Plasma optical sensing probe for online trace detection of biological threat factors

Abstract

The invention relates to an optical probe, in particular to a plasma optical sensing probe for online trace detection of biological threat factors. The sensing probe is composed of a microstructure optical fiber and a nano gold wire; the optical fiber is provided with two micro grooves which are symmetrically distributed, and the gold nanowires are located at the bottoms of the grooves; four inner-layer large air holes and two outer-layer small air holes are formed in the cladding of the optical fiber, and every two of the four inner-layer large air holes form a group and are symmetrically distributed relative to the groove; and the two outer-layer small air holes are symmetrically distributed relative to the micro groove. The radius of the optical fiber is 16 microns; the depth of the micro groove is 8 microns; the radius of the nano gold wire is 500 nm; the radius of each inner-layer large air hole is 4 microns, and among the four inner-layer large air holes, the horizontal circle center distance of the inner-layer large air holes is 13 microns, and the vertical circle center distance of the inner-layer large air holes is 11 microns; and the radius of the small air holes in the outer layer is 1.5 microns. According to the probe, efficient and accurate biomolecule detection is realized, and reliable technical support is provided for early diagnosis and timely treatment.

Description

Technical Field

[0001] The present invention relates to an optical probe, and particularly to a surface plasmon optical sensing probe for on-line trace detection of biological threat factors. Background Art

[0002] Biosensing technology, as a key detection means in the modern medical and health system, is playing an increasingly important role. Among them, the Surface Plasmon Resonance (SPR) technology, as an important breakthrough in the field of biosensing, is based on a 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 thin film, it will excite the collective oscillation of electrons to form surface plasmons, resulting in a characteristic attenuation of the reflected light energy. This mechanism endows the SPR technology with three core advantages: high sensitivity, label-free, and fast response. Particularly, the SPR technology is extremely sensitive to the change of the refractive index of the medium on the metal surface, and can realize the non-destructive analysis of trace biological samples. The SPR technology is promoting the development of medical detection towards more accurate, efficient, and trace directions, providing strong technical support for the modern medical and health cause.

[0003] Microstructured optical fiber (MOF) realizes precise control of the light transmission mode by introducing periodic or aperiodic air hole arrangements into traditional optical fibers. The unique waveguide structure endows it with significant advantages such as flexible design, adjustable optical properties, low transmission loss, and single-mode transmission without cut-off, making it an ideal carrier for SPR sensing research. After long-term development, the microstructured optical fiber SPR sensor has continuously made breakthroughs in structural design and application research, showing broad application prospects.

[0004] With the continuous improvement of public health awareness and the continuous growth of medical needs, sudden public health events and long-term health threats such as early cancer screening have put forward higher requirements for biological detection technology. At present, for the detection of biological threat factors such as cancer cells and viruses, although a variety of MOF-SPR sensors have been developed, there are three key defects in the existing technology: one is the single functionality, and the existing sensors cannot simultaneously detect cancer cells and viruses; the second is the structural complexity, and the multi-channel design not only increases the preparation difficulty, but also hinders the actual clinical application; the third is the detection limitation, and the traditional structure is difficult to meet the rapid analysis requirements of trace biological samples. Summary of the Invention

[0005] In order to solve the technical problems in the background art, the present invention provides a surface plasmon optical sensing probe with few air holes for multi-functional on-line trace detection of biological threat factors, so as to achieve efficient and accurate biomolecule detection and provide reliable technical support for early diagnosis and timely treatment.

[0006] The technical solution adopted by the present invention is as follows: An on-line trace detection biosensing threat factor plasmonic optical sensing probe, which is composed of a microstructure optical fiber and a nano gold wire; there are 2 symmetrically distributed micro-grooves on the microstructure optical fiber, and the nano gold wire is embedded at the bottom of the micro-grooves; there are 4 inner large air holes and 2 outer small air holes in the cladding of the microstructure optical fiber, and the 4 inner large air holes and the 2 outer small air holes are arranged in a periodic alternating pattern. Every 2 of the 4 inner large air holes are symmetrically arranged with respect to the micro-groove; the 2 outer small air holes are symmetrically distributed with respect to the micro-groove, and the 2 outer small air holes are located on the symmetry axis of the 2 micro-grooves.

[0007] The radius of the microstructure optical fiber is 16 μm; the depth of the micro-groove is 7.5 μm - 8.5 μm; the radius of the nano gold wire is 300 nm - 500 nm; the radius of the inner large air hole is 3.5 μm - 4.5 μm. Among the 4 inner large air holes, the center distance between the two inner large air holes in the horizontal direction is 12 μm - 14 μm, and the center distance between the two inner large air holes in the vertical direction is 10 μm - 12 μm; the radius of the outer small air hole is 1 μm - 2 μm.

[0008] Further, the depth of the micro-groove is 8 μm; the radius of the nano gold wire is 500 nm; the radius of the inner large air hole is 4 μm. Among the 4 inner large air holes, the center distance between the two inner large air holes in the horizontal direction is 13 μm, and the center distance between the two inner large air holes in the vertical direction is 11 μm; the radius of the outer small air hole is 1.5 μm.

