Plasmon optical sensing probe for online trace detection of biological threat agents

Abstract

The present invention relates to an optical probe, specifically an optical sensing probe for online trace detection of biological threat factor plasma. The sensing probe consists of a microstructured optical fiber and gold nanowires. The optical fiber is provided with two symmetrically distributed microgrooves, with the gold nanowires located at the bottom of the grooves. The optical fiber's cladding is provided with four inner large air holes and two outer small air holes. The four inner large air holes are arranged symmetrically about the grooves in groups of two, and the two outer small air holes are symmetrically distributed about the microgrooves. The radius of the optical fiber is 16 μm; the depth of the microgrooves is 8 μm; the radius of the gold nanowires is 500 nm; the radius of the inner large air holes is 4 μm, and the horizontal center distance of the four inner large air holes is 13 μm, and the vertical center distance is 11 μm; the radius of the outer small air holes is 1.5 μm. This probe achieves efficient and accurate biomolecule detection, providing reliable technical support for early diagnosis and timely treatment.

Description

Technical Field

[0001] The invention relates to an optical probe, in particular to an optical sensing probe for online trace detection of biological threat factors. Background Art

[0002] Biosensor technology, as a key detection method in the modern medical and health system, is playing an increasingly important role. Among them, surface plasmon resonance (SPR) technology, as an important breakthrough in the field of biosensing, is based on the unique photon-electron coupling effect. When the incident light wave matches the wave vector of the free electron cloud on the surface of the metal film, it will stimulate the collective oscillation of electrons to form plasma excitons, resulting in a characteristic attenuation of the reflected light energy. This mechanism gives SPR technology the three core advantages of high sensitivity, label-free, and rapid response. What is particularly outstanding is that SPR technology is extremely sensitive to changes in the refractive index of metal surface media, and can realize non-destructive analysis of trace biological samples. SPR technology is driving medical testing towards a more accurate, efficient, and trace direction, providing strong technical support for modern medical and health care.

[0003] Microstructured optical fiber (MOF) achieves precise control of light transmission patterns by introducing periodic or aperiodic air hole arrangements into conventional optical fibers. Its unique waveguide structure offers significant advantages, including flexible design, tunable optical properties, low transmission loss, and continuous single-mode transmission, making it an ideal medium for SPR sensing research. After years of development, microstructured optical fiber SPR sensors have continuously achieved breakthroughs in structural design and application research, demonstrating broad application prospects.

[0004] With the continuous improvement of public health awareness and the continued growth of medical needs, public health emergencies and long-term health threats such as early cancer screening have placed higher demands on biodetection technology. Currently, although a variety of MOF-SPR sensors have been developed for the detection of biological threat factors such as cancerous cells and viruses, existing technologies have three key shortcomings: first, the single function, the existing sensors cannot achieve dual detection of cancer cells and viruses; second, the structural complexity, the multi-channel design not only increases the difficulty of preparation, but also hinders actual clinical application; third, the detection limitations, traditional structures cannot meet the needs of rapid analysis of trace biological samples. Summary of the Invention

[0005] To address the technical issues raised in the background art, the present invention provides a multifunctional, low-pore, online trace detection plasma optical sensing probe for biological threat factors. This allows for efficient and accurate biomolecule detection, providing reliable technical support for early diagnosis and timely treatment.

[0006] The technical solution adopted by the present invention is: a plasma optical sensing probe for online trace detection of biological threat factors, the plasma optical sensing probe is composed of a microstructured optical fiber and nano-gold wires; the microstructured optical fiber is provided with two symmetrically distributed micro-grooves, and the nano-gold wires are embedded in the bottom of the micro-grooves; the cladding of the microstructured optical fiber is provided with four inner-layer large air holes and two outer-layer small air holes, the four inner-layer large air holes and the two outer-layer small air holes are arranged in a periodic alternating pattern, and the four inner-layer large air holes are arranged symmetrically about the micro-grooves in groups of two; the two outer-layer small air holes are symmetrically distributed about the micro-grooves, and the two outer-layer small air holes are located on the symmetry axes of the two micro-grooves.

