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CN-122012240-A - Microfluidic organ chip and system, application thereof and multi-organ co-culture method

CN122012240ACN 122012240 ACN122012240 ACN 122012240ACN-122012240-A

Abstract

The application relates to the technical field of biological tissue engineering and discloses a microfluidic organ chip, which comprises a chip body provided with a plurality of culture modules, wherein each culture module comprises a culture area comprising a first culture area and a second culture area which are communicated, two first liquid storage tanks which are respectively communicated with the first culture area, two second liquid storage tanks which are respectively communicated with the second culture area, a porous membrane is arranged between the first culture area and the second culture area to realize material exchange, and the culture area, the two first liquid storage tanks and the two second liquid storage tanks of each culture module are arranged corresponding to array hole sites of an orifice plate. Each culture module is arranged corresponding to the hole site of the hole plate array, can be seamlessly connected with high-flux detection equipment, and can be directly applied to scenes such as large-scale drug screening, drug effect evaluation and the like. Can realize gravity driven or pump driven perfusion culture, and can also realize single organ co-culture and multi-organ co-culture. The application also discloses a microfluidic organ chip system, application thereof and a multi-organ co-culture method.

Inventors

  • XIAO RONGRONG
  • ZHANG FENG
  • ZHOU YU

Assignees

  • 北京大橡科技有限公司

Dates

Publication Date
20260512
Application Date
20260413

Claims (10)

