Bionic micro-fluidic chip for simulating in-vivo microorganism-intestine-brain axis signal transduction process

A microfluidic chip, signal transduction technology, applied in the determination/inspection of microorganisms, the method of supporting/immobilizing microorganisms, the method of stress-stimulating the growth of microorganisms, etc.

Active Publication Date: 2021-06-15
BEIHANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although, the existing in vitro bionic chips already include gut chips that can simulate the interaction between gut microbes and intestinal epithelial cells, and neuro-vascular unit (NVU) chips that can simulate metabolic processes in vivo (including blood-brain barrier and brain unit), but there is no bionic microfluidic chip that organically combines the intestinal tract, blood-brain barrier and brain unit through the blood circulation system, which can simulate the signal transduction process of the MGB axis in vivo

Method used

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  • Bionic micro-fluidic chip for simulating in-vivo microorganism-intestine-brain axis signal transduction process
  • Bionic micro-fluidic chip for simulating in-vivo microorganism-intestine-brain axis signal transduction process
  • Bionic micro-fluidic chip for simulating in-vivo microorganism-intestine-brain axis signal transduction process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Design and fabricate microfluidic chips, such as figure 1 shown.

[0037] The microfluidic chip is mainly composed of a top chip, a nanoporous membrane, a microporous membrane and a bottom chip. The top chip is divided into left and right parts. The main passage entrance (101) and the first back-shaped main passage exit (102) are composed, and the right part of the top chip is composed of the first upper semicircular passage (2), the first upper semicircular passage entrance (201) and the first Upper semicircular channel outlet (202), the first helical main channel (3), the first helical main channel inlet (301) and the first helical main channel outlet (302), the first lower semicircular channel ( 4) and the first lower semicircular channel entrance (401) and the first lower semicircular channel outlet (402); the bottom chip is also divided into left and right parts, and the left part of the bottom chip is composed of the second back-shaped main channel ( 5), the sec...

Embodiment 2

[0047] Integrity Identification of MGB Axis Bionic Microfluidic Chip

[0048] The two-layer PDMS of the microfluidic chip after 5 days of culture and operation was disassembled, and the intestinal epithelial cells Caco-2 and intestinal microorganisms co-cultured on the nanoporous membrane of the intestinal unit were stained for live dead cells and observed by fluorescence microscopy its coexistence state, such as figure 2 As shown in a, it can be seen that intestinal microorganisms and Caco-2 cells can coexist in the intestinal unit. Routine immunofluorescence staining was used to characterize the expression of ZO-1 protein on the surface of intestinal barrier Caco-2 cells and blood-brain barrier hBMECs cells, such as figure 2 As shown in b and 2c, it can be seen that tight junctions have been formed and have a barrier structure; the differentiation of human hippocampal neural stem cells in the bottom chip of the brain unit was observed by confocal fluorescence microscopy, ...

Embodiment 3

[0050] Permeability identification of MGB axis biomimetic microfluidic chip

[0051] Add FITC-labeled dextran to the channel (1) of the top chip of the intestinal unit, and collect the bottom channel outlet (502) and The perfusate of the top channel outlet (202) of the BBB inflow unit and the top channel outlet (402) of the BBB efflux unit was detected in a microplate reader, and the absorption wavelength was 490nm. The blank control group was MGB without cell attachment Axis biomimetic microfluidic chip. Such as image 3 As shown, with the increase of time, the permeation amount of dextran with cell barrier on the porous membrane gradually increases, the curve rises gently, and reaches an equilibrium state after 4-5h; The membrane penetration rate of dextran is fast, the curve rises rapidly, and the equilibrium state can be reached within 1-2 hours. The results showed that when cells were cultured on the porous membrane of the chip above, the membrane permeation rate of de...

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Abstract

The invention discloses a bionic micro-fluidic chip for simulating an in-vivo microorganism-intestine-brain axis signal transduction process. The micro-fluidic chip mainly comprises a top-layer chip, a nano porous membrane, a micron porous membrane and a bottom-layer chip. The micro-fluidic chip comprises an intestinal tract unit, a blood-brain barrier inflow and efflux unit and a brain unit, intestinal microorganisms and various human cells are inoculated on the chip, and signal transduction processes of metabolism, immunity, hormone and the like of microorganism-intestinal-brain axis in vivo can be simulated. The micro-fluidic chip can be used for carrying out molecular mechanism research of the action of intestinal flora and a central nervous system and screening and evaluation research of psychotropic drugs and psychotropic probiotics. According to the invention, intestinal microorganisms, the intestinal unit, the blood brain barrier and the brain unit are organically integrated on one chip, a system capable of simulating an in-vivo MGB axis signal transduction process is constructed, the problem of function simplification of a conventional chip is solved, the intestinal microorganisms are introduced, so that the chip is closer to an in-vivo real microenvironment, and the microenvironment of the chip is improved. A new therapy can be more easily found in the field of central nervous system diseases, and the development of personalized medicine is promoted.

Description

technical field [0001] The present invention relates to the application of microfluidic chip technology to the field of simulation and application of in vivo tissue engineering. Specifically, the present invention relates to a bionic microfluidic chip that simulates the signal transduction process of microorganism-gut-brain axis in vivo and its application. Background technique [0002] Bidirectional communication between the brain and the gut (known as the gut-brain axis) has long been recognized: the brain regulates the GI tract through motility regulation, i.e., the secretion and absorption of metabolites from the bloodstream; Tao also affects the function and behavior of the brain. In recent years, with the discovery that there is also a bidirectional interaction between gut microbes and the brain, the gut-brain axis has developed into the microbe-gut-brain (MGB) axis. The MGB axis is a key two-way communication path for signal transduction between gut microbes and the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01L3/00C12M3/00C12M3/06C12M1/34C12M1/12C12M1/00C12N5/09C12N5/071C12N5/079C12N5/0797C12N1/20C12Q1/02
CPCB01L3/502707C12M23/16C12M25/02C12M29/10C12M35/08C12M41/46C12N5/0693C12N5/069C12N5/0622C12N5/0623C12N1/20C12Q1/02C12Q1/025G01N33/5005G01N33/5032G01N33/5058C12N2502/30C12N2502/28C12N2502/086C12N2502/088C12N2503/02G01N2500/10
Inventor 郝梓凯刘义元刘红
Owner BEIHANG UNIV
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