[0007] The radius of the microstructured optical fiber is 16μm; the depth of the micro groove is 7.5μm-8.5μm; the radius of the gold nanowire is 300nm-500nm; the radius of the inner large air hole is 3.5μm-4.5μm, and among the four inner large air holes, the center distance between the two inner large air holes in the horizontal direction is 12μm-14μm, and the center distance between the two inner large air holes in the vertical direction is 10μm-12μm; the radius of the outer small air hole is 1μm-2μm.

[0008] Furthermore, the depth of the micro-groove is 8μm; the radius of the gold nanowire is 500nm; the radius of the inner large air pore is 4μm, and among the four inner large air pores, the center distance between the two inner large air pores in the horizontal direction is 13μm, and the center distance between the two inner large air pores in the vertical direction is 11μm; the radius of the outer small air pore is 1.5μm.

[0009] Furthermore, the microstructured optical fiber is of the refractive index guided type.

[0010] Furthermore, the micro groove is not a through groove, and the width of the micro groove is slightly larger than the diameter of the nano-gold wire.

[0011] Furthermore, the probe is a new type of plasmonic optical sensing probe that integrates multifunctional detection, simplifies pore structure, and supports microfluidic trace analysis.

[0012] Beneficial effects of the present invention: To address the technical problems of this application, a multifunctional, low-pore, plasmon optical sensing probe for online trace detection of biological threat factors is provided, specifically a MOF-SPR sensing probe (MOF-SPR stands for microstructured fiber-surface plasmon resonance). Its main advantages are as follows:

[0013] (1) Plasmon optical sensing probes can not only diagnose a variety of cancerous cells, but also screen a variety of viruses, thus realizing the integrated detection of biological threat factors.

[0014] (2) Plasma optical sensing probes have good optical properties when detecting biological threat factors. The refractive index detection range of the sample to be tested is 1.33-1.40, the maximum spectral sensitivity is 40000 nm / RIU, and the resolution is 2.5×10 -6 RIU.

[0015] (3) Micro-grooves are arranged inside the MOF carrier of the plasma optical sensing probe to realize microflow trace detection of special biological samples.

[0016] (4) The plasma optical sensing probe has few pores in the MOF carrier, and its structure is simple, the design is convenient, and it is easy to actually manufacture and apply. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 is a cross-sectional view of the plasmonic optical sensing probe.

[0018] Figure 2 This is the front view of the plasma optical sensing probe.

[0019] Figure 3 The graph is a relationship between each limiting loss and the resonance wavelength when the refractive index is in the range of 1.33-1.40 when the plasma optical sensing probe detects the sample to be tested.

[0020] Figure 4 This is a graph showing the relationship between the plasma optical sensing probe detecting different groups of normal cells and their corresponding cancer cells.

[0021] Figure 5 This is a graph showing the relationship between the limiting loss and the resonance wavelength at different refractive indices when the plasmonic optical sensing probe detects the SARS-CoV-2 virus spike receptor binding domain (RBD).

[0022] Figure 6 This is a graph showing the relationship between the limiting loss and the resonance wavelength at different refractive indices when the plasmon optical sensing probe detects mutant virus single-stranded ribonucleic acid (RNA).

[0023] Figure 7 This is a graph showing the relationship between limiting loss and resonance wavelength at different refractive indices when detecting human monoclonal antibody immunoglobulin G (IgG).

[0024] Figure numerals: 1. gold nanowire; 2. large air holes in the inner layer; 3. cladding; 4. small air holes in the outer layer; 5. microstructured optical fiber; 6. micro grooves. DETAILED DESCRIPTION

[0025] Example 1

[0026] like Figure 1 and Figure 2As shown, the plasma optical sensing probe for online trace detection of biological threat factors consists of a microstructured optical fiber 5 and a gold nanowire 1; the microstructured optical fiber 5 is provided with two microgrooves 6 symmetrically distributed about the central axis of the optical fiber, and the gold nanowire 1 is embedded in the bottom of the microgrooves 6; the cladding 3 of the microstructured optical fiber 5 is provided with four inner layer large air holes 2 and two outer layer small air holes 4, the inner layer large air holes 2 and the outer layer small air holes are arranged in a periodic alternating pattern, and the four inner layer large air holes 2 are arranged symmetrically about the microgrooves 6 in groups of two; the two outer layer small air holes 4 are symmetrically distributed about the microgrooves 6, and the two outer layer small air holes 4 are located on the symmetry axes of the two microgrooves 6.

