Microfluid control system for separating, focusing and sorting of rare cells and application

A microfluidic system and rare cell technology, which is applied in the detection field of rare cells, can solve the problems of difficult CTCs release, incomplete separation, and low purity, to achieve online detection and rapid sorting, improve sensitivity and stability, The effect of improving sensitivity

Active Publication Date: 2019-08-23
SHANDONG NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The inventors believe that although these methods represent important advances in this field, their technical bottlenecks still exist; first, the single antibody capture that currently relies on the epithelial marker EpCAM causes epithelial-derived missing CTCs to fail to be captured, thereby cause missed detection
Second, the release of CTCs based on antibody capture is difficult, which is not conducive to the high-throughput sorting and subsequent analysis of CTCs.
Thirdly, although separation methods based on physical properties are relatively simple to operate, have high throughput, and are not de

Method used

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  • Microfluid control system for separating, focusing and sorting of rare cells and application
  • Microfluid control system for separating, focusing and sorting of rare cells and application
  • Microfluid control system for separating, focusing and sorting of rare cells and application

Examples

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Embodiment 1

[0033] refer to figure 1 and 2 , a microfluidic system for separation, focusing and sorting of rare cells, its core component is a microfluidic system including "separation unit 1, focusing unit 2, sorting unit 3 and flow resistance matching unit 4" Chip device I; wherein:

[0034] The separation unit 1 is a clockwise or counterclockwise "spiral" channel structure, one end of the "spiral" channel structure is provided with a sample inlet 101, and the other end of the "spiral" channel structure is provided with inner, Two outer outlets, the inner outlet 102 is connected to the inlet of the focusing unit 2, and the outer outlet 103 is connected to the inlet of the flow resistance matching unit 4, which constitutes the separation of rare cells and other cells in the body fluid, and passes through the inner, The outer two outlets lead rare cells and other cells into focusing unit 2 and flow resistance matching unit 4 respectively;

[0035] The focusing unit 2 is a direct coupli...

Embodiment 2

[0040] As a further technical solution, in a microfluidic system for rare cell separation, focusing and sorting described in Example 1: the microfluidic chip device I is "glass-PDMS-glass" or " PDMS-PDMS-glass" three-layer structure chip; the curved channel 201 is an asymmetrical sinusoidal channel structure; the straight channel 202, the optical detection channel 301, the rare cell sorting channel 302 and the waste liquid The flow channels 303 are straight channels with a high aspect ratio greater than or equal to 2:1.

Embodiment 3

[0042] In this example, the microfluidic system described in Example 1 was used as the test device, and three fluorescent microsphere mixtures (mixing ratio of 1×10) with diameters of 5 μm (yellow), 10 μm (red) and 15 μm (green) 9 / mL: 1×10 6 / mL: 1×10 3 / mL), to simulate blood samples and red blood cells, white blood cells and CTCs in blood samples, and to illustrate the workflow and basic principles of the microfluidic system designed in the present invention by testing three kinds of fluorescent microsphere mixtures.

[0043] First, the mixture of three kinds of fluorescent microspheres (or the body fluid sample marked with multicolor fluorescence) is injected into the separation unit of the microfluidic chip device from the sample inlet by the micro-syringe pump. In this unit (i.e., inertial separation based on helical channels), using the inertial lift F L and Dean Drag Force F D Dependence on microsphere size (F L / F D ∝a P 3 ), three kinds of fluorescent microsph...

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Abstract

The invention relates to the technical field of detection of rare cells, in particular to a microfluid control system for separating, focusing and sorting of rare cells and application. A microfluid control chip device comprising a separating unit, a focusing unit, a sorting unit and a flow resistance matching unit serves as the core of the system. The system is characterized in that the system can integrate operation like separation, focusing, single-cell analysis and sorting on the rare cells in body fluid such as blood in a continuous mode on one chip for completion, and therefore, the system can be widely applied to separation and sorting of the rare cells in the body fluid, and disease diagnosis, drug screening, individual-based treatment and other fields based on the rare cells.

Description

technical field [0001] The invention relates to the technical field of detection of rare cells, in particular to a microfluidic system and application for separation, focusing and sorting of rare cells. Background technique [0002] The information disclosed in the Background of the Invention is only intended to increase the understanding of the general background of the invention, and is not necessarily to be taken as an acknowledgment or any form of suggestion that the information constitutes the prior art that is already known to those skilled in the art. [0003] Human blood and other body fluids contain some rare cells that are rare but have important clinical value, such as circulating tumor cells (CTCs), fetal nucleated red blood cells (Fetal NRBCs), and virus-infected or parasitic cells. These rare cells can directly or indirectly reflect the health status of the body. Among them, CTCs called "liquid biopsy" are of great significance for the study of cancer stage dia...

Claims

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Application Information

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IPC IPC(8): C12M1/36C12M1/34C12M1/00
CPCC12M23/16C12M29/26C12M41/48C12M47/04
Inventor 李清岭续悦函李璐唐波
Owner SHANDONG NORMAL UNIV
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