CN115137298A - Signal collecting device, system and method for subcutaneous biomarkers - Google Patents
Signal collecting device, system and method for subcutaneous biomarkers Download PDFInfo
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- CN115137298A CN115137298A CN202110336907.5A CN202110336907A CN115137298A CN 115137298 A CN115137298 A CN 115137298A CN 202110336907 A CN202110336907 A CN 202110336907A CN 115137298 A CN115137298 A CN 115137298A
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Abstract
The invention provides a signal collecting device of a subcutaneous biomarker, which comprises an excitation light source, a wavefront control module and a focusing module, wherein the excitation light source, the wavefront control module and the focusing module are arranged along a light path, the excitation light source is used for emitting excitation light, and the excitation light emits signal light after being emitted or refracted by the subcutaneous biomarker; the wavefront control module comprises a wavefront analyzer, a control unit and a spatial light modulator which are sequentially in communication connection; the control unit comprises a processor, and the processor learns the feedback received from the wavefront analyzer based on a neural network convolution algorithm, calculates an optimized wavefront and controls the emergent wavefront of the spatial light modulator. The wave-front distortion is improved, the high-efficiency excitation of a subcutaneous specific position is realized, and the collection efficiency is also improved. The signal collecting system and the signal collecting method have corresponding advantages due to the adoption of the signal collecting device, and are beneficial to further popularization and application of a noninvasive optical detection technology.
Description
Technical Field
The invention belongs to the technical field of optical detection, and particularly relates to a signal collecting device, a signal collecting system and a signal collecting method for subcutaneous biomarkers.
Background
This section is intended to provide a background or context to the embodiments of the invention that are recited in the claims. The description herein is not admitted to be prior art by inclusion in this section.
The application of the optical detection technology has been popularized in various fields in life, and particularly, the optical detection technology has universal application in medical examination related to human health and further needs to be further deepened and popularized. The biological characteristics can be reflected through the characteristics of the optical information, and the treatment and the daily health monitoring can be powerfully supported after the analysis.
For example, the measurement method based on near infrared spectroscopy can improve the problems of the conventional detection method by the characteristics of painlessness, non-invasiveness, simplicity, rapidness and the like, and is one of potential methods for applying the non-invasive biochemical analysis of blood. For example, the Raman spectrum detection technology can reflect the change of human tissue cell molecules in the application of the Raman spectrum detection technology in the field of biomedicine, and is a new technology for early-stage lesion detection. Different Raman peaks are the characteristics of certain specific molecules, so that the Raman spectrum has the functions of qualitative analysis and distinguishing similar substances, the peak intensity of the Raman spectrum is in direct proportion to the concentration of the corresponding molecules, and the Raman spectrum can also be used for quantitative analysis and can provide a theoretical basis for clinical diagnosis. Whether the blood sample is affected by the disease can be judged according to the characteristic peak intensity of the blood sample in the Raman spectrum in the future.
Taking the raman detection device as an example, the raman signal light is collected and transmitted to the detection module, and the raman signal intensities at different wavelengths are detected. Therefore, how to effectively and sufficiently collect signals in optical detection is a prominent problem of the design of the optical path in the optical detection device and is one of the key designs to be optimized in the current technology. On the other hand, the problem before collection is how to accurately focus the excitation light to the location to be detected, which concerns the complexity of sample preparation and whether it can be deployed outside the laboratory. If the exciting light is accurately focused on a specific position on the sample, under the condition that the design of the light path is not changed, a reasonable sample frame or a sample table obviously needs to be designed, and possible pretreatment is carried out on the surface of the sample, so that the testing efficiency is influenced, the sample is adjusted every time, the efficiency is low, and the cost can be increased. The application outside the laboratory limits the test conditions, and the medium between the sample to be tested and the light source is a problem which influences the gathering of the excitation light to a specific position and the subsequent signal collection and is difficult to avoid.
Especially in applications of subcutaneous biomarker detection. The skin, the organ with the largest surface area and the most useful, is the largest and the total weight of the human body is about eight percent of the human body's weight, it contains 25% -30% of the total circulating blood of the human body and the skin tissue is basically composed of epidermis, dermis and subcutaneous fat. Tissue fluid or blood under the skin contains many biospecific markers that are closely related to the health and disease status of the human body. However, many of the current medical techniques are difficult to detect the biomarkers through the skin in a non-invasive manner, for example, blood glucose detection requires blood drawing tests or finger-prick blood drawing tests. The use of optical detection techniques is essential if they can be used for non-invasive subcutaneous medical detection, especially if the general population can monitor the health of an individual outside a medical laboratory. The skin is a turbid scattering medium, and can scatter incident light, so that the wavefront of photons entering the skin is greatly deviated, the effect of focusing the photons to a specific subcutaneous position is greatly reduced, and the collection efficiency needs to be improved urgently. Therefore, it is necessary to develop a signal collecting device, a corresponding system and a corresponding method, which can accurately focus on a specific detection portion, and is beneficial to improving the collecting efficiency and ensuring the reliable detection result.
