Fiber-optic microcavity laser device with integrated biochemical sensing and random labeling

Abstract

The invention discloses an optical fiber microcavity laser device with integrated biochemical sensing and random labeling dual functions, and relates to the field of laser sensors. The invention utilizes hollow-core photonic bandgap optical fiber. When pump light is irradiated onto the optical fiber of the invention, the Bragg reflection structure composed of alternating thin films of high and low refractive index on the inner wall of the optical fiber of the invention can be used as a Fabry-Perot cavity to form laser resonance. Due to the characteristics of the Bragg reflection structure, the short-wavelength laser passes through the Fabry-Perot cavity and is reflected back into the cavity by the random microstructure in the cladding, causing self-mixing interference, thereby generating random longitudinal mode signals. It has the characteristics of small detection unit volume, small amount of detection sample, and large label encoding capacity.

Description

Technical Field

[0001] The present invention belongs to the field of laser sensors, and in particular relates to an optical fiber microfluidic laser biochemical analysis device integrating biochemical sensing and large-capacity random labeling, which realizes the two functions of biochemical detection and large-capacity random labeling. Background Art

[0002] Immunoturbidimetry is a common bioanalytical method in clinical testing. Antigen and antibody specifically bind to form immune complex particles, which cause turbidity in the reaction liquid and scatter the incident light. The intensity of the scattered light is proportional to the concentration and size of the complex particles. The antigen concentration can be obtained by detecting the intensity difference before and after the incident light passes through the reaction liquid. However, traditional detection methods have disadvantages such as low sensitivity and large reagent usage.

[0003] Hollow-core photonic bandgap fiber is composed of an air core, a Bragg reflection structure and a cladding composed of a protective layer. The Bragg reflection structure is composed of multiple layers of concentric circles of media with different refractive indices, which can achieve high reflectivity in a specific band by adjusting the refractive index of the film material and the thickness of the film. Combined with microfluidic fiber laser technology, the tubular shape of the hollow-core photonic bandgap fiber can be used as a microfluidic channel to fill gain liquid and reaction liquid; at the same time, its high-reflectivity Bragg reflection structure can provide optical feedback for laser emission and generate resonance of the Fabry-Perot cavity in the radial direction of the fiber cross section. Multiple air channels are embedded in the cladding of the hollow-core photonic bandgap fiber, which reflects the generated short-wave laser back into the cavity and self-mixes with the signal in the cavity. Since the shape of the cladding air channel cannot be precisely controlled during the fiber drawing process, the laser signals collected at different positions of the fiber are random. In the application scenario of large-scale detection, both biological detection function and sample labeling function are indispensable, but the existing technology does not have a device that can simultaneously achieve high-sensitivity biological detection function and large-capacity random labeling. Summary of the invention

[0004] The purpose of the present invention is to provide an optical fiber microcavity laser device with integrated biochemical sensing and random labeling functions to address the defects mentioned in the background technology. The device has the characteristics of small detection unit volume, small detection sample dosage, large label encoding capacity, etc.

[0005] In order to achieve the above technical objectives, the solution proposed by the present invention is: an optical fiber microcavity laser device with dual functions of integrated biochemical sensing and random labeling, which includes a pump light source module I, a sample control and detection module II, and a signal collection and processing module III, a total of three parts:

[0006] The pump light source module I is used to provide pump laser to the sample control and detection module II;

[0007] The sample control and detection module II comprises: an electric displacement stage (5) and a hollow-core photonic bandgap optical fiber (6); the inner wall of the hollow-core photonic bandgap optical fiber (6) has a Bragg reflection structure, and each cross section along the optical fiber axis in the optical fiber cladding is embedded with a random microstructure; the pump laser is vertically incident on the hollow-core photonic bandgap optical fiber (6) to generate an optical signal output; under low-energy laser pumping, the longitudinal mode wavelength interval of the generated laser signal A is uniform and stable, and the device is used for biochemical sensing; under high-energy laser pumping, the longitudinal mode wavelength interval of the generated laser signal B is random and changes randomly with the position of the optical fiber, and the device is used to generate large-capacity random labels; the boundary between the low-energy laser pumping and the high-energy laser pumping is E, and E is greater than 15 μJ / mm 2 The electric translation stage (5) will accurately move the hollow-core photonic bandgap fiber (6) along the axial direction to obtain multiple groups of random optical signal outputs at different positions of the optical fiber;

