrane layer 400, respectively. Liquids 70 and 70′ can be, for example, the same or different culture media.

[0036] Both chip sets 10 and 10a may further include a plurality of covers 600, which are adapted to respectively mate with the first communication port 231, the second communication port 232, the first communication hole 251, and the second communication hole 252 of the organ chip 100' and to shield the openings 271a, 271b, 272a, and 273c. The first communication port 231, the second communication port 232, the first communication hole 251, and / or the second communication hole 252 of the organ chip 100' that are not used for connection with adjacent organ chips 100', as well as the opening 273a of the third flow channel 273, may be provided with covers 600 to prevent the liquids 70, 70' from contacting the external environment. The covers 600 may have any form; any structure that mates with the shape of the communication port or communication hole and shields the opening may serve as the cover 600. The covers 600 may fit over the communication port or fill the communication hole.

[0037] The chipset of the present invention can be used in biomimetic systems. Bionic systems can simulate the microenvironment within a living organism, allowing for in vitro experiments or research, such as those involving physiology, pharmacology, pathology, and toxicology. When the chipset of the present invention is used in a biomimetic system, the first surface 401 and second surface 402 of the membrane layer 400 can be used to culture the same or different cells, respectively. Liquids 70 and 70' can be formulated based on the cell type, research and development requirements, and / or experimental conditions to act on the cells on both sides of the membrane layer 400. Liquids 70 and 70' can be the same or different. Because multiple organ chips 100' can be combined into different configurations, and the fluidic system allows the liquids 70 and 70' to be injected into the receiving grooves 320 and receiving holes 210 of each organ chip 100', the chipset of the present invention is flexible and scalable. It can be applied to various biomimetic systems to meet different research and development requirements and experimental conditions. Because the fluidic system has exposed openings 271a, 271b, 272a, and 273a, it can be used in an open design.

[0038] The present invention also provides a bionic system. FIG10 is a side view schematic diagram of a bionic system according to an embodiment of the present invention, and FIG11 is a top view schematic diagram of a bionic system according to an embodiment of the present invention. The bionic system according to an embodiment of the present invention includes a chipset as described above. As shown in FIG10-11 , the bionic system 1 includes a chipset 10b and a culture solution 71, and cells are cultured on at least one surface of the membrane layer 400 in the chipset 10b (not shown). For example, the first surface 401 of the membrane layer 400 can culture vascular endothelial cells, and the second surface 402 can culture tissue-specific epithelial cells. In the field of drug research and development, for example, the culture solution 71 may contain specific drugs that can act on two types of cells to test the effects of the drugs on the cells.

[0039] As shown in Figures 10-11, the biomimetic system 1 also includes a liquid delivery device 18 for delivering culture fluid 71 to the chipset 10b. The liquid delivery device 18 may include a piping system 19 and, for example, a pump (not shown). The piping system 19 communicates with the first flow channel 271 of the organ chip 100' in the chipset 10b. The culture fluid 71 flows through the piping system 19 and the first flow channel 271 into the plurality of receiving holes 210 and can contact the first surface 401 of the membrane layer 400. In this embodiment, another piping system 19' communicates with the second flow channel 272 and the third flow channel 273. The culture fluid 71' flows through the piping system 19', the second flow channel 272, and the third flow channel 273 into the plurality of receiving tanks 320 and can contact the second surface 402 of the membrane layer 400. The piping systems 19 and 19' may each include a main pipe and branch pipes connected to the first and second connecting holes 251 and 252, respectively, but the present invention is not limited thereto. The culture solutions 71 and 71 ′ in the organ chip 100 ′ can flow to the adjacent organ chip 100 ′ through the first communication port 231 and the second communication port 232 .

