A microfluidic chip integrated surface-enhanced Raman spectroscopy detection system

Abstract

This invention relates to the field of spectral analysis technology, and more particularly to a microfluidic chip-integrated surface-enhanced Raman spectroscopy (SERS) detection system. The system includes a microfluidic chip module, an optical detection module, a SERS enhancement substrate, and a signal processing module. The microfluidic chip module has a sample flow channel and a reaction flow channel, with the SERS enhancement substrate disposed within the reaction flow channel. The optical detection module employs a confocal microscopic optical path design, where excitation light is focused by a microscope objective and then incident perpendicularly onto the enhancement substrate. Raman scattered light is collected in the opposite direction along the same optical path and then enters the spectrometer. This invention achieves full-process integration of sample pretreatment, reaction enhancement, and spectral detection, achieving a detection limit of 10⁻⁹ to 10⁻¹² mol / L, and improving optical transmission efficiency and detection sensitivity.

Description

Technical Field

[0001] This invention relates to the field of spectral analysis technology, and in particular to a microfluidic chip-integrated surface-enhanced Raman spectroscopy detection system. Background Technology

[0002] Surface-enhanced Raman spectroscopy, as a highly sensitive molecular detection technique, relies on the electromagnetic field enhancement effect generated by nanoscale metal structures. By adsorbing the analyte onto the surface of noble metal nanoparticles or nanostructures, single-molecule-level detection sensitivity can be achieved. This characteristic has led to its widespread application in fields such as chemical analysis, biosensing, and environmental monitoring.

[0003] Integrating microfluidic chips with surface-enhanced Raman spectroscopy (SERS) represents a significant development direction in analytical detection technology. However, existing technologies face irreconcilable contradictions in practical applications. The microchannel structure of microfluidic chips requires analytes to pass through the detection region at high speeds to achieve high-throughput detection. This rapid flow results in insufficient interaction time between the analyte and the substrate. Limited by the molecular diffusion rate, analytes cannot fully adsorb onto the nanostructure surface and form effective electromagnetic field coupling within the extremely short passage time, leading to significant fluctuations in Raman signal intensity and a marked decrease in detection repeatability. This lack of detection stability directly restricts the application potential of microfluidic integrated SERS technology in real-world scenarios. Summary of the Invention

[0004] The purpose of this invention is to provide a microfluidic chip-integrated surface-enhanced Raman spectroscopy detection system to solve the technical problems of insufficient integration between the surface-enhanced Raman spectroscopy detection system and the microfluidic chip, separation of sample pretreatment and detection processes, low optical coupling efficiency, and unstable detection sensitivity.

[0005] This invention provides a microfluidic chip integrated surface-enhanced Raman spectroscopy detection system, including a microfluidic chip module, an optical detection module, a surface-enhanced Raman spectroscopy enhancement substrate, and a signal processing and control module;

[0006] The microfluidic chip module has a sample channel and a reaction channel. The sample channel is used to introduce the sample solution to be detected, and the reaction channel is provided with a surface-enhanced Raman spectroscopy enhancement substrate.

[0007] The optical detection module includes a laser source, a microscope objective, a spectrometer, and an optical coupling assembly. The excitation light emitted by the laser source is guided to the microscope objective via the optical coupling assembly, focused, and then incident perpendicularly onto the surface-enhanced Raman spectroscopy (SERS) substrate in the reaction channel. The sample to be detected in the reaction channel generates SERS on the surface of the SERS substrate, and the generated Raman scattered light is collected by the microscope objective and then guided to the spectrometer via the optical coupling assembly.

[0008] The signal processing and control module is electrically connected to the laser source, the spectrometer, and the microfluidic drive unit in the microfluidic chip module. It is used to control the light emission timing of the laser source, acquire the Raman spectral signal output by the spectrometer, and perform noise reduction, baseline correction, and characteristic peak extraction processing on the acquired Raman spectral data.

