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CN-121994771-A - SERS substrate, preparation method thereof and integrated microfluidic detection system

CN121994771ACN 121994771 ACN121994771 ACN 121994771ACN-121994771-A

Abstract

The invention provides a SERS substrate, a preparation method thereof and an integrated microfluidic detection system, which belong to the technical field of optical and biological sensing intersection, wherein the SERS substrate comprises a substrate layer for supporting the integral structure of the SERS substrate from bottom to top, and the substrate layer is made of silicon; the light-emitting diode comprises a substrate layer, an adhesion layer, a reflecting layer, a waveguide layer and a light-emitting diode, wherein the lower surface of the reflecting layer is adhered to the upper surface of the substrate layer through the adhesion layer, the waveguide layer is adhered to the upper surface of the reflecting layer, the upper surface of the waveguide layer is provided with a nano groove array, and a nano grass structure is arranged in a groove of the nano groove array. The SERS substrate provided by the invention has higher sensitivity and lower detection limit, and can realize rapid and convenient detection of tumor markers.

Inventors

  • Zou Qiushun
  • Guo Ruansheng
  • XU ANG
  • Zhuo Youming
  • ZHAO HONGSEN
  • SHEN XIANG
  • LIU ZIJUN

Assignees

  • 宁波大学

Dates

Publication Date
20260508
Application Date
20251230

Claims (10)

  1. 1. A SERS substrate, comprising, from bottom to top: the substrate layer (1) is used for supporting the integral structure of the SERS substrate, and the substrate layer (1) is made of silicon; an adhesive layer (2); A reflecting layer (3), wherein the lower surface of the reflecting layer (3) is adhered to the upper surface of the substrate layer (1) through the adhesive layer (2); The waveguide layer (4) is adhered to the upper surface of the reflecting layer (3), the upper surface of the waveguide layer (4) is provided with a nano groove array (41), and a nano grass structure (42) is arranged in a groove of the nano groove array (41).
  2. 2. The SERS substrate according to claim 1 wherein the adhesion layer (2) is made of any one of titanium, chromium, titanium tungsten alloy.
  3. 3. SERS substrate according to claim 1, wherein the reflective layer (3) is gold or silver.
  4. 4. The SERS substrate according to claim 1 wherein the material of the waveguide layer (4) is selected from any one of polystyrene, polymethyl methacrylate, polydimethylsiloxane.
  5. 5. The SERS substrate of claim 1 wherein the nano-grass structure (42) is selected from any one of gold, silver, platinum group metals.
  6. 6. A method for preparing a SERS substrate according to any one of claims 1 to 5, comprising the steps of: S1, taking a first silicon wafer as a substrate layer (1); S2, sequentially depositing an adhesion layer (2) and a reflecting layer (3) on the substrate layer (1) by adopting an electron beam evaporation technology; s3, spin-coating a polystyrene-chlorobenzene solution on the surface of the reflecting layer (3) to form a waveguide layer (4); S4, spin-coating polymethyl methacrylate on a second silicon wafer, defining a nanopore groove array on the surface of the polymethyl methacrylate by utilizing an electron beam lithography technology, etching the nanopore groove array by utilizing an inductively coupled plasma etching technology, and removing the polymethyl methacrylate to obtain a silicon template; S5, casting the PDMS solution on a silicon template, and cutting after curing to obtain a PDMS imprinting template; S6, coating a PDMS stamping template on the surface of the waveguide layer (4), and forming a nano groove array (41) on the waveguide layer (4) by adopting a nano stamping technology; And S7, preparing a nano grass structure (42) in the nano groove array (41) of the waveguide layer (4) through an oblique angle deposition technology to obtain the SERS substrate.
  7. 7. A microfluidic chip, the microfluidic chip comprising: At least one reaction zone, wherein the SERS substrate of any one of claims 1 to 5 is disposed in the reaction zone; The micro-flow channel is used for guiding the sample to flow to the reaction zone; A tumor marker specific antibody immobilized on a surface of a nanograss structure (42) of a SERS substrate.
  8. 8. The microfluidic chip of claim 7, wherein said tumor marker specific antibody comprises at least one of IL-6, CA724, CA199, CEA, CA125, CASA.
  9. 9. A microfluidic detection system, the microfluidic detection system comprising: The SERS substrate of any one of claims 1 to 5 or the microfluidic chip of any one of claims 7 to 8; a spectrometer for spectral generation.
  10. 10. The microfluidic detection system of claim 9, further comprising a data analysis module for calculating tumor marker concentrations from spectra generated by the spectrometer.