[0009] Further, the microstructure optical fiber is refractive index guiding type.

[0010] Further, 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] Further, the probe is a new type of plasmonic optical sensing probe that integrates multi-functional detection, simplifies the pore structure, and supports microfluidic trace analysis.

[0012] The beneficial effects of the present invention: In order to solve the technical problems of this application, a multi-functional on-line trace detection biosensing threat factor plasmonic optical sensing probe with fewer air holes is provided, specifically a MOF-SPR sensing probe (MOF-SPR is the abbreviation of microstructure optical fiber - surface plasmon resonance). Its main advantages are as follows: (1), While diagnosing various cancer cells, the plasmonic optical sensing probe can also complete the screening of various viruses, realizing the integration of biosensing threat factor detection.

[0013] (2) When the plasmonic optical sensing probe detects biological threat factors, it has good optical properties. The refractive index detection range of the sample to be measured is 1.33 - 1.40, the maximum spectral sensitivity is 40000 nm / RIU, and the resolution is 2.5×10 -6 RIU.

[0014] (3) Micro-grooves are arranged in the MOF carrier of the plasmonic optical sensing probe to achieve micro-fluidic trace detection of special biological samples.

[0015] (4) There are few air holes arranged in the MOF carrier of the plasmonic optical sensing probe, its structure is simple, the design is convenient, and it is easy to be actually fabricated and applied. Description of the Drawings

[0016] Figure 1 is a cross-sectional view of the plasmonic optical sensing probe.

[0017] Figure 2 is the front view of the plasmonic optical sensing probe.

[0018] Figure 3 is a relationship curve diagram of the respective confinement losses and resonance wavelengths within the refractive index range of 1.33 - 1.40 when the plasmonic optical sensing probe detects the sample to be measured.

[0019] Figure 4 is a relationship curve diagram of the plasmonic optical sensing probe when detecting different groups of normal cells and their corresponding cancer cells.

[0020] Figure 5 is a relationship curve diagram of the confinement losses and resonance wavelengths at different refractive indices when the plasmonic optical sensing probe detects the spike receptor binding domain (RBD) of SARS-CoV-2 virus.

[0021] Figure 6 is a relationship curve diagram of the confinement losses and resonance wavelengths at different refractive indices when the plasmonic optical sensing probe detects the single-stranded ribonucleic acid (RNA) of the mutant virus.

[0022] Figure 7 is a relationship curve diagram of the confinement losses and resonance wavelengths at different refractive indices when detecting human monoclonal antibody immunoglobulin G (IgG).

[0023] Reference Numerals: 1, nano-gold wire; 2, large inner air holes; 3, cladding; 4, small outer air holes; 5, micro-structured optical fiber; 6, micro-grooves. Detailed Description of the Invention

[0024] Example 1 As Figure 1 and Figure 2As shown in the figure, the on-line trace detection bio-threat factor plasmonic optical sensing probe is composed of a microstructure optical fiber 5 and a nano-gold wire 1; there are 2 micro-grooves 6 symmetrically distributed with respect to the optical fiber central axis on the microstructure optical fiber 5, and the nano-gold wire 1 is embedded at the bottom of the micro-groove 6; there are 4 inner large air holes 2 and 2 outer small air holes 4 in the cladding 3 of the microstructure optical fiber 5, and the inner large air holes 2 and the outer small air holes are arranged in a periodic alternating pattern. Every 2 of the 4 inner large air holes 2 are in a group and symmetrically arranged with respect to the micro-groove 6; the 2 outer small air holes 4 are symmetrically distributed with respect to the micro-groove 6, and the 2 outer small air holes 4 are located on the symmetry axis of the 2 micro-grooves 6.

[0025] The radius of the microstructure optical fiber 5 is 16 μm; the depth of the micro-groove 6 is 8 μm; the radius of the nano-gold wire 1 is 500 nm; the radius of the inner large air hole 2 is 4 μm. Among the 4 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.

[0026] The background material of the microstructure optical fiber 5 is silica. The microstructure optical fiber 5 is of refractive index guiding type.

[0027] Example Two On the basis of the technical solution of Example One, the depth of the micro-groove 6 is 7.5 μm; the radius of the nano-gold wire 1 is 300 nm; the radius of the inner large air hole 2 is 3.5 μm. Among the 4 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.

[0028] Example Three On the basis of the technical solution of Example One, the depth of the micro-groove 6 is 8.5 μm; the radius of the nano-gold wire 1 is 400 nm; the radius of the inner large air hole 2 is 4.5 μm. Among the 4 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.

