Controllable SERS (Surface Enhanced Raman Scattering) detection system for capturing gold-coated hairline microspheres by gold-coated hairline sub-wavelength optical fiber optical tweezers

Abstract

The invention discloses a controllable SERS (Surface Enhanced Raman Scattering) detection system for capturing gold-coated hairline microspheres by gold-coated hairline sub-wavelength optical fiber optical tweezers. The controllable SERS detection system comprises the following parts: a 1485nm optical fiber laser, a four-degree-of-freedom micropositioner, a 1485nm single-mode optical fiber jumper, the gold-coated hairline sub-wavelength optical fiber optical tweezers, a Raman spectrum detection system, an objective table, gold-coated hairline photonic crystal microspheres and the like. When a 1485nm optical fiber laser is turned on, 1485nm laser is introduced into the sub-wavelength optical fiber tweezers with the gold-coated hairlines and extends into a solution to be detected, a fundamental mode high-gradient convergent light field is formed at the sub-wavelength position of the sub-wavelength optical fiber tweezers with the gold-coated hairlines through the photothermal effect of the 1485nm laser, and gold-coated hairline microspheres are captured; the captured gold-coated hairline microspheres are attached to the end of the sub-wavelength optical fiber optical tweezers with the gold-coated hairlines on the surfaces, and stable Raman signal enhancement is achieved; enhanced detection of Raman signals in a solution is realized through a Raman signal detection system.

Description

Technical Field

[0001] This invention belongs to the field of biochemical analysis instruments and mainly relates to a controllable SERS detection system for capturing gold-coated microspheres with subwavelength fiber optic tweezers. Background Technology

[0002] Raman spectroscopy, pioneered in 1928 by Indian physicist Raman, was instrumental in the discovery of Raman scattering. During his experiments, Raman made the first observation of this unique phenomenon, earning him the Nobel Prize in Physics in 1930. For decades after its discovery, Raman spectroscopy played a crucial role in molecular structure research, becoming a powerful tool for exploring the microscopic molecular world. However, Raman spectroscopy itself suffered from several significant drawbacks, such as the relatively weak signal and the difficulty in collecting the detection signal. These problems severely hampered its further development, leading to a near standstill in research on Raman spectroscopy for many years. It wasn't until the 1960s, with the advent of laser technology, that Raman detection was revolutionized. The high energy and high coherence of lasers significantly enhanced the Raman scattering signal of the analyte, revitalizing Raman detection research and attracting numerous researchers back to the field.

[0003] In addition, Fleischmann et al. made another significant discovery during their experiments in 1974. They observed for the first time an extremely strong Raman scattering enhancement signal on the surface of a rough silver electrode adsorbed with pyridine. This phenomenon was named SERS (Surface-Enhanced Raman Scattering). The emergence of SERS successfully overcame the relatively weak signal in traditional Raman detection methods, increasing the Raman scattering signal intensity of the analyte to several orders of magnitude greater. This allows researchers to obtain molecular vibrational information that is difficult to obtain using conventional Raman detection methods, making it possible to detect signals that were previously extremely weak and difficult to detect. It is precisely because of this superior characteristic that SERS has shown extremely broad application prospects in the detection and sensing of weak biological signals, and has also sparked a new wave of Raman research.

[0004] Through continuous and in-depth research, scientists have gradually discovered that the strength of Raman spectroscopy enhancement is closely related to the properties of the substrate material and structure, with these properties playing a decisive role in the enhancement effect. Currently, Raman spectroscopy enhancement substrates mainly consist of rough surfaces of noble metals (such as gold and silver), nano-noble metal particles, or aggregates of nano-noble metal particles deposited on the surface of photonic crystal microspheres. Among these, photonic crystal microspheres, with their excellent dispersibility, high stability, outstanding biocompatibility, and ease of handling, have become a hot research topic in the field of SERS enhancement substrates.

