A method for detecting cholesterol based on polydopamine / β-cyclodextrin modified micro-nano optical fiber

Abstract

The application is suitable for the field of biological detection, and provides a cholesterol detection method based on polydopamine / β-cyclodextrin modified micro-nano optical fiber.The method comprises a narrow line width erbium-doped fiber light source, a multimode fiber jumper, a sensing unit, a spectrometer and a computer.The sensing unit is prepared by removing the coating layer of the multimode fiber through Miller forceps and is made into a biconical fiber (waist diameter 8 μm, length 12 mm) through hydrogen flame tapering, and the surface is modified with a polydopamine / β-cyclodextrin combination (dopamine solution concentration 2 mg / mL, β-cyclodextrin solution concentration 5 mg / mL).During detection, the light beam of the light source (center wavelength 1550 nm) passes through the sensing unit, and due to the local refractive index change, further causes the evanescent field distribution and leads to the red shift of the characteristic wavelength of the signal light, the wavelength drift amount is observed by the spectrometer, and the data is transmitted into the computer for wavelength demodulation to realize the quantitative analysis of cholesterol.The method has the advantages of low cost, high sensitivity, strong anti-interference and integration by improving the light source stability through the double-ring cavity light source, increasing the sensing area through the biconical fiber and using specific coating recognition molecules, and provides a new technical scheme for cholesterol detection.

Description

Technical Field

[0001] This invention relates to the field of biomedical detection technology, specifically to a method for quantitative cholesterol detection based on optical sensing principles and a specific molecular coating, which is particularly suitable for rapid analysis of cholesterol concentration in clinical samples or in vitro diagnostic scenarios. Background Technology

[0002] In traditional cholesterol detection methods, enzymatic methods are commonly used in clinical practice, but they rely on biological reagents such as cholesterol oxidase. Not only are the storage conditions strict (low-temperature refrigeration is required to prevent inactivation), but the detection process also involves multiple enzymatic reactions, making the operation cumbersome and susceptible to interference from environmental factors such as pH and temperature, resulting in high costs per test. High-performance liquid chromatography (HPLC) requires expensive instruments (such as HPLC) and professional operators, and the sample pretreatment is complex (such as derivatization), with detection cycles lasting several hours, making it difficult to meet the needs of real-time detection.

[0003] Optical sensing technology offers a new approach to solving the aforementioned problems, with fiber optic sensing becoming a research hotspot due to its high sensitivity (down to the nanomolar level) and fast response speed (second-level response). However, existing methods still face challenges: the output wavelength of the light source can cause baseline drift or fluctuations in the detection signal, reducing detection accuracy; non-specific adsorption (such as impurities like proteins and lipids adhering to the sensing surface) can interfere with the evanescent field signal, reducing detection specificity. Therefore, further improvements in light source design (such as using distributed feedback to stabilize the laser wavelength through a grating structure) and surface anti-contamination modifications (such as polyethylene glycol coatings to suppress non-specific binding) are needed to enhance the practicality of optical sensing systems.

[0004] This invention proposes an integrated scheme based on a biconical fiber optic sensing unit and a polydopamine / β-cyclodextrin functional layer, which solves the problems of low sensitivity and poor anti-interference in traditional technologies. Summary of the Invention

[0005] The purpose of this invention is to solve the above problems and provide a highly sensitive, anti-interference, and integrated cholesterol detection method that achieves rapid quantitative analysis of cholesterol concentration by analyzing the wavelength response of the spectral spectrum.

[0006] The technical solution adopted by the present invention to solve its technical problem is as follows:

[0007] Technical solution: A cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers includes a narrow-linewidth erbium-doped fiber light source, multimode fiber jumpers, a sensing unit, a spectrometer, and a computer;

[0008] The narrow-linewidth erbium-doped fiber light source includes a pump source, a wavelength division multiplexer, an erbium-doped fiber, an optical isolator, a single-mode fiber, a first fiber coupler, a second fiber coupler, a tunable filter, and an erbium-doped fiber amplifier.