[0027] The radius of the microstructured optical fiber 5 is 16 μm; the depth of the micro-groove 6 is 8 μm; the radius of the gold nanowire 1 is 500 nm; the radius of the inner large air hole 2 is 4 μm, and among the four inner large air holes 2, the center distance between the two inner large air holes 2 in the horizontal direction is 13 μm, and the center distance between the two inner large air holes 2 in the vertical direction is 11 μm; the radius of the outer small air hole 4 is 1.5 μm.

[0028] The background material of the microstructured optical fiber 5 is silica. The microstructured optical fiber 5 is of the refractive index guided type.

[0029] Example 2

[0030] Based on the technical solution of Example 1, the depth of the micro-groove 6 is 7.5 μm; the radius of the gold nanowire 1 is 300 nm; the radius of the inner large air hole 2 is 3.5 μm, and among the four inner large air holes 2, the center distance between the two inner large air holes 2 in the horizontal direction is 12 μm, and the center distance between the two inner large air holes 2 in the vertical direction is 10 μm; the radius of the outer small air hole 4 is 1 μm.

[0031] Example 3

[0032] Based on the technical solution of Example 1, the depth of the micro-groove 6 is 8.5 μm; the radius of the gold nanowire 1 is 400 nm; the radius of the inner large air hole 2 is 4.5 μm, and among the four inner large air holes 2, the center distance between the two inner large air holes 2 in the horizontal direction is 14 μm, and the center distance between the two inner large air holes 2 in the vertical direction is 12 μm; the radius of the outer small air hole 4 is 2 μm.

[0033] The MOF-SPR sensor probe uses gold nanowires embedded in microgrooves as the sensing medium. Its operating principle is based on the phase-matched coupling mechanism between evanescent waves and surface plasmon waves (SPPs). In the MOF, large inner air pores and small outer air pores are periodically alternating. This design not only effectively constrains the transmission of the evanescent wave but also significantly enhances the interaction between the evanescent field and the gold nanowires by optimizing the light field distribution. When evanescent waves of different wavelengths propagate along the MOF axis in a specific pattern, the surface plasmon waves in the gold nanowires always maintain a fixed transmission pattern. When the wave vector of an evanescent wave of a certain wavelength in the MOF reaches phase matching with the wave vector of the surface plasmon wave of the gold nanowire, the evanescent field energy is efficiently coupled into the gold nanowire, resulting in significant energy loss in the MOF transmitted light field. By monitoring the resonant wavelength corresponding to the energy loss extreme in the loss spectrum, a highly sensitive wavelength-modulated sensing response mechanism can be established.

[0034] Refractive index detection performance of MOF-SPR sensing probes and their biomedical applications, such as Figure 3 As shown in the figure, within the refractive index range of 1.33-1.40, the probe exhibits significant refractive index response characteristics. As the refractive index increases in increments of 0.01, the resonance wavelength redshifts, the resonance peak increases, and the half-peak width decreases, indicating that the coupling strength between the core guided mode and the plasmon mode continues to increase. When the refractive index increases from 1.39 to 1.40, the probe performance reaches its peak, with a sensitivity and resolution of up to 40,000 nm / RIU and 2.5×10 -6 RIU. In biological detection applications, Figure 4 As shown in the figure, the probe can distinguish healthy cells from cancerous cells (including skin, cervical, blood, Adr, Bre1, Bre2 and other types). Based on the increase in the refractive index of cancerous cells due to the increase in protein content, it can achieve early diagnosis of cancer through the change in refractive index. The experimental results show that the maximum sensitivity and resolution are 36428 nm / RIU respectively. Figure 5 、 Figure 6 and Figure 7The results further demonstrate the probe's advantages in virus detection, allowing for the quantification of viral concentrations in patients using three different approaches based on different ligand-analyte binding pairs. The plasmonic optical probe effectively detects the SARS-CoV-2 virus spike receptor binding domain (RBD), variant viral single-stranded RNA (RNA), and human monoclonal antibody immunoglobulin G (IgG). Experimental results demonstrate that the maximum sensitivity for detecting the three different viral components (antigen, nucleic acid, and antibody) is 7833 nm / RIU, 13158 nm / RIU, and 7863 nm / RIU, respectively. Its sensitivity continuously increases with the refractive index of the detection object, demonstrating excellent potential for pathogen screening. These results demonstrate that the MOF-SPR sensing probe has important application value in the field of biomedical testing.

