Photo-thermal detection device for non-invasive glucose detection

Abstract

The invention relates to a photo-thermal detection device for non-invasive glucose detection, which comprises a quantum cascade laser, a DFB detection laser, an optical medium, a dove prism, a parabolic reflector, an optical chopper, an optical polarizer, a photoelectric detector, a lock-in amplifier, a data acquisition card and a computer, the invention innovatively provides a photo-thermal detection technology based on interference intensity demodulation. A miniaturized dove prism absorption cell structure is combined with an FPE (Fabry-Perot cavity), so that the absorption cell has better anti-vibration capability. According to the device, a non-invasive detection mode is adopted, the blood glucose concentration can be detected in real time without blood sampling, the pain of a patient is reduced, and the detection convenience and comfort are improved. The method has important significance on the development of biomedical detection.

Description

Technical Field

[0001] The invention belongs to the technical field of photothermal detection and relates to a method and system for non-invasively analyzing substances. Background Art

[0002] With the development of science and technology, the prevention and treatment of diabetes has become a global health issue. Traditional blood sugar detection methods mostly involve blood sampling and the use of chemical reagents for testing, which is a cumbersome and painful process. In recent years, research based on non-invasive detection technology has gradually attracted attention. Photothermal detection technology has become a research hotspot in the biomedical field, especially in blood sugar monitoring, due to its advantages such as high sensitivity, non-invasiveness, and real-time monitoring.

[0003] Most existing glucose detection technologies focus on directly detecting glucose molecules in solution through sensors or performing qualitative analysis through spectral characteristics, but these technologies often have problems such as signal interference, insufficient sensitivity, and limited scope of application in practical applications. Therefore, how to design a more efficient, sensitive, and stable photothermal detection device to achieve accurate glucose concentration detection is still a technical problem that needs to be solved urgently.

[0004] After searching, the application publication number is CN106535760B, a method and system for analyzing a substance (100). The method comprises the following steps: arranging an optical medium (10) on a surface of a substance so that at least one area of ​​a surface (12) of the optical medium (10) contacts the surface of the substance; emitting an excitation light beam having an excitation wavelength, which passes through an area of ​​the surface (12) of the optical medium (10) in contact with the surface of the substance to the surface of the substance; emitting a measurement light beam, which passes through the optical medium (10) to an area of ​​the surface (12) of the optical medium (10) in direct contact with the surface of the substance, so that the measurement light beam and the excitation light beam overlap at an interface between the optical medium (10) and the surface of the substance, and the measurement light beam is reflected at the interface; directly or indirectly detecting a deflection of the reflected measurement light beam according to the wavelength of the excitation light beam; and analyzing the substance (100) according to the wavelength of the excitation light beam based on the detected deflection of the measurement light beam.

[0005] The basis for signal demodulation and inversion in this patent is mainly derived from the tiny deflection of the detection beam caused by the direct or indirect detection reflection of the wavelength of the excitation beam, which requires the entire device to have strong vibration resistance, which is relatively demanding on the external environment. The present invention inverts the refractive index and information of the sample being tested by detecting the change in the interference intensity of the transmitted light of the detection beam, which can solve this problem well and make it have stronger vibration resistance. Summary of the invention

[0006] The present invention aims to solve the above problems of the prior art. A photothermal detection device for non-invasive glucose detection is proposed. The technical solution of the present invention is as follows:

[0007] A photothermal detection device for non-invasive glucose detection, comprising: a quantum cascade laser, a DFB distributed feedback laser, an optical medium, a dove prism, a parabolic reflector, an optical chopper, an optical polarizer, a photodetector, a phase-locked amplifier, a data acquisition card and a computer, wherein the quantum cascade laser is respectively connected to the data acquisition card, the computer end and the optical polarizer, the optical polarizer first passes through the optical chopper and then is connected to the dove prism through the parabolic reflector, the optical chopper is also connected to the computer end, the phase-locked amplifier is respectively connected to the photodetector and the data acquisition card, the photodetector is connected to the dove prism, the data acquisition card is connected to the computer, and the DFB detection laser is also connected to the dove prism;

