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Micro-fluidic chip-based multiple-organ tumor targeting drug testing platform and application thereof

A technology of microfluidic chip and testing platform, which is applied to the measurement/inspection of microorganisms, the method of supporting/immobilizing microorganisms, biochemical instruments, etc., and can solve problems such as being in the blank stage

Pending Publication Date: 2017-06-09
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

At present, in the evaluation of new drugs, the simulation of tissue engineering using microfluidic chips, especially the research and analysis of building a multi-organ tumor-targeted drug testing platform is still in a blank stage

Method used

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  • Micro-fluidic chip-based multiple-organ tumor targeting drug testing platform and application thereof
  • Micro-fluidic chip-based multiple-organ tumor targeting drug testing platform and application thereof
  • Micro-fluidic chip-based multiple-organ tumor targeting drug testing platform and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Establishment of multi-organ tumor targeting drug testing platform chip

[0027] Design and manufacture chips, the upper chip 1 is a cell culture chamber 4, the lower chip 2 is three parallel independent channels, the structure is as follows figure 1 as shown in b. The porous filter membrane 3 is placed on a glass slide for UV activation for 1 hour, silanized for 30 minutes, sealed with the upper chip 1 by oxygen plasma, and placed in an oven at 80 degrees for 30 minutes. Use a PDMS polymer with a monomer-to-initiator ratio of 20:1, and throw it on a glass slide to a thickness of 10um-50um. After dipping the upper surface of the lower chip 2 into thin PDMS, it is aligned and bonded to the porous filter membrane 3 sealed with the upper chip. , 80 degrees, 30 minutes to cure completely. The result is as figure 1 as shown in a.

Embodiment 2

[0029] Characterization of a multi-organ tumor-targeted drug testing platform

[0030] The microfluidic chip designed and manufactured by the laboratory itself has a structure such as figure 1 as shown in b. After Hepg2 cells were treated with green cell membrane dye for 30 min, they were inserted into cell culture chamber 4 on the upper chip. After MDA-MB-231 cells, A549 cells, and GES-1 cells were treated with red cell membrane dye for 30 minutes, they were respectively inserted into the three channels of the lower chip, 1# channel 5, 2# channel 6, and 3# channel 7. Use a fluorescence microscope to photograph the cells in the cell culture chamber 4 on the upper layer of the chip, and the results are as follows figure 2 As shown in a, the cells of channel 1# channel 5, channel 2# channel 6, and channel 3# 7 of the lower chip channel were photographed with a fluorescent microscope, and the results are as follows figure 2 as shown in b. Merge the fluorescence image of the...

Embodiment 3

[0032] Testing the effect of capecitabine on different cells using a multi-organ tumor-targeted drug testing platform

[0033] Using the microfluidic chip designed and manufactured by the laboratory, the structure is as follows: figure 1 as shown in b. Prepare a type I mouse tail collagen working solution with a concentration of 100 μg / mL, inject it into the chip through the cell inlet pool, let it stand at room temperature overnight, remove the collagen working solution after 24 hours, and wash the channel 3 times with the cell culture solution. When the upper chip was inoculated / not inoculated with Hepg2 cells, the three units of the lower chip were inoculated with MDA-MB-231, U87, and GES-1 cells, and H-DMEM medium containing 80 μM capecitabine was added to the upper culture chamber. After 48 hours, the toxic effect of the drug on different cells was detected by a dead / alive staining kit and a CCK8 kit. The result is as image 3 a and image 3 As shown in b, when capeci...

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Abstract

The invention provides a micro-fluidic chip-based multiple-organ tumor targeting drug testing platform and application thereof. A micro-fluidic chip consists of an upper layer chip, a lower layer chip and a porous filter membrane, wherein the upper part of the porous filter membrane is connected with the upper layer chip, and the lower part of the porous filter membrane is connected with the lower layer chip; the structure of the upper layer chip is of a large cell culture chamber, and the structure of the lower layer chip is of independent multiple channels, wherein the number of the channels is 1-9. A construction method of the micro-fluidic chip-based multiple-organ tumor targeting drug testing platform comprises the following steps: (1) manufacturing and modifying the chip; (2) inoculating and culturing cells in the upper layer chip; (3) inoculating and culturing cells in the lower layer chip. The upper layer chip is inoculated with hepatocytes so as to simulate the process of liver metabolism in a body, the lower layer chip is inoculated with different tumor cells and normal tissue cells, so that the effect of drugs, subjected to liver metabolism, on the different cells can be observed, and the effects of drugs, subjected to liver metabolism, on multiple groups of cells can be also observed; therefore, the screening and testing of the tumor targeting drugs can be realized, and the medicine formation rate of the screened drugs is greatly improved.

Description

technical field [0001] The invention belongs to the technical field of microfluidic chips, and in particular relates to a microfluidic chip-based multi-organ tumor targeting drug testing platform and an application thereof. Background technique [0002] Chemotherapy is one of the main means of comprehensive treatment of malignant tumors. The traditional method of drug testing generally relies on biological toxicity, without considering the metabolic process and bioselectivity of the drug in the body. The active drugs obtained in this way are often stranded due to toxicity and metabolic problems after being developed into the clinic, and the drug success rate is extremely low. An ideal targeted drug testing platform should be able to test and screen drugs that kill tumor cells without damaging normal tissue cells. It can simultaneously test the effects of drugs on different tumors and normal tissues, and can also simulate the enhanced activity of oral drugs after liver metabo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12M3/00C12M1/12C12Q1/02
CPCC12M23/16C12Q1/025
Inventor 秦建华李中玉王丽
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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