[0009] In some embodiments, the microfluidic chip module includes a chip substrate, a capping layer, and a microfluidic channel structure disposed between the chip substrate and the capping layer; the microfluidic channel structure includes at least a sample inlet, a sample channel, a reaction channel, a waste liquid outlet, and a mixing zone disposed between the sample channel and the reaction channel; the mixing zone is provided with microstructured flow-disrupting elements for enhancing the sample mixing effect.

[0010] In some embodiments, the width of the microfluidic channel structure ranges from 50 micrometers to 500 micrometers, the height ranges from 20 micrometers to 200 micrometers, and the length of the reaction channel ranges from 5 millimeters to 50 millimeters.

[0011] In some embodiments, the surface-enhanced Raman spectroscopy (SERS) enhancement substrate is disposed on the bottom wall surface or side wall surface of the reaction channel; the SERS enhancement substrate includes at least a substrate material layer and a nanostructure enhancement layer disposed on the surface of the substrate material layer; the nanostructure enhancement layer is an array of metal nanoparticles; the material of the metal nanoparticle array is any one or more alloys of gold, silver, or copper; the particle size of the metal nanoparticles ranges from 10 nanometers to 200 nanometers, and the gap between adjacent metal nanoparticles is from 1 nanometer to 50 nanometers.

[0012] In some embodiments, the optical coupling assembly includes a first filter, a second filter, and a reflector; the first filter is disposed in the optical path between the laser source and the microscope objective to filter out stray light emitted by the laser source; the second filter is disposed in the optical path between the microscope objective and the spectrometer to filter out scattered light of the excitation wavelength; the reflector is used to change the direction of the optical path so that the excitation light and the Raman scattered light are transmitted along the confocal optical path.

[0013] In some embodiments, the optical detection module employs a confocal microscopic optical path design; the confocal pinhole of the confocal microscopic optical path design is disposed in the optical path between the second filter and the spectrometer, for filtering out background light from outside the focal plane; the numerical aperture of the microscope objective ranges from 0.5 to 1.4.

[0014] In some embodiments, the emission wavelength of the laser source is any one of 532 nm, 633 nm, 785 nm, or 1064 nm; the power range of the laser source is 1 mW to 500 mW; the spectral detection range of the spectrometer is 200 cm⁻¹ to 3500 cm⁻¹, and the spectral resolution is less than or equal to 1 cm⁻¹.

[0015] In some embodiments, the signal processing and control module includes at least a signal acquisition unit, a data processing unit, and a control unit; the signal acquisition unit is used to acquire the analog Raman spectral signal output by the spectrometer and convert the analog Raman spectral signal into a digital Raman spectral signal; the data processing unit is used to perform filtering, noise reduction, baseline correction, peak calibration, and quantitative analysis on the digital Raman spectral signal; the control unit is used to control the switching and power of the laser source, the flow rate and volume of the microfluidic drive unit, and the integration time and number of acquisitions of the spectrometer.

[0016] In some embodiments, a temperature control module is further included, the temperature control module including a temperature control element and a temperature sensor;

[0017] The temperature control element is located at the bottom or side of the microfluidic chip module and is used to heat or cool the sample to be tested in the reaction channel.

[0018] The temperature sensor is located near the reaction channel and is used to monitor the temperature of the reaction channel in real time.

[0019] The signal processing and control module performs feedback control on the temperature control element based on the temperature data collected by the temperature sensor, so that the temperature of the reaction channel is maintained within the set temperature range.

[0020] In some embodiments, a multi-channel detection unit is further provided, the multi-channel detection unit comprising at least a plurality of parallel microfluidic channel structures and a plurality of surface-enhanced Raman spectroscopy enhancement substrates corresponding to the microfluidic channel structures;

[0021] The multiple microfluidic channel structures correspond to different samples to be tested or different detection conditions; the optical detection module sequentially acquires Raman spectra of multiple surface-enhanced Raman spectroscopy-enhanced substrates by scanning or spectrophotometry to achieve high-throughput parallel detection.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. This invention deeply integrates microfluidic chip technology with surface-enhanced Raman spectroscopy detection technology, realizing the integration of the entire process of sample pretreatment, reaction enhancement and spectral detection. It eliminates the intermediate steps of sample transfer and processing in traditional detection methods, avoids sample loss and contamination, and improves detection efficiency and detection sensitivity.

