A method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane.

Abstract

This invention relates to the field of biomedical detection technology and provides a method for glucose detection based on a hollow antiresonant optical fiber using a polylysine and phenylboronic acid composite membrane. The detection method includes a light source, an optical fiber isolator, a first single-mode optical fiber patch cord, a microfluidic device, a hollow antiresonant optical fiber, a second single-mode optical fiber patch cord, a spectrometer, and a computer. The hollow antiresonant optical fiber is fabricated using a stacked drawing and pressure-assisted splicing process. Gold wires are filled within two selected symmetrical small antiresonant tubes, and the outer wall of these tubes is coated with a polylysine and phenylboronic acid composite membrane. The microfluidic device integrates filtration, temperature control, flow rate control, and pressure monitoring functions. When the polylysine and phenylboronic acid composite membrane specifically binds to glucose molecules in the test solution, the refractive index of the composite membrane is changed, further altering the resonance conditions of surface plasmon resonances, ultimately causing a quantitative shift of the loss peak. The spectrometer collects data, and the computer analyzes the glucose concentration. This method features high sensitivity, strong specificity, good anti-interference, good stability, and integration, providing a new solution for glucose detection and meeting the needs of medical testing and health monitoring.

Description

Technical Field

[0001] This invention belongs to the field of biosensing and detection technology, specifically relating to a method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane. It is particularly suitable for rapid and accurate analysis of glucose concentration in clinical samples, in vitro diagnostics, or point-of-care testing scenarios, and can meet the needs of medical testing, health monitoring, and other scenarios for high-sensitivity and interference-resistant detection. Background Technology

[0002] Glucose detection is a key technology in diabetes diagnosis, clinical monitoring, and optimization of bio-fermentation processes, and is widely used in medical and health, bioengineering, and scientific research. In the medical field, rapid and accurate glucose detection provides data support for adjusting treatment plans for diabetic patients and screening for gestational diabetes. In bio-fermentation, glucose, as a core carbon source, has its concentration dynamics directly affecting fermentation efficiency and product quality. In scientific research, glucose metabolism monitoring is an important part of biosensor technology research and cell metabolism experiments.

[0003] In existing glucose detection technologies, traditional bio-fiber sensors mostly use micro- and nano-fibers as the sensing carrier, which suffers from drawbacks such as high dispersion, strong nonlinearity, and large optical transmission loss, resulting in limited detection sensitivity and easy signal distortion. Furthermore, the sensitive membranes of traditional sensors have insufficient specific binding capacity for glucose, making them susceptible to interference from substances such as fructose, galactose, and proteins in urine, blood, and fermentation broth, thus compromising detection accuracy. In addition, traditional detection devices have weak resistance to electromagnetic interference and poor corrosion resistance, making them difficult to adapt to complex detection environments. They also have narrow detection ranges and low resolution, failing to meet the needs for precise detection of glucose at different concentrations.

[0004] To address the aforementioned shortcomings of existing technologies, this invention proposes a method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite film, thus solving the technical problems of low sensitivity, weak anti-interference, and signal distortion in existing devices. Summary of the Invention

[0005] To address the shortcomings of existing technologies, such as low sensitivity, weak anti-interference capability, and easy signal distortion, and to meet the need for improvement, this invention provides a glucose detection method based on a hollow-core anti-resonant optical fiber using a polylysine and phenylboronic acid composite film. This method aims to utilize the low dispersion, low loss, and anti-interference characteristics of hollow-core anti-resonant optical fibers, combined with the high response advantage of surface plasmon resonance (SPR) effects, and further integrated with a specific composite film and an integrated microfluidic device, to achieve high sensitivity, high specificity, and wide-range detection of glucose. This better solves the technical problems of existing devices in terms of sensitivity, anti-interference capability, and signal stability.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A method for glucose detection based on a hollow anti-resonant optical fiber using a polylysine and phenylboronic acid composite film includes a light source, an optical fiber isolator, a first single-mode optical fiber jumper, a microfluidic device, a hollow anti-resonant optical fiber, a second single-mode optical fiber jumper, a spectrometer, and a computer.

[0008] The microfluidic device includes a test liquid channel, a filter screen, a temperature controller, a micro injection pump, and a pressure sensor.

[0009] The hollow anti-resonant optical fiber includes a cladding, a large anti-resonant tube, a small anti-resonant tube, a fiber core, a polylysine and phenylboronic acid composite film, and gold wire.