[0029] The MOF-SPR sensing probe uses a nano-gold wire embedded in a micro-groove as the sensing medium, and its working principle is based on the phase-matching coupling mechanism between the evanescent wave and the surface plasmon polariton (SPP). In the MOF, the large air holes in the inner layer and the small air holes in the outer layer are arranged in a periodic alternating pattern. This design not only effectively confines the transmission of the evanescent wave but also significantly enhances the interaction between the evanescent field and the nano-gold wire by optimizing the light field distribution. When evanescent waves of different wavelengths propagate along the MOF axis in a specific mode, the surface plasmon polaritons in the nano-gold wire always maintain a fixed transmission mode. When the wave vector of an evanescent wave with a certain wavelength in the MOF reaches the phase-matching condition with the wave vector of the surface plasmon polaritons on the nano-gold wire surface, the energy of the evanescent field will be efficiently coupled into the nano-gold wire, resulting in a significant energy loss in the light field transmitted by the MOF. By monitoring the resonance wavelength corresponding to the extreme value of the energy loss in the loss spectrum, a highly sensitive wavelength-modulated sensing response mechanism can be established.

[0030] Based on the refractive index detection performance of the MOF-SPR sensing probe and its biomedical applications, such as Figure 3 shown, in 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, phenomena such as red shift of the resonance wavelength, increase in the peak value of the resonance peak, and decrease in the full width at half maximum are observed, 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 40000 nm / RIU and 2.5×10 -6 RIU, respectively. In terms of biomedical detection applications, Figure 4 shown, the probe's ability to distinguish between healthy cells and cancer cells (including various types such as skin, cervical, blood, Adr, Bre1, Bre2, etc.) is based on the characteristic of increased refractive index in cancer cells due to elevated protein content, enabling early cancer diagnosis through refractive index changes. The experimental results show that the maximum sensitivity and resolution are 36428 nm / RIU, respectively. As Figure 5 , Figure 6 and Figure 7As shown, it further confirms the advantages of this probe in virus detection, allowing the quantification of virus concentration in patients in three different ways based on different ligand-analyte binding pairs. The plasmonic optical probe can effectively detect the spike receptor-binding domain (RBD) of SARS-CoV-2 virus, mutant virus single-stranded ribonucleic acid (RNA), and human monoclonal antibody immunoglobulin G (IgG). The experimental results show that the maximum sensitivities for detecting the above three different components of the virus (antigen, nucleic acid, antibody) are 7833 nm / RIU, 13158 nm / RIU, and 7863 nm / RIU respectively. Its sensitivity continuously improves with the increase in the refractive index of the detection object, demonstrating excellent potential for pathogen screening. The results indicate that this MOF-SPR sensing probe has important application value in the field of biomedical detection.

[0031] This sensing probe adopts a specially designed MOF cladding structure with two different sizes of air holes inside the cladding, and micro-grooves are symmetrically arranged on both the upper and lower sides of the MOF, with nano-gold wires embedded in the grooves. This structure innovatively constructs a microfluidic trace detection channel and simultaneously opens an evanescent field leakage window. By optimizing the energy transmission path and combining SPR technology and the principle of energy coupling, high-sensitivity online detection of refractive index changes of biological threat factors is achieved. This biological probe has the ability to detect multiple targets and can simultaneously detect multiple types of cancer cells (skin, Cervical, blood, Adr, Bre1, Bre2) and three typical viruses (spike receptor-binding domain (RBD) of SARS-CoV-2 virus, mutant virus single-stranded ribonucleic acid (RNA), and human monoclonal antibody immunoglobulin G (IgG)). Experimental data show that this plasmonic biosensing probe exhibits excellent optical properties, with a maximum spectral sensitivity of 36428 nm / RIU for cancer cell detection and 13158 nm / RIU for virus detection. The sensing probe has the characteristics of simple fabrication and convenient application, achieving optimization in terms of probe structure and functional performance.

Claims

1. An on-line trace detection biosensing probe for biological threat agents, characterized in that: The plasmonic optical sensing probe is composed of a microstructure optical fiber (5) and a nano gold wire (1); two symmetrically distributed micro-grooves (6) are formed on the microstructure optical fiber (5), and the nano gold wire (1) is embedded at the bottom of the micro-groove (6); four inner large air holes (2) and two outer small air holes (4) are arranged in the cladding (3) of the microstructure optical fiber (5), and the four inner large air holes (2) and the two outer small air holes (4) are arranged in a periodic and alternating manner. Two of the four inner large air holes (2) are symmetrically arranged about the micro-groove (6) as a group; the two outer small air holes (4) are symmetrically distributed about the micro-groove (6), and the two outer small air holes (4) are located on the symmetry axis of the two micro-grooves (6). The radius of the microstructure optical fiber (5) is 16 μm; the depth of the micro-groove (6) is 7.5 μm - 8.5 μm; the radius of the nano gold wire (1) is 300 nm - 500 nm; the radius of the inner large air hole (2) is 3.5 μm - 4.5 μm. 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 - 14 μm, and the center distance between the 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 online trace detection biothreat agent plasmonic optical sensing probe according to claim 1, wherein: The depth of the micro-groove (6) is 8 μm; the radius of the nano gold wire (1) is 500 nm; the radius of the inner large air hole (2) is 4 μm. 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.

3. The online trace detection biosensing probe for biological threat factors based on the surface plasmon optics according to claim 1 or 2, characterized in that: The background material of the microstructure optical fiber (5) is silica.

4. The online trace detection biological threat factor plasmonic optical sensing probe according to claim 3, characterized in that: The microstructure optical fiber (5) is of refractive index guiding type.

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