[0024] 2. Employing a confocal microscopic optical path design with perpendicular incidence, coupled with a high numerical aperture microscope objective, significantly improves the collection efficiency of Raman scattered light, effectively enhancing the intensity of surface-enhanced Raman spectral signals, and achieving a detection limit of 10⁻⁻⁶. 9 Ultra-high sensitivity level of 10⁻¹² moles per liter;

[0025] 3. The temperature of the reaction channel is precisely controlled by the temperature control module to ensure that the surface-enhanced Raman spectroscopy reaction is carried out under optimal temperature conditions, thereby improving the reproducibility and reliability of the detection results;

[0026] 4. The sample flow rate and reaction time are precisely controlled by the microfluidic drive unit, and the microstructured perturbation element in the mixing zone is used to achieve full mixing of the sample and the enhanced substrate, shortening the detection response time and enabling real-time continuous monitoring;

[0027] 5. By setting up a multi-channel detection unit, multiple samples or multiple detection conditions can be detected in parallel at the same time, meeting the application requirements of high-throughput detection;

[0028] 6. The entire system has a compact structure and high integration, making it easy to carry and deploy on-site. It can be widely used in the detection of trace substances in fields such as environmental monitoring, food safety, medical diagnosis, and real-time monitoring of chemical reactions. Attached Figure Description

[0029] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0030] Figure 1 This is an architectural diagram of the microfluidic chip-integrated surface-enhanced Raman spectroscopy detection system of the present invention;

[0031] Figure 2 This is a schematic diagram of the integration of the microfluidic chip and the surface-enhanced Raman spectroscopy substrate in this invention. Detailed Implementation

[0032] The following will be based on embodiments of the present invention. Figures 1-2 The technical solutions in the embodiments of the present invention will be clearly and completely described together. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0033] Application Overview

[0034] Microfluidic chip technology, with its ability to precisely manipulate micro-fluids, has become an important experimental platform in the fields of analytical chemistry and life sciences. Microfluidic technology enables functions such as sample introduction, fluid mixing, and reaction control through micron-level channels, significantly reducing sample consumption and analysis time.

[0035] Example

[0036] The system of this invention mainly includes: a microfluidic chip module, an optical detection module, a surface-enhanced Raman spectroscopy enhancement substrate, and a signal processing module. The modules form a complete detection process, realizing the automatic introduction of the sample to be detected, reaction enhancement, spectral acquisition, and data processing.

[0037] The microfluidic chip module has a sample channel and a reaction channel. One end of the sample channel is connected to a sample introduction device to introduce the sample solution to be detected; the other end of the sample channel is connected to the reaction channel. Under the action of the microfluidic driving unit, the sample solution to be detected flows from the sample channel into the reaction channel. A surface-enhanced Raman spectroscopy (SERS) enhancement substrate is disposed within the reaction channel to capture the target molecules and generate SERS effect. The other end of the reaction channel is connected to a waste liquid collection device to collect the waste liquid after the reaction.

[0038] The surface-enhanced Raman spectroscopy (SERS) substrate is disposed on the bottom or sidewall surface of the reaction channel. The SERS substrate comprises a substrate material layer and a nanostructured reinforcement layer disposed on the surface of the substrate material layer. The nanostructured reinforcement layer is an array of metal nanoparticles. When excitation light emitted from a laser source is focused by a microscope objective and incident perpendicularly onto the surface of the nanostructured reinforcement layer, a strong electromagnetic field coupling effect is generated between the metal nanoparticles, forming electromagnetic field hotspots that significantly enhance the Raman scattering signal. When the sample molecules flow through the reaction channel, they are adsorbed onto the surface or near the surface of the metal nanoparticles, generating SERS light under the irradiation of the excitation light. The generated Raman scattered light is collected by the microscope objective along the reverse optical path and then enters the optical detection module for spectral analysis.

[0039] Furthermore, the microfluidic chip module includes a chip substrate, a capping layer, and a microfluidic channel structure disposed between the chip substrate and the capping layer.