The above information disclosed in the background section is only for enhancement of understanding of the background of the present disclosure and therefore it may contain information that does not constitute prior art that is known to a person of ordinary skill in the art. The statements in this background section merely represent techniques known to the public and are not, of course, representative of the prior art.
Disclosure of Invention
The invention aims to solve all or part of problems in the prior art, and provides a signal collecting device of subcutaneous biomarkers and a corresponding system and method, so that the wave front of exciting light is matched with the wave front in the skin, interstitial fluid or blood below the skin can be efficiently detected, information of some biomarkers can be obtained, and diseases or health conditions can be accurately and efficiently reflected.
The following description is made of some of the principles and concepts that may be employed to facilitate understanding of the invention, and is intended to be illustrative and not limiting, and is not intended to limit the scope of the invention.
The surface of the equiphase surface where the wave propagates to a certain position is called a wavefront. The wavefront is a wave front, or wavefront. The invention utilizes the spatial light modulator to regulate and control the wavefront phase of incident light of a random medium, so that the light beam penetrating through the random medium generates coherent enhancement at a target point, and the wavefront modulation focusing is realized. The signal collecting device provided by the invention is based on the wave front adjustment focusing design, and the regulation and control of the feedback wave front signal realize higher quality, higher speed and more accurate specific position focusing of light transmitting through a random medium. The basic principle of the signal collection device of the present invention is to optimize the incident wavefront, and at a specific position behind the scattering medium, the optical phases (initially randomly distributed) of the multiple wavelets become matched, so that constructive interference is formed by the linear relationship between the two, i.e., the optimal wavefront information is found. The signal collection apparatus of the present invention thus more easily produces focusing because the optical path length of each wavelet or the optical phase delay of each spatial frequency component can be precisely matched at focus.
The main function of a wavefront analyzer is to measure optical aberrations at the pupil plane location.
A Spatial Light Modulator (SLM) includes a Digital Micromirror Device (DMD) including an array capable of being independently addressed and controlled, each of which can be independently controlled by an optical signal or an electrical signal to deflect, and change its optical property according to a control signal, so that an incoming Light wave can be modulated according to some characteristics of an electric field form of a controlled voltage. Under the active control, the phase is modulated through the refractive index, and the purpose of light wave modulation is achieved.
The artificial neural network algorithm simulates a biological neural network, and is a pattern matching algorithm. Are commonly used to solve classification and regression problems. Artificial neural networks are a huge branch of machine learning, of which deep learning is one type of algorithm.
The invention provides a signal collecting device of a subcutaneous biomarker, which comprises a signal excitation light path and a signal collecting light path, wherein the signal excitation light path is used for exciting a signal; an excitation light source, a wavefront control module and a focusing module are arranged along a signal excitation light path, the excitation light source is used for emitting excitation light, and the excitation light emits signal light after being emitted or refracted by a subcutaneous biomarker; the signal collection light path is provided with a detection module for collecting signal light for subsequent analysis; the signal receiving surface of the detection module and the focus of the focusing module are on a pair of conjugate surfaces; the wave front control module comprises a wave front analyzer, a control unit and a spatial light modulator which are sequentially in communication connection; excitation light of the excitation light source enters the spatial light modulator after being collimated, and emergent light enters the focusing module after being modulated and is focused subcutaneously by the focusing module; the control unit comprises a processor, and the processor learns the feedback received from the wavefront analyzer based on a neural network convolution algorithm, calculates the optimized wavefront, and controls the emergent wavefront of the spatial light modulator.
In a specific case, excitation light of the excitation light source enters a collimating optical fiber and is incident to the spatial light modulator through an optical fiber coupler. Preferably, the numerical aperture of the optical fiber coupler connected to the excitation light source is 0.22.
The wavefront control module further comprises a first beam splitting unit; the first beam splitting unit is arranged between the spatial light modulator and the focusing module, and splits emergent light of the spatial light modulator to respectively enter the wavefront analyzer and the focusing module; and the wavefront analyzer compares the received wavefront information of photons inside the skin with the current wavefront information of the emergent light and feeds back the result to the control unit. Through the arrangement of the first beam splitting unit, the emergent light beam modulated by the spatial light modulator can be received by the wavefront analyzer, so that the iterative optimization of the wavefront can be continuously realized by the control unit according to the acquired feedback.
The first beam splitting unit includes, but is not limited to, a half mirror, a laser beam splitter, a beam splitter prism, or a thin film beam splitter.
The first beam splitting unit splits emergent light of the spatial light modulator into two beams with an included angle of 90 degrees.
The focal length range of the focusing module is 5mm-900mm. Preferably, the focal length of the focusing module is 300mm.