[0035] The sensor probe utilizes a specially designed MOF cladding structure with air pores of two different sizes. Microgrooves are symmetrically arranged on the upper and lower sides of the MOF, with gold nanowires embedded within the grooves. This innovative structure creates a microfluidic trace detection channel while simultaneously opening an evanescent field leakage window. By optimizing the energy transmission path and combining SPR technology with energy coupling principles, it achieves highly sensitive online detection of refractive index changes in biological threat factors. The bioprobe exhibits multi-target detection capabilities, enabling simultaneous detection of multiple cancerous cells (skin, cervical, blood, Adr, Bre1, and Bre2) and three typical viruses (SARS-CoV-2 spike receptor binding domain (RBD), mutant viral single-stranded RNA (RNA), and human monoclonal antibody immunoglobulin G (IgG)). Experimental data demonstrate that the plasmonic biosensor probe exhibits excellent optical properties, with a maximum spectral sensitivity of 36,428 nm / RIU for cancerous cell detection and 13,158 nm / RIU for virus detection. The sensing probe is easy to manufacture and easy to use, and has achieved optimization in probe structure and functional performance.

Claims

1. A plasma optical sensing probe for online trace detection of biological threat factors, characterized by: The plasma optical sensing probe is composed of a microstructured optical fiber (5) and a nano-gold wire (1); two symmetrically distributed micro-grooves (6) are opened on the microstructured optical fiber (5), and the nano-gold wire (1) is embedded in the bottom of the micro-grooves (6); four inner-layer large air holes (2) and two outer-layer small air holes (4) are provided in the cladding (3) of the microstructured optical fiber (5), and the four inner-layer large air holes (2) and the two outer-layer small air holes (4) are arranged alternately in a periodic manner, and the four inner-layer large air holes (2) are arranged symmetrically about the micro-grooves (6) in groups of two; the two outer-layer small air holes (4) are symmetrically distributed about the micro-grooves (6), and the two outer-layer small air holes (4) are located on the symmetry axes of the two micro-grooves (6); The radius of the microstructured optical fiber (5) is 16 μm; the depth of the micro groove (6) is 7.5 μm-8.5 μm; the radius of the gold nanowire (1) is 300 nm-500 nm; the radius of the inner large air hole (2) is 3.5 μm-4.5 μm, and among the four inner large air holes (2), the center distance between two inner large air holes (2) in the horizontal direction is 12 μm-14 μm, and the center distance between two inner large air holes (2) in the vertical direction is 10 μm-12 μm; the radius of the outer small air hole (4) is 1 μm-2 μm.

2. The on-line trace detection of biological threat factor plasma optical sensing probe according to claim 1, characterized in that: The depth of the micro groove (6) is 8 μm; the radius of the gold nanowire (1) is 500 nm; the radius of the inner large air pore (2) is 4 μm, and among the four inner large air pores (2), the distance between the centers of two inner large air pores (2) in the horizontal direction is 13 μm, and the distance between the centers of two inner large air pores (2) in the vertical direction is 11 μm; the radius of the outer small air pore (4) is 1.5 μm.

3. The on-line trace detection of biological threat factor plasma optical sensing probe according to claim 1 or 2, characterized in that: The background material of the microstructured optical fiber (5) is silicon dioxide.

4. The on-line trace detection of biological threat factor plasma optical sensing probe according to claim 3, characterized in that: The microstructured optical fiber (5) is of a refractive index guided type.

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