[0040] The microfluidic channel structure includes a sample inlet, a sample channel, a mixing zone, a reaction channel, and a waste outlet. The sample inlet is used to connect to a sample injection device, and the waste outlet is used to connect to a waste collection device. The mixing zone is located between the sample channel 101 and the reaction channel and is used to pretreat or mix the incoming sample solution.

[0041] In this embodiment, a microstructured turbulence element is provided in the mixing zone to enhance the sample mixing effect. This microstructured turbulence element can be multiple staggered microstructured turbulence columns or microstructured turbulence channels. The diameter of the microstructured turbulence columns ranges from 10 micrometers to 100 micrometers, and the spacing between adjacent microstructured turbulence columns ranges from 20 micrometers to 200 micrometers. When the sample solution to be tested flows through the mixing zone, the microstructured turbulence element can increase the turbulence of the fluid, breaking the laminar flow state and promoting full contact between the sample to be tested and the surface-enhanced Raman spectroscopy (SERS) enhancement substrate in the reaction channel. This shortens the mixing reaction time between the sample and the enhancement substrate, thereby improving the detection response speed and sensitivity.

[0042] Furthermore, the cross-sectional shape of the microfluidic channel structure can be rectangular, trapezoidal, or circular. The width of the microfluidic channel structure ranges from 50 micrometers to 500 micrometers, and the height ranges from 20 micrometers to 200 micrometers. The length of the reaction channel ranges from 5 millimeters to 50 millimeters to ensure sufficient surface-enhanced Raman spectroscopy reaction time for the sample to be detected within the reaction channel. The chip substrate and capping layer are made of any of quartz, glass, or polymer. When the optical detection module adopts a perpendicular incident light path design, the chip substrate and capping layer use optically transparent materials to ensure the transmission of excitation light and Raman scattered light; the transmittance of the optically transparent material is greater than or equal to 90%.

[0043] Furthermore, the nanostructured reinforcing layer of the surface-enhanced Raman spectroscopy (SERS) substrate can be any one of the following: a metal nanoparticle array, a nanopore array, a nanorod array, or a metal-dielectric composite nanostructure. The metal nanoparticle array is made of any one or more alloys of gold, silver, or copper. The particle size of the metal nanoparticles ranges from 10 nm to 200 nm, and the gap between adjacent metal nanoparticles ranges from 1 nm to 50 nm. By optimizing the particle size and gap between the metal nanoparticles, the local electromagnetic field intensity on the surface of the nanostructured reinforcing layer can be controlled, optimizing the electromagnetic field hotspot effect and thus maximizing the enhancement of the Raman scattering signal.

[0044] Furthermore, the optical detection module includes a laser source, a microscope objective, a spectrometer, and an optical coupling assembly.

[0045] The laser source emits wavelengths of any one of 532 nm, 633 nm, 785 nm, or 1064 nm. The power of the laser source ranges from 1 milliwatt to 500 milliwatts and can be adjusted according to the characteristics of the sample to be tested and the required detection sensitivity.

[0046] The optical coupling assembly includes a first filter, a second filter, and a mirror. The first filter is positioned in the optical path between the laser source and the microscope objective to filter out stray light emitted from the laser source (such as Rayleigh scattering and fluorescence), ensuring that the light entering the microscope objective is monochromatic excitation light. The second filter is positioned in the optical path between the microscope objective and the spectrometer to filter out scattered light of the excitation wavelength (especially Rayleigh scattering), allowing only Raman scattering light to enter the spectrometer. The mirror is used to change the direction of the optical path, allowing the excitation light and Raman scattering light to propagate along the confocal optical path. In this embodiment, the optical detection module adopts a confocal microscopic optical path design. The confocal pinhole of the confocal microscopic optical path design is positioned in the optical path between the second filter and the spectrometer. The confocal pinhole is located on the confocal plane of the microscope objective, which can further filter out background light from outside the focal plane (such as fluorescence or scattered light from the microfluidic chip material itself), significantly improving the signal-to-noise ratio of the Raman spectral signal. The numerical aperture of the microscope objectives ranges from 0.5 to 1.4, and the working distance ranges from 1 mm to 5 mm. High numerical aperture microscope objectives can provide a larger light collection angle, thereby improving the collection efficiency of Raman scattered light.

