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Array type continuously-flowing microfluidic chip device and manufacture method and application thereof

A microfluidic chip and microchip technology, applied in chemical instruments and methods, chemical/physical/physical chemical processes, chemical/physical processes, etc., can solve complex and expensive external equipment reaction reagents, cannot transport fresh reaction liquid in time, etc. problems, to achieve low-cost effects

Active Publication Date: 2014-01-29
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The solid-phase synthesis technology based on the microchip platform is currently also reported (Science, 2007, 318, 1888-1888., Proteomics, 2003, 3, 2135-2141., invention patent: combined compound array chip and preparation method, 03112772. X), but these solid-phase synthesis is often a static reaction, cannot transport fresh reaction solution in time, and requires complex and expensive external equipment and special reaction reagents

Method used

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  • Array type continuously-flowing microfluidic chip device and manufacture method and application thereof
  • Array type continuously-flowing microfluidic chip device and manufacture method and application thereof
  • Array type continuously-flowing microfluidic chip device and manufacture method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1, Fabrication of arrayed continuous flow microfluidic chip device

[0048] (1) Fabrication of six-channel synthesis reaction microchip

[0049] The fabrication process of the six-channel synthetic reaction microchip is as follows: image 3 As shown, wherein, step A represents the exposure step, step B represents the development step, step C represents the chrome removal step, step D represents the corrosion step, step E represents the step of removing chrome from the light-removing glue, and step F represents the bonding step.

[0050] The microchannel size design of the synthetic reaction microchip is as follows: figure 1 As shown, the designed synthetic reaction microchip pattern is made into a film mask by laser phototypesetting; the film mask is covered on a 63.5mm×63.5mm×1.5mm homogeneous chrome plate (chrome type: LRC; chrome thickness: 145nm; glue thickness: 570nm), exposed to UV light (365nm) for 8 seconds; the exposed chromium plate was developed in ...

Embodiment 2

[0061] Example 2. Using the continuous flow microfluidic chip device made in Example 1 to perform polypeptide synthesis reactions in each reaction unit

[0062] (1) Preparation of solid phase carrier

[0063] The cross-linking degree of carrier king resin used in conventional container solid-phase peptide synthesis is relatively low, and it swells in an organic solvent atmosphere. If the swollen resin is filled into the reaction cavity of the microfluidic chip, it will deform and block the microchannel. Therefore, the highly cross-linked rigid carrier microspheres suitable for the microfluidic chip device of the present invention were prepared by using the seed one-step swelling polymerization method. The specific preparation method is as follows:

[0064] a. Preparation of polyethylene (PS) seeds: According to literature (Macromolecules, 1990, 23, 3104-3109.), PS seeds with a particle size of about 10 μm were prepared.

[0065] b. The oil phase of the reaction system includ...

Embodiment 3

[0085] Example 3, using the Fmoc-Leu, Fomc-Ser and Fmoc-Phe modified solid-phase peptide synthesis carrier prepared in Example 2 as a solid-phase carrier, the continuous flow microfluidic chip device made in Example 1 was used for integrated solid-phase Phase peptide synthesis reaction

[0086](1) According to the method reported in the literature (Combinatorial Chemistry, Oxford University Press, 1998, ch.3, pp.42-43.) Synthesize six species with higher affinity activities in the anti-β-endorphin 3E7 mAb affinity polypeptide library Polypeptides YGAFLS (AR1), YGAFS (AR2), YGAFL (AR3), YGGFLS (AR4), YGAF (AR5) and YGALS (AR6).

[0087] Concrete synthetic steps are as follows:

[0088] a. Use a precision syringe pump to push a 1mL syringe through the sub-injection port 3 and inject the hydroxymethylphenol methyl polystyrene resin microspheres prepared in Example 2 dispersed in DMF into the reaction chamber 4 respectively. Each reaction Six parts of the resin prepared in Examp...

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Abstract

The invention provides an array type continuously-flowing microfluidic chip device and a manufacture method and application thereof. The device comprises a synthetic reaction microchip, a flow splitting microchip and a reagent charge cell, wherein reaction cavity bodies of various reaction units in the synthetic reaction microchip are internally provided with multiple layers of fences and barrages with cofferdam type structures, so that a solid-phase synthesis carrier can be effectively bounded, and the continuous fluid is also guaranteed to be smooth; and a charge module is composed of the flow splitting microchip and the reagent charge cell, so that independent and simultaneously sample introduction of different reagents can be conducted into various reaction units of the synthesis microchip. The microfluidic chip device provided by the invention can be used for the multi-step solid-phase synthesis reaction, the efficiency is high, the amount of reagents used is few, and the manufacture cost is low.

Description

technical field [0001] The invention relates to an array type continuous flow microfluidic chip device and its manufacturing method and application, belonging to the technical field of microreactors. Background technique [0002] Lab on a chip (Lab on a chip) has developed into one of the most cutting-edge technological fields in the world today (Sens.Actutors, B, 1990, 1, 244-248.). Chemistry, biology, medicine and other fields have very attractive development prospects. Microfluidic chip technology integrates or basically integrates the basic operation units involved in the fields of chemistry and biology, such as pretreatment, sample addition, reaction, separation, analysis, and cell culture, into a square-sized chip to replace conventional chemistry. Or a technical platform for various functions of the biological laboratory. The microfluidic chip has the characteristics of large specific surface area, fast mass and heat transfer rate, low reagent consumption, environme...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): B01J19/00
Inventor 赵睿王蔚芝黄嫣嫣刘吉众刘国诠
Owner INST OF CHEM CHINESE ACAD OF SCI
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