[0005] Numerous researchers both domestically and internationally have utilized Raman photonic crystal microspheres as biological detectors, conducting a series of in-depth and extensive studies that have greatly expanded the application fields of Raman photonic crystal microspheres. For example, researchers such as Liu ingeniously embedded Raman dyes into the gold core and silver shell interface of bimetallic nanoparticles, successfully constructing SERS nanotags. This innovative method enabled trace detection of protein molecules, providing new ideas and methods for the precise detection of biomolecules. Li et al., using Raman photonic crystal microspheres combined with density "hotspot" active substrate method, tyramine signal amplification method, and nano-mimetic enzyme SERS immunoassay, effectively enhanced the Raman signal of detected tumor marker molecules. This not only further improved the sensitivity of the Raman enhanced signal but also enabled the determination of Raman signals for multiple tumor marker molecules, providing strong technical support for the early diagnosis of tumor diseases.

[0006] However, using photonic crystal microspheres as Raman enhancement substrates is not without its limitations and several problems remain to be solved. Among the most prominent are the randomness of the enhancement effect and the insufficient reproducibility of the spectrum. These phenomena are primarily due to the fact that the photonic crystal microspheres exist as a dispersed system within the liquid environment formed by the analyte. The interactions between some of the photonic crystal microsphere systems are very weak, with enhanced signals only generated upon collision and contact. Consequently, the location of "hot spots" is relatively random, and the quality of these "hot spots" is difficult to control effectively.

[0007] Currently, research on these systems with low coverage, in motion, and weak interactions has become a major hurdle for many researchers. Because randomly generated "hot spots" in the analyte solution are difficult to effectively capture again by the Raman detection laser, the reproducibility of the Raman spectrum is poor; and the uncontrollable quality of these "hot spots" is a key reason why the Raman enhancement coefficient is difficult to guarantee. In view of the above, in order to further improve the application of Raman photonic crystal microspheres in biomolecular testing, it is urgent to explore an effective and powerful method to achieve the controlled and localized generation of "hot spots" in Raman photonic crystal microspheres.

[0008] In this work, we propose a novel method for a controllable SERS detection system using subwavelength fiber tweezers to capture gold-coated microspheres with gold-coated fiber optic tweezers. The core objective is to solve the challenge of locating the Raman detection spot and the Raman "hotspot." Specifically, leveraging the ability of fiber tweezers to directionally capture and focus Raman photonic crystal microspheres, we artificially generate a controllable Raman "hotspot" at the tip of a tapered fiber. Subsequently, we perform targeted Raman detection within this "hotspot" region, thus generating repeatable, high-quality Raman enhanced spectra. This further optimizes the application of the Raman photonic crystal microsphere research system in biomolecular testing, providing stronger support for the development of Raman spectroscopy in the field of biodetection. Summary of the Invention

[0009] This invention aims to solve the related problems existing in the current Raman spectroscopy detection. This invention designs and discloses a controllable SERS detection system for capturing gold-coated microspheres with subwavelength fiber tweezers.

[0010] According to some embodiments of the present invention, a controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber tweezers is provided, wherein the output power of the 1485 nm fiber laser is between 80 mW and 500 mW. The power is selected within this range mainly to prevent the analyte from being damaged by excessive power and to prevent the capture from being completed by insufficient power.

[0011] According to some embodiments of the present invention, a controllable SERS detection system for capturing gold-coated microspheres in subwavelength fiber optic tweezers is provided, wherein the four-degree-of-freedom micro-motion stage is made of PEEK (polyether ether ketone plastic) and can realize displacement micro-motion in four degrees of freedom (X, Y, Z, and around Z) and has fiber optic clamping function.

