Optical fiber optical tweezers surface enhanced Raman microfluid detection system

Abstract

The utility model relates to an optical fiber optical tweezers surface enhanced Raman microfluid detection system, and belongs to the field of biochemical analysis instruments. The system comprises a fishbone-shaped microfluidic substrate, a microsphere control optical fiber, a Raman excitation light transmission optical fiber, a Raman signal receiving optical fiber, a capture light source, a Raman excitation light source, a spectrograph, an electric control displacement platform and a control system, the fishbone-shaped microflow substrate provides a groove for fluid to pass through, and also provides grooves for placing the microsphere control optical fiber, the Raman excitation light transmission optical fiber and the Raman signal receiving optical fiber; the microsphere control optical fiber is arranged on the electric control displacement platform and is connected with the capture light source, so that the distance between microspheres can be regulated and controlled, and the sensitivity enhancement factor of the detection system can be dynamically regulated; the front ends of the Raman signal receiving optical fiber and the Raman exciting light transmission optical fiber are immersed into a central detection area of the fishbone-shaped microflow substrate, and the rear ends of the Raman signal receiving optical fiber and the Raman exciting light transmission optical fiber are respectively connected with the spectrometer and the Raman exciting light source.

Description

Technical Field

[0001] This utility model belongs to the field of biochemical analysis instruments, and relates to Raman spectroscopy, particle optical manipulation and biomedicine, specifically to a fiber optic tweezers surface-enhanced Raman microfluidic detection system. Background Technology

[0002] Raman spectroscopy is a spectroscopic technique that uses optical Raman scattering to study molecular vibrations. It can reveal microscopic information about a sample, including its morphology, molecular structure, phase state, chemical composition, and crystal state. Currently, compared to other detection techniques, Raman spectroscopy is widely used in various fields such as biomedicine, materials science, chemical analysis, and art and archaeology due to its non-destructive, rapid, and simple sample preparation capabilities, as well as its rich information content. Surface-enhanced Raman spectroscopy (SERS) not only inherits the advantages of traditional Raman spectroscopy but also enhances the Raman signal of molecules adsorbed on metal nanostructures by 10⁻¹⁰ through the localized surface volume resonance electric field enhancement (LSPR) mechanism. 4 Up to 10 15 This high sensitivity allows SERS to detect extremely low concentrations of molecules, making it widely used in trace analysis, biomedical detection, and environmental monitoring. However, current SERS technology still faces three major challenges: ① Complex substrate preparation processes and insufficient precision in controlling the uniformity of nanostructures lead to poor signal reproducibility; ② The spatial distribution of "hot spots" is random, making it difficult to accurately locate target molecules to the enhancement regions; ③ The biocompatibility of metal nanostructures with the detection environment restricts their in vivo application.

[0003] Advances in optical manipulation technology have provided new solutions to the aforementioned bottlenecks. Optical tweezers, a typical example of photomechanical effects, are based on the principle of gradient force and scattering force balance proposed by Arthur Ashkin in 1986. When a focused laser beam acts on dielectric particles, it can produce piconewton-level (10⁻⁶) scattering forces. -12 Optical tweezers utilize optical potential traps (N) to achieve three-dimensional non-contact manipulation of micro and nanoparticles. Modern optical tweezers systems have evolved into various forms, such as holographic optical tweezers and fiber optic tweezers, and have been widely used in fields such as single-cell sorting and DNA mechanical property measurement. However, the integration of traditional optical tweezers technology with spectral detection systems faces significant technical barriers: ① High-power capture lasers pose a risk of thermal damage to samples and have poor compatibility with fragile biological samples; ② The spatial coupling precision requirements between the optical tweezers optical path and the detection optical path are at the sub-micron level, and the multi-module discrete design results in a large system size; ③ The spatial pose of particles changes randomly during dynamic capture, making it difficult to achieve stable and reliable in-situ spectral acquisition.