[0047] The spectrometer has a spectral detection range of 200 cm⁻¹ to 3500 cm⁻¹ and a spectral resolution of less than or equal to 1 cm⁻¹. This high spectral resolution enables clear identification of the characteristic Raman peaks of the sample, achieving accurate qualitative analysis and quantitative detection.

[0048] Furthermore, the signal processing and control module is electrically connected to the laser source, spectrometer, and microfluidic drive unit in the microfluidic chip module. The signal processing and control module includes a signal acquisition unit, a data processing unit, and a control unit. The signal acquisition unit is used to acquire the analog Raman spectral signal output by the spectrometer and convert it into a digital Raman spectral signal. The signal acquisition unit typically includes an analog-to-digital converter (A / D converter), and the sampling rate can be set according to the output rate of the spectrometer.

[0049] The data processing unit is used to filter, denoise, correct baselines, calibrate peak positions, and perform quantitative analysis on digital Raman spectral signals. Specific processing algorithms include, but are not limited to: smoothing filtering (such as Savitzky-Golay filtering) for removing high-frequency noise; deconvolution algorithms for improving peak resolution; polynomial fitting algorithms for baseline correction and eliminating fluorescence background interference; peak search algorithms for determining the peak positions and full width at half maximum (FWHM) of characteristic peaks; and standard curve methods or internal standard methods for quantitative analysis.

[0050] The control unit is used to control the switching and power of the laser source, the flow rate and volume of the microfluidic drive unit, the temperature setting of the temperature control module, and the integration time and number of acquisitions of the spectrometer. The control unit is usually implemented using a microprocessor (such as a microcontroller or embedded system) and executes the corresponding control logic through preset programs or host computer software instructions.

[0051] Furthermore, the microfluidic drive unit is either a microfluidic pump or a microfluidic valve. The microfluidic pump can be any one of a syringe pump, peristaltic pump, or pressure pump. The microfluidic valve can be any one of a solenoid valve or a pneumatic valve. The microfluidic drive unit is used to drive the sample solution to be tested to flow sequentially from the sample inlet through the sample channel, mixing zone, and reaction channel, and finally out from the waste liquid outlet. The control unit precisely adjusts the flow rate and flow volume of the sample solution by sending control commands (such as PWM pulse width modulation signals or step pulses) to the microfluidic drive unit, thereby achieving precise control of the reaction time.

[0052] Furthermore, the surface-enhanced Raman spectroscopy detection system integrated into the microfluidic chip also includes a temperature control module. This module comprises a temperature control element and a temperature sensor. The temperature control element, located at the bottom or side of the microfluidic chip module, is used to heat or cool the sample to be detected in the reaction channel. The temperature sensor, positioned near the reaction channel, monitors the temperature of the reaction channel in real time. The signal processing and control module provides feedback control (such as a PID control algorithm) to the temperature control element based on the temperature data collected by the temperature sensor, maintaining the temperature of the reaction channel within a set temperature range. The set temperature range is -20 degrees Celsius to 400 degrees Celsius. Precise temperature control ensures that the surface-enhanced Raman spectroscopy reaction proceeds under optimal temperature conditions, improving the reproducibility and reliability of the detection results, and is applicable to the detection of temperature-sensitive special chemical reactions or biomolecules.

[0053] Furthermore, the microfluidic chip module also includes a surface modification layer. This surface modification layer is disposed on the inner wall surface of the microfluidic channel structure. The surface modification layer is made of either a hydrophilic or hydrophobic material. When the sample to be tested is an aqueous solution, the surface modification layer uses a hydrophilic material (such as polyethylene glycol) to promote the uniformity of flow of the sample solution within the microfluidic channel structure and prevent bubble formation. When the sample to be tested is an oil phase or an organic solvent solution, the surface modification layer uses a hydrophobic material (such as fluorosilane) to enhance the wettability of the sample.