The focusing module includes a focusing lens. Preferably, the number of the focusing lenses is at least 2, and the focusing lenses form a focusing lens group; the focal length of the focusing lens group is adjustable.
The focusing module further comprises a light shield, the focusing lens group is arranged in the light shield, an aperture diaphragm is arranged on the light shield along the light path direction, and the size of the aperture diaphragm is matched with the numerical aperture of the focusing lens group. The wave front signals at the central excitation point and nearby can be shielded by the light shield, so that the subsequent signal light collection is facilitated, and the fluorescence interference is reduced.
The focusing module comprises a focusing optical fiber, and the focusing optical fiber is connected with the wavefront control module through an optical fiber coupler. The focusing optical fiber is matched with the optical fiber coupler to realize that the optical path connection is favorable for the optical path design of the signal collecting device, so that the optical path turning can be realized according to the design requirement of an actual structure, and the miniaturization requirement of device design is met.
The detection module comprises a detector and a collection optical fiber bundle, and a condenser and a second beam splitting unit are arranged along a signal collection light path; the second beam splitting unit has dichroism, is arranged in a signal excitation light path between the first beam splitting unit and the focusing module, and is used for transmitting excitation light and reflecting signal light generated by excitation; the condenser lens and the focusing module form a conjugate optical device, and the incident end surface of the collection optical fiber bundle is the receiving surface of the detection module. And a dichroic second beam splitting unit is adopted to realize that the signal excitation light path and the signal collection light path are partially overlapped, so that the flexibility of structural design is facilitated.
The second beam splitting unit includes, but is not limited to, a dichroic mirror.
The excitation light source includes, but is not limited to, 785nm semiconductor laser, 830nm semiconductor laser.
In another aspect, the present invention provides a signal collecting method using the signal collecting device of the subcutaneous biomarker of the present invention, comprising: s1, implanting a biocompatible and degradable fluorescence inducer below skin; s2, irradiating the fluorescence inducer by exciting light, detecting fluorescence and scattered light by a wavefront analyzer, and analyzing wavefront information of photons in the skin; feeding back wavefront information to the control unit; s3, the control unit controls the spatial light modulator to remodulate the wave front of the exciting light; step S2 and step S3 are carried out in an iterative mode; s4, focusing the excitation light subjected to wavefront optimization to the excitation signal light under the skin through the focusing module; and S5, the detection module collects the signal light through the signal collection light path to perform subsequent signal analysis.
In the step S2, the method further includes detecting current wavefront information of emergent light of the spatial light modulator by a wavefront analyzer, comparing the current wavefront information with wavefront information of photons inside the skin in real time, and feeding back a comparison result to the control unit.
Before the step S3, the control unit performs deep learning on the feedback information of the wavefront analyzer, trains a self-adaptive optimal algorithm, and performs iterative calculation to obtain an optimal wavefront. In the specific embodiment, according to the intensity of the characteristic signal of the intravascular or subcutaneous characteristic molecule, an artificial intelligence technology is used for deep learning, a self-adaptive optimal algorithm is trained, and the parameters of the spatial light modulator are intelligently adjusted to obtain the optimal subcutaneous wavefront.
The invention also provides a signal collecting system for non-invasively detecting the blood biomarker information of a nail bed, which comprises an optical chamber and a support, wherein the optical chamber and the support form a finger or toe end placing chamber for accommodating a finger or toe; the support piece is movably connected with the optical bin; the optical chamber is used for integrating the parts of the signal collecting device except the excitation light source, the control unit and the detector; one surface of the optical bin, which faces the supporting piece, is provided with an optical window, and the placing bin corresponds to the optical window; the excitation light provided by the optical bin is projected to the nail bed of the finger or toe to be detected through the optical window, the biological marker in the blood of the nail bed is detected, and the reflected or refracted signal light is collected, so that the information of the biological marker in the blood of the nail bed is obtained.
The optical bin provides exciting light and collects returned signal light, the exciting light is emitted through the optical window, and the returned signal light is collected. The supporting piece is used for supporting the finger or toe end of the living creature to be detected. The signal collection system is used for collecting nail bed characteristic signals of the finger or toe end of a living being in a non-invasive mode. When the biological marker in the nail bed blood is detected, the biological finger or toe end to be detected is placed in the biological finger or toe end placing bin, and the nail is correspondingly placed under the optical window, so that noninvasive detection can be performed, the operation is simple and efficient, the information of the biological marker in the nail bed blood is detected, and the disease or health condition of the nail bed is accurately reflected.
The optical chamber is connected with the supporting piece through a rotating piece, and a biological finger or toe end placing chamber is formed between the optical chamber and the supporting piece. The biological finger or toe end placing bin is used for placing the biological finger or toe end to be detected.