[0004] Current technological development exhibits two major trends: On the one hand, SERS substrate fabrication is moving towards controllability and functionalization. For example, periodic nanoarrays fabricated using electron beam lithography can improve signal uniformity, but the manufacturing cost is high. On the other hand, photomechanical-spectral coupling technology has become a cutting-edge hot topic. For instance, the "optical tweezers-SERS probe" developed by the Harvard University team can capture a single virus particle while simultaneously acquiring its Raman fingerprint. However, existing methods require alternating switching between capture and detection lasers, and timing control errors lead to signal loss. How to achieve in-situ synchronous detection of photomechanical manipulation and enhanced spectroscopy, and break through the spatial resolution and detection sensitivity limits of existing technologies, has become a core technical challenge that urgently needs to be overcome in this field. Utility Model Content

[0005] In view of this, the purpose of this invention is to provide a novel fiber optic tweezers surface-enhanced Raman microfluidic detection system. Addressing the shortcomings of existing Raman detection systems, such as low sensitivity, lack of flexibility, complex detection systems, poor controllability of LSPR hotspot enhancement, and poor repeatability, this invention combines high sensitivity and excellent repeatability with the advantages of highly controllable LSPR hotspot location and dynamically adjustable sensitivity enhancement factor. Furthermore, compared to traditional Raman detection systems, this invention reduces system complexity while maintaining good system stability and flexibility.

[0006] To achieve the above objectives, this utility model provides the following technical solution:

[0007] A fiber optic tweezers surface-enhanced Raman microfluidic detection system includes a "fishbone" shaped microfluidic substrate, microsphere control fiber I 4, microsphere control fiber II 5, Raman excitation light transmission fiber 6, Raman signal receiving fiber 3, a trapping light source 12, a Raman excitation light source 13, a spectrometer 11, an electrically controlled displacement platform 15, and a control system 14.

[0008] The "fishbone" shaped microfluidic substrate provides grooves for fluid to pass through, and also provides grooves for placing microsphere control fiber I 4, microsphere control fiber II 5, Raman excitation light transmission fiber 6 and Raman signal receiving fiber 3.

[0009] The microsphere control fiber I (4) and microsphere control fiber II (5) are placed on the electrically controlled displacement platform 15. The ends of the microsphere control fiber I (4) and microsphere control fiber II (5) are connected to the light source 12, which can adjust the distance between the microspheres and thus realize the dynamic adjustment of the sensitivity enhancement factor of the detection system.

[0010] The front ends of the Raman signal receiving fiber 3 and the Raman excitation light transmission fiber 6 are embedded in the central detection area 10 of the "fishbone" shaped microfluidic substrate, and the rear ends are connected to the spectrometer 11 and the Raman excitation light source 13, respectively.

[0011] The spectrometer 11, the light-capturing source 12, the Raman excitation light source 13, and the electrically controlled displacement platform 15 are all connected to the control system 14.

[0012] Preferably, the "fishbone" type microfluidic substrate includes a main "spine" groove (i) and eight side "fishbone" grooves (a, b, g, h, c, d, e, f); wherein, four side "fishbone" grooves (a, b, g, h) and one main "spine" groove (i) are grooves for fluid to pass through, and four side "fishbone" grooves (c, d, e, f) are grooves for placing functional optical fibers.

[0013] Preferably, the "fishbone" shaped microfluidic substrate further includes a microfluidic channel inlet I1 and a microfluidic channel inlet II2. The fluid to be tested is injected into the system through these two channels, which can realize functions such as solution flow rate regulation, multiphase fluid ratio mixing and controllable generation of microdroplets according to experimental requirements.

[0014] Preferably, the "fishbone" shaped microfluidic substrate further includes a microfluidic channel outlet I7 and a microfluidic channel outlet II8.

[0015] Preferably, the "fishbone" shaped microfluidic substrate has a channel switch 9 at the intersection of microfluidic channel outlet I7 and microfluidic channel outlet II8, which is connected to the control system 14 and used to control the fluid output channel.

[0016] Preferably, by controlling the channel switch 9 through the control system 14, the user can also classify the fluid.