[0010] The detection method device consists of a light source, an optical fiber isolator, a first single-mode optical fiber jumper, a microfluidic device, a hollow anti-resonant optical fiber, a second single-mode optical fiber jumper, a spectrometer, and a computer connected in sequence. The detection data from the spectrometer is transmitted to the computer for data analysis.

[0011] Furthermore, the light source outputs a spectrum with a center wavelength of 3297 nm and a bandwidth of 30 nm, covering the SPR resonance wavelength response range of 3286 nm-3308 nm during glucose detection.

[0012] Furthermore, the microfluidic device uses a 0.22 μm pore size filter membrane to intercept particulate matter such as protein precipitates and cell debris in the test solution; a temperature controller stabilizes the device temperature at 25±0.5 ℃; a pressure sensor with a range of 0-10 kPa monitors the channel pressure in real time; and a micro-injection pump controls the flow rate of the test solution to 1-10 μL / min.

[0013] Furthermore, the hollow antiresonant optical fiber is fabricated using a stacked drawing and pressure-assisted splicing process, the process steps of which are as follows:

[0014] High-purity silica thin plates are inserted into silica capillaries to assemble a two-layered connecting tube structure with a total of 12 anti-resonant tubes. The anti-resonant tubes are divided into six groups, each containing one large and one small anti-resonant tube. The radial lines connecting adjacent groups, with the fiber core's central axis as the vertex, form an angle of 60°. All 12 resonant tubes are 0.4 μm thick. A short, solid silica rod supports the 10 μm radius fiber core region to prevent capillary collapse. The assembled fiber structure is then drawn into a millimeter-thin tube. Next, pre-fabricated gold wire is placed into an additional D-shaped capillary with a 4 μm pore radius. The D-shaped capillary is heated and melted, then fused onto the fiber end face, with the temperature rising to the gold melting point of 1064 °C. The pre-fabricated gold wire is then pressed into two selected symmetrical small anti-resonant tubes using high-pressure argon gas. Rapid drawing is achieved by controlling the gas pressure in the fiber core and capillary regions, with the core region at 1.5 kPa and the capillary region at 1.2 kPa. kPa; After drawing, the pore radius of the large anti-resonant tube is 5 μm and the pore radius of the small anti-resonant tube is 4 μm; Polylysine and phenylboronic acid composite film is coated on the outer wall of the two small anti-resonant tubes pressed into gold wire using microcapillary directional delivery technology; The diameter of the gold wire is 8 μm and the thickness of the composite film is 220 nm.

[0015] Furthermore, when the test liquid enters the hollow anti-resonant optical fiber, the boric acid groups of phenylboronic acid on the surface of the polylysine and phenylboronic acid composite film will specifically bind with the cis-diol structure of glucose molecules, changing the refractive index of the film layer, further changing the resonance conditions of surface plasmon polaritons, and ultimately causing a quantitative shift in the loss peak.

[0016] The present invention has the following advantages over the prior art:

[0017] 1. The microfluidic device of the present invention integrates multiple protection functions, significantly improving detection stability and reliability.

[0018] 2. The hollow anti-resonant optical fiber of the present invention improves the efficiency of light-matter interaction and SPR excitation, resulting in higher detection sensitivity.

[0019] 3. The polylysine and phenylboronic acid composite membrane of the present invention effectively reduces the non-specific adsorption of impurities and improves the detection specificity by specifically binding glucose molecules through cyclic boron ester bonds.

[0020] 4. The detection method and device of the present invention have a high degree of integration, a compact structure, and are easy to design for portability, which can meet the needs of real-time detection scenarios. Attached Figure Description

[0021] Figure 1 This is a structural diagram of a hollow anti-resonant optical fiber glucose detection method based on a polylysine and phenylboronic acid composite membrane according to an embodiment of the present invention.

[0022] Figure 2 This is a structural diagram of a microfluidic device for a hollow anti-resonant optical fiber glucose detection method based on a polylysine and phenylboronic acid composite membrane, according to an embodiment of the present invention.

[0023] Figure 3 This is a structural diagram of the hollow anti-resonant optical fiber used in the glucose detection method based on a polylysine and phenylboronic acid composite film, according to an embodiment of the present invention. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings of the embodiments of the present invention. However, the embodiments and protection scope of the present invention are not limited thereto, and all substantially the same as the present invention are within the protection scope of the present invention.

[0025] The following embodiments, in conjunction with the accompanying drawings, illustrate the specific implementation of the glucose detection method based on a hollow anti-resonant optical fiber using a polylysine and phenylboronic acid composite membrane proposed in this invention. Example:

[0026] The detection method has the following structure: Figure 1 As shown, it includes a light source (1), an optical fiber isolator (2), a first single-mode optical fiber patch cord (3), a microfluidic device (4), a hollow-core anti-resonant optical fiber (5), a second single-mode optical fiber patch cord (6), a spectrometer (7), and a computer (8).