[0008] The quantum cascade laser is used to generate a pump beam. After the pump beam passes through an optical polarizer, the transmitted light will be modulated by an optical chopper to form a pulsed laser that meets the conditions. The modulated pump beam passes through a parabolic reflector and is vertically incident on the dove prism. The DFB laser is used to generate a detection beam, which is vertically incident on the dove prism from the side. When the test sample is in full contact with the total reflection surface, the absorption of the pump beam will cause the optical medium to generate a thermal gradient, which will then cause its refractive index to change and the surface to deform slightly. The change in the refractive index of the optical medium will cause the detection beam to The interference intensity of the Perot cavity changes. The Fabry-Perot cavity is composed of two high-reflection mirrors on the side and a total reflection surface on the top. The transmitted light of the detection beam will irradiate the photodetector to bring out the corresponding signal. Finally, the electrical signal detected by the photodetector is modulated and amplified by a phase-locked amplifier, and then transmitted to the data acquisition card to be converted into a digital signal; finally, it is transmitted to the computer for storage and processing to obtain the medium refractive index change information carried by the transmitted light, and further demodulate the thermal wave information carried by the medium refractive index change, and finally the glucose concentration information in the sample is obtained by inversion, thereby realizing the detection of glucose concentration in the sample.

[0009] Furthermore, the quantum cascade laser is used as a pump light source, and the tunable spectral range is about 1000-1245cm -1 The wavenumbers are used to cover the entire mid-infrared absorption band of the glucose absorption spectrum, and the peak pulse power it provides is 150mW. The repetition frequency is set to 100khz, the duty cycle is 5%, and the corresponding average power is about 7.5mW.

[0010] Furthermore, the dove prism has a Fabry-Perot cavity, which is composed of a first high-reflection mirror, a total reflection mirror, and a second high-reflection mirror. The detection beam emitted by the DFB laser is incident on the dove prism perpendicular to the first high-reflection mirror, and has a highly overlapping area with the light spot formed at the contact interface by the pump beam that passes through the parabolic reflector and is perpendicularly incident on the dove prism.

[0011] Furthermore, the upper inner mirror surface of the dove prism is a total reflection surface, the lower mirror surface is a total transmission mirror surface, and the inner side of the side surface is a high reflection surface. The high reflection surface obtains high reflectivity through a gold-plated film, and forms an FP cavity on the upper total reflection surface. When the detection light beam enters the cavity, interference will occur. Since the change in the refractive index of the optical medium will cause a change in the interference intensity, the glucose concentration information in the sample can be inverted to achieve the purpose of non-invasive detection.

[0012] Furthermore, the quantum cascade laser adopts a 6-9um mid-infrared laser, the DFB distributed feedback laser adopts a 1550nm DFB laser, the photodetector adopts an MCT-12-0TE amplified detector, and the lock-in amplifier adopts a DC-250kHz dual-channel lock-in amplifier.

[0013] The advantages and beneficial effects of the present invention are as follows:

[0014] The present invention proposes a photothermal detection system for non-invasive glucose detection, and innovatively proposes a photothermal detection technology based on interference intensity demodulation. The miniaturized dove prism absorption cell structure is combined with the FPE (Fabry-Perot cavity) to make it have better vibration resistance. The device adopts a non-invasive detection method and can detect blood glucose concentration in real time without blood sampling, which reduces the pain of patients and improves the convenience and comfort of detection. It is of great significance to the development of biomedical detection.

[0015] By coating, the simple FP cavity formed by the high-reflection mirror 11, the total-reflection mirror 9 and the high-reflection mirror 12 can emit the detection light beam multiple times, making it more sensitive to the interference intensity changes caused by small changes in the refractive index. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is an overall structural block diagram of a photothermal detection system for non-invasive glucose detection according to a preferred embodiment of the present invention.

[0017] Figure 2 It is a simulated path diagram of the light path in the dove prism according to an embodiment of the present invention.

[0018] Figure 31 is a graph showing the interference transmission light and phase difference spectrum (a) and a graph showing the relationship between the FP cavity length L and the output light intensity I (b) according to an embodiment of the present invention.

[0019] Marks and corresponding parts names in the attached drawings:

[0020] 1- quantum cascade laser, 2- optical polarizer, 3- optical chopper, 4- parabolic reflector, 5- DFB laser, 6- photodetector, 7- total transmission mirror, 8- optical medium, 9- total reflection mirror, 10- detection sample, 11- first high reflection mirror, 12- second high reflection mirror, 13- phase-locked amplifier, 14- data acquisition card, 15- computer. DETAILED DESCRIPTION

[0021] The following will describe the technical solutions in the embodiments of the present invention in detail in conjunction with the accompanying drawings in the embodiments of the present invention. The described embodiments are only part of the embodiments of the present invention.

