A photothermal detection device for non-invasive glucose detection

Abstract

The application claims a photothermal detection device for non-invasive glucose detection, comprising a quantum cascade laser, a DFB detection laser, an optical medium, a dove prism, a parabolic mirror, an optical chopper, an optical polarizer, a photodetector, a lock-in amplifier, a data acquisition card and a computer, and innovatively proposes an interferometric intensity demodulation-based photothermal detection technology. The miniaturized dove prism absorption cell structure is combined with the FPE (Fabry-Perot cavity), so that it has better vibration resistance. The device adopts a non-invasive detection method, can detect the blood glucose concentration in real time without blood sampling, reduces the pain of patients, improves the convenience and comfort of detection, and has important significance for the development of biological medical detection.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of photothermal detection, and relates to a method and system for non-invasively analyzing a substance. BACKGROUND

[0002] With the development of science and technology, the prevention and treatment of diabetes mellitus has increasingly become a global health problem. Traditional blood glucose detection methods are mostly blood sampling and detection using chemical reagents, which are cumbersome and painful. In recent years, research based on non-invasive detection technology has gradually attracted attention. Photothermal detection technology has become a research hotspot in the field of biomedicine, especially blood glucose monitoring, due to its high sensitivity, non-invasiveness, real-time monitoring and other advantages.

[0003] Existing glucose detection technologies mostly focus on directly detecting glucose molecules in a solution through a sensor or qualitatively analyzing through spectral characteristics, but these technologies often have problems such as signal interference, insufficient sensitivity, limited application range, etc. in actual application. Therefore, how to design a more efficient, sensitive and stable photothermal detection device to realize accurate glucose concentration detection is still a technical problem to be solved at present.

[0004] After searching, application publication No. CN106535760B discloses a method and system for analyzing a substance (100). The method comprises the following steps: arranging an optical medium (10) on a substance surface, so that at least one region of a surface (12) of the optical medium (10) is in contact with the substance surface; emitting an excitation light beam having an excitation wavelength, which passes through the region of the surface (12) of the optical medium (10) in contact with the substance surface to the substance surface; emitting a measurement light beam, which passes through the optical medium (10) to the region of the surface (12) of the optical medium (10) in direct contact with the substance surface, so that the measurement light beam and the excitation light beam overlap on the interface between the optical medium (10) and the substance surface, and the measurement light beam is reflected at the interface; detecting deflection of the reflected measurement light beam directly or indirectly 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 demodulation and inversion of the signal in this patent mainly come from the detection of the slight deflection of the probe light beam caused by the reflection according to the wavelength of the excitation light beam, which requires the entire device to have strong anti-vibration ability, which is relatively harsh for the external environment. The present application can well solve this problem by inverting the refractive index and information of the detected sample through the change in the transmission light interference intensity of the probe light beam, so that it has stronger anti-vibration ability. SUMMARY

[0006] The present application 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 application is as follows:

[0007] A photothermal detection device for non-invasive glucose detection comprises a quantum cascade laser, a DFB distributed feedback laser, an optical medium, a dove prism, a parabolic mirror, an optical chopper, an optical polarizer, a photodetector, a lock-in amplifier, a data acquisition card, and a computer. The quantum cascade laser is connected to the data acquisition card and the computer, and the optical polarizer is connected to the optical chopper and the parabolic mirror. The optical chopper is also connected to the computer. The lock-in amplifier is connected to the photodetector and the data acquisition card. The photodetector is connected to the dove prism, and the data acquisition card is connected to the computer. The DFB probe 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 is modulated by an optical chopper to form a pulsed laser that meets the conditions. The modulated pump beam is vertically incident into the dove prism through a parabolic mirror. The DFB laser is used to generate a probe beam, which is vertically incident into the dove prism from the side. When the sample is in full contact with the total reflection surface, the absorption of the pump beam will cause a thermal gradient in the optical medium, which will in turn cause a change in the refractive index of the optical medium and a slight deformation of the surface. The change in the refractive index of the optical medium will cause a change in the interference intensity of the probe beam in the Fabry-Perot cavity, which is composed of two high-reflectivity mirrors on the side and a total reflection surface above. The transmitted light of the probe beam will be incident on the photodetector, bringing out the corresponding signal. Finally, the electrical signal detected by the photodetector is modulated and amplified by the lock-in amplifier, and then transmitted to the data acquisition card to convert it into a digital signal. Finally, the refractive index change information carried by the transmitted light is obtained by storing and processing in the computer, and the thermal wave information carried by the refractive index change is further demodulated. Finally, the concentration information of glucose in the sample is obtained by inversion, and the detection of glucose concentration in the sample is realized.

[0009] Further, the quantum cascade laser is used as a pump light source, which has a tunable spectral range of about 1000-1245 cm -1 The peak pulse power provided by the quantum cascade laser is 150 mW, the repetition frequency is set to 100 kHz, and the duty cycle is 5%. The corresponding average power is about 7.5 mW.