[0054] Furthermore, the microfluidic chip-integrated surface-enhanced Raman spectroscopy detection system also includes a calibration module. The calibration module comprises a calibration light source and a calibration sample cell. The calibration light source emits calibration light of a known wavelength (such as a 632.8 nm laser emitted by a helium-neon laser). The calibration sample cell contains a calibration sample (such as a silicon wafer, potassium nitrate solution, or a standard substance with known Raman characteristic peaks) to provide a standard Raman spectrum with known Raman characteristic peaks. The signal processing and control module performs wavelength and intensity calibration on the spectrometer by comparing the acquired standard Raman spectrum with the known Raman characteristic peaks, ensuring the accuracy of the spectral measurements.

[0055] Furthermore, the detection limit of the surface-enhanced Raman spectroscopy detection system integrated into the microfluidic chip reaches 10⁻ 9 The detection limit is 10⁻¹² moles per liter. The detection limit is achieved through the following techniques: optimizing the spacing between metal nanoparticles in the nanostructure reinforcement layer to enhance the electromagnetic field hotspot effect; using a high numerical aperture microscope objective to improve light collection efficiency; and using a long integration time spectrometer acquisition mode to increase signal accumulation.

[0056] Furthermore, the microfluidic chip-integrated surface-enhanced Raman spectroscopy (SERS) detection system also incorporates a multi-channel detection unit. This multi-channel unit comprises multiple parallel microfluidic channel structures and multiple SERS enhancement substrates corresponding to these microfluidic channel structures. Each microfluidic channel structure corresponds to a different sample or different detection conditions. The optical detection module sequentially acquires Raman spectra from the multiple SERS enhancement substrates via scanning, such as a two-dimensional electrically controlled displacement stage, or by spectroscopic methods, such as a multi-channel spectrometer, achieving high-throughput parallel detection.

[0057] The microfluidic chip-integrated surface-enhanced Raman spectroscopy detection system proposed in this invention eliminates the intermediate steps of sample transfer and processing in traditional detection methods, avoiding sample loss and contamination, and improving detection efficiency and sensitivity. It employs a vertically incident confocal microscopic optical path design, combined with a high numerical aperture microscope objective, significantly improving the collection efficiency of Raman scattered light and effectively enhancing the intensity of the surface-enhanced Raman spectroscopy signal. A temperature control module precisely controls the temperature of the reaction channel, ensuring that the surface-enhanced Raman spectroscopy reaction occurs under optimal temperature conditions, improving the reproducibility and reliability of the detection results. A microfluidic drive unit precisely controls the sample flow rate and reaction time, and a microstructured perturbation element in the mixing zone ensures thorough mixing of the sample and the enhancement substrate, shortening the detection response time and enabling real-time continuous monitoring. By setting up a multi-channel detection unit, it can simultaneously detect multiple samples or multiple detection conditions in parallel, meeting the application requirements of high-throughput detection.

[0058] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered illustrative and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the scope of the invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

[0059] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A microfluidic chip integrated surface-enhanced Raman spectroscopy detection system, characterized in that, It includes a microfluidic chip module, an optical detection module, a surface-enhanced Raman spectroscopy substrate, and a signal processing module; The microfluidic chip module has a sample channel and a reaction channel. The sample channel is used to introduce the sample solution to be detected, and the reaction channel is provided with a surface-enhanced Raman spectroscopy enhancement substrate. The optical detection module includes a laser source, a microscope objective, a spectrometer, and an optical coupling assembly. The excitation light emitted by the laser source is guided to the microscope objective via the optical coupling assembly, focused, and then incident perpendicularly onto the surface-enhanced Raman spectroscopy (SERS) substrate in the reaction channel. The sample to be detected in the reaction channel generates SERS on the surface of the SERS substrate, and the generated Raman scattered light is collected by the microscope objective and then guided to the spectrometer via the optical coupling assembly. The signal processing and control module is electrically connected to the laser source, the spectrometer, and the microfluidic drive unit in the microfluidic chip module. It is used to control the light emission timing of the laser source, acquire the Raman spectral signal output by the spectrometer, and perform noise reduction, baseline correction, and characteristic peak extraction processing on the acquired Raman spectral data.

