Bionic multi-organ chip and preparation method therefor and application of bionic multi-organ chip

A multi-organ and chip technology, applied in the field of bionic multi-organ chip and its preparation, can solve the problems of overlapping upper and lower cells, unfavorable observation, etc., and achieve the effect of enhancing reliability

Pending Publication Date: 2020-06-02
苏州济研生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The multi-layer structure of the organ chip has problems such as overlapping cells in the upper and lower layers, which is not conducive to observation
And most of the chips cultured on the upper and lower layers can only cultivate two kinds of organs

Method used

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  • Bionic multi-organ chip and preparation method therefor and application of bionic multi-organ chip
  • Bionic multi-organ chip and preparation method therefor and application of bionic multi-organ chip

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1. Preparation of a multi-organ chip

[0038] Design the schematic diagram of the chip by computer, such as figure 1 and figure 2 As shown, the second layer 200 and the third layer 300 constitute the upper layer cell three-dimensional culture area. The middle area of ​​the second layer is a square structure, arranged with porous structures, circular holes 201 with a size of 50-400 microns, and a pitch of 50-100 microns. The third layer is a porous membrane with a size between 0.22-20 microns, and the material is a variety of transparent or translucent microporous membranes such as PC, PET, and PDMS. Filter membranes are used for material exchange. The fourth layer contains independent tissue and organ culture channels. It includes fluid inlets 401, 402 and two fluid outlets 403, 404 respectively. The upper layer and the lower layer have communication areas 407, 408. This area is a rectangular structure with a width larger than the fluid passage, which is co...

Embodiment 2

[0041] Example 2. Construction of bionic multi-organ chip

[0042] Before inoculating cells, the inside of the chip channel needs to be washed 3-5 times with PBS. Firstly, two kinds of cells were respectively inoculated in two independent culture areas on the lower layer. In this example, hepatocytes are taken as an example. After the primary mouse hepatocytes are extracted, they are prepared into a suspension, counted according to the 7th power of 1x10, and inoculated into one of the channels of the lower layer. After the cells settle in the three-dimensional culture area, apply The slow fluid washes away the cells in the microchannel, and only retains the cells in the three-dimensional culture area. In the same manner, cardiomyocytes derived from human induced pluripotent stem cells were inoculated in another channel. Static culture for 12-24 hours to promote liver and cardiomyocytes to form three-dimensional cell spheres.

[0043] After the lower layer of cell spheres is...

Embodiment 3

[0045] Example 3. Drug testing using a bionic multi-organ chip

[0046] This example realizes the co-cultivation of three tissues and organs of liver-heart-ovary cancer. In order to simulate the tumor-killing effect of clinical anticancer drugs, the toxic effect on the myocardium, the toxicity to the liver, and the effect of the drug metabolized by the liver, this embodiment takes doxorubicin as an example. Add doxorubicin-containing medium to the upper ovarian cancer inlet. After passing through the ovarian cancer layer, the culture medium on the upper layer penetrates into the lower layer through the porous membrane, and is respectively received by the liver and heart channels. Slow fluid is applied to the lower layer to promote the diffusion of the culture medium from the upper layer to flow into the lower liver and heart culture areas.

[0047] The drug evaluation implemented in this implementation can simulate multiple clinical cycles of chemotherapy, as well as the chro...

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Abstract

The invention belongs to the technical field of biological micro-fluidic control, in particular to a bionic multi-organ chip and a preparation method therefor. The chip consists of four layers, and comprises upper layer culture regions and lower layer culture regions; and each layer of cell culture region is provided with a microstructure inside to promote formation of a three-dimensional tissue cell; the upper layer cell culture regions and the lower layer cell culture regions communicate through porous membranes, and thus, substance exchange and drug penetration can be performed. Each culture region on the lower layer is provided with a liquid inlet and a liquid outlet, and the liquid inlet and the liquid outlet are used for cell inoculation and culture medium replacement. The multi-organ chip can culture three or more different types of tissue cells, thus realizing effects and influences of externally applied substances including drugs and the like on different organs, as well as interaction between upper layer tissue cells and lower layer tissue cells. The multi-organ chip can simulate the complex processes of drugs or other substances acting on different human organs of humanbody, and can also simulate disease models involved with multiple human organs.

Description

technical field [0001] The invention belongs to the technical field of biological microfluidics, and in particular relates to a bionic multi-organ chip and its preparation method and application. Background technique [0002] The in vitro model for drug safety evaluation is mainly based on cells. The static two-dimensional orifice culture method is mainly used, which is economical, convenient and easy to operate. However, due to the inability to simulate the dynamic stability of cell metabolism and nutrient supply maintained by blood circulation in the body, and the lack of interaction between tissues and organs from different sources (such as drug metabolism organs and toxic organs belonging to different organs), the entire culture system is different from The physiological microenvironment in the body is very different, especially in drug availability, toxicity and metabolism research, and the actual three-dimensional solid tissue in the body is quite different, resulting...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12M3/00C12M3/06C12N5/071C12N5/077C12N5/09C12Q1/02B01L3/00
CPCB01L3/5027B01L3/502707B01L2300/0861B01L2300/0887B01L2300/0893C12M21/08C12M23/16C12M23/22C12M29/04C12M35/08C12N5/0657C12N5/0671C12N5/0682C12N5/0693C12N2503/02C12N2513/00G01N33/5014G01N33/5017G01N2500/10
Inventor 魏文博王丽王南
Owner 苏州济研生物医药科技有限公司
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