[0017] Preferably, when the control system 14 receives a signal from the spectrometer 11, it sends a signal to the electrically controlled displacement platform 15 and the light source 12 according to the user's needs. Under the combined action of the two, the position of the two coated metal particle microspheres 101 is adjusted by the microsphere control optical fibers I and II (4, 5), thereby realizing the dynamic adjustment of the sensitivity enhancement factor of the detection system.

[0018] The beneficial effects of this invention are as follows: The fiber optic tweezers surface-enhanced Raman microfluidic detection system provided by this invention not only inherits the advantages of traditional Raman detection systems, but also possesses advantages such as high sensitivity, high repeatability, and high reliability, and has broad application prospects in biomedicine, environmental monitoring, and materials science. Specific beneficial effects are manifested as follows:

[0019] (1) High sensitivity and dynamically adjustable enhancement factor: Through the synergistic effect of microsphere control fiber and electronically controlled displacement platform, the position of two metal-coated microspheres can be precisely controlled to achieve precise positioning and enhancement intensity adjustment of local surface plasmon resonance (LSPR) hotspots.

[0020] (2) Multi-dimensional system integration and structural optimization: The innovative "fishbone" shaped microfluidic substrate achieves spatial optimization of the fluid channels and functional fiber optic channels through a spine-branch channel design. Among them, the two microfluidic channel inlets can realize functions such as solution flow rate regulation, multiphase fluid ratio mixing and controllable microdroplet generation according to experimental needs; the two microfluidic channel outlets, combined with the channel switch design, can be used to control the fluid output channel and the classification of fluids.

[0021] (3) Automated control and repeatability improvement: A closed-loop feedback control system is adopted to monitor the LSPR enhancement status in real time through the spectrometer signal and automatically adjust the stepping accuracy of the displacement platform and the captured light power.

[0022] (4) Modular design: The system enables rapid replacement of fiber optic tweezers probes through standardized fiber optic interfaces.

[0023] (5) System stability: The integrated packaging design reduces the vibration sensitivity of optical components and minimizes baseline drift under environmental temperature and humidity fluctuations.

[0024] Other advantages, objectives, and features of this invention will be set forth in part in the description which follows, and in part will be apparent to those skilled in the art from the following examination and study, or may be learned from practice of this invention. The objectives and other advantages of this invention can be realized and obtained through the following description. Attached Figure Description

[0025] To make the objectives, technical solutions, and advantages of this utility model clearer, the preferred embodiments of this utility model will be described in detail below with reference to the accompanying drawings, wherein:

[0026] Figure 1 This is a schematic diagram of the fiber optic tweezers surface-enhanced Raman detection system provided in an embodiment of the present invention;

[0027] Figure 2 for Figure 1 A magnified schematic diagram of a portion of the central core detection section;

[0028] Figure labels: 1-Microfluidic channel inlet I, 2-Microfluidic channel inlet II, 3-Raman signal receiving fiber, 4-Microsphere control fiber I, 5-Microsphere control fiber II, 6-Raman excitation light transmission fiber, 7-Microfluidic channel outlet I, 8-Microfluidic channel outlet II, 9-Channel switch, 10-Central detection area, 11-Spectrometer, 12-Capture light source, 13-Raman excitation light source, 14-Control system, 15-Electrically controlled displacement platform; 101-Coated metal particle microsphere, 102-Particle to be tested; a, b, i, g, h are the first to fifth grooves for fluid passage, c, d, e, f are the first to fourth grooves for placing functional optical fibers. Detailed Implementation

[0029] The following specific examples illustrate the implementation of this utility model. Those skilled in the art can easily understand other advantages and effects of this utility model from the content disclosed in this specification. This utility model can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of this utility model. It should be noted that the illustrations provided in the following embodiments are only schematic representations of the basic concept of this utility model. Unless otherwise specified, the following embodiments and features can be combined with each other.