2. The system according to claim 1, characterized in that, The microfluidic chip module includes a chip substrate, a cover layer, and a microfluidic channel structure disposed between the chip substrate and the cover layer; the microfluidic channel structure includes at least a sample inlet, a sample channel, a reaction channel, a waste liquid outlet, and a mixing zone disposed between the sample channel and the reaction channel; the mixing zone is provided with microstructured flow-disrupting elements for enhancing the sample mixing effect.

3. The system according to claim 2, characterized in that, The width of the microfluidic channel structure ranges from 50 micrometers to 500 micrometers, and the height ranges from 20 micrometers to 200 micrometers; the length of the reaction channel ranges from 5 millimeters to 50 millimeters.

4. The system according to claim 1, characterized in that, The surface-enhanced Raman spectroscopy (SERS) substrate is disposed on the bottom or sidewall surface of the reaction channel; the SERS substrate comprises at least a substrate material layer and a nanostructure reinforcement layer disposed on the surface of the substrate material layer; the nanostructure reinforcement layer is an array of metal nanoparticles; the material of the metal nanoparticle array is any one or more alloys of gold, silver, or copper; the particle size of the metal nanoparticles ranges from 10 nanometers to 200 nanometers, and the gap between adjacent metal nanoparticles is from 1 nanometer to 50 nanometers.

5. The system according to claim 1, characterized in that, The optical coupling assembly includes a first filter, a second filter, and a reflector; the first filter is disposed in the optical path between the laser source and the microscope objective to filter out stray light emitted by the laser source; the second filter is disposed in the optical path between the microscope objective and the spectrometer to filter out scattered light of the excitation wavelength; the reflector is used to change the direction of the optical path so that the excitation light and the Raman scattered light are transmitted along the confocal optical path.

6. The system according to claim 5, characterized in that, The optical detection module adopts a confocal microscopic optical path design; the confocal pinhole of the confocal microscopic optical path design is set in the optical path between the second filter and the spectrometer to filter out background light from outside the focal plane; the numerical aperture of the microscope objective ranges from 0.5 to 1.

4.

7. The system according to claim 1, characterized in that, The laser source has an emission wavelength of 532 nm, 633 nm, 785 nm, or 1064 nm; the power range of the laser source is 1 mW to 500 mW; the spectrometer has a spectral detection range of 200 cm⁻¹ to 3500 cm⁻¹ and a spectral resolution of less than or equal to 1 cm⁻¹.

8. The system according to claim 1, characterized in that, The signal processing and control module includes at least a signal acquisition unit, a data processing unit, and a control unit. The signal acquisition unit is used to acquire the analog Raman spectral signal output by the spectrometer and convert the analog Raman spectral signal into a digital Raman spectral signal. The data processing unit is used to perform filtering, noise reduction, baseline correction, peak calibration, and quantitative analysis on the digital Raman spectral signal. The control unit is used to control the switching and power of the laser source, the flow rate and volume of the microfluidic drive unit, and the integration time and number of acquisitions of the spectrometer.

9. The system according to claim 1, characterized in that, It also includes a temperature control module, which includes a temperature control element and a temperature sensor; The temperature control element is located at the bottom or side of the microfluidic chip module and is used to heat or cool the sample to be tested in the reaction channel. The temperature sensor is located near the reaction channel and is used to monitor the temperature of the reaction channel in real time. The signal processing and control module performs feedback control on the temperature control element based on the temperature data collected by the temperature sensor, so that the temperature of the reaction channel is maintained within the set temperature range.

10. The system according to claim 1, characterized in that, It also includes a multi-channel detection unit, which includes at least a plurality of parallel microfluidic channel structures and a plurality of surface-enhanced Raman spectroscopy enhancement substrates corresponding to the microfluidic channel structures; The multiple microfluidic channel structures correspond to different samples to be tested or different detection conditions; The optical detection module sequentially acquires Raman spectra of multiple surface-enhanced Raman spectroscopy-enhanced substrates by scanning or spectrophotometry, thereby achieving high-throughput parallel detection.

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