[0027] like Figure 1 As shown, this embodiment is a structural diagram of a hollow anti-resonant optical fiber glucose detection method based on a polylysine and phenylboronic acid composite membrane provided by the present invention. The test liquid enters the test liquid channel (4-1) in the microfluidic device (4), and impurities in the test liquid are intercepted by the filter screen (4-2) to prevent blockage of the solution flow area of ​​the hollow anti-resonant optical fiber (5). After being processed by the temperature controller (4-3), pressure sensor (4-5), and micro-injection pump (4-4), it enters the core (5-4) region of the hollow anti-resonant optical fiber (5). The output spectrum of the light source (1) has a center wavelength of 3297 nm and a bandwidth range of 30 nm. A light beam of nm enters the fiber isolator (2) to prevent the light signal reflection from interfering with the stability of the light source. Then, it is transmitted with low loss and high precision to the core (5-4) of the hollow anti-resonant fiber (5) through the first single-mode fiber jumper (3). In the core (5-4), the light signal is converted into a sensing signal carrying the glucose concentration. It is then transmitted to the spectrometer (7) through the second single-mode fiber jumper (6) to complete the spectral acquisition. Finally, the spectral signal is processed by the computer (8), and the glucose concentration is calculated by the built-in pre-established linear calibration equation of wavelength and concentration.

[0028] like Figure 1As shown, this embodiment is a structural diagram of a hollow anti-resonant optical fiber glucose detection method based on a polylysine and phenylboronic acid composite film provided by the present invention. When the optical signal is transmitted in the hollow anti-resonant optical fiber (5), the evanescent wave generated will couple with the free electrons on the surface of the gold wire (5-6) to excite surface plasmon polaritons. When the two meet the phase matching condition, that is, when the transverse wave vector of the evanescent wave is equal to the wave vector of the plasmon polariton, the SPR will be excited, resulting in an obvious loss peak at the corresponding wavelength in the spectrum. The change in the resonance condition of the surface plasmon polariton causes the wavelength of the loss peak to drift. When the boric acid group on the surface of the polylysine and phenylboronic acid composite film (5-5) specifically combines with the cis-diol structure of the glucose molecule, a stable cyclic boron ester bond is formed, which changes the refractive index of the polylysine and phenylboronic acid composite film (5-5), further changes the resonance condition of the surface plasmon polariton, and finally causes a quantitative shift of the loss peak, thereby calibrating the glucose concentration.

[0029] like Figure 1 As shown in the figure, this embodiment is a structural diagram of a hollow anti-resonant optical fiber glucose detection method based on a polylysine and phenylboronic acid composite film provided by the present invention. The method has a linear detection range of 0.1-20 mM for glucose concentration. When the glucose concentration is less than 0.1 mM, the number of molecules binding to the polylysine and phenylboronic acid composite film (5-5) is extremely small, resulting in a very small change in the film refractive index. The corresponding SPR resonance peak wavelength shift is close to the resolution limit of the spectrometer. When the glucose concentration is greater than 20 mM, the specific recognition sites of phenylboronic acid in the polylysine and phenylboronic acid composite film (5-5) reach saturation. At this time, it exceeds the effective detection range of the method. Further increasing the concentration cannot further improve the film refractive index, and the SPR resonance peak shift no longer changes linearly with increasing concentration.

[0030] like Figure 2 As shown, this embodiment provides a microfluidic device for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane. The device includes a test liquid channel (4-1), a filter screen (4-2), a temperature controller (4-3), a micro-injection pump (4-4), and a pressure sensor (4-5).

[0031] like Figure 2As shown, this embodiment provides a microfluidic device for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane. The microfluidic device (4) has a built-in filter (4-2) with a pore size of 0.22 μm in the test liquid channel (4-1) to effectively intercept particulate matter such as protein precipitates and cell debris in the sample. The temperature controller (4-3) uses a micro semiconductor cooling chip with a temperature control accuracy of ±0.1 ℃ to stabilize the temperature of the test liquid at 25 ℃. The flow rate adjustment range of the micro-injection pump (4-4) is 1-10 μL / min to ensure that the test liquid has sufficient residence time in the hollow anti-resonant optical fiber (5) to ensure sufficient binding reaction. The pressure sensor (4-5) has a range of 0-10 kPa and a measurement accuracy of ±0.1 kPa. When the channel pressure is too high, it automatically sends a signal to the micro-injection pump (4-4) to stop it from working, avoiding damage to the optical fiber or composite membrane due to excessive pressure.

