Micro-fluidic chip and manufacturing method thereof

Abstract

The invention provides a micro-fluidic chip, which includes: a substrate; shaping electrode on a substrate; a gear shaping electrode on the substrate; an insulating layer covering the gear shaping electrode on the substrate; an electrode slice in the insulating layer and in electrical contact with the gear shaping electrode; a patterned bonding member with a hollow structure on the insulating layer; and a cover plate for sealing the hollow structure of the patterned bonding member therein, wherein the cover plate has an inlet hole and an outlet hole that are both communicated with the hollow structure. The invention also provides a manufacturing method of the micro-fluidic chip. The invention combines immune adsorption with the electrical characteristics of cells, a non-uniform electric field can be formed in a flow channel through the gear shaping electrode structure simply, cells receive a dielectrophoresis force, and non-targeted cells can break away without affecting targeted cell adsorption, thus maintaining high efficiency of cell immune adsorption while improving the adsorption purity under a flow rate conducive to specific adsorption.

Description

technical field [0001] The invention belongs to the technical field of semiconductor processing, and in particular relates to a microfluidic chip and a manufacturing method thereof. Background technique [0002] Circulating tumor cells (CTCs), as an important marker of cancer metastasis, are tumor cells that are generated from the lesion in the early stage of cancer and spread to other organs through the peripheral blood. Sensitive detection of CTCs from peripheral blood cells is of great significance for the diagnosis and prevention of early tumors. High-purity, high-efficiency capture and effective analysis of CTCs is expected to further understand the formation mechanism of tumors and prevent the occurrence of lesions from the root. However, due to the rarity of circulating tumor cells (1 / 10 7 ), a large number of impurity cells will surely become an obstacle in its efficient and high-purity separation and capture process, how to obtain target cells (ie circulating tumo...

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Problems solved by technology

[0009] 1. In the immunomagnetic bead method, the separation and capture process is complicated, and the separation cost is high; and the sample volume used in batch processing is large, and the separation efficiency is low

In addition, the immunomagnetic bead method requires pretreatment of the cells, which inevitably causes cell loss during the transfer process, which may affect the detection results for rare cells

Furthermore, in the immunomagnetic bead method, although fluorescent dyes are used to distinguish different cells, due to serious cell contamination, it is unfavorable for cell identification, technology and cell analysis.

[0010] 2. The existing microfluidic technology that only uses physical methods to separate cells has no obvious difference in physical characteristics such as size and deformation, and even some characteristic areas overlap. The purity of separation is often low, and further capture of cells is still required. Obtain specific cells, and can only be effective for one or several types of cells, and need to be redesigned for other separation objects, which increases design and manufacturing costs

The sieve-like structure is more harmful to cell activity, and often causes structural failure due to blockage.

[0011] 3. In the existing microfluidic chip that combines fluid mechanics and immunoadsorption, the shear force of the fluid destroys the contact between the non-targeted cells and the surface of the channel, increases the purity, and greatly shortens the time of the adsorption reaction, making The efficiency of adsorption decreases

[0012] In summary, in practical applications, the importance of purity and efficiency needs to be weighed according to the purpose of the experiment, and it is difficult to find a fluid shear force that can satisfy both high efficiency and high purity, that is, low purity while meeting high capture efficiency

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