[0008] When the device is used for biochemical sensing, the generated laser spectrum results are integrated;

[0009] When the device is used to generate a large-capacity random label, the generated laser spectrum is converted into a binary string; multiple groups of optical signal outputs obtained at different positions of the optical fiber are converted into multiple groups of binary strings with the same number of bits, forming a two-dimensional random binary label.

[0010] Furthermore, the pump light source module I comprises: a pulse laser (1), a beam splitter (2), an energy meter (3), and a cylindrical lens (4); the pulse laser (1) outputs a pump laser, which is divided into two vertical beams after passing through the beam splitter (2), one of which is incident on the energy meter (3) to monitor the beam energy in real time; the other laser beam passes through the cylindrical lens (4) to form a strip-shaped light spot, which is vertically converged on the hollow-core photonic bandgap fiber (6);

[0011] The signal collection and processing module III comprises: an adjustable neutral density filter (7), a collecting element (8), a transmission optical fiber (9), a spectrum analyzer (10) and a computer (11); the adjustable neutral density filter (7) adjustably attenuates the signal light, the collecting element (8) converges and collects the signal light and couples it to the transmission optical fiber (8), and further transmits it to the spectrum analyzer (10), and the spectrum result will be transmitted to the computer (11) and data processing will be performed according to the required function.

[0012] Furthermore, when the device is used to generate large-capacity random labels, under high-energy laser pumping, a section of the laser signal B is taken and the rule for converting the laser spectrum at this end into a two-dimensional random binary label is as follows:

[0013] Step 1: Find the highest amplitude of the laser longitudinal mode intensity in the spectrum, and set 10% of the amplitude as the threshold; then find the wavelength position where the intensity of all laser longitudinal modes in the spectrum is higher than the threshold;

[0014] Step 2: Divide the wavelength range into 50 wavelength intervals at intervals of 0.38 nm, and correspond to 50 binary characters, of which the first 49 intervals are left closed and right open intervals, and the last interval is a closed interval;

[0015] Step 3: If the wavelength position obtained in step 1 is within a certain wavelength interval, the bit corresponding to this interval is digital "1", otherwise it is digital "0";

[0016] Step 4: The N groups of optical signal outputs obtained at different positions of the optical fiber are converted into N groups of binary strings of the same length according to steps 1-3, and a 50×N two-dimensional digital matrix is ​​obtained to form a two-dimensional random binary label; the N value can be adjusted and expanded according to application requirements to obtain a coding capacity of 2 50×N Two-dimensional random binary labels.

[0017] Furthermore, the Bragg reflection structure on the inner wall of the hollow-core photonic bandgap optical fiber (6) has a reflectivity greater than 80% at 620 nm to 720 nm.

[0018] Furthermore, the wavelength of the pulse laser (1) is continuously adjustable between 400 nm and 800 nm, and the output pulse laser energy is continuously adjustable between 1 μJ and 1 mJ.

[0019] Furthermore, when outputting the laser signal, the pumping threshold of the laser signal A is less than the pumping threshold of the laser signal B.

[0020] Furthermore, the central wavelength of laser signal A is longer than the central wavelength of laser signal B, and the bandwidths of laser signal A and laser signal B do not overlap.

[0021] The present invention utilizes a hollow-core photonic bandgap optical fiber. When pump light is irradiated onto the optical fiber of the present invention, the Bragg reflection structure composed of alternating films of high and low refractive indexes on the inner wall of the optical fiber of the present invention can be used as a Fabry-Perot cavity to form laser resonance. Due to the characteristics of the Bragg reflection structure, short-wavelength laser light passes through the Fabry-Perot cavity and is reflected back into the cavity by the random microstructure in the cladding, causing self-mixing interference, so that the laser signal B is a random longitudinal mode signal.