[0032] like Figure 3 As shown, this embodiment provides a method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite film. The hollow anti-resonant optical fiber (5) includes a cladding (5-1), a large anti-resonant tube (5-2), a small anti-resonant tube (5-3), a fiber core (5-4), a polylysine and phenylboronic acid composite film (5-5), and a gold wire (5-6).

[0033] like Figure 3As shown, this embodiment provides a method for glucose detection using hollow anti-resonant optical fiber based on a composite film of polylysine and phenylboronic acid. The hollow anti-resonant optical fiber (5) is fabricated using a stacked drawing and pressure-assisted splicing process. The specific process steps are as follows: a high-purity silica thin plate is inserted into a silica capillary tube and assembled into a connecting tube structure with two layers and a total of 12 anti-resonant tubes. The anti-resonant tubes are divided into six groups, each group containing a large anti-resonant tube (5-2) and a small anti-resonant tube (5-3). The angle between the central radial lines of the two adjacent groups is 60° with the central axis of the fiber core (5-4) as the vertex. The thickness of the 12 resonant tubes is 0.4 μm. A short silica solid rod is used to support the fiber core (5-4) region with a radius of 10 μm to prevent the capillary from collapsing. A pre-made gold wire is placed in an additional D-type capillary tube with a pore radius of 4 μm. The D-type capillary tube is heated and melted and then fused onto the end face of the optical fiber. The temperature then rises to 1064°C. The melting point of gold is ℃; molten pre-made gold wire is pressed into two selected symmetrical small anti-resonant tubes (5-3) by high-pressure argon gas; the gas pressure of the fiber core (5-4) and the capillary region is controlled to complete the rapid drawing, wherein the gas pressure in the fiber core (5-4) region is 1.5 kPa and the gas pressure in the capillary region is 1.2 kPa; after the drawing is completed, the pore radius of the large anti-resonant tube (5-2) is 5 μm and the pore radius of the small anti-resonant tube (5-3) is 4 μm; using microcapillary directional delivery technology, a polylysine and phenylboronic acid composite film (5-5) is coated on the outer wall of the two small anti-resonant tubes (5-3) with gold wire (5-6) pressed in; the diameter of the gold wire (5-6) is 8 μm and the thickness of the composite film (5-5) is 220 nm; finally, a complete hollow core anti-resonant optical fiber (5) sensing structure is obtained.

[0034] The glucose detection method constructed in this embodiment can achieve linear quantitative detection of glucose solution in the concentration range of 0.1-20 mM. It has excellent specificity, anti-interference ability and signal stability, and can stably complete the rapid and accurate detection of glucose concentration in clinical samples, in vitro diagnostics and other scenarios.

Claims

1. A method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane, characterized in that: The method includes a light source (1), an optical fiber isolator (2), a first single-mode optical fiber jumper (3), a microfluidic device (4), a hollow anti-resonant optical fiber (5), a second single-mode optical fiber jumper (6), a spectrometer (7), and a computer (8). The hollow anti-resonant fiber optic glucose detection method based on polylysine and phenylboronic acid composite membrane includes the following microfluidic device (4): a test liquid channel (4-1), a filter screen (4-2), a temperature controller (4-3), a micro-injection pump (4-4), and a pressure sensor (4-5). The hollow anti-resonant optical fiber (5) structure includes: cladding (5-1), large anti-resonant tube (5-2), small anti-resonant tube (5-3), fiber core (5-4), polylysine and phenylboronic acid composite film (5-5), and gold wire (5-6). In the detection method, the glucose solution to be tested is pretreated by a microfluidic device (4) and then introduced into the core (5-4) region of a hollow anti-resonant optical fiber (5); the light source (1) outputs a stable optical signal, which enters the core (5-4) of the hollow anti-resonant optical fiber (5) after passing through an optical fiber isolator (2) and a first single-mode optical fiber jumper (3); the optical signal is converted into a sensing signal carrying the glucose concentration in the core (5-4), and is transmitted to a spectrometer (7) through a second single-mode optical fiber jumper (6) to complete the spectral acquisition. Finally, the spectral signal is processed by a computer (8) to obtain the glucose concentration in the solution to be tested. In the detection method, the evanescent wave generated when the optical signal is transmitted in the hollow anti-resonant optical fiber (5) will couple with the free electrons on the surface of the gold wire (5-6) to excite surface plasmon polaritons. When the two meet the phase matching condition, that is, when the transverse wave vector of the evanescent wave is equal to the wave vector of the plasmon polariton, SPR (surface plasmon resonance) will be excited, resulting in an obvious loss peak at the corresponding wavelength in the spectrum. The change in the resonance condition of the surface plasmon polariton causes the wavelength of the loss peak to drift. When the boric acid group on the surface of the polylysine and phenylboronic acid composite film (5-5) specifically combines with the cis-diol structure of the glucose molecule, a stable cyclic boron ester bond is formed, which changes the refractive index of the polylysine and phenylboronic acid composite film (5-5), further changes the resonance condition of the surface plasmon polariton, and finally causes a quantitative shift of the loss peak, thereby calibrating the glucose concentration.