[0009] The sensing system of the detection method consists of a narrow-linewidth erbium-doped fiber light source, a multimode fiber jumper, a sensing unit, a spectrometer, and a computer connected in sequence. The detection data from the spectrometer is then transmitted to the computer for demodulation.

[0010] Furthermore, the narrow-linewidth erbium-doped fiber light source has a single-wavelength tunable range of 60 nm (1520-1580 nm), covering the C+L band.

[0011] Furthermore, the sensing unit includes a biconical optical fiber (8 μm waist diameter and 12 mm waist length) with a surface modified with a polydopamine / β-cyclodextrin conjugate to form the sensing unit.

[0012] The sensing unit is fabricated from a 20 cm long multimode optical fiber: First, a 1 cm long coating layer in the middle section of the fiber is stripped using Miller pliers. Then, the multimode fiber is drawn into a biconical fiber structure with a waist diameter of 8 μm and a waist length of 12 mm using the oxyhydrogen flame melting tapering method. Next, β-cyclodextrin is directly adhered to the surface of polydopamine to form a polydopamine / β-cyclodextrin conjugate. β-cyclodextrin is added to deionized water to prepare a β-cyclodextrin solution. The supernatant is aspirated into the polydopamine solution using a pipette and stirred. Finally, the polydopamine / β-cyclodextrin conjugate is further modified onto the surface of the biconical optical cone. Finally, the non-sensing parts are wiped clean.

[0013] Furthermore, when the cholesterol solution is dropped into the micro-nano fiber region of the sensing unit, a large number of holes in the β-cyclodextrin on the surface of the polydopamine / β-cyclodextrin functional layer will rapidly combine with cholesterol molecules, resulting in a significant increase in the local refractive index of the micro-nano fiber surface, which further causes the evanescent field distribution and causes a redshift in the characteristic wavelength of the signal light.

[0014] The present invention has the following advantages over the prior art:

[0015] 1. The narrow-linewidth erbium-doped fiber light source of the present invention has a tunable wavelength, which improves the tunability of optical signal wavelength.

[0016] 2. The double-conical optical fiber of the present invention increases the sensing area, improves the efficiency of light-matter interaction, and increases the sensitivity of detection.

[0017] 3. The polydopamine / β-cyclodextrin functional layer of the present invention specifically recognizes cholesterol molecules, reducing non-specific adsorption.

[0018] 4. The detection method of the present invention has a compact system structure, is compatible with existing optical devices, and is suitable for portable design. Attached Figure Description

[0019] Figure 1This is a structural diagram of the cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers implemented in this invention.

[0020] Figure 2 This is a structural diagram of the narrow-linewidth erbium-doped fiber light source for the cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers, which is an embodiment of the present invention.

[0021] Figure 3 This is a structural diagram of the sensing unit of the cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers implemented in this invention. Detailed Implementation

[0022] 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.

[0023] The following embodiments, in conjunction with the accompanying drawings, illustrate the specific implementation of a cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers proposed in this invention. Example

[0024] The system structure of the detection method is as follows: Figure 1 As shown, it includes a narrow linewidth erbium-doped fiber light source (1), a multimode fiber (2), a sensing unit (3), a spectrometer (4), and a computer (5).

[0025] like Figure 1 As shown in the figure, this embodiment is a structural diagram of a cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fiber provided by the present invention: The narrow linewidth erbium-doped fiber light source (1) is turned on, and based on the coordinated work of internal components such as pump source (1-1), wavelength division multiplexer (1-2), and erbium-doped fiber (1-3), a stable laser beam with specific wavelength and narrow linewidth characteristics is generated. The generated laser beam is transmitted through a multimode fiber jumper (2). Due to its large core diameter, the multimode fiber jumper (2) allows the beam to be transmitted in multiple modes, efficiently transmitting the optical signal to the next stage. The optical signal enters the sensing unit (3), and the optical signal is processed using the interference principle at the micro / nano scale. Through the interference phenomenon of light, external physical quantities (such as strain, temperature, refractive index changes, etc.) are converted into changes in the phase, intensity, and other characteristics of the optical signal. The optical signal modulated by the sensing unit (3) is transmitted to the spectrometer (4). The spectrometer accurately measures the spectral characteristics of the light signal, and then transmits the collected light signal data to the computer (5) for processing. Through the built-in algorithm or by comparing with the pre-set standard data, the specific value of the detected physical quantity is calculated, and the detection and analysis results are finally output.