[0022] Microfluidic lasers have been realized and can be used for biosensing and the generation of two-dimensional random binary labels. In applications such as large-scale detection, sensing and labeling functions can be highly integrated, reducing sample and reagent consumption and lowering costs.

[0023] Compared with the prior art, the present invention has the following advantages:

[0024] 1. The present invention proposes a dual-function fiber optic microfluidic laser biochemical analysis device, which has biochemical sensing and large-capacity random labeling functions, and can solve the detection and labeling needs of a large number of samples in large-scale detection application scenarios.

[0025] 2. The present invention utilizes hollow-core photonic bandgap optical fiber as a sensing unit, and its hollow-core structure is small in size, which effectively reduces the consumption of detection samples and reagents.

[0026] 3. The present invention utilizes hollow-core photonic bandgap optical fiber, which can be prepared in large quantities of hundreds of meters through optical fiber drawing technology. Generating a 2500-bit binary label only requires an optical fiber with a length of 7.5 mm, thus reducing costs.

[0027] 4. The laser signal B obtained by the present invention utilizes the narrow line width characteristics of the laser longitudinal mode, increases the laser wavelength range by increasing the length of the scanning optical fiber, and replaces the type of organic dye, thereby achieving the expansion of the coding capacity. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a schematic structural diagram of the optical fiber microcavity laser device with integrated biochemical sensing and random labeling dual functions provided by the present invention.

[0029] Figure 2 The present invention provides a curve showing the variation of the optical fiber microfluidic laser spectrum with pump energy density of the optical fiber microcavity laser device with integrated biochemical sensing and random labeling dual functions.

[0030] Figure 3 This is an example diagram of random labeling of the optical fiber microcavity laser device with integrated biochemical sensing and random labeling dual functions provided by the present invention.

[0031] Figure 4 The present invention provides a curve of laser intensity variation with urine microalbumin concentration for an optical fiber microcavity laser device with integrated biochemical sensing and random labeling dual functions.

[0032] Figure 5 A cross-sectional view of a hollow-core photonic bandgap fiber of an optical fiber microcavity laser device with integrated biochemical sensing and random labeling dual functions provided by the present invention. DETAILED DESCRIPTION

[0033] The present invention is further described below in conjunction with the accompanying drawings and specific examples.

[0034] This embodiment provides an optical fiber microcavity laser device with integrated biochemical sensing and random labeling dual functions. The system principle block diagram is as follows: Figure 1 As shown, it specifically includes: a pump light source module I, a sample control and detection module II, and a signal collection and processing module III, wherein:

[0035] The pump light source module I comprises: a pulse laser (1), a beam splitter (2), an energy meter (3), and a cylindrical lens (4). The pulse laser (1) outputs a pump laser, which is divided into two vertical beams after passing through the beam splitter (2), one of which is incident on the energy meter (3) to monitor the beam energy in real time; and the other laser beam passes through the cylindrical lens (4) to form a strip-shaped light spot, which is vertically converged on a hollow-core photonic bandgap optical fiber (6).

[0036] The sample control and detection module II comprises: an electric displacement stage (5) and a hollow-core photonic bandgap optical fiber (6); the inner wall of the hollow-core photonic bandgap optical fiber (6) is a Bragg reflection structure composed of thin films with alternating high and low refractive indices; a plurality of air channels are embedded in the optical fiber cladding along the axial direction of the optical fiber, and the cross-sectional shape of each air channel is random ( Figure 5 ). The pump laser is vertically incident on the hollow core photonic bandgap fiber (6) to generate an optical signal output. Figure 2 As shown, when the device is used for biochemical sensing, under low-energy laser pumping, the longitudinal mode wavelength interval of the generated laser signal A is uniform and stable. When the device is used to generate large-capacity random tags, under high-energy laser pumping, the longitudinal mode wavelength interval of the generated laser signal B is random and changes randomly with the position of the optical fiber. The electric translation stage (5) will accurately move the hollow-core photonic bandgap optical fiber (6) along the axial direction with a step length of 0.15 mm, and obtain multiple groups of random optical signal outputs at different positions of the optical fiber.