The rotating member is a hinge or a bearing. The optical bin can rotate anticlockwise through the hinge or the bearing, the optical bin preferably rotates 90 degrees anticlockwise, the light transmission condition of the optical window is convenient to check, and the optical window is convenient to replace when damaged.
The entrance of the biological finger or toe end placing bin is provided with a detachable rubber ring. The rubber ring is used for fixing the finger or toe end of the living creature to be detected and can be replaced according to the size of the finger or toe end of the living creature to be detected. The diameter of the rubber ring is preferably 10mm to 20mm.
The optical bin and the support can also be slidably connected. A sliding groove is formed in the optical bin, and a sliding rail is arranged on the supporting piece; the supporting piece is fixed, the optical bin slides towards the direction far away from the supporting piece, and a biological finger or toe end placing bin is formed between the optical bin and the supporting piece according to the size of the biological finger or toe end to be detected.
Or the optical bin is provided with a slide rail, and the supporting piece is provided with a sliding groove; the optical bin is fixed, the supporting piece slides towards the direction far away from the optical bin, and a biological finger or toe end placing bin is formed between the optical bin and the supporting piece according to the size of the biological finger or toe end to be detected.
Or the optical bin and the supporting piece are in sliding connection through a sliding connecting piece. The optical cartridge and the support are simultaneously slidable, forming the biological finger or toe end placement cartridge between the optical cartridge and the support.
The optical window is a sheet structure. The thickness range of the optical window is 0.5mm-10mm, and preferably 1mm; when the optical window is a circular sheet structure, the diameter of the optical window ranges from 0.5mm to 25mm, and preferably ranges from 5mm.
The optical window is made of transparent resin or quartz glass. The optical window should be selected of a material that has a high transmittance and allows excitation light of a wavelength preferably 785nm or 830nm to pass through.
The invention also provides another signal collection system for detecting biomarker information under limb skin, which comprises an optical bin, an optical fiber transmission structure and a bandage, wherein the optical fiber transmission structure is used for optically connecting the optical bin and the bandage, and the bandage is used for accommodating limbs in a surrounding manner; the surface of the optical bin is provided with a light through hole, and the optical bin is used for integrating the parts of the signal collecting device except the excitation light source, the control unit and the controller; the optical fiber transmission structure comprises an optical fiber bundle, a first optical fiber coupling system and a second optical fiber coupling system, wherein the optical fiber coupling systems are connected with two ends of the optical fiber bundle, the first optical fiber coupling system is used for leading the exciting light out of the optical bin, leading the exciting light into the binding band along the optical fiber bundle and the second optical fiber coupling system in sequence, reflecting or refracting the exciting light by a biomarker under limb skin to emit signal light, and leading the signal light into the optical bin along the second optical fiber coupling system, the optical fiber bundle and the first optical fiber coupling system in sequence; the optical fiber bundle is connected with the light through hole through the optical fiber coupling system. Transmitting the exciting light provided in the optical bin to the surface of the limb to be measured through the optical fiber transmission structure; and re-couples and re-transmits the signal light returned by the surface into the optical bin. The optical fiber bundle is suitable for different scenes, the length of the optical fiber bundle is changed to meet the requirement that the optical bin and the limb to be measured are located at different spatial positions, and the signal collecting device is integrated through the optical bin and is convenient to use.
Compared with the prior art, the invention has the main beneficial effects that:
1. according to the signal collecting device for the subcutaneous biomarker, the spatial light modulator is combined with the wavefront analyzer to optimize the wavefront of the exciting light entering the skin, so that accurate convergence of a specific subcutaneous position is realized, the excitation efficiency is improved, and the signal collecting efficiency in optical detection is improved; the optimal subcutaneous wavefront can be obtained by the control unit through a convolutional neural network algorithm, and the spatial light modulator is controlled by the control unit so as to obtain the optimal excitation light wavefront, so that the optical detection efficiency is improved, and the reliability and the accuracy of the optical detection are greatly improved. The signal collection system has corresponding advantages due to the integration of the signal collection device, is suitable for specific application scenes, is convenient to use, has high structural integration degree, is convenient to produce, and is beneficial to application and popularization of noninvasive detection in family scenes. The two signal collecting systems are integrated with the signal collecting device of the subcutaneous biomarker, so that the signal collecting system is suitable for the application requirements of specific scenes, and is good in portability, simple in structure and convenient to use.
2. The signal collection method provided by the invention has corresponding advantages due to the adoption of the signal collection device, can intelligently control the spatial light modulator through deep learning, applies an artificial intelligence technology to the field of optical detection, and is extremely beneficial to further popularization and application of a noninvasive optical detection technology.
Drawings
Fig. 1 is a schematic diagram of a signal excitation optical path and a related structure according to a first embodiment of the present invention.
Fig. 2 (a) is a schematic diagram of a signal collection device according to a second embodiment of the present invention.
Fig. 2 (b) is a schematic view of a focusing module according to a second embodiment of the present invention.
