CN-121972242-A - Micro-fluidic chip with substrate surface functionally modified and crystallization control method

CN121972242ACN 121972242 ACN121972242 ACN 121972242ACN-121972242-A

Abstract

The invention relates to a micro-fluidic chip with a substrate surface modified by functionalization and a crystallization control method, which solve the technical problem of how to precisely control the crystallization process by using the micro-fluidic chip, and comprise a substrate and a cover plate, wherein the substrate is provided with a patterned SAMs, the cover plate comprises an upper layer and a lower layer, the upper layer is provided with a gas channel and a gas accommodating chamber, the upper layer is provided with a gas input through hole, a gas output through hole, a liquid input through hole and a liquid output through hole, the lower layer is provided with a liquid channel and a reaction chamber, the lower layer of the cover plate is bonded with the substrate, and the patterned SAMs is positioned in the reaction chamber. The method is suitable for the precise preparation of medicine crystals, biological materials, ceramic materials, nano materials and optical elements, and can be widely applied to the industries of pharmacy, biomedical engineering, advanced material synthesis and the like.

Inventors

WANG YILIN
CHEN WENLONG
ZHANG HEFENG
ZOU LINGLONG

Assignees

温州康瑞佰欧生物技术有限公司

Dates

Publication Date: 20260505
Application Date: 20251229

Claims (12)

1. A microfluidic chip with a substrate surface subjected to functional modification is characterized by comprising a substrate and a cover plate, wherein the substrate is provided with a patterned SAMs, the cover plate is of a double-layer structure and comprises an upper layer and a lower layer which are bonded together, the bottom surface of the upper layer is provided with a gas channel and a gas accommodating chamber, the upper layer is provided with a gas input through hole, a gas output through hole, a liquid input through hole and a liquid output through hole, the gas input through hole is communicated with the gas accommodating chamber through the gas channel, the gas output through hole is communicated with the gas accommodating chamber through the gas channel, the bottom surface of the lower layer is provided with a liquid channel and a reaction chamber, the lower layer is provided with a liquid input through hole and a liquid output through hole, the liquid input through hole of the upper layer is communicated with the liquid input through hole of the lower layer, the liquid output through hole of the upper layer is communicated with the liquid output through hole of the lower layer, the gas accommodating chamber corresponds to the reaction chamber, and the gas accommodating chamber is positioned above the reaction chamber; The lower layer of the cover plate is bonded to the substrate, and the patterned SAMs is located in a reaction chamber.
2. The microfluidic chip with the functionalized and modified substrate surface according to claim 1, wherein the substrate is a composite substrate comprising glass, a Cr layer and an Au layer, the Cr layer is positioned between the Au layer and the glass, and the lower layer of the cover plate is bonded with the Au layer of the composite substrate.
3. The microfluidic chip with the functionalized and modified substrate surface according to claim 2, wherein the surface roughness of the Au layer is less than or equal to 0.5nm.
4. The microfluidic chip with the functionalized substrate surface modified according to claim 1, wherein the upper layer of the cover plate is made of PDMS, and the lower layer of the cover plate is made of PDMS.
5. The microfluidic chip of claim 1, wherein the gas containing chamber is located at a central position of the reaction chamber in a radial direction.
6. The microfluidic chip of claim 1, wherein the patterned SAMs are circular units distributed in a square array.
7. The microfluidic chip with the functionalized substrate surface modified according to any one of claims 1 to 6, wherein the plurality of gas containing chambers are connected in series through gas channels, the gas input through hole is communicated with a first gas containing chamber of the plurality of gas containing chambers connected in series through the gas channels, and the gas output through hole is communicated with a tail gas containing chamber of the plurality of gas containing chambers connected in series through the gas channels; The reaction chambers are connected in series through liquid channels, the liquid input through holes at the lower layer of the cover plate are communicated with the first reaction chambers in the reaction chambers connected in series through the liquid channels, and the liquid output through holes at the lower layer of the cover plate are communicated with the tail reaction chambers in the reaction chambers connected in series through the liquid channels; The substrate has a plurality of sets of patterned SAMs thereon, one set of patterned SAMs in each reaction chamber.
8. The microfluidic chip for substrate surface functionalization modification according to any one of claims 1 to 6, wherein a cylindrical array is provided in the reaction chamber.
9. The microfluidic chip for substrate surface functionalization modification according to any one of claims 1 to 6, wherein the reaction chamber is circular, and the gas containing chamber is circular.
10. A crystallization control method using the micro-fluidic chip functionally modified on a substrate surface according to any one of claims 1 to 9, comprising the steps of: First, preparing a reaction system: preparing a liquid phase; Preparing a gas phase; And secondly, micro-fluidic parameter adjustment: Liquid injection, namely injecting liquid into the reaction chamber from a liquid input through hole at the upper layer of the cover plate, enabling the liquid to flow at a certain flow speed, and enabling the liquid to flow out from a liquid output through hole at the upper layer of the cover plate; And (3) gas injection, namely injecting gas into the gas accommodating chamber from the gas input through hole at the upper layer of the cover plate, and flowing out from the gas output through hole at the upper layer of the cover plate, wherein the gas in the gas accommodating chamber permeates into the reaction chamber to react with liquid in the reaction chamber, so that crystals grow on the patterned SAMs.
11. The crystallization control method according to claim 10, wherein the microfluidic chip is placed under an inverted microscope to monitor the crystal growth process in real time.
12. The crystallization control method according to claim 10 or 11, wherein in the preparation of the first-step reaction system, the liquid phase is CaCl 2 solution, and the gas is a mixed gas of NH3 and CO 2.