[0037] The signal collection and processing module III includes: an adjustable neutral density filter (7), a collecting element (8), a transmission optical fiber (9), a spectrum analyzer (10) and a computer (11). The adjustable neutral density filter (7) adjustably attenuates the signal light, the collecting element (8) converges and collects the signal light and couples it to the transmission optical fiber (8), and further transmits it to the spectrum analyzer (10). The spectrum result will be transmitted to the computer (11) and data processing will be performed according to the required function. When the device is used for biochemical sensing, the generated laser spectrum result is integrated. When the device is used to generate a large-capacity random label, the generated laser spectrum is converted into a binary string according to a certain rule; multiple groups of optical signal outputs obtained at different positions of the optical fiber are converted into multiple groups of binary strings with the same number of bits to form a two-dimensional random binary label.

[0038] When the device is used to generate large-capacity random labels, the pump energy is high, and the adjustable neutral filter (7) is adjusted to a high-density state. Most of the laser signal A is absorbed, and only a small amount is transmitted to the spectrum analyzer (10). The intensity of the laser signal B is greatly enhanced. A wavelength range of 19nm is taken within the spectral range of the laser signal B. The generated laser spectrum is converted into a two-dimensional random binary label. First, the longitudinal mode wavelength position of all laser longitudinal mode intensities in the spectrum is higher than 10% of the highest intensity in the entire range; the wavelength range is divided into 50 wavelength intervals at intervals of 0.38nm, and corresponds to 50 binary characters, of which the first 49 intervals are left-closed and right-open intervals, and the last interval is a closed interval; if the longitudinal mode wavelength position is in a certain wavelength interval, the bit corresponding to this interval is a digital "1", otherwise it is a digital "0". Figure 3 As shown in the figure, 50 groups of optical signal outputs obtained at different positions of the optical fiber are converted into 50 groups of binary strings of the same length, obtaining a 50×50 two-dimensional digital matrix, forming a two-dimensional random binary label. The coding capacity is 2 2500 Two-dimensional random binary labels.

[0039] When the device is used for biosensing, under low-energy laser pumping, the adjustable neutral filter (7) is adjusted to a low-density state to generate only laser signal A. The standard (urinary microalbumin) is diluted according to a 10-fold concentration gradient, and equal amounts of the test protein of each concentration and deionized water are added to the detection reagent to form a test reaction group and a blank control group. After incubation at 37° for 10 minutes, 83 μL of 1.2 mM rhodamine B aqueous solution is added to each group of liquids and mixed evenly. First, the blank control group is sucked into the hollow-core photonic bandgap fiber (6) through capillary action, and the energy of the pulsed laser (1) is adjusted so that the spectral intensity of the laser signal A reaches the maximum value as a reference value. The spectral intensity corresponding to the test reaction liquid of each concentration after incubation at 37° for 10 minutes is detected under the same pulsed laser (1) energy. The difference in spectral integrated intensity between the blank control group and the test reaction liquid of each concentration is calculated to obtain a curve of the change of the spectral integrated intensity difference of the laser signal A relative to the reference value with the change of the urine microalbumin concentration ( Figure 4 ).

[0040] For the sample to be tested, the above measurement steps are repeated, and the spectral integrated intensity difference of the obtained laser signal A is brought into the above variation curve to obtain the concentration of the sample to be tested.