2. The method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane according to claim 1, characterized in that: In the microfluidic device (4), a filter screen (4-2) with a pore size of 0.22 μm is used to intercept impurities in the test liquid flowing into the test liquid channel (4-1) to prevent particulate matter from clogging the solution flow area of ​​the hollow fiber; a temperature controller (4-3) is used to maintain the system temperature at 25±0.5 ℃ to prevent temperature fluctuations from interfering with the detection results; a micro-injection pump (4-4) is used to control the flow rate of the test liquid in the channel to be stable at 1-10 μL / min to ensure that the test liquid has sufficient residence time in the fiber. The pressure sensor (4-5) has a range of 0-10 kPa and is used to monitor the pressure in the channel in real time. When the pressure is abnormal, it can automatically trigger the micro injection pump to stop running, so as to avoid pressure overload damage to the optical fiber or composite membrane.

3. The method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane according to claim 1, characterized in that: The hollow anti-resonant optical fiber (5) is prepared by stacking and pressure-assisted splicing process, and the process steps are as follows: A high-purity silica thin plate is inserted into a silica capillary tube and assembled into a connecting tube structure with two layers and a total of 12 anti-resonant tubes. The anti-resonant tubes are divided into six groups, each group containing a large anti-resonant tube (5-2) and a small anti-resonant tube (5-3). The radial lines connecting the centers of adjacent groups are 60° with the central axis of the fiber core (5-4) as the vertex. The thickness of each of the 12 resonant tubes is 0.4 μm. A short silica solid rod is used to support the fiber core (5-4) region with a radius of 10 μm to prevent the capillary from collapsing. The assembled optical fiber structure is then drawn into a millimeter-thin tube. The pre-fabricated gold wire was placed in an additional D-shaped capillary with a pore radius of 4 μm. The D-shaped capillary was heated and melted, and then fused onto the end face of the optical fiber. The temperature was then raised to the melting point of gold at 1064 ℃. The pre-fabricated gold wire was pressed into two selected symmetrical small anti-resonant tubes (5-3) using high-pressure argon gas. The gas pressure in the fiber core (5-4) and the capillary region was controlled to complete the rapid drawing process, with the pressure in the fiber core (5-4) region being 1.5 kPa and the pressure in the capillary region being 1.2 kPa. After the drawing process was completed, the pore radius of the large anti-resonant tube (5-2) was 5 μm, and the pore radius of the small anti-resonant tube (5-3) was 4 μm. Using microcapillary directional delivery technology, a polylysine and phenylboronic acid composite film (5-5) is coated on the outer wall of the two small anti-resonant tubes (5-3) of the gold wire (5-6) as described above; the diameter of the gold wire (5-6) is 8 μm; the thickness of the polylysine and phenylboronic acid composite film (5-5) is 220 nm.

4. The method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane according to claim 1, characterized in that: The output spectrum of the light source (1) has a center wavelength of 3297 nm and a bandwidth of 30 nm, covering the SPR resonance wavelength response range of 3286 nm-3308 nm during glucose detection.

5. The method for glucose detection using a hollow anti-resonant optical fiber based on a polylysine and phenylboronic acid composite membrane according to claim 1, characterized in that: The computer (8) calculates the glucose concentration using a pre-established linear calibration equation for wavelength and concentration. The detection range of the method is 0.1-20 mM. Within this range, the glucose concentration and the SPR resonance peak wavelength have a good linear response. When the SPR resonance peak wavelength shift is below 0.1 mM, it approaches the resolution limit of the spectrometer and is set as the lower detection limit. When the SPR resonance peak wavelength shift is above 20 mM, the specific recognition sites of the composite membrane are saturated, and the wavelength and concentration response is nonlinear and is set as the upper detection limit.

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