[0012] According to some embodiments of the present invention, a controllable SERS detection system for capturing gold-coated fiber microspheres using gold-coated fiber subwavelength optical tweezers is provided. The gold-coated fiber subwavelength optical tweezers are used to draw single-mode optical fibers using a high-precision fiber fusion tapering machine. By precisely controlling the melting temperature (1100-1200℃) and the stretching rate (5-10 mm / s), a subwavelength optical fiber structure with a tapered region length of about 5 cm is finally formed, and the diameter of the thinnest part of the tapered region is precisely controlled at about 10 μm. The gold-coated cone region was achieved through in-situ growth. First, the fiber surface underwent functionalization modification. The drawn subwavelength fiber was vertically immersed in a 3-5% APTES (3-aminopropyltriethoxysilane) ethanol solution and allowed to stand at room temperature for 10 minutes. This allowed amino groups to be covalently grafted onto the fiber surface via silicon-oxygen bonds, forming a uniform aminated interface layer. This step significantly improved the subsequent gold seed adsorption efficiency. Next, gold seed coating was performed. The aminated fiber was transferred to a 5 nm gold seed colloidal solution and immersed in a 30 °C constant-temperature water bath for 1 hour. Utilizing the electrostatic adsorption between amino groups and gold nanoparticles, the gold seeds uniformly adhered to the surface of the fiber cone region, forming a dense seed layer that provided active sites for subsequent gold-coated fiber growth. Finally, the fiber was immersed in a mixed growth solution containing 0.55 mM 4-MBA, 1.7 mM HAuCl4, and 4.1 mM L-ascorbic acid for 15 minutes, completing the fabrication of the gold-coated subwavelength fiber optical tweezers.

[0013] According to some embodiments of the present invention, a controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber tweezers is provided. The Raman detection system has microscopic imaging capabilities and the ability to excite and collect Raman scattering signals. It can display the position of the fiber tweezers cone region in real time and realize the excitation and acquisition of signals during the capture and detection processes.

[0014] For a long time, the Raman-enhanced spectra generated by Raman photonic crystal microsphere research systems have suffered from problems such as poor stability and randomness in enhancement effects. The main reason for these problems is that when detecting analyte solutions, the generation location of Raman "hot spots" is often relatively random, making effective control difficult. Compared with existing technologies, the features of this invention are: Compared with previous related technologies, the solution proposed in this invention exhibits significant advantages. The generation position of its Raman enhancement signal is highly stable, the acquired Raman spectrum has stronger reproducibility, and the generated spectral quality is also higher, providing more reliable and higher-quality technical support for the application of Raman detection technology in related fields. Attached Figure Description

[0015] Figure 1 is a schematic diagram of the principle of a controllable SERS detection system for capturing gold-coated microspheres with subwavelength fiber optic tweezers in an embodiment of the present invention.

[0016] Part numbers in the diagram: 1-1485 nm fiber laser, 2-1485 nm single-mode fiber jumper, 3-four-degree-of-freedom microstage, 4-Raman spectroscopy detection system, 5-stage, 6-gold-coated photonic crystal microsphere, 7-gold-coated subwavelength fiber tweezers.

[0017] Figure 2 is an electron microscope image of a gold-coated photonic crystal microsphere in an embodiment of the present invention.

[0018] Part number in the image: 6-Gold-coated photonic crystal microspheres.

[0019] Figure 3 is an electron microscope image of a gold-coated fiber tweezers subwavelength optical tweezers according to an embodiment of the present invention.

[0020] Part number in the image: 7-1485 nm single-mode fiber optic patch cord. Detailed Implementation

[0021] The specific embodiments of the present invention are described in detail below. Examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout.

[0022] The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention. In the description of the present invention, it should be understood that directional descriptions, such as up, down, etc., indicating directions or positional relationships, are based on the directions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention 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, and therefore should not be construed as limiting the present invention.

[0023] In the description of this invention, "multiple" refers to two or more. If "first" or "second" is mentioned, it is only for the purpose of distinguishing technical features and should not be construed as indicating or implying relative importance, or implicitly indicating the number of technical features indicated, or implicitly indicating the order of the technical features indicated. In the description of this invention, unless otherwise explicitly defined, terms such as "setting," "installing," and "connecting" should be interpreted broadly. Those skilled in the art can reasonably determine the specific meaning of the above terms in this invention in conjunction with the specific content of the technical solution.

[0024] The present invention will now be described in further detail with reference to the accompanying drawings: refer to Figure 1 A controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber optic tweezers.