  1. 1. The microfluidic organ chip is characterized by comprising a chip body, wherein a plurality of culture modules are arranged on the chip body, and each culture module comprises: the culture area comprises a first culture area and a second culture area which are communicated, and a porous membrane is arranged between the first culture area and the second culture area to realize material exchange; the two first liquid storage tanks are respectively communicated with the first culture area, and the communication positions are positioned on two opposite sides of the first culture area; The two second liquid storage tanks are respectively communicated with the second culture areas, and the communication positions are positioned on two opposite sides of the second culture areas; wherein, the culture area, the two first liquid storage tanks and the two second liquid storage tanks of each culture module are arranged corresponding to the array hole sites of the pore plate.
  2. 2. The microfluidic organ chip according to claim 1, wherein, The culture region comprises a channel-type culture region or a pore-type culture region, and/or The culture area comprises a channel-type culture area, the ratio of the length to the width of the channel-type culture area is 3-6:1, and/or the length of the channel-type culture area is 5-10 mm, and/or the width of the channel-type culture area is 1.5-3 mm, and/or The culture region comprises a porous culture region, the distance between the two opposite side edges of the porous culture region is 3-5 mm, and/or The depths of the first culture area and the second culture area are respectively 200-800 mu m.
  3. 3. The microfluidic organ chip according to claim 1, wherein, The communication positions of the two first liquid storage tanks and the first culture area are positioned at two opposite ends of the first culture area in the first direction, the communication positions of the two second liquid storage tanks and the second culture area are positioned at two opposite ends of the second culture area in the first direction, and/or The first liquid storage pool is communicated with the first culture area through a first communication channel, and the included angle alpha 1 between the first communication channel and the first direction of the first culture area is more than 90 degrees and less than 180 degrees, and/or The second liquid storage pool is communicated with the second culture area through a second communication channel, and the included angle alpha 2 between the second communication channel and the first direction of the second culture area is more than 90 degrees and less than 180 degrees, and/or The connection line of the two first liquid storage tanks is intersected with the connection line of the two second liquid storage tanks, and/or Two first liquid storage tanks are arranged along two sides of the first direction of the first culture area, two second liquid storage tanks are arranged along two sides of the first direction of the second culture area, and/or A first liquid storage tank and a second liquid storage tank are arranged at one side of the first direction of the culture area, and the other first liquid storage tank and the other second liquid storage tank are arranged at the other side of the first direction of the culture area, and/or The distance between the first liquid storage pool and the second liquid storage pool which are arranged on the same side along the first direction of the culture area is 0.5-1 mm.
  4. 4. A microfluidic organ chip according to any one of claims 1 to 3, wherein, A culture zone, two first liquid reservoirs and two second liquid reservoirs of each culture module are arranged corresponding to one 3X 3 array hole site of the pore plate, wherein the culture zone corresponds to the hole site (2, 2), the two first liquid reservoirs and the two second liquid reservoirs correspond to the hole site (1, 1), the hole site (1, 3), the hole site (3, 1) and the hole site (3, 3) are arranged, and/or The vertical projection of the first and second reservoirs falling outside the culture zone, and/or An observation window is arranged above the culture area.
  5. 5. A microfluidic organ chip, comprising: a bearing frame on which a plurality of bearing positions are arranged; The chip unit comprises a unit body and a plurality of culture modules arranged on the unit body, wherein the culture modules adopt the co-culture chip as claimed in any one of claims 1 to 4.
  6. 6. The microfluidic organ chip according to claim 5, wherein, A plurality of bearing positions arranged side by side, and/or The frame comprises a frame body and a partition frame, wherein the partition frame is arranged in the frame body to divide the space in the frame body into a plurality of unit spaces which are used as bearing positions for adaptively arranging chip units, and/or At least the bottom of the bearing position of the bearing frame is hollowed out, and/or The side wall of the chip unit is an inclined side wall which is contracted from top to bottom along the thickness direction of the chip unit, the included angle between the inclined side wall and the vertical is 0.5-5 degrees, and/or A plurality of culture modules on a chip unit are arranged in a single row or column.
  7. 7. A microfluidic organ-on-chip system, comprising: a microfluidic organ chip according to any one of claims 1 to 4 or a microfluidic organ chip according to claim 5 or 6; the plurality of communication joints, each communication joint includes the first connecting portion and the second connecting portion of intercommunication, and first connecting portion is used for sealing the butt joint with first reservoir or second reservoir, and second connecting portion is used for being connected with external part, realizes the pump drive perfusion culture of co-cultivation district.
  8. 8. The microfluidic organ-chip system according to claim 7, wherein, The second connecting part of the communication joint is used for connecting with the luer joint, or the second connecting part is constructed as the luer joint, and/or The microfluidic organ chip system further comprises a cover plate, a plurality of communication joints and/or a plurality of connecting joints, wherein the cover plate can be covered on the microfluidic organ chip, the plurality of communication joints are fixedly or detachably arranged on the plate surface of the cover plate in a mode corresponding to the positions of the first liquid storage tank and the second liquid storage tank on the microfluidic organ chip, the first connecting parts of the communication joints are positioned at the first side of the cover plate and are used for being in sealing butt joint with the first liquid storage tank or the second liquid storage tank, the second connecting parts of the communication joints are positioned at the second side of the cover plate and are used for being connected with external parts, so that pump-driven perfusion culture of a culture area is realized, and/or When the microfluidic chip is adopted by the microfluidic organ chip according to claim 5 or 6, the microfluidic organ chip system further comprises a unit cover plate, and the communication joint is fixed or detachably arranged on the plate surface of the unit cover plate in a mode corresponding to the positions of the first liquid storage pool and the second liquid storage pool on the chip unit, wherein a first connecting part of the communication joint is positioned at the first side of the unit cover plate and is used for being in sealing butt joint with the first liquid storage pool or the second liquid storage pool, and a second connecting part of the communication joint is positioned at the second side of the unit cover plate and is used for being connected with an external part, so that pump-driven perfusion culture of a culture area is realized.
  9. 9. Use of a microfluidic organ chip according to any one of claims 1 to 6 or a microfluidic organ chip system according to claim 7 or 8 for in vitro construction of single organ models, single organ co-culture models and multi-organ co-culture models.
  10. 10. A method of performing multi-organ co-cultivation using the microfluidic organ-chip of claim 5 or 6, comprising: Respectively culturing organ models with different culture periods on different chip units, wherein the organ models with different culture periods are controlled to respectively reach cell states required by co-culture when being cultured to the same time node; When organ modules on different chip units reach cell states required by co-culture, the chip units are arranged on a bearing frame, and then the different chip units are communicated to perform multi-organ co-culture.