[0040] The culture solution 71 and / or 71' can then be left stationary in the receiving hole 210 or the receiving groove 320, or can be circulated in the chip set 10b. In some embodiments of the present invention, a cover 600 is provided on the first communication port 231 and / or the second communication port 232 of the organ chip 100' at the end, and the culture solution 71 and / or 71' does not flow. In other embodiments, the pump of the liquid delivery device 18 can pump the culture solution 71 out through the first communication port 231, thereby allowing the culture solution 71 to circulate in the chip set 10b, and / or can pump the culture solution 71' out through the second communication port 232, thereby allowing the culture solution 71' to circulate in the chip set 10b, but the present invention is not limited thereto.

[0041] The present invention also provides a method for assembling a biomimetic system, comprising step S810: providing a plurality of first bodies of organ chips, wherein the lower surface of the first bodies is bonded to a film layer; step S820: culturing first cells and second cells on the first surface and the second surface of the film layer, respectively; step S830: providing a plurality of second bodies of organ chips, connecting each of the second bodies with each of the first bodies to form a plurality of organ chips, wherein each of the chips has a first flow channel, a second flow channel, and a third flow channel; step S840: connecting the organ chips to form a chipset; and step S850: delivering at least one liquid to the chipset.

[0042] As described above, the membrane layer 400 in step S810 can be bonded to the lower surface 202 of the first body 200 by any known means, such as heat pressing, welding, or other means. The membrane layer 400 can be a porous scaffold or mesh, and its material can be a polymer such as polyethylene terephthalate (PETE), polydimethylsiloxane (PDMS), polyurethane, styrene-ethylene-butylene-styrene (SEBS), poly(hydroxyethyl methacrylate) (pHEMA), polyethylene glycol or polyvinyl alcohol, or polycarbonate (PC). Depending on experimental conditions, R&D requirements, and the types of first and second cells in step S820, the pore size of the membrane layer 400 can be larger or smaller, for example, within the range of 1-30 microns (μm), a small pore size of 0.3-5 μm, or a pore size of 5-20 μm or larger. Cells generally do not pass through the membrane layer 400, but the present invention is not limited thereto. Cell metabolic products may also pass through the membrane layer 400. In addition, the flow channel system is generally used to transport liquids. However, depending on experimental conditions and R&D needs, cells and cellular metabolic products may move through the flow channel system.

[0043] In a preferred embodiment of the present invention, step S810 also includes assembling a plurality of first bodies 200 to a support structure 9 as shown in FIG12 . The support structure 9 has a plurality of wells 91 on which a plurality of first bodies 200 can be detachably assembled. The number of wells 91 can be the number of organ chips 100' preset in the chipset 10, and the arrangement of the wells 91 is not limited to 6*2, and can also be various forms such as 3*3, 4*4, 6*4, 8*3, etc. The support structure 9 can be used for batch processing of subsequent steps. In step S820, first cells such as liver / kidney tissue-specific epithelial cells can be cultured on the first surface 401 of the membrane layer 400 of the plurality of first bodies 200 on the support structure 9. Then, the support structure 9 can be flipped over together with the plurality of first bodies 200 and second cells such as vascular endothelial cells can be cultured on the second surface 402. In some embodiments of the present invention, the first cells are, for example, renal podocytes, and the second cells are glomerular capillary endothelial cells. Step S830 may include assembling and connecting the first body 200 and the second body 300 on the support structure 9. In some embodiments of the present invention, the screw holes 290 of the first body 200 and the screw holes 390 of the second body 300 can be aligned and then fastened together with screws. Step S840 can also be completed on the support structure 9. For example, the support structure 9 can be used to complete the chip set 10 with a 6*2 arrangement of the organ chip 10', but this is not limited to this.

[0044] In summary, the organ-chip 100 of the present embodiment can provide at least two separable spaces above and below the membrane layer 400. The multiple connection ports 230 and multiple connection holes 250 provide for connections between organ-chips 100, thereby providing the chipset 10 with scalability and flexibility in layout, thereby forming a flow channel system including a first flow channel 271, and a flow channel system including a second flow channel 272 and a third flow channel 273. The multiple connection ports 230 and multiple connection holes 250 can also be used in conjunction with a cover 600 or connected to external pipes 19, 19', thereby enabling the chipset 10 to meet the requirements of a bionic system that is independent of the external environment or an open system, and can be modified in various ways to meet R&D needs and experimental conditions.