Fig. 3 is a schematic diagram of a signal collection method according to a second embodiment of the invention.
Fig. 4 is a schematic diagram of a signal collection system according to a third embodiment of the present invention.
Fig. 5 is a schematic diagram of a signal collection system according to a fourth embodiment of the present invention.
Fig. 6 is a schematic diagram illustrating the rotation of an optical chamber according to a fourth embodiment of the present invention.
Fig. 7 is a schematic diagram of a signal collection system and a related structure in a fifth embodiment of the invention.
Detailed Description
The technical solutions in the specific embodiments of the present invention will be clearly and completely described below, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments taken in conjunction with the accompanying drawings. In the figures, parts of the same structure or function are denoted by the same reference numerals, and not all parts shown are denoted by the associated reference numerals in all figures for reasons of clarity of presentation.
Example one
The signal collecting device of the subcutaneous biomarker is integrated through an optical bin I-1, and the optical bin I-1 is provided with a light-transmitting window. The signal collecting device comprises a signal excitation light path and a signal collecting light path; as shown in fig. 1, an excitation light source 1, a wavefront control module and a focusing module 3 are arranged along a signal excitation light path, wherein the excitation light source 1 is used for emitting excitation light, and the excitation light is reflected or refracted by a subcutaneous biomarker and then emits signal light; the signal collection light path is provided with a detection module for collecting the signal light for subsequent analysis; the signal receiving surface of the detection module and the focus of the focusing module are on a pair of optical conjugate surfaces. The wavefront control module comprises a wavefront analyzer 21, a control unit 22 and a spatial light modulator 23 which are sequentially connected in a communication manner; excitation light of the excitation light source 1 enters the spatial light modulator 23 after being collimated, and then emergent light enters the focusing module 3 after being modulated, and is focused under the skin 4 through the focusing module 3, and the embodiment takes the position needing focusing as the blood vessel 40 as an example for explanation. The initial wavefront of the excitation light is illustrated as 1w in fig. 1. The control unit 22 includes a processor, and the processor of this embodiment learns the feedback received from the wavefront analyzer 21 based on a neural network convolution algorithm, calculates an optimized wavefront, and controls the emergent wavefront of the spatial light modulator 23 accordingly. In this embodiment, the excitation light source 1 is a semiconductor laser with a wavelength of 830nm, and the excitation light is collimated by the collimating optical fiber 101 and the optical fiber coupler 102 and then enters the spatial light modulator 23. The numerical aperture of the fiber coupler 102 is 0.22. The focusing module 3 includes a focusing lens, and in some practical scenarios, the focusing optical fiber may also be used to implement optical path connection with the wavefront control module through the optical fiber coupler, which is not limited. In this embodiment, in addition to the excitation light source 1 and the control unit 22, other components of the signal excitation optical path are integrated within the optical chamber I-1.
Example two
The main difference between the second embodiment of the present invention and the first embodiment of the present invention is that, as shown in fig. 2 (a), the wavefront control module further includes a first beam splitting unit 24; the first beam splitting unit 24 is arranged between the spatial light modulator 23 and the optical path of the focusing module 3, and splits the emergent light of the spatial light modulator 23 to enter the wavefront analyzer 21 and the focusing module 3 respectively; the wavefront analyzer 21 compares the received wavefront information of photons inside the skin 4 with the current wavefront information 23w of the emergent light, and feeds back the result to the control unit 22. The arrangement of the first beam splitting unit 24 enables the outgoing beam modulated by the spatial light modulator 23 to be received by the wavefront analyzer, which is more beneficial for the control unit 22 to continuously realize the iterative optimization of the wavefront according to the acquired feedback. The focused wavefront through the skin 4 is schematically shown at 4w in fig. 2 (a).
In this embodiment, the first beam splitting unit 24 uses a common dichroic-free beam splitter, and the ratio of the transmitted power to the reflected power is preferably 90:10. in some embodiments, a half-mirror, a laser beam splitter, a beam splitter prism, or a thin film beam splitter is used, but not limited thereto, and a beam splitting structure that splits a beam without changing a wavefront may be used. The first beam splitting unit splits emergent light of the spatial light modulator into two beams with an included angle of 90 degrees. In this embodiment, the beam splitter forms an angle of 45 ° with the outgoing light beam modulated by the spatial light modulator 23.
In this embodiment, the detection module includes a detector 5 and a collection optical fiber bundle 51, and a condenser 52 and a second beam splitting unit 53 are disposed along the signal collection optical path L2; the second beam splitting unit 53 has optical dichroism, and is disposed in the signal excitation optical path L1 between the first beam splitting unit 24 and the focusing module 3 for transmitting the excitation light and reflecting the generated signal light, with the reflection angle being 45 ° in this embodiment. The condenser 52 and the focusing module 3 form a conjugate optical device, and collects the incident end face of the fiber bundle 51, i.e. the receiving face of the detection module. The second dichroic beam splitting unit is adopted to realize that the signal excitation light path and the signal collection light path are partially overlapped, and the second beam splitting unit is a dichroic mirror in the embodiment. Wherein, the detector 5 is arranged outside the optical bin I-1 and is connected with the signal collecting light path L2 in the optical bin I-1 through a collecting optical fiber bundle 51.