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

[0011] Furthermore, the upper inner mirror of the dove prism is a total reflection surface, the lower mirror is a total transmission surface, and the inner side 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 probe beam enters the cavity, interference occurs. Since the change in the refractive index of the optical medium causes a change in the interference intensity, the glucose concentration information in the sample can be retrieved, achieving a non-invasive detection purpose.

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

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

[0014] This invention proposes a non-invasive photothermal detection system for glucose monitoring, innovatively employing a photothermal detection technology based on interference intensity demodulation. By combining a miniaturized Dove prism absorption cell structure with a Fabry-Perot cavity (FPE), its vibration resistance is significantly improved. This non-invasive detection method allows for real-time blood glucose concentration monitoring without blood sampling, reducing patient discomfort and enhancing convenience and comfort. It holds significant importance for the development of biomedical testing.

[0015] By coating the simple FP cavity formed by the first high-reflection mirror 11, the total reflection mirror 9, and the second high-reflection mirror 12, the probe beam can be reflected multiple times within it, making it more sensitive to changes in interference intensity caused by minute changes in refractive index. Attached Figure Description

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

[0017] Appendix Figure 2 This is a simulated optical path diagram of the Dove prism in an embodiment of the present invention.

[0018] Appendix Figure 3The diagram shows the interference transmission light and phase difference spectrum (a) and the relationship between the FP cavity length L and the output light intensity I in an embodiment of the present invention (b).

[0019] The attached diagram shows the markings and corresponding component names:

[0020] 1-Quantum cascade laser, 2-Optical polarizer, 3-Optical chopper, 4-Parabolic mirror, 5-DFB laser, 6-Photodetector, 7-Fully transmissive mirror, 8-Optical medium, 9-Total internal reflection mirror, 10-Sample to be tested, 11-First high-reflectivity mirror, 12-Second high-reflectivity mirror, 13-Lock-in amplifier, 14-Data acquisition card, 15-Computer. Detailed Implementation

[0021] The technical solutions of the embodiments of the present invention will be clearly and thoroughly described below with reference to the accompanying drawings. The described embodiments are merely some embodiments of the present invention.

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

[0023] As attached Figure 1 As shown in the diagram, this is an overall structural block diagram of a non-invasive photothermal detection system for glucose detection according to an embodiment of the present invention. A quantum cascade laser 1 is used as the pump source, with a tunable spectral range of approximately 1000-1245 cm⁻¹. -1The range can better cover the whole mid-infrared absorption band of glucose absorption spectrum between the wave numbers, and it provides a peak pulse power of 150 mW, the repetition frequency is set to 100 kHz, and the duty cycle is 5%, and the corresponding average power is about 7.5 mW. The pump beam is finally focused on the contact interface of the total reflection mirror 9 and the detection sample 10, and the spot size is about 300 μm. In order to realize the synchronization of the laser wavelength tuning process and the modulation frequency, a Python script is developed in the computer 15 to control the optical chopper 3 and the quantum cascade laser 1. At the same time, the frequency of the chopper is also used as the reference frequency of the lock-in amplifier 13. The probe beam is emitted by the DFB laser 5, and is incident into the dove prism perpendicularly to the first high reflection mirror 11, and has a high overlap area with the spot formed by the contact interface of the pump beam. When the detection sample 10 is in full contact with the total reflection mirror 9, the absorption of the pump beam will cause a thermal gradient in the optical medium 8, which in turn causes a change in the refractive index of the optical medium 8 and a slight deformation of the surface; the change in the refractive index of the optical medium 8 will cause a change in the interference intensity of the probe beam in the Fabry-Perot cavity (the Fabry-Perot cavity composed of the two high reflection mirrors 11 and 12 on the side and the total reflection mirror 9 above), and the transmitted light of the probe beam will irradiate the photodetector 6 to bring out the corresponding signal. Finally, the electrical signal detected by the photodetector 6 is first modulated and amplified by the lock-in 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 refractive index change information carried by the transmitted light, further demodulate the thermal wave information carried by the refractive index change of the medium, and finally obtain the concentration information of glucose in the sample through inversion, thereby realizing the detection of the glucose concentration in the sample.

[0024] As shown in the accompanying drawings, Figure 2 The high reflection mirror 11 and the high reflection mirror 12 are treated with gold film to have high reflectivity, the probe beam emitted by the laser DFB is vertically incident into the dove prism, and multiple reflections occur in the simple F-P cavity formed by the high reflection mirror 11, the total reflection mirror 9 and the high reflection mirror 12, and finally the transmitted light perpendicular to the high reflection mirror 12 carries the interference information after fully reacting with the optical medium 8.