Description

Microfluidic organ chip and system, application thereof and multi-organ co-culture method Technical Field The application relates to the technical field of biological tissue engineering, in particular to a microfluidic organ chip and a microfluidic organ system, application of the microfluidic organ chip and a multi-organ co-culture method. Background Organ-on-a-Chip (OoC) is a microfluidic cell culture device that simulates critical structures and physiological functions of human organs on a microscale Chip by integrating micro-nano processing, cell biology and biomaterial technologies. This technique reproduces the complex physiological response at the organ level by precisely controlling the mechanical properties of the fluid, the biochemical microenvironment and the intercellular interactions by culturing living cells in a continuously perfused multi-chamber structure. Compared with the traditional research model, the organ chip solves the core pain point which puzzles biomedical research for a long time, wherein two-dimensional cell culture can not simulate the three-dimensional dynamic characteristics of a tissue interface (such as blood vessel-tissue barrier), and the animal model has the inherent defects of obvious inter-species difference, high cost, low flux, ethical disputes and the like. The current organ chip is divided into three designs, namely a multi-organ co-culture complex organ chip system, a bionic micro-environment regulation type chip and a high-flux drug screening chip, which have respective advantages and corresponding limitations. For example, multi-organ co-culture complex organ-chip systems typically rely on complex fluidic systems, which are often highly customizable in terms of equipment, flow path interfaces, etc., and therefore costly to procure for operation, as well as cross-platform compatibility. In order to realize specific mechanical force, the bionic microenvironment regulation type chip needs to use elastic materials such as PDMS, and the like, and the materials have the problem of lipophilic drug adsorption, so that the drug evaluation accuracy can be influenced. In the high-flux drug screening chip, the existing design depends on the formation of a channel by using matrine gel, and the preparation success rate is low, so that the practical test flux is limited, and meanwhile, the system is in pursuit of high-flux, and the fluid driving mode is to drive fluid to flow by using liquid level difference and gravity. In the process of realizing the embodiment of the disclosure, the related technology is found to have at least the following problems that the existing microfluidic organ chip cannot be in seamless connection with high-flux detection equipment and cannot be used for both gravity-driven perfusion culture and fluid pump perfusion culture. Disclosure of Invention The following presents a simplified summary in order to provide a basic understanding of some aspects of the disclosed embodiments. This summary is not an extensive overview, and is intended to neither identify key/critical elements nor delineate the scope of such embodiments, but is intended as a prelude to the more detailed description that follows. The embodiment of the disclosure provides a microfluidic organ chip and a system, application thereof and a multi-organ co-culture method, so as to solve the problems that the existing microfluidic organ chip cannot be in seamless connection with high-flux detection equipment and cannot be used for both gravity-driven perfusion culture and fluid pump perfusion culture. In some embodiments, the microfluidic organ chip comprises a chip body, wherein a plurality of culture modules are arranged on the chip body, each culture module comprises a culture area, two first liquid storage tanks are respectively communicated with the first culture area and are positioned on two opposite sides of the first culture area, two second liquid storage tanks are respectively communicated with the second culture area and are positioned on two opposite sides of the second culture area, and the culture area, the two first liquid storage tanks and the two second liquid storage tanks of each culture module are arranged corresponding to array hole sites of a pore plate. In some embodiments, the microfluidic organ chip comprises a bearing frame, a plurality of chip units and a plurality of culture modules, wherein the bearing frame is provided with a plurality of bearing positions, the chip units are movably arranged at the bearing positions, the chip units comprise unit bodies and the culture modules are arranged on the unit bodies, and the culture modules are the culture modules in the co-culture chip. In some embodiments, the microfluidic organ chip system includes any one of the microfluidic organ chips described above and a plurality of communication connectors, each of the communication connectors including a first connection portion and a second connection portion that are in