In this embodiment, as shown in fig. 2 (b), the focusing module 3 includes a focusing lens group with adjustable focal length formed by 2 focusing lenses 30, and more focusing lenses 30 may be provided according to the actual application scenario, without limitation. The focusing lens 30 is arranged in a light shield 31, and the light shield 31 is provided with an aperture stop along the light path direction, and the size of the aperture stop is matched with the numerical aperture of the focusing lens group. The focal length range of the focusing module 3 is 5mm-900mm. Preferably, in the present embodiment, the focal length of the focusing module 3 is 300mm. The excitation light source 1 adopts a semiconductor laser with the wavelength of 785nm, and the excitation light source can be selected according to the requirements of practical application scenes.
In this embodiment, as shown in fig. 3, the signal collection method includes: s1, implanting a biocompatible and degradable fluorescence inducer below skin; in this embodiment, some detectable microspheres or particles are temporarily implanted under the skin as fluorescence inducers, the microspheres or particles are biocompatible, biodegradable and capable of emitting fluorescence, and the implantation position is preferably the dermis layer and is about 200-300 μm subcutaneous. S2, irradiating the fluorescence inducer by exciting light, detecting fluorescence and scattered light by a wavefront analyzer, and analyzing wavefront information of photons in the skin; feeding back wavefront information to the control unit; s3, the control unit controls the spatial light modulator to remodulate the wavefront of the exciting light; step S2 and step S3 are carried out in an iterative mode; s4, focusing the excitation light subjected to wavefront optimization to the position under the skin through the focusing module to excite the excitation light to generate signal light; and S5, the detection module collects the signal light through the signal collection light path to perform subsequent signal analysis.
In the step S2, the method further includes detecting current wavefront information of emergent light of the spatial light modulator by a wavefront analyzer, comparing the current wavefront information with wavefront information of photons inside the skin in real time, and feeding back a comparison result to the control unit. Before the step S3, the control unit performs deep learning on the feedback information of the wavefront analyzer, trains a self-adaptive optimal algorithm, and performs iterative calculation to obtain an optimal wavefront. In the embodiment, according to the intensity of the characteristic signal of the intravascular or subcutaneous characteristic molecule, an artificial intelligence technology is used for deep learning, a self-adaptive optimal algorithm is trained, and the parameters of the spatial light modulator are intelligently adjusted to obtain the optimal subcutaneous wavefront.
EXAMPLE III
The signal collecting system in the embodiment is used for non-invasively detecting the biomarkers in the blood of the nail bed under the nail, and comprises an optical chamber I-1 and an optical window I-2 arranged on the optical chamber I-1, and is shown in figure 4. The optical bin I-1 is used for integrating the signal collecting device, providing exciting light and collecting returned signal light, projecting the exciting light to the nail bed to be detected through the optical window I-2, and collecting the returned signal light.
In this embodiment, the optical window I-2 is a circular sheet-like structure. The thickness of the optical window I-2 is 1mm, and the diameter of the optical window is 5mm. In other embodiments, the optical window I-2 can also be configured as an oval, square, rectangle, or the like. The material of the optical window I-2 is transparent resin, and the selected material has high transmittance and can allow excitation light with the wavelength of 785nm or 830nm to transmit. During detection, the fingernail of the finger to be detected is placed under the optical window I-2, the excitation light provided by the optical bin I-1 is projected to the nail bed to be detected through the optical window I-2, the biomarker in the blood of the nail bed is detected, and the returned signal light is collected, so that the information of the biomarker in the blood of the nail bed is obtained.
Example four
The present embodiment integrates the signal collecting device of any one of the first to third embodiments, and provides a signal collecting system for non-invasively detecting biomarkers in blood of a nail bed, referring to fig. 5, comprising an optical chamber i-1 and a support member i-5, wherein the optical chamber i-1 is movably connected with the support member i-5, in particular, connected through a rotating member; a finger or toe end placement chamber I-4 is formed between the optical chamber I-1 and the support member I-5 to accommodate a finger or toe. The optical chamber I-1 is used for integrating the parts of the optical signal collecting device except the excitation light source, the control unit and the detector in the first embodiment to the third embodiment of the invention, when in use, the optical chamber I-1 is externally connected with the excitation light source, the control unit and the detector to provide excitation light, and the optical chamber I-1 is used for collecting signal light reflected or refracted by skin; an optical window I-2 is further arranged on the optical bin I-1, and the optical window I-2 is arranged on one surface, facing the support piece I-5, of the optical bin I-1. In this embodiment, the optical window I-2 is in a square sheet structure, but not limited to a square sheet structure, and the side length of the optical window I-2 is 10mm, and the thickness is 1mm; the material of the optical window I-2 is fused silica glass, and the selected material has high transmittance and can allow excitation light with the wavelength of 785nm or 830nm to transmit. The excitation light provided by the optical bin I-1 is projected to a nail bed to be detected through the optical window I-2, the biological marker in the blood of the nail bed is detected, and the returned signal light is collected, so that the information of the biological marker in the blood of the nail bed is obtained.
