Liver-Brain Barrier System Based on Microfluidic Chip to Simulate Metabolic Processes in vivo

A microfluidic chip and blood-brain barrier technology, which is applied to the measurement/testing of microorganisms, the method of supporting/immobilizing microorganisms, the culture device of tissue cells/viruses, etc., can solve the problem of in situ observation of mesenchymal stem cells, It is difficult to construct a blood-brain barrier model and other issues to achieve the effect of resolving secondary vaccination and reducing the failure rate

Active Publication Date: 2021-03-09
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Since the development of cell biology, the existing in vitro blood-brain barrier simulation methods mainly focus on commercialized orifice plates or Transwell chambers to study the structure and function of the two-dimensional blood-brain barrier model. The main problem is that the orifice plate or Transwell It is difficult for the small chamber to construct a blood-brain barrier model in vitro with interface conversion from two-dimensional plane to three-dimensional space, and it is difficult to realize in situ observation of mesenchymal stem cells crossing the blood-brain barrier for intracerebral tumor treatment
[0008] At present, the use of microfluidic technology to construct functional complex multi-organ chips for related research and analysis is still in a blank stage. If it can be realized, it will have great application prospects in biological research and pharmaceutical research and development.

Method used

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  • Liver-Brain Barrier System Based on Microfluidic Chip to Simulate Metabolic Processes in vivo
  • Liver-Brain Barrier System Based on Microfluidic Chip to Simulate Metabolic Processes in vivo
  • Liver-Brain Barrier System Based on Microfluidic Chip to Simulate Metabolic Processes in vivo

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Design and fabricate microfluidic chips, such as figure 1 shown.

[0044] The microfluidic chip is mainly composed of a top chip, a porous filter membrane, and a bottom chip. sealing; the top chip is formed by connecting the U-shaped main channel 1 of the top chip and the main channel entrance 11 of the top chip;

[0045] The bottom chip consists of left main channel 3, right main channel 6, collagen channel 7, collagen channel entrance 8, bottom chip left main channel entrance 9, and bottom chip right main channel entrance 10. Collagen channel 7 is connected to the left Main channel 3, right connected to right main channel 6;

[0046] The main channel 1 of the top chip is connected to the main channel 3 on the left side of the bottom chip through the porous filter membrane 5;

[0047] The main channel 3 on the left side of the bottom chip is I-shaped, the main channel 6 on the right side of the bottom chip is U-shaped, and the collagen channel 7 of the bottom chip c...

Embodiment 2

[0056] Blood-brain barrier penetration evaluation application of drugs.

[0057] After 24 hours, add paclitaxel (PTX) 2.34nM, capecitabine (CAP) 80μM, temozolomide (TMZ) 40μM cell culture medium to culture respectively, after 48 hours of treatment, CCK-8 cells were treated for U87 cells in the right main channel Vitality assays, results such as image 3 As shown in b, perform Live / Dead staining, the result is as follows image 3 as shown in a. It can be seen that after paclitaxel is metabolized by the liver, the cytotoxicity is reduced, and it is difficult to pass through the blood-brain barrier, so the cytotoxicity is further reduced. After capecitabine is metabolized by the liver, its cytotoxicity is significantly enhanced, and it can pass through the blood-brain barrier system. Temozolomide has no significant change in cytotoxicity before and after hepatic metabolism, and it can easily pass through the blood-brain barrier. The drug is converted into metabolites through ...

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Abstract

A liver-blood-brain barrier system based on a microfluidic chip for simulating metabolic processes in vivo. The microfluidic chip is mainly composed of a top chip, a porous filter membrane, and a bottom chip. The top chip is inoculated with liver cells, which can simulate the liver metabolism process of drugs in vivo; the bottom chip is mainly connected by the left main channel and the right main channel through the collagen channel, and the brain glial cell layer and the brain microvascular endothelial cell layer are seeded on the collagen interface Can simulate blood-brain barrier function. The invention integrates the construction and characterization of the in vitro blood-brain barrier model and the evaluation of the barrier permeability of the drug through the liver metabolism process, and can be used for the in vitro simulation of the blood-brain barrier model and the application of drug evaluation. The invention solves the problem of secondary inoculation and long time consumption of the cell co-culture model, adds flow conditions, is more in line with the real environment in the body, and significantly reduces the consumption of cells and reagents, and can obtain multiple experimental related parameters at the same time.

Description

technical field [0001] The invention relates to the application of microfluidic chip technology to the field of simulation and application of in vivo tissue engineering, in particular to a microfluidic chip-based liver-blood-brain barrier system for simulating metabolic processes in vivo. Background technique [0002] Animal experiments occupy an extremely important position in modern medicine and biology, but funding and animal ethics have also become unavoidable issues. Combining microfluidic technology and bioscience technology, an "organ chip" has been created, which can replicate the functions of human organs with microchips, making medical experiments easier. [0003] After drugs enter the body, they often go through processes such as absorption, distribution, metabolism, and excretion. The drug enters the blood circulation through the shielding membrane composed of cells from the outside or the site of administration, and enters the liver through the portal vein. Und...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12M3/00C12Q1/02
CPCC12M23/16C12M25/04G01N33/5014G01N33/5067
Inventor 秦建华郭雅琼李中玉许慧
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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