[0045] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment as above, it is not intended to limit the present invention. Any technician familiar with this profession can make slight changes or modifications to equivalent embodiments of equivalent changes using the above-disclosed methods and technical contents without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A chipset, characterized in that, Comprising a plurality of organ chips, and each of the plurality of organ chips includes a first body, a second body and a membrane layer; the membrane layer is disposed between the first body and the second body, and the first body and the second body are connected to each other, wherein: The first body has: A receiving hole, disposed at the center of the first body and communicating with the upper surface and the lower surface of the first body; A plurality of connection ports and a plurality of connection holes, disposed on the side of the first body, and the plurality of organ chips are connected to each other through the plurality of connection ports and the plurality of connection holes; A first flow channel; the first flow channel passes through the receiving hole, and extends in two different directions from the receiving hole and opens on the side of the first body; A second flow channel; the second flow channel communicates the side of the first body with the lower surface, and opens on the side and the lower surface of the first body respectively; and A third flow channel; the third flow channel communicates the upper surface and the lower surface of the first body, and opens on the upper surface and the lower surface respectively; The membrane layer is connected to the lower surface of the first body to shield the receiving hole from the lower surface; and The upper surface of the second body faces the lower surface of the first body and is connected to the first body; the second body has: A receiving groove, disposed at the center of the second body, and the second flow channel communicates the receiving groove with the side of the first body, and the third flow channel communicates the receiving groove with the upper surface of the first body.

2. The chipset according to claim 1, characterized in that, The plurality of connection ports further include a first communication port and a second communication port, and the first flow channel passes through the first communication port and opens on the side of the first body, and the second flow channel passes through the second communication port and opens on the side of the first body.

3. The chipset according to claim 2, characterized in that, The plurality of connection holes further include a first communication hole and a second communication hole, and the first flow channel opens into the first communication hole, and the second communication hole communicates with the third flow channel.

4. The chipset according to claim 3, characterized in that, The side of the first body further includes an adjacent first side and a second side, and the first communication port is located on the first side, and the second communication port is located on the second side.

5. The chipset according to claim 4, wherein The side of the first body further includes an adjacent third side and a fourth side, and the third side and the first side are respectively located on opposite sides of the first body, the fourth side and the second side are respectively located on opposite sides of the first body, and the first communication hole is located on the third side, and the second communication hole is located on the fourth side.

6. The chipset according to claim 4, characterized in that, The plurality of organ chips are further arranged along a first direction, and the first direction is parallel to the second side; the first communication port and the first communication hole of each of the plurality of organ chips are respectively matched and connected with the first communication hole and the first communication port of the adjacent organ chip, and the first flow channel of each of the plurality of organ chips communicates the receiving hole of the organ chip and the receiving hole of the adjacent organ chip.

7. The chipset according to claim 4, wherein The plurality of organ chips are further arranged along a second direction, and the second direction is parallel to the first side; the second communication ports and the second communication holes of each of the plurality of organ chips are respectively mated with the second communication holes and the second communication ports of adjacent organ chips for connection, and the second flow channels of each of the plurality of organ chips communicate the accommodation grooves of the organ chips and the accommodation grooves of the adjacent organ chips.

8. The chipset according to claim 1, wherein, Each of the plurality of organ chips further includes a first elastomer and a second elastomer; the first elastomer is disposed between the first body and the second body, and the second elastomer is disposed between adjacent ones of the plurality of organ chips.

9. The chipset according to claim 8, characterized in that, The first elastomer further surrounds the accommodation groove and demarcates an inner side and an outer side, and the accommodation groove, the opening of the second flow channel of the first body on the lower surface, and the opening of the third flow channel on the lower surface are located inside the first elastomer; the second elastomer is disposed between the connection ports of each of the plurality of organ chips and the connection holes of adjacent organ chips.