Referring to fig. 6, the optical chamber I-1 is connected with the supporting member I-5 through a rotating member I-3, the rotating member I-3 is a hinge, the optical chamber I-1 can rotate counterclockwise through the hinge, the counterclockwise rotation angle of the optical chamber I-1 is preferably 90 degrees, the light transmission condition of the optical window I-2 can be conveniently checked, and the optical window I-2 can be conveniently replaced when damaged.
A finger or toe end placing bin I-4 is formed between the optical bin I-1 and the supporting piece I-5, the finger or toe end placing bin I-4 corresponds to the optical window I-2 to accommodate a finger or toe, and the finger or toe end placing bin I-4 is used for placing a finger to be detected; the support piece I-5 is used for supporting the finger to be detected. When a finger to be detected is placed in the finger or toe end placing bin I-4, the fingernail of the finger to be detected is placed right below the optical window I-2. The rubber ring I-6 is arranged at the entrance of the finger or toe end placing bin I-4, and the rubber ring I-6 can be detached and replaced and is used for fixing the finger to be detected and preventing detection errors caused by accidental sliding of the finger to be detected. The rubber ring I-6 can be made into different sizes so as to be suitable for fingers to be detected with different thicknesses. In this embodiment, the diameter of the rubber ring I-6 is preferably 15mm.
When the biomarkers in the nail bed blood of the finger need to be detected, the finger to be detected is placed in the finger or toe end placing bin I-4, the nail of the finger to be detected is correspondingly placed under the optical window I-2, the excitation light provided by the optical bin I-1 is projected to the nail bed to be detected through the optical window I-2, the biomarkers in the nail bed blood are detected, and the returned signal light is collected, so that the information of the biomarkers in the nail bed blood is obtained.
Preferably, the optical chamber i-1 is used for integrating any one of the signal collecting devices according to the first to third embodiments of the present invention, and includes the excitation light source, the control unit, and the controller.
EXAMPLE five
The present embodiment integrates any one of the signal collection devices of the first to third embodiments, and provides a signal collection system for detecting biomarker information under limb skin. Referring to fig. 7, the signal collection system comprises an optical bin i-1, an optical fiber transmission structure and a binding band ii-5, wherein the optical fiber transmission structure is used for optically connecting the optical bin i-1 and the binding band ii-5, and the binding band ii-5 is used for surrounding and accommodating a limb ii-7. The optical bin I-1 is used for integrating the parts of any signal collecting device except the excitation light source, the control unit and the controller in the first embodiment to the third embodiment of the invention; when the device is used, the optical bin is externally connected with the excitation light source and the control unit and is used for providing excitation light to be transmitted to the skin through the optical bin, and the optical bin is used for collecting signal light reflected or refracted by the skin and analyzing the signal light. And a signal collecting window II-4 is arranged on the binding band. The optical fiber transmission structure comprises a first optical fiber coupling system II-2, a second optical fiber coupling system II-3 and an optical fiber bundle II-6, wherein the first optical fiber coupling system II-2 and the second optical fiber coupling system II-3 are connected with the light through hole. The optical fiber transmission structure transmits the exciting light provided in the optical bin I-1 to the skin surface of the limb to be detected; and the signal light returned from the surface of the skin is transmitted to the optical bin I-1 again for analysis. The optical fiber transmission structure connects the optical bin I-1 with the signal collection window II-4. The signal collecting windows II-4 are arranged on the outer side of the binding band II-5, the number of the signal collecting windows II-4 is 4 to 15, and the signal collecting windows II-4 are uniformly distributed on the binding band II-5; preferably, the number of collection windows II-4 is 12. Each signal collection window II-4 can be correspondingly connected with an optical bin I-1, when the biological markers in tissue fluid or blood below the skin of the limb are detected, the limb II-7 is placed on the inner side of the binding band II-5, in the embodiment, the binding band II-5 is made of nylon materials and can be directly attached to the limb, the excitation light in the optical bin I-1 is transmitted to the surface of the skin of the limb to be detected through the optical fiber transmission structure, and then the signals returned by the detected skin are transmitted to the optical bin I-1 through the optical fiber transmission structure and are analyzed.
