Microfluidic chip capable of realizing cell three-dimensional culture and drug screening and application

A microfluidic chip, three-dimensional culture technology, used in drug screening, tissue cell/virus culture devices, compound screening, etc., can solve the problems of inability to meet concentration gradients, low mixing efficiency, instability, etc. and detection effect

Inactive Publication Date: 2019-10-25
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, at present, most microfluidic chips are only used for the delivery and control of single-component or two-component microfluidics. For the mixing of fluids with more than three components, there are still disadvantages of low mixing efficiency and instability, which cannot meet the requirements of drug screening. Requirements for rapid formation of stable concentration gradients for multiple drugs
In addition, many studies have shown that cells cannot truly reflect their biological characteristics and functions in vivo in a flat two-dimensional culture environment. Therefore, it is necessary to combine microfluidic technology with three-dimensional culture of cells to establish a more in vivo environment An in vitro platform for drug screening

Method used

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  • Microfluidic chip capable of realizing cell three-dimensional culture and drug screening and application
  • Microfluidic chip capable of realizing cell three-dimensional culture and drug screening and application
  • Microfluidic chip capable of realizing cell three-dimensional culture and drug screening and application

Examples

Experimental program
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Effect test

Embodiment 1

[0041] As shown in Figures 1 and 2, a microfluidic chip that can realize three-dimensional cell culture and drug screening includes an upper chip 8 and a lower chip 7, the upper chip 8 is provided with channels of different geometric structures, and the channels Including cell culture chamber 3, serpentine channel 4, and triangular baffle 5; fluid inlet 1 is set on concentric circles, the concentric circles are not closed, and the center of the circle is set as fluid outlet 2, and the channel depth is 100 microns, except for oval cell culture chamber 3 , the width of the overall channel is 100 microns, and the angle α between the branch channel connecting the two concentric circles and the tangent line of the outer circle is 40°. Described lower layer chip 7 is provided with spherical groove 6 (as Figure 1bAs shown, each small circle is called a spherical groove), its cross-sectional diameter is 120 microns, and the depth of the spheres is 100 microns, which are evenly distrib...

Embodiment 2

[0043] As shown in Figure 3, the difference from Example 1 is that on the basis of three concentric circles, one concentric circle is added to form four different fluid concentration gradients, and the number of concentric circles can be increased or decreased according to the needs of the experiment. Concentration gradients of various fluids can be formed, and the layout is not limited to this embodiment.

experiment example 1

[0045] In order to calculate the substance concentration gradient in the cell culture chamber, three parallel experiments were carried out on the microfluidic chip of Example 1 of the present invention. Specifically, in these three experiments, the fluorescent reagent Rh123 was introduced into the outer ring, middle ring and inner ring respectively, and ultrapure water was loaded into the other two inlets of each experiment, and after perfusion at a flow rate of 1 μL / min for 10 min, Take fluorescence pictures with an inverted fluorescence microscope. Obtained by calculating the fluorescence intensity in the cell culture chamber as Figure 4 The line graph shown. It can be seen that the fluids of the three inlets are distributed in different proportions under the final concentration gradient, which verifies that the design of the middle and upper chip of the present invention can accurately control the fluids and quickly and stably generate the concentration gradients of the t...

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Abstract

The invention relates to a microfluidic chip capable of realizing cell three-dimensional culture and drug screening. The microfluidic chip comprises two layers of PDMS structure, an upper-layer chip is used for generating concentration gradient, a passage is mainly composed of a concentric round passage and a cell culture chamber leading to the center of a circle, an inlet of liquid is positionedon the circle while an outlet of the same is positioned at the center of the circle, and the concentration gradient of multi-component fluid is formed through constant flow diversion and concentrationof the liquid; a lower-layer chip is provided with a spherical groove which corresponds to the cell culture chamber of the upper-layer chip in position, the spherical groove is used for spherical three-dimensional culture of cells, and the two layers of the PDMS structure are combined through thermal bonding. The microfluidic chip has the advantages that the concentration gradient can be formed quickly and stably, the spherical groove is conducive to cell clustering growth, and cell clusters are locked in the groove, so that convenience is brought to observation and detection.

Description

technical field [0001] The invention relates to the field of microfluidic devices, in particular to a microfluidic chip and its application. Background technique [0002] In vitro cell experiment is an effective means to study drug efficacy, disease mechanism and provide reference for in vivo experiments. While routine experiments on 96-well plates can assess synergy between drugs, the number of possible combinations increases exponentially with the number of drugs considered. This will be even more complicated for personalized treatments of complex diseases and cellular environment considerations. Therefore, an in vitro platform that effectively predicts drug synergy and its optimal dosage is essential to guide clinical methods and discover reasonable combination therapies. [0003] At present, microfluidic chip technology is widely used in the fields of biology and medical research. Its highly integrated characteristics enable it to integrate preparation, reaction, separ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12M3/00C12M1/34
CPCC12M23/16G01N33/5008C12N2503/02G01N2500/10
Inventor 胡坪陈雨晴孙威宁柯张敏王月荣章弘扬
Owner EAST CHINA UNIV OF SCI & TECH
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