[0026] like Figure 1 As shown, this embodiment is a structural diagram of a cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fiber provided by the present invention: The detection method is for cholesterol content detection in the range of 0.001-1.00 mM, of which 0.001-0.05 mM is the linear detection region. Within this range, the detection sensitivity of cholesterol can reach up to 1.74 nm / mM. When the cholesterol concentration increases to 0.05 mM, a large number of holes of β-cyclodextrin on the surface of the sensing unit (3) tend to be saturated, and the characteristic wavelength is basically stable at 1545 nm, marking the appearance of the saturation boundary point. The entire detection process is carried out at room temperature of 25 ℃. The sensing unit (3) can reach a stable response 10 min after contacting the sample and record the data. The wavelength drift is observed by the spectrometer (4) and transmitted to the computer for wavelength demodulation to realize the detection of cholesterol concentration. When the cholesterol concentration is in the linear response range of 0.001-0.05 mM, let the wavelength shift be Y and the concentration be X. The linear relationship between concentration and wavelength shift is Y = 0.405 + 12.7X. When the concentration is in the range of 0.05-1.00 mM, the relationship between cholesterol concentration and wavelength shift is non-linear, and the relationship between concentration and wavelength shift is Y = 1.74log(X) + 0.55.

[0027] like Figure 2 As shown, this embodiment provides a narrow-linewidth erbium-doped fiber light source for cholesterol detection based on polydopamine / β-cyclodextrin modified micro / nano optical fibers. The light source includes a pump source (1-1), a wavelength division multiplexer (1-2), an erbium-doped fiber (1-3), an optical fiber isolator (1-4), a single-mode fiber (1-5), a first optical fiber coupler (1-6), a second optical fiber coupler (1-7), a tunable filter (1-8), and an erbium-doped fiber amplifier (1-9).

[0028] like Figure 2 As shown, this embodiment provides a cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers. The narrow-linewidth erbium-doped fiber light source adopts a nested ring cavity structure, which is composed of a large ring cavity and a small ring cavity. The pump source (1-1) outputs laser light, which is coupled into the large ring cavity through a wavelength division multiplexer (1-2). The optical signal passes through the erbium-doped fiber (1-3), the fiber isolator (1-4), and the single-mode fiber (1-5) in the large ring cavity in sequence, and arrives at the first fiber coupler (1-6). Part of the signal is output as a light source, and the other part is split into two paths again through the second fiber coupler (1-7). One path is connected to the wavelength division multiplexer (1-2) to form a large ring cavity loop, and the other path is connected to the small ring cavity loop composed of the second fiber coupler (1-7), a tunable filter (1-8), and an erbium-doped fiber amplifier (1-9). The second fiber coupler (1-7) is the nested junction node between the large ring cavity and the small ring cavity.

[0029] In the further described narrow-linewidth erbium-doped fiber light source (1), the pump source (1-1) provides an adjustable-power optical signal source, which is connected to a large ring cavity through a 1550 nm wavelength division multiplexer (1-2); after entering the large ring cavity, the optical signal first passes through a 7 m long erbium-doped fiber (1-3); the erbium-doped fiber (1-3) is the core medium for laser gain, utilizing the stimulated emission of 1550 nm narrowband laser light from erbium ions in the 974 nm band; subsequently, an optical fiber isolator (1-4) ensures unidirectional transmission of light within the large ring cavity; the large ring cavity contains 600... The single-mode fiber is used to match the cavity length ratio, reduce mode competition, and realize the amplification, transmission and basic distribution of optical signals, thereby improving spectral stability. The small ring cavity is composed of a 90:10 second fiber coupler (1-7) and an erbium-doped fiber amplifier (1-9) forming a closed loop, with a built-in manually tunable filter (1-8) for optimizing spectral characteristics. At the same time, the erbium-doped fiber amplifier (1-9) and the pump source (1-1) form a dual-pump structure, and the spectral power distribution is controlled by adjusting its output power, which is further modulated in conjunction with the filter branch. Finally, after the optical power and cycle stability are guaranteed by the nesting of the large and small ring cavities, the optical signal is output through the 50:50 first fiber coupler (1-6), forming a complete narrow-linewidth erbium-doped fiber light source system.