[0025] A controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber tweezers with gold-coated fiber optics is disclosed. A 1485nm fiber laser (1) is inserted into a 1485nm single-mode fiber optic patch cord (2) via an adapter flange, and a 1485nm single-wavelength laser beam is fed into the patch cord (2). To achieve precise three-dimensional manipulation, the 1485nm single-mode fiber optic patch cord (2) is firmly held by a high-precision four-degree-of-freedom micro-stage (3). The four-degree-of-freedom micro-stage is made of PEEK (polyetheretherketone plastic). This micro-stage (3) allows the 1485nm single-mode fiber optic patch cord (2) and the subsequently connected gold-coated subwavelength fiber tweezers (7) to perform nanometer-level precision displacement adjustments in the X, Y, and Z axes (translational degrees of freedom) and the rotational degree of freedom around the Z axis. This flexible manipulation capability is crucial for finding, locating, and ultimately capturing the target microsphere. A 1485 nm single-mode fiber optic jumper (2) is connected to a gold-coated fiber tweezers (7) with a gold-coated filament tip via a transition flange. This allows a 1485 nm single-wavelength laser beam to escape from the subwavelength conical region of the gold-coated filament subwavelength fiber tweezers (7) into the aqueous solution on the stage (5), forming radiation pressure and achieving active capture of the gold-coated filament photonic crystal microsphere (6) with a refractive index different from that of the aqueous solution. Finally, the scattered Raman signal is collected and displayed by the Raman spectroscopy detection system (4). The output power of the 1485 nm fiber laser (1) is between 80 mW and 500 mW. Setting the upper limit of the power below 500 mW is mainly to prevent excessively high laser power from causing irreversible damage to the captured gold-coated filament microsphere (6) itself and the analyte molecules or biological samples that may be attached to it. Setting the lower limit of the power above 80 mW is to ensure that a sufficiently strong gradient force can be generated to effectively capture and stably manipulate the target gold-coated filament microsphere (6). The laser needs to provide sufficient optical pressure to overcome interference factors such as Brownian motion, gravity and fluid drag of the gold-coated microspheres (6) in the solution.

[0026] refer to Figure 2 Electron micrograph of a gold-coated subwavelength fiber tweezers.

[0027] A controllable SERS detection system for gold-coated fiber optic tweezers capturing gold-coated fiber optic microspheres is disclosed. The gold-coated fiber optic photonic crystal microspheres (6) are coated with gold fibers through an in-situ growth method. The microspheres are immersed in an APTES solution for 10 minutes. Then, the aminated microspheres are immersed in a 5 nm gold seed solution for 1 hour, and finally immersed in a mixed growth solution containing 0.55 mM 4-MBA, 1.7 mM HAuCl4, and 4.1 mM L-ascorbic acid for 15 minutes to complete the fabrication of the gold-coated fiber optic photonic crystal microspheres (6).

[0028] refer to Figure 3 Electron micrograph of a gold-coated subwavelength fiber tweezers.

[0029] A controllable SERS detection system for capturing gold-coated microspheres using gold-coated subwavelength fiber optical tweezers is provided. The gold-coated subwavelength fiber optical tweezers (7) are used to draw single-mode optical fibers using a high-precision fiber fusion tapering machine. By precisely controlling the melting temperature (1100-1200 ℃) and stretching rate (5-10 mm / s), a subwavelength fiber structure with a tapered region length of about 5 cm is finally formed, and the diameter of the thinnest part of the tapered region is precisely controlled at about 10 μm. The gold-coated tapered region is achieved through in-situ growth. First, the fiber surface is functionalized by vertically immersing the drawn subwavelength fiber in a 3-5% APTES (3-aminopropyltriethoxysilane) ethanol solution and allowing it to stand at room temperature for 10 minutes. This allows amino groups to be covalently grafted onto the fiber surface through silicon-oxygen bonds, forming a uniform aminated interface layer. This step significantly improves the adsorption efficiency of subsequent gold seeds. Then, gold seed coating is performed by transferring the aminated fiber into a 5 nm gold seed colloidal solution and immersing it in a 30°C constant temperature water bath for 1 hour. Utilizing the electrostatic adsorption between amino groups and gold nanoparticles, the gold seeds are uniformly attached to the surface of the fiber tapered region, forming a dense seed layer that provides active sites for the subsequent growth of the gold-coated region. Finally, the subwavelength fiber tweezers (7) with gold-coated filaments were immersed in a mixed growth solution containing 0.55 mM 4-MBA, 1.7 mM HAuCl4, and 4.1 mM L-ascorbic acid for 15 minutes to complete the fabrication.