Description

Micro-fluidic chip with substrate surface functionally modified and crystallization control method Technical Field The invention relates to the technical field of intersection of microfluidic technology and crystallization regulation, in particular to a microfluidic chip with a substrate surface functionally modified and a crystallization control method. Background The microfluidic chip (Microfluidics chip) is a chip which can realize various functions of performing conventional physical, chemical or biological experiments on micro-scale chips on micro-fluid. Microfluidic chips have become a powerful tool for studying biological systems at single cell resolution. Meanwhile, the microfluidic chip can be widely applied to control and generate micro-droplets, micro-fluid diffusion screening and detection of interaction between proteins and ligands, and can also be used for realizing molecular determination in biochemistry. In the field of precise preparation of crystal systems such as calcium carbonate crystals, drug crystals, nanomaterials and the like, precise control of crystallization processes (including size, morphology, polymorphism and orientation) is a central need. The micro-fluidic chip is used in crystallization technology, and the technology has the following technical problems that crystal nucleation orientation is dispersed, crystallization orientation is difficult to precisely control, crystallization effect consistency is poor, and morphology is difficult to control. Therefore, how to precisely control the crystallization process to improve the crystallization effect is a technical problem to be solved by those skilled in the art. Disclosure of Invention The application provides a micro-fluidic chip for modifying the surface of a substrate in a functionalization way and a crystallization control method, which aim to solve the technical problem of precisely controlling the crystallization process by using the micro-fluidic chip. The micro-fluidic chip comprises a substrate and a cover plate, wherein the substrate is provided with patterned SAMs, the cover plate is of a double-layer structure and comprises an upper layer and a lower layer which are bonded together, a gas channel and a gas accommodating chamber are arranged on the bottom surface of the upper layer, a gas input through hole, a gas output through hole, a liquid input through hole and a liquid output through hole are arranged on the upper layer, the gas input through hole is communicated with the gas accommodating chamber through the gas channel, the gas output through hole is communicated with the gas accommodating chamber through the gas channel, a liquid channel and a reaction chamber are arranged on the bottom surface of the lower layer, the liquid input through hole is communicated with the reaction chamber through the liquid channel, the liquid output through hole is communicated with the reaction chamber through the liquid channel, the liquid input through hole of the upper layer is communicated with the liquid input through hole of the lower layer, the liquid output through hole of the upper layer is communicated with the liquid output through hole of the lower layer, the gas accommodating chamber corresponds to the reaction chamber, and the gas accommodating chamber is positioned above the reaction chamber; the lower layer of the cover plate is bonded to the substrate and the patterned SAMs is located in the reaction chamber. Preferably, the substrate is a composite substrate comprising glass, a Cr layer and an Au layer, the Cr layer is positioned between the Au layer and the glass, and the lower layer of the cover plate is bonded with the Au layer of the composite substrate. Further preferably, the surface roughness of the Au layer is 0.5nm or less. Preferably, the upper layer of the cover plate is made of PDMS, and the lower layer of the cover plate is made of PDMS. Preferably, the gas containing chamber is located at a central position of the reaction chamber in the radial direction. Preferably, the patterned SAMs is circular cells distributed in a square array. Preferably, the plurality of gas accommodating chambers are connected in series through gas channels, the gas input through holes are communicated with the first gas accommodating chamber in the plurality of gas accommodating chambers connected in series through the gas channels, and the gas output through holes are communicated with the tail gas accommodating chamber in the plurality of gas accommodating chambers connected in series through the gas channels; The reaction chambers are connected in series through liquid channels, a liquid input through hole at the lower layer of the cover plate is communicated with the first reaction chamber in the reaction chambers connected in series through the liquid channels, and a liquid output through hole at the lower layer of the cover plate is communicated with the tail reaction chamber in the reaction chambers connected