Claims

1. A fiber microcavity laser device with integrated biochemical sensing and random labeling functions, which includes a pump light source module I, a sample control and detection module II, and a signal collection and processing module III, a total of three parts: The pump light source module I is used to provide pump laser to the sample control and detection module II; The sample control and detection module II includes: An electric translation stage (5) and a hollow-core photonic bandgap optical fiber (6); the inner wall of the hollow-core photonic bandgap optical fiber (6) has a Bragg reflection structure, and each cross section along the optical fiber axis in the optical fiber cladding is embedded with a random microstructure; the pump laser is vertically incident on the hollow-core photonic bandgap optical fiber (6) to generate an optical signal output; under low-energy laser pumping, the longitudinal mode wavelength interval of the generated laser signal A is uniform and stable, and the device is used for biochemical sensing; under high-energy laser pumping, the longitudinal mode wavelength interval of the generated laser signal B is random and changes randomly with the position of the optical fiber, and the device is used to generate large-capacity random labels; the boundary between the low-energy laser pumping and the high-energy laser pumping is E, and E is greater than 15 μJ / mm 2 The electric translation stage (5) will accurately move the hollow-core photonic bandgap fiber (6) along the axial direction to obtain multiple groups of random optical signal outputs at different positions of the optical fiber; When the device is used for biochemical sensing, the generated laser spectrum results are integrated; When the device is used to generate a large volume of random tags, the generated laser spectrum is converted into a binary string; Multiple groups of optical signal outputs obtained at different positions of the optical fiber are converted into multiple groups of binary strings with the same number of bits, forming a two-dimensional random binary label; The pump light source module I comprises: a pulse laser (1), a beam splitter (2), an energy meter (3), and a cylindrical lens (4); the pulse laser (1) outputs a pump laser, which is divided into two vertical beams after passing through the beam splitter (2), one of which is incident on the energy meter (3) to monitor the beam energy in real time; the other laser beam passes through the cylindrical lens (4) to form a strip-shaped light spot, which is vertically converged on the hollow-core photonic bandgap optical fiber (6); The signal collection and processing module III comprises: an adjustable neutral density filter (7), a collecting element (8), a transmission optical fiber (9), a spectrum analyzer (10) and a computer (11); the adjustable neutral density filter (7) adjustably attenuates the signal light, the collecting element (8) converges and collects the signal light and couples it to the transmission optical fiber (8), and further transmits it to the spectrum analyzer (10), and the spectrum result will be transmitted to the computer (11) and data processing will be performed according to the required function; When the device is used to generate large-capacity random labels, under high-energy laser pumping, a section of the laser signal B is taken and the laser spectrum of the section of the laser signal B is converted into a two-dimensional random binary label according to the following rules: Step 1: Find the highest amplitude of the laser longitudinal mode intensity in the spectrum, and set 10% of the amplitude as the threshold; then find the wavelength position where the intensity of all laser longitudinal modes in the spectrum is higher than the threshold; Step 2: Divide the wavelength range into 50 wavelength intervals at intervals of 0.38 nm, and correspond to 50 binary characters, of which the first 49 intervals are left closed and right open intervals, and the last interval is a closed interval; Step 3: If the wavelength position obtained in step 1 is within a certain wavelength interval, the bit corresponding to this interval is digital "1", otherwise it is digital "0"; Step 4: The N groups of optical signal outputs obtained at different positions of the optical fiber are converted into N groups of binary strings of the same length according to steps 1-3, and a 50×N two-dimensional digital matrix is ​​obtained to form a two-dimensional random binary label; the N value can be adjusted and expanded according to application requirements to obtain a coding capacity of 2 50×N 2D random binary labels of ; The Bragg reflection structure on the inner wall of the hollow-core photonic bandgap optical fiber (6) has a reflectivity greater than 80% at 620nm to 720nm; When outputting laser signals, the pumping threshold of laser signal A is less than the pumping threshold of laser signal B; The central wavelength of laser signal A is longer than the central wavelength of laser signal B, and the bandwidths of laser signal A and laser signal B do not overlap; A plurality of air channels are embedded in the optical fiber cladding along the axial direction of the optical fiber, and the cross-sectional shape of each air channel is random.

2. The optical fiber microcavity laser device with integrated biochemical sensing and random labeling dual functions as claimed in claim 1, characterized in that: The wavelength of the pulse laser (1) is continuously adjustable between 400 nm and 800 nm, and the output pulse laser energy is continuously adjustable between 1 μJ and 1 mJ.

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