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Multi-organ chip and application thereof in drug evaluation

A multi-organ and chip technology, applied in the measurement/inspection of microorganisms, biochemical instruments, biomass post-processing, etc., can solve problems such as powerlessness, and achieve the effect of simple oxygen control methods

Active Publication Date: 2022-04-12
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the limitations of the principle, the above-mentioned traditional methods are unable to adjust the differential oxygen concentration of multiple organs in the human body chip, and new technologies need to be developed to solve this problem of the bionic human body chip

Method used

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  • Multi-organ chip and application thereof in drug evaluation
  • Multi-organ chip and application thereof in drug evaluation
  • Multi-organ chip and application thereof in drug evaluation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1: Construction of microalgae-gut-liver-tumor organ chip

[0053]Intestine-liver-tumor organ chip is the latest in vitro platform for oral anti-tumor drug screening. It can investigate the anti-tumor effect of drugs after intestinal absorption and liver metabolism at one time, which is more advanced than conventional in vitro anti-tumor drug screening platforms. In vivo, the liver is oxygen-rich, the intestine is oxygen-free, and the tumor is hypoxic. However, in the intestinal-liver-tumor organ-on-a-chip reported so far, the oxygen content in each organ is the same, which is not consistent with the situation in vivo. This will lead to insufficient biomimeticity, thereby reducing the reference value of drug evaluation results.

[0054] The difficulty in oxygen control of intestine-liver-tumor organ chip lies in: constructing oxygen-enriched area, anaerobic area and hypoxic area at the same time in one chip, adopting any traditional oxygen control method will ca...

Embodiment 2

[0068] Example 2: Application of microalgae-gut-liver-tumor organ chip in evaluating the antitumor activity of cyclophosphamide

[0069] The broad-spectrum antineoplastic drug cyclophosphamide itself is a weakly active drug. After being metabolized by CYP450 enzymes (mainly CYP2B6) in the body, it is transformed into the active substance aldophosphamide, and then transported into the tumor tissue to form phosphoramide mustard to inhibit cancer. effect on cell growth.

[0070] Cells and green algae were inoculated on the microalgae-intestine-liver-tumor organ chip according to the previously described method, and cultured in an incubator equipped with an LED system and an oxygen content monitoring system for 24 hours, waiting for the cells to completely adhere to the wall, and using Oxygen sensors monitor each chamber until a physiological oxygen concentration is reached in each chamber. The control group removed the light source and green algae, and was placed in an ordinary ...

Embodiment 3

[0075] Example 3: Application of Microalgae-Intestine-Liver-Tumor Organ Chip in Evaluation of Paclitaxel Antitumor Activity

[0076] The anti-cancer mechanism of paclitaxel is that the compound itself can induce and promote tubulin polymerization, inhibit microtubule depolymerization, induce cell cycle arrest and promote apoptosis, thereby exerting an anti-tumor effect. It will be blocked by CYP3A4 in the liver in vivo. Enzyme metabolism into metabolites with weak anticancer activity.

[0077] Cells and green algae were inoculated on the microalgae-intestine-liver-tumor organ chip according to the previously described method, and cultured in an incubator equipped with an LED system and an oxygen content monitoring system for 24 hours, waiting for the cells to completely adhere to the wall, and using Oxygen sensors monitor each chamber until a physiological oxygen concentration is reached in each chamber. The control group removed the light source and green algae, and was plac...

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Abstract

The invention discloses a multi-organ chip, which comprises a chip substrate and a chip cover plate attached to the chip substrate, at least two cell culture chambers are formed on the chip substrate, and the at least two cell culture chambers are respectively used for culturing different types of cells to simulate different organs; at least one cell culture chamber is provided with a microalgae culture chamber, and the microalgae culture chamber is formed on the chip substrate and is used for culturing microalgae to generate or consume oxygen; the cell culture chambers are communicated with the corresponding microalgae culture chambers, and gas exchange is allowed; the oxygen concentration in each cell culture chamber is independently controlled by adjusting the intensity of photosynthesis or respiration of microalgae in different microalgae culture chambers. According to the multi-organ chip, oxygen control of different organ areas on the chip is achieved, and the problem that an existing method is not suitable for oxygen content control on the multi-organ chip is solved.

Description

technical field [0001] The invention relates to the technical field of organ chips, in particular to a multi-organ chip and its application in drug evaluation. Background technique [0002] Drug development is a long and costly process. Most new drugs fail to enter the clinic. The main reason is that the existing in vitro cell culture technology and animal models cannot truly reflect the microenvironment in the human body. Organ-on-a-chip was proposed under this background. It is a kind of organ physiological microsystem constructed on a slide-sized chip, which contains key elements of organ microenvironment, such as living cells, tissue interface, biological fluid and mechanical force. . It can simulate the main structural and functional characteristics of different tissues and organs of the human body and the complex relationship between organs in vitro, so as to predict the human body's response to drugs or different external stimuli. Fields such as prediction and biode...

Claims

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Application Information

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IPC IPC(8): C12M3/00C12M3/02C12M3/04C12M1/36C12M1/34C12M1/04C12M1/00C12Q1/02
CPCC12Q1/02C12M1/36C12M1/04C12M1/34C12M3/04C12M3/02C12M1/00C12M3/00
Inventor 张秀莉刘远贵罗勇
Owner SUZHOU UNIV
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