[0030] like Figure 3 The sensing unit shown includes a multimode optical fiber (3-1), a polydopamine / β-cyclodextrin functional layer (3-2), and a micro / nano optical fiber (3-3).

[0031] like Figure 3 As shown, the preparation scheme of the functionalized coating polydopamine / β-cyclodextrin functional layer (3-2) is as follows: 2 mL of tris(hydroxymethyl)aminomethane hydrochloride is placed in a beaker, and 4 mg of dopamine is added to prepare a dopamine solution with a concentration of 2 mg / mL. The solution is stirred at room temperature for 30 min, and dopamine gradually polymerizes to form polydopamine. 10 mg of β-cyclodextrin is added to 2 mL of deionized water to prepare β-cyclodextrin with a concentration of 5 mg / mL. The solution is allowed to stand for 10 min until the upper liquid is clear. The clear liquid is then pipetted into the polydopamine solution and stirred at room temperature for 15 min to form a polydopamine / β-cyclodextrin conjugate.

[0032] like Figure 3 As shown, the sensor unit fabrication steps are as follows: The sensor unit (3) is fabricated from a 20 cm long multimode optical fiber (3-1); firstly, the 1 cm long coating layer in the middle section of the optical fiber is stripped using Miller pliers; secondly, the multimode optical fiber is drawn into a biconical optical fiber structure by hydrogen-oxygen flame melting tapering method: waist diameter 8 μm and waist length 12 mm; finally, the polydopamine / β-cyclodextrin functional layer (3-2) is modified on the waist cone region of the micro-nano optical fiber (3-3) by surface grafting modification method to form the sensor unit (3).

[0033] In this embodiment, the output power of the pump source (1-1) is 2.2 mW, the center wavelength is 1550 nm, and the spectral range is 600 nm to 1700 nm, thereby analyzing cholesterol concentration.

Claims

1. A method for cholesterol detection based on polydopamine / β-cyclodextrin modified micro / nano optical fibers, characterized in that: The detection method system includes a narrow linewidth erbium-doped fiber light source (1), a multimode fiber jumper (2), a sensing unit (3), a spectrometer (4), and a computer (5); In the cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fiber, a stable narrow-band optical signal is provided by a narrow-linewidth erbium-doped fiber light source (1). The signal is transmitted to a spectrometer (4) through a multimode fiber jumper (2) and a sensing unit (3) in sequence, and finally processed by a computer (5). The narrow-linewidth erbium-doped fiber light source (1) adopts a nested ring cavity structure on both sides, which is composed of a large ring cavity and a small ring cavity. The pump source (1-1) outputs laser light, which is coupled into the large ring cavity through a wavelength division multiplexer (1-2). The optical signal passes through the erbium-doped fiber (1-3), the fiber isolator (1-4), and the single-mode fiber (1-5) in the large ring cavity in sequence, and arrives at the first fiber coupler (1-6). Part of it is used as the light source output, and the other part is split into two paths again through the second fiber coupler (1-7). One path is connected to the wavelength division multiplexer (1-2) to form a large ring cavity loop, and the other path is connected to the small ring cavity loop composed of the second fiber coupler (1-7), the tunable filter (1-8), and the erbium-doped fiber amplifier (1-9). The second fiber coupler (1-7) is the nested junction node between the large ring cavity and the small ring cavity. The sensing unit (3) includes a multimode optical fiber (3-1), a polydopamine / β-cyclodextrin functional layer (3-2), and a micro / nano optical fiber (3-3).