[0030] A controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber tweezers with gold-coated fibers, wherein the Raman detection system has microscopic imaging capabilities and the ability to excite and collect Raman scattering signals, can display the position of the fiber tweezers cone region in real time, and realize signal excitation and acquisition during the capture and detection processes.

Claims

1. A controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber optic tweezers, characterized in that, It includes the following parts: The output end of the 1485 nm fiber laser (1) is inserted into a 1485 nm single-mode fiber jumper (2) through an adapter flange, and the 1485 nm single-wavelength laser beam is passed into the 1485 nm single-mode fiber. The four-degree-of-freedom micro-motion stage (3) holds the 1485 nm single-mode fiber jumper (2) and makes it move slightly in the four degrees of freedom of X, Y, Z and around Z with the four-degree-of-freedom micro-motion stage (3). The 1485 nm single-mode fiber jumper (2) is connected to the gold-coated subwavelength fiber tweezers (7) at the tip through the adapter flange, and the 1485 nm single-wavelength laser beam is diffused into the aqueous solution on the stage (5) in the subwavelength cone region of the gold-coated subwavelength fiber tweezers (7) to form radiation pressure and realize the active capture of the gold-coated photonic crystal microspheres (6) with different refractive indices than the aqueous solution. Finally, the scattered Raman signal is collected and displayed by the Raman spectroscopy detection system (4).

2. The controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber optic tweezers according to claim 1, characterized in that: A 1485 nm fiber laser (1) with a power of 80 mW or more and 500 mW or less can achieve photopressure capture of gold-coated photonic crystal microspheres (6) in solution.

3. The controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber optic tweezers according to claim 1, characterized in that: The four-degree-of-freedom micro-motion stage (3) can realize displacement micro-motion in four degrees of freedom: X, Y, Z and around Z, and has fiber optic clamping function.

4. The controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber optic tweezers according to claim 1, characterized in that: The gold-coated subwavelength fiber tweezers (7) are drawn by a fiber fusion tapering machine, with a tapered section length of about 5 cm and a minimum diameter of about 10 μm.

5. The controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber optic tweezers according to claim 4, characterized in that: The gold-coated subwavelength fiber optical tweezers (7) are coated with gold fiber in the cone region by in-situ growth method. First, the subwavelength fiber is immersed in APTES solution for 10 minutes; then, the aminated subwavelength fiber is immersed in 5nm gold seed solution for 1 hour to complete the gold seed coating of subwavelength fiber.

6. The controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber optic tweezers according to claim 5, characterized in that: The gold-coated subwavelength fiber tweezers (7) complete the gold seed coating of subwavelength fiber and are immersed in a mixed growth solution containing 0.55 mM 4-MBA, 1.7 mM HAuCl4 and 4.1 mM L-ascorbic acid for 15 minutes to complete the gold-coated subwavelength fiber tweezers (7).

7. The controllable SERS detection system for capturing gold-coated microspheres using subwavelength fiber optic tweezers according to claim 1, characterized in that: The gold-fiber photonic crystal microspheres (6) are coated with gold fibers through an in-situ growth method. The photonic crystal microspheres are immersed in APTES solution for 10 minutes. Then, the aminated photonic crystal microspheres are immersed in a 5 nm gold seed solution for 1 hour, and finally immersed in a mixed growth solution containing 0.55 mM 4-MBA, 1.7 mM HAuCl4, and 4.1 mM L-ascorbic acid for 15 minutes to complete the gold-fiber photonic crystal microspheres (6).

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