[0022] The technical solution of the present invention to solve the above technical problems is:

[0023] As attached Figure 1 As shown in the overall structural block diagram of a photothermal detection system for non-invasive glucose detection in an embodiment of the present invention, a quantum cascade laser 1 is used as a pump light source, and a tunable spectral range of about 1000-1245cm is selected. -1wavenumber, this range can better cover the entire mid-infrared absorption band of the glucose absorption spectrum. And it provides a peak pulse power of 150mW, sets the repetition frequency to 100khz, and the duty cycle is 5%, corresponding to an average power of about 7.5mW. The pump beam is finally focused on the contact interface between the total reflection surface 9 and the detection sample 10, and the spot size is about 300μm. In order to achieve the synchronization of the laser wavelength tuning process and the modulation frequency, a Python script was developed in the computer terminal 15 to control the optical chopper 3 and the quantum cascade laser 1. At the same time, the chopping frequency is also used as the reference frequency of the phase-locked amplifier 13. The detection beam is emitted by the DFB laser 5 and is incident on the dove prism perpendicular to the first high-reflection mirror 11, and has a highly overlapping area with the spot formed by the pump beam at the contact interface. When the detection sample 9 is in full contact with the total reflection surface 10, the absorption of the pump light beam will cause the optical medium 8 to generate a thermal gradient, thereby causing its refractive index to change and a slight deformation of the surface; and the change in the refractive index of the optical medium 8 will cause the interference intensity of the detection light beam in the Fabry-Perot cavity (the Fabry-Perot cavity composed of two high-reflection mirrors 11 and 12 on the side and the total reflection surface 10 above) to change, and the transmitted light of the detection light beam will irradiate the photodetector 6 to bring out a corresponding signal, and finally the electrical signal detected by the photodetector 6 is first modulated and amplified by the phase-locked amplifier 13, and then transmitted to the data acquisition card 14 to be converted into a digital signal, and finally transmitted to the computer 15 for storage and processing to obtain the medium refractive index change information carried by the transmitted light, and further demodulate the thermal wave information carried by the medium refractive index change, and finally obtain the glucose concentration information in the sample by inversion, thereby realizing the detection of the glucose concentration in the sample.

[0024] like Figure 2 As shown, it is a simulated optical path in the dove prism of an embodiment of the present invention. The inner surfaces of the high-reflection mirror 11 and the high-reflection mirror 12 are treated with a gold film to make them have a high reflectivity. The detection light beam emitted by the laser DFB is vertically incident on the dove prism, and is emitted multiple times in the simple FP cavity formed by the high-reflection mirror 11, the total reflection mirror 9, and the high-reflection mirror 12. Finally, the transmitted light emitted vertically from the optical lens 12 brings out the interference information after fully reacting with the medium 8.

[0025] like Figure 3 As shown in the figure, it is the interference transmission light and phase difference spectrum (a) of the embodiment of the present invention and the relationship diagram between the FP cavity length L and the output light intensity I (b), Figure 3(a) is a relationship diagram between the transmitted light intensity and the phase difference under different reflectivity. It can be seen from the figure that the greater the reflectivity, the greater the sharpness near the maximum value of the transmitted light intensity. When r2<<1, the transmitted light intensity curve changes in a sinusoidal form. Since the transmission process of light in the FP cavity will produce energy loss, the gold-plated film method is generally used to increase the reflectivity of the mirrors 11 and 12, so as to achieve the purpose of increasing the transmitted light intensity. Interference-intensity demodulation is a demodulation method that uses the certain relationship between the FP cavity and the light intensity to obtain the change in cavity length. The DFB laser is scanned to limit the working point to the point with the maximum slope, that is, the phase difference is π / 2. As Figure 3 (b) Relationship diagram between FP cavity length L and output light intensity I (b). The interference light intensity signal curve is a quasi-sine curve. Therefore, when the transmitted light intensity is constant, the corresponding cavity length L value will change due to the change of refractive index, that is, L is not unique, but changes periodically.

[0026] The systems, devices, modules or units described in the above embodiments may be implemented by computer chips or entities, or by products with certain functions. A typical implementation device is a computer. Specifically, the computer may be, for example, a personal computer, a laptop computer, a cellular phone, a camera phone, a smart phone, a personal digital assistant, a media player, a navigation device, an email device, a game console, a tablet computer, a wearable device, or a combination of any of these devices.

[0027] Computer readable media include permanent and non-permanent, removable and non-removable media that can be implemented by any method or technology to store information. Information can be computer readable instructions, data structures, program modules or other data. Examples of computer storage media include, but are not limited to, phase change memory (PRAM), static random access memory (SRAM), dynamic random access memory (DRAM), other types of random access memory (RAM), read-only memory (ROM), electrically erasable programmable read-only memory (EEPROM), flash memory or other memory technology, compact disk read-only memory (CD-ROM), digital versatile disk (DVD) or other optical storage, magnetic cassettes, magnetic tape magnetic disk storage or other magnetic storage devices or any other non-transmission media that can be used to store information that can be accessed by a computing device. As defined herein, computer readable media does not include temporary computer readable media (transitory media), such as modulated data signals and carrier waves.