2. The cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers according to claim 1, characterized in that: In the narrow-linewidth erbium-doped fiber light source (1), the pump source (1-1) provides an adjustable-power optical signal source, which is connected to a large ring cavity through a 1550 nm wavelength division multiplexer (1-2); after entering the large ring cavity, the optical signal first passes through a 7 m long erbium-doped fiber (1-3); the erbium-doped fiber (1-3) is the core medium for laser gain, utilizing the stimulated emission of 1550 nm narrowband laser light from erbium ions in the 974 nm band; the fiber isolator (1-4) ensures unidirectional transmission of light within the large ring cavity; the large ring cavity contains 600... The single-mode fiber is used to match the cavity length ratio, reduce mode competition, and realize the amplification, transmission and basic distribution of optical signals, thereby improving spectral stability. The small ring cavity is composed of a 90:10 second fiber coupler (1-7) and an erbium-doped fiber amplifier (1-9) forming a closed loop, with a built-in manually tunable filter (1-8) for optimizing spectral characteristics. At the same time, the erbium-doped fiber amplifier (1-9) and the pump source (1-1) form a dual-pump structure, and the spectral power distribution is controlled by adjusting its output power, which is further modulated in conjunction with the filter branch. Finally, after the optical power and cycle stability are guaranteed by the nesting of the large and small ring cavities, the optical signal is output through the 50:50 first fiber coupler (1-6), forming a complete narrow-linewidth erbium-doped fiber light source system.

3. The cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers according to claim 1, characterized in that: The sensing unit (3) is fabricated from a 20 cm long multimode optical fiber (3-1). First, the 1 cm long coating layer in the middle section of the fiber is stripped using Miller pliers. Then, the multimode optical fiber is drawn into a biconical fiber structure using the hydrogen-oxygen flame melting tapering method: waist diameter 8 μm and waist length 12 mm. Finally, a polydopamine / β-cyclodextrin functional layer (3-2) is coated on the surface of the waist cone region of the micro-nano optical fiber (3-3) using the surface grafting modification method. When the cholesterol solution is dropped into the micro-nano fiber (3-3) region in the sensing unit (3), a large number of holes of β-cyclodextrin on the surface of the polydopamine / β-cyclodextrin functional layer (3-2) will quickly combine with cholesterol molecules, causing a significant increase in the local refractive index on the surface of the micro-nano fiber (3-3), resulting in a change in the evanescent field distribution, which further leads to a redshift of the characteristic wavelength of the signal light.

4. The cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers according to claim 1, characterized in that: The narrow linewidth erbium-doped fiber light source (1) has a tunable output laser band. By adjusting the output power of the pump source (1-1) and the erbium-doped fiber amplifier (1-9) and adjusting the cavity length of the tunable filter (1-8), the single wavelength tunable range can reach 60 nm (1520-1580 nm), covering the C+L band.

5. The cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers according to claim 1, characterized in that: The detection method is applicable to cholesterol content in the range of 0.001-1.00 mM, of which 0.001-0.05 mM is the linear detection region. Within this range, the detection sensitivity of cholesterol can reach up to 1.74 nm / mM. When the cholesterol concentration increases to 0.05 mM, the holes of β-cyclodextrin on the surface of the sensing unit (3) tend to be saturated, and the characteristic wavelength stabilizes at 1545 nm, marking the appearance of the saturation boundary point. The entire detection process is carried out at room temperature of 25 ℃. The sensing unit (3) can reach stability after 10 min of contact with the sample. The data is recorded and the wavelength drift is observed using a spectrometer (4). The computer performs wavelength demodulation to realize the detection of cholesterol concentration.

6. The cholesterol detection method based on polydopamine / β-cyclodextrin modified micro / nano optical fibers according to claim 1, characterized in that: When the cholesterol concentration is in the linear response range of 0.001-0.05 mM, let the wavelength shift be Y and the concentration be X. The relationship between concentration and wavelength is Y = 0.405 + 12.7X. When the concentration is in the range of 0.05-1.00 mM, the relationship between cholesterol concentration and wavelength shift is Y = 1.74log(X) + 0.55.

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