[0025] As shown in the accompanying drawings, Figure 3The figure shows the interference transmission light and phase difference map (a) and the relationship between the F-P cavity length L and the output light intensity I (b) of the embodiment of the application, and the figure 3-a is the relationship between the transmission light intensity and the phase difference under different reflectivity. As can be seen from the figure, the greater the reflectivity, the greater the sharpness near the maximum value of the transmission light intensity. When r2<<1, the transmission light intensity curve changes in a sinusoidal form. Because the transmission process of light in the F-P cavity will cause energy loss, therefore, the method of gold plating film is generally used to increase the reflectivity of the mirror 11, 12, so as to increase the transmission light intensity. The interference-intensity demodulation is a kind of demodulation method for obtaining the cavity length change by using the certain relationship between the F-P cavity and the light intensity. Through the scanning of the DFB laser, the working point is limited at the place where the slope is maximum, that is, the phase difference is π / 2. As shown in the figure 3-b, the relationship between the F-P cavity length L and the output light intensity I (b), the interference light intensity signal curve is a sinusoidal curve, so when the transmission light intensity is constant, the corresponding cavity length L value will change due to the change of the refractive index, that is, L is not unique, but changes periodically.

[0026] The systems, apparatuses, modules, or units illustrated in the above embodiments can be specifically implemented by computer chips or entities, or by products with certain functions. A typical implementation device is a computer. Specifically, the computer may, for example, be 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] The computer readable medium includes permanent and non-permanent, removable and non-removable media, which can be implemented by any method or technology to store information. The 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 disc read-only memory (CD-ROM), digital versatile disc (DVD) or other optical storage, magnetic cassette, magnetic tape, magnetic disk storage or other magnetic storage device, or any other non-transmission medium that can be used to store information accessible by a computing device. According to the definition in this paper, computer readable medium does not include transitory computer readable medium, such as modulated data signal and carrier wave.

[0028] It is also to be noted that the terms "comprising", "including", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but can also include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element proceeded by "comprises a... " does not, without more constraints, exclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[0029] The above examples are to be understood only as illustrative of the application and not a restriction on the scope of protection of the application. After reading the specification, the skilled person can make various changes or modifications to the application, and these equivalent changes and modifications also fall within the scope defined by the claims of the application.

Claims

1. A photothermal probing device for non-invasive glucose detection, characterized in that, It includes: Quantum cascade laser, DFB distributed feedback laser, optical medium, dove prism, parabolic mirror, optical chopper, optical polarizer, photodetector, lock-in amplifier, data acquisition card and computer, the optical medium is dove prism, the quantum cascade laser is connected with data acquisition card, computer end and optical polarizer respectively, the optical polarizer is connected with parabolic mirror and dove prism after passing through optical chopper, the optical chopper is also connected with computer end, the lock-in amplifier is connected with photodetector and data acquisition card respectively, the photodetector is connected with dove prism, the data acquisition card is connected with computer, and the DFB distributed feedback laser is also connected with dove prism; Wherein, the quantum cascade laser is used to generate pump beam, after the pump beam passes through an optical polarizer, the transmitted light is modulated by the optical chopper to form a pulse laser meeting the condition, and the modulated pump beam is vertically incident into the dove prism through a parabolic mirror; the DFB laser is used to generate probe beam, which is vertically incident into the dove prism from the side; when the sample is in full contact with the total reflection surface, the absorption of the pump beam will cause the optical medium to produce thermal gradient, and then cause the change of the refractive index and the slight deformation of the surface; the change of the refractive index of the optical medium will cause the change of the interference intensity of the probe beam in the Fabry-Perot cavity, which is composed of two high reflective mirrors on the side and the upper total reflection surface, and the transmitted light of the probe beam will irradiate on the photodetector to bring corresponding signal, finally the electrical signal detected by the photodetector is modulated and amplified by the lock-in amplifier, and then transmitted to the data acquisition card to convert into digital signal; finally, the computer is transmitted to store and process the refractive index change information carried by the transmitted light, further demodulate the thermal wave information carried by the refractive index change, and finally obtain the concentration information of glucose in the sample through inversion, so as to realize the detection of glucose concentration in the sample; The dove prism has a Fabry-Perot cavity, which is composed of a first high reflective mirror, a total reflection mirror and a second high reflective mirror, and the probe beam emitted by the DFB laser is vertically incident into the dove prism through the first high reflective mirror, and has an overlapping area with the light spot formed by the pump beam vertically incident into the dove prism through the parabolic mirror.

2. The photothermal probing device for non-invasive glucose detection according to claim 1, wherein, The quantum cascade laser is selected as a pump light source, and has a tunable spectral range of 1000-1245 cm -1 The quantum cascade laser is selected as a pump light source, and has a tunable spectral range of 1000-1245 cm 3. The photothermal probing device for non-invasive glucose detection according to claim 1, wherein, The upper inner mirror of the dove prism is a total reflection mirror, the lower mirror is a total transmission mirror, and the side inner mirror is a high reflective mirror, which obtains high reflectivity through gold film coating and forms an F-P cavity with the upper total reflection mirror; the probe beam enters the cavity and interference occurs, and the change of the refractive index of the optical medium will cause the change of the interference intensity, so that the glucose concentration information in the sample can be obtained through inversion, and the non-invasive detection purpose is realized.

4. The photothermal probing device for non-invasive glucose detection according to claim 1, wherein, The quantum cascade laser adopts a 6-9um mid-infrared laser, the DFB distributed feedback laser adopts a 1550nm DFB laser, the photodetector adopts a MCT-12-0TE amplification detector, and the lock-in amplifier adopts a DC-250kHz double-channel lock-in amplifier.

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