[0030] The accompanying drawings are for illustrative purposes only and are schematic diagrams, not actual pictures. They should not be construed as limiting the present invention. To better illustrate the embodiments of the present invention, some parts in the drawings may be omitted, enlarged, or reduced, and do not represent the actual product dimensions. It is understandable to those skilled in the art that some well-known structures and their descriptions may be omitted in the drawings.

[0031] In the accompanying drawings of this utility model, the same or similar reference numerals correspond to the same or similar components. In the description of this utility model, it should be understood that if terms such as "upper," "lower," "left," "right," "front," and "rear" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, they are only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, the terms used to describe positional relationships in the drawings are only for illustrative purposes and should not be construed as limiting this utility model. For those skilled in the art, the specific meaning of the above terms can be understood according to the specific circumstances.

[0032] Example 1:

[0033] Please see Figures 1-2 This embodiment provides a novel fiber optic tweezers-assisted microfluidic detection system with controllable LSPR hotspot location, such as... Figure 1 As shown, the detection system mainly consists of a "fishbone" shaped microfluidic substrate, microsphere control optical fibers (4, 5), Raman excitation light transmission optical fiber 6, Raman signal receiving optical fiber 3, capture light source 12, Raman excitation light source 13, spectrometer 11, electrically controlled displacement platform 15, and control system 14.

[0034] Figure 1In the diagram, the "fishbone" shaped microfluidic substrate consists of a main "spine" groove and eight side "fishbone" grooves. Grooves a, b, i, g, and h are for fluid flow, while grooves c, d, e, and f are for placing functional optical fibers. A partial magnification of the central detection region 10 of the "fishbone" shaped microfluidic substrate is shown below. Figure 2 As shown, Figure 2 In the diagram, 3 and 6 are the Raman light receiving fiber and the Raman excitation light transmission fiber, respectively. 4 and 5 are microsphere control fibers, capable of adjusting the distance between two surface-coated metal microspheres according to actual measurement needs. 101 is the coated metal microsphere, used to form an LSPR hotspot, achieving electromagnetic enhancement and increasing the Raman signal intensity. 102 is the particle to be measured, which can be a single molecule, a large molecular cluster, or a cell, etc.

[0035] Figure 1 In the diagram, 1 and 2 are microfluidic channel inlets I and II, through which the fluid to be tested is injected into the system. This allows for functions such as solution flow rate control, multiphase fluid ratio mixing, and controllable microdroplet generation, depending on experimental requirements. 3 is a Raman signal receiving fiber, its front end extending into the central detection region and its rear end connected to the spectrometer 11. 4 and 5 are microsphere control fibers I and II, placed on the electrically controlled displacement platform 15. The ends of microsphere control fibers I and II (4 and 5) are connected to the capturing light source 12. Under the combined action of the capturing light source 12 and the electrically controlled displacement platform 15, the positions of the two coated metal microspheres 101 are controlled via the microsphere control fibers I and II (4 and 5), thereby achieving dynamic adjustment of the sensitivity enhancement factor of the detection system. 6 is a Raman excitation light transmission fiber, its front end submerged in the central detection region 10 and its rear end connected to the Raman excitation light source 13. 7 and 8 are the microfluidic channel outlets. Figure 1 In the middle, 9 is a channel switch, which is connected to the control system 14 and can control the fluid output channel. Figure 1 In this system, the spectrometer 11, the light-capturing source 12, the Raman excitation source 13, and the electrically controlled displacement platform 15 are all connected to the control system 14. When the control system 14 receives a signal from the spectrometer 11, it sends signals to the electrically controlled displacement platform 15 and the light-capturing source 12 according to the user's needs. Under the combined action of the two, the distance between the coated metal particle microspheres 101 is controlled by the microsphere control optical fibers I and II (4, 5), thereby realizing the dynamic adjustment of the sensitivity enhancement factor of the detection system.

[0036] Example 2:

[0037] Based on the detection system structure of Embodiment 1, the user can also classify fluids by controlling the channel switch 9 through the control system 14. For example:

[0038] 1) Detection and classification of multi-component sample solutions;

[0039] 2) Cell screening in mixed solutions of various cell types.