[0028] It should also be noted that the terms "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, commodity or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, commodity or device. In the absence of more restrictions, the elements defined by the sentence "comprises a ..." do not exclude the existence of other identical elements in the process, method, commodity or device including the elements.

[0029] The above embodiments should be understood to be only used to illustrate the present invention and not to limit the protection scope of the present invention. After reading the contents of the present invention, technicians can make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

Claims

1. A photothermal detection device for non-invasive glucose detection, characterized in that: include: A quantum cascade laser, a DFB distributed feedback laser, an optical medium, a dove prism, a parabolic reflector, an optical chopper, an optical polarizer, a photodetector, a phase-locked amplifier, a data acquisition card and a computer. The quantum cascade laser is respectively connected to the data acquisition card, the computer end and the optical polarizer. The optical polarizer first passes through the optical chopper and then is connected to the dove prism through the parabolic reflector. The optical chopper is also connected to the computer end. The phase-locked amplifier is respectively connected to the photodetector and the data acquisition card. The photodetector is connected to the dove prism. The data acquisition card is connected to the computer. The DFB detection laser is also connected to the dove prism. The quantum cascade laser is used to generate a pump beam. After the pump beam passes through an optical polarizer, the transmitted light will be modulated by an optical chopper to form a pulsed laser that meets the conditions. The modulated pump beam passes through a parabolic reflector and is vertically incident on the dove prism. The DFB laser is used to generate a detection beam, which is vertically incident on the dove prism from the side. When the test sample is in full contact with the total reflection surface, the absorption of the pump beam will cause the optical medium to generate a thermal gradient, which will then cause its refractive index to change and the surface to deform slightly. The change in the refractive index of the optical medium will cause the detection beam to The interference intensity of the Perot cavity changes. The Fabry-Perot cavity is composed of two high-reflection mirrors on the side and a total reflection surface on the top. The transmitted light of the detection beam will irradiate the photodetector to bring out the corresponding signal. Finally, the electrical signal detected by the photodetector is modulated and amplified by a phase-locked amplifier, and then transmitted to the data acquisition card to be converted into a digital signal; finally, it is transmitted to the computer for storage and processing to obtain the medium refractive index change information carried by the transmitted light, and further demodulate the thermal wave information carried by the medium refractive index change, and finally the glucose concentration information in the sample is obtained by inversion, thereby realizing the detection of glucose concentration in the sample.

2. A photothermal detection device for non-invasive glucose detection according to claim 1, characterized in that: The quantum cascade laser is used as a pump light source, and the tunable spectral range is about 1000-1245cm -1 The wavenumbers are used to cover the entire mid-infrared absorption band of the glucose absorption spectrum, and the peak pulse power it provides is 150mW. The repetition frequency is set to 100khz, the duty cycle is 5%, and the corresponding average power is about 7.5mW.

3. A photothermal detection device for non-invasive glucose detection according to claim 1, characterized in that: The dove prism has a Fabry-Perot cavity, which is composed of a first high-reflection mirror, a total reflection mirror, and a second high-reflection mirror. The detection beam emitted by the DFB laser is incident on the dove prism perpendicularly to the first high-reflection mirror, and has a highly overlapping area with the light spot formed on the contact interface with the pump beam perpendicularly incident on the dove prism through the parabolic reflector.

4. A photothermal detection device for non-invasive glucose detection according to claim 1, characterized in that: The upper inner mirror surface of the dove prism is a total reflection surface, the lower mirror surface is a total transmission mirror surface, and the inner side of the side surface is a high reflection surface. The high reflection surface obtains high reflectivity through a gold-plated film, and forms an FP cavity with the upper total reflection surface. When the detection light beam enters the cavity, interference will occur. Since the change in the refractive index of the optical medium will cause a change in the interference intensity, the glucose concentration information in the sample can be inverted to achieve the purpose of non-invasive detection.

5. A photothermal detection device for non-invasive glucose detection according to claim 1, characterized in that: The quantum cascade laser adopts a 6-9um mid-infrared laser, the DFB distributed feedback laser adopts a 1550nm DFB laser, the photodetector adopts an MCT-12-0TE amplified detector, and the lock-in amplifier adopts a DC-250kHz dual-channel lock-in amplifier.

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