10. The chipset according to claim 1, characterized in that, The membrane layer has a first surface and a second surface; the first surface and the second surface face the accommodation hole and the accommodation groove respectively, and are suitable for cell adhesion.

11. The chipset according to claim 3, wherein, The chip set further includes a plurality of covers; the plurality of covers are respectively suitable for mating with the first communication ports, the second communication ports, the first communication holes and the second communication holes of each of the plurality of organ chips to shield the plurality of openings.

12. An organ-on-a-chip, characterized in that, Comprising a first body, a second body and a membrane layer; the membrane layer is disposed between the first body and the second body, and the first body and the second body are connected to each other, wherein: The first body has: An accommodation hole, disposed at the center of the first body and communicating the upper surface and the lower surface of the first body; A plurality of connection ports and a plurality of connection holes, disposed on the side of the first body, and the plurality of connection ports and the plurality of connection holes are suitable for the mutual connection of a plurality of organ chips; A first flow channel; the first flow channel passes through the accommodation hole, and extends in two different directions from the accommodation hole and opens on the side of the first body; A second flow channel; the second flow channel communicates the side of the first body with the lower surface, and opens on the side and the lower surface of the first body respectively; and A third flow channel; the third flow channel communicates the upper surface and the lower surface of the first body, and opens on the upper surface and the lower surface respectively; The membrane layer is connected to the lower surface of the first body to shield the accommodation hole from the lower surface; and The upper surface of the second body faces the lower surface of the first body and is connected to the first body; the second body has: An accommodation groove, disposed at the center of the second body, and the second flow channel communicates the accommodation groove with the side of the first body, and the third flow channel communicates the accommodation groove with the upper surface of the first body.

13. The organ chip according to claim 12, wherein The plurality of connection ports further includes a first communication port and a second communication port, and the first flow channel passes through the first communication port and opens at a side of the first body, and the second flow channel passes through the second communication port and opens at a side of the first body.

14. The organ-on-a-chip according to claim 13, characterized in that, The plurality of connection holes further includes a first communication hole and a second communication hole, and the first flow channel opens into the first communication hole, and the second communication hole communicates with the third flow channel.

15. The organ-on-a-chip according to claim 12, wherein Each of the plurality of organ chips further includes an elastomer; the elastomer is disposed between the first body and the second body.

16. The organ chip according to claim 15, characterized in that, The elastomer further surrounds the accommodation groove and separates an inner side and an outer side, and the accommodation groove, the opening of the second flow channel of the first body on the lower surface, and the opening of the third flow channel on the lower surface are located inside the elastomer.

17. The organ-on-a-chip according to claim 12, wherein The membrane layer has a first surface and a second surface; the first surface and the second surface face the accommodation hole and the accommodation groove respectively, and are suitable for cell attachment.

18. A bionic system, characterized in that, Comprising a chip set according to any one of claims 1-11, at least one culture solution and at least one liquid delivery device, wherein the at least one liquid delivery device delivers the at least one culture solution to the chip set.

19. The organ-on-a-chip according to claim 18, wherein, The at least one liquid delivery device includes a pipeline system; the pipeline system communicates with the plurality of first flow channels of the plurality of organ chips, and the at least one culture solution flows into the plurality of accommodation holes through the pipeline system and the plurality of first flow channels, and covers the surface of the membrane layer facing the accommodation holes.

20. The organ chip according to claim 18, characterized in that, The at least one liquid delivery device includes a pipeline system; the pipeline system communicates with the plurality of second flow channels and the plurality of third flow channels of the plurality of organ chips, and the at least one culture solution flows into the plurality of accommodation grooves through the pipeline system, the plurality of second flow channels and the plurality of third flow channels, and covers the surface of the membrane layer facing the accommodation grooves.

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