[0040] Example 3:

[0041] The control system 14 can be a simple feedback control system based on an FPGA platform. The system receives signals from the spectrometer 11 and then sends signals to the electrically controlled displacement platform 15 and the capture light source 12 to control the precession of the electrically controlled displacement platform 15 and the power of the Raman excitation light source 13. The two together control the capture effect of the microsphere control optical fibers (4, 5) on the coated metal particle microspheres 101, thereby controlling the distance between the coated metal particle microspheres 101 and realizing the regulation of the Raman enhancement factor and the LSPR hot spot position of the system.

[0042] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of this utility model and are not intended to limit it. Although this utility model has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solution of this utility model without departing from the spirit and scope of this technical solution, and all such modifications or substitutions should be covered within the scope of the claims of this utility model.

Claims

1. A fiber optic tweezers surface-enhanced Raman microfluidic detection system, characterized in that, It includes a "fishbone" type microfluidic substrate, microsphere control fiber I (4), microsphere control fiber II (5), Raman excitation light transmission fiber (6), Raman signal receiving fiber (3), capture light source (12), Raman excitation light source (13), spectrometer (11), electrically controlled displacement platform (15), and control system (14). The "fishbone" shaped microfluidic substrate provides grooves for fluid to pass through, and also provides grooves for placing microsphere control fiber I (4), microsphere control fiber II (5), Raman excitation light transmission fiber (6) and Raman signal receiving fiber (3); The microsphere control fiber I (4) and microsphere control fiber II (5) are placed on the electrically controlled displacement platform (15), and the ends of the microsphere control fiber I (4) and microsphere control fiber II (5) are connected to the capture light source (12). The front ends of the Raman signal receiving fiber (3) and the Raman excitation light transmission fiber (6) are inserted into the central detection area (10) of the "fishbone" shaped microfluidic substrate, and the rear ends are connected to the spectrometer (11) and the Raman excitation light source (13), respectively. The spectrometer (11), the captured light source (12), the Raman excitation light source (13), and the electrically controlled displacement platform (15) are all connected to the control system (14).

2. The fiber optic tweezers surface-enhanced Raman microfluidic detection system according to claim 1, characterized in that, The "fishbone" type microfluidic substrate includes a main "spine" groove (i) and eight side "fishbone" grooves (a, b, g, h, c, d, e, f); wherein, four side "fishbone" grooves (a, b, g, h) and one main "spine" groove (i) are grooves for fluid to pass through, and four side "fishbone" grooves (c, d, e, f) are grooves for placing functional optical fibers.

3. The fiber optic tweezers surface-enhanced Raman microfluidic detection system according to claim 1 or 2, characterized in that, The "fishbone" shaped microfluidic substrate also includes a microfluidic channel inlet I (1) and a microfluidic channel inlet II (2), through which the fluid to be tested is injected into the detection system.

4. The fiber optic tweezers surface-enhanced Raman microfluidic detection system according to claim 1 or 2, characterized in that, The "fishbone" type microfluidic substrate also includes microfluidic channel outlet I (7) and microfluidic channel outlet II (8).

5. The fiber optic tweezers surface-enhanced Raman microfluidic detection system according to claim 4, characterized in that, The "fishbone" shaped microfluidic substrate has a channel switch (9) at the intersection of microfluidic channel outlet I (7) and microfluidic channel outlet II (8), which is connected to the control system (14) and used to control the fluid output channel.

6. The fiber optic tweezers surface-enhanced Raman microfluidic detection system according to claim 5, characterized in that, By controlling the channel switch (9) through the control system (14), the user can also classify the fluid.

7. The fiber optic tweezers surface-enhanced Raman microfluidic detection system according to claim 1, characterized in that, When the control system (14) receives a signal from the spectrometer (11), it sends a signal to the electrically controlled displacement platform (15) and the light source (12) according to the user's needs. Under the combined action of the two, the position of the two coated metal particle microspheres (101) is adjusted by the microsphere control optical fibers I and II (4, 5).

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