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Liver-blood brain barrier system for simulating in-vivo metabolic process based on micro-fluidic chip

A microfluidic chip and blood-brain barrier technology, which is applied in the measurement/inspection of microorganisms, the method of supporting/immobilizing microorganisms, and the cultivation device of tissue cells/viruses, etc. It is difficult to build a blood-brain barrier model and other problems to achieve the effect of solving the secondary vaccination and reducing the failure rate

Active Publication Date: 2018-04-24
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • 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-blood brain barrier system for simulating in-vivo metabolic process based on micro-fluidic chip
  • Liver-blood brain barrier system for simulating in-vivo metabolic process based on micro-fluidic chip
  • Liver-blood brain barrier system for simulating in-vivo metabolic process based on micro-fluidic chip

Examples

Experimental program
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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

The invention provides a liver-blood brain barrier system for simulating the in-vivo metabolic process based on a micro-fluidic chip. The micro-fluidic chip is mainly composed of a top chip, a porousfilter membrane and a bottom chip, wherein liver cells are inoculated to the top chip, so that the liver metabolic process of the medicine in the body can be simulated; the bottom chip is mainly formed in a manner that a left main channel and a right main channel are connected through a collagen channel, and a brain colloid cell layer and a brain microvascular endothelial cell layer are inoculatedto a collagen interface, so that the blood brain barrier function can be simulated. According to the system, the construction and representation of an in-vitro blood brain barrier model are integrated with the evaluation for the permeability of the liver metabolism process of the medicine on a barrier, and the system can be applied to in-vitro simulation of the blood brain barrier model and the medicine evaluation. With the system provided by the invention, the problems of secondary inoculation and long consumed time of a cell co-culture model are solved, the flow conditions are added, so that the real environment in the body is well conformed, meanwhile, the consumption amount of cells and reagents is obviously reduced, and a plurality of experimental relevant parameters can be simultaneously obtained at one 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 Applications(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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