Description

SERS substrate, preparation method thereof and integrated microfluidic detection system Technical Field The invention relates to the technical field of optical and biological sensing intersection, in particular to a SERS substrate, a preparation method thereof and an integrated microfluidic detection system. Background The Surface Enhanced Raman Scattering (SERS) technology has great application potential in the field of biomedical detection, in particular to the detection of tumor markers due to the advantages of high sensitivity, high specificity, nondestructive detection and the like. The SERS technology can remarkably enhance the Raman scattering signal of molecules through a specially designed nanostructure substrate, and realize the detection of extremely low concentration molecules. Currently, the methods for detecting tumor markers commonly used in clinic mainly comprise enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) and the like. Although the traditional methods are widely applied to clinic, the defects of large equipment volume, complex operation, long detection time and the like still exist, and the requirements of rapid and high-sensitivity detection are difficult to meet. In contrast, the detection method based on the SERS technology has the advantages of high detection sensitivity, simplicity and convenience in operation, short detection time and the like, and provides a new technical path for early detection of tumor markers. The Chinese patent application with publication number CN115356325A realizes effective transmission of incident light through the sum design of a substrate layer, a dielectric waveguide layer, a cladding layer, a long-range surface plasma waveguide part and a micro-channel part, thereby increasing the Raman signal of sample molecules, but the structure can improve the detection sensitivity, but the preparation process is complex, the preparation cost is high, and large-scale production cannot be realized temporarily. The Chinese patent application with publication number of CN117470826A reduces the preparation cost of the SERS substrate by a method for inducing and depositing the silver nano array in the micro-fluidic cavity on the premise of guaranteeing the sensitivity and uniformity of the SERS substrate, however, the micro-nano structure prepared by the method has lower stability. Based on the detection method, the SERS substrate and the microfluidic detection system thereof with simple structure, controllable preparation process, high detection sensitivity and good stability are developed, and the detection method has important significance for improving the early detection capability of tumor markers. Disclosure of Invention The invention aims to solve the technical problem of improving the detection sensitivity and stability of the SERS substrate while reducing the production cost of the SERS substrate. To solve the above technical problem, a first aspect of the present invention provides a SERS substrate, The SERS substrate comprises the following components from bottom to top: The substrate layer is used for supporting the integral structure of the SERS substrate, and the substrate layer is made of silicon; An adhesive layer; a reflecting layer, wherein the lower surface of the reflecting layer is adhered to the upper surface of the substrate layer through the adhesive layer; the waveguide layer is adhered to the upper surface of the reflecting layer, the upper surface of the waveguide layer is provided with a nano groove array, and a nano grass structure is arranged in a groove of the nano groove array. In the SERS substrate provided by the invention, the substrate layer provides mechanical support for other structures, the adhesion layer is used for enhancing interlayer bonding capacity, the reflection layer is used for optimizing light reflection, the upper surface of the waveguide layer is provided with the nano groove array, and the nano grass structure is embedded in the nano groove array; in the structure of the SERS substrate, the nano grass structure is positioned in the nano groove array of the waveguide layer, so that the local electric field effect of the nano grass can be effectively enhanced, the strength and stability of SERS signals can be further improved, meanwhile, the nano grass structure can effectively increase the number of adsorption sites for detecting antibodies, the nano groove array of the waveguide layer can also provide more reaction areas for the antibodies, in addition, the SERS substrate is coupled with the reflecting layer, the light energy leaked from the nano grass can be effectively reduced, the light energy loss is reduced, and the SERS performance of the nano grass is improved. Preferably, the material of the adhesion layer is selected from any one of titanium, chromium and titanium tungsten alloy. Preferably, the material of the reflecting layer is gold or silver. Preferably, the material of the wave