Preferably, the optical chamber i-1 is used for integrating any one of the optical signal collecting devices in the first to third embodiments of the present invention, and includes the excitation light source, the control unit, and the controller.
For clarity of description, the use of certain conventional and specific terms and phrases is intended to be illustrative and not restrictive, but rather to limit the scope of the invention to the particular letter and translation thereof. It is further noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation 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 may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
The present invention has been described in detail, and the structure and operation principle of the present invention are explained by applying specific embodiments, and the above description of the embodiments is only used to help understanding the method and core idea of the present invention. It will be apparent to those skilled in the art that various changes and modifications can be made without departing from the principles of the invention, and it is intended to cover such changes and modifications as fall within the scope of the appended claims.
Claims (10)
1. A signal collection device for subcutaneous biomarkers, comprising: the device comprises a signal excitation light path and a signal collection light path; an excitation light source, a wavefront control module and a focusing module are arranged along a signal excitation light path, the excitation light source is used for emitting excitation light, and the excitation light emits signal light after being emitted or refracted by a subcutaneous biomarker; the signal collection light path is provided with a detection module for collecting the signal light for subsequent analysis; the signal receiving surface of the detection module and the focus of the focusing module are on a pair of conjugate surfaces;
the wavefront control module comprises a wavefront analyzer, a control unit and a spatial light modulator which are sequentially in communication connection; the excitation light enters the spatial light modulator after being collimated, and emergent light enters the focusing module after being modulated and is focused subcutaneously by the focusing module;
the control unit comprises a processor, and the processor learns the feedback received from the wavefront analyzer based on a neural network convolution algorithm, calculates the optimized wavefront, and controls the emergent wavefront of the spatial light modulator.
2. The subcutaneous biomarker signal collection device according to claim 1, wherein: the wavefront control module further comprises a first beam splitting unit;
the first beam splitting unit is arranged between the spatial light modulator and the focusing module, and splits emergent light of the spatial light modulator to respectively enter the wavefront analyzer and the focusing module;
the wavefront analyzer compares the received wavefront information of photons inside the skin with the current wavefront information of the emergent light and feeds back the wavefront information to the control unit.
3. The subcutaneous biomarker signal collection device according to claim 2, wherein: the detection module comprises a detector and a collection optical fiber bundle, and a condenser and a second beam splitting unit are arranged along a signal collection light path;
the second beam splitting unit has dichroism, is arranged in a signal excitation light path between the first beam splitting unit and the focusing module, and is used for transmitting the excitation light and reflecting the signal light;
the condenser lens and the focusing module form a conjugate optical device, and the incident end surface of the collection optical fiber bundle is the receiving surface of the detection module.
4. A signal collecting device for subcutaneous biomarkers according to any one of claims 1-3, wherein: the focusing module comprises a focusing lens; the number of the focusing lenses is at least 2, and a focusing lens group is formed; the focal length of the focusing lens group is adjustable.
5. A subcutaneous biomarker signal collection device according to claim 4, wherein: the focusing module further comprises a light shield, the focusing lens group is arranged in the light shield, an aperture diaphragm is arranged on the light shield along the light path direction, and the size of the aperture diaphragm is matched with the numerical aperture of the focusing lens group.
6. A signal collection system for non-invasively detecting blood biomarker information for a nail bed, comprising: comprises an optical chamber and a support member, the optical chamber and the support member forming a finger or toe end placement chamber for receiving a finger or toe; the optical chamber is used for integrating the parts of the signal collecting device except the excitation light source, the control unit and the detector in any one of claims 1-5; one surface of the optical bin, which faces the supporting piece, is provided with an optical window, and the placing bin corresponds to the optical window; the excitation light provided by the optical bin is projected to the nail bed of the finger or toe to be detected through the optical window, the biological marker in the blood of the nail bed is detected, and the reflected or refracted signal light is collected, so that the information of the biological marker in the blood of the nail bed is obtained.
7. A signal collection system for detecting biomarker information under the skin of a limb, characterized by: comprising an optical cartridge, an optical fiber transmission structure for optically connecting the optical cartridge and the strap, and a strap for encircling a receiving limb; the optical chamber is used for integrating the parts of the signal collecting device of any one of claims 1-5 except the excitation light source, the control unit and the detector; the optical fiber transmission structure comprises an optical fiber bundle, a first optical fiber coupling system and a second optical fiber coupling system, wherein the first optical fiber coupling system and the second optical fiber coupling system are connected with two ends of the optical fiber bundle, the first optical fiber coupling system is used for leading exciting light out of the optical bin, the exciting light is led into the binding band along the optical fiber bundle and the second optical fiber coupling system in sequence, signal light is emitted after being reflected or refracted by biological markers under limb skin, and the signal light is led into the optical bin along the second optical fiber coupling system, the optical fiber bundle and the first optical fiber coupling system in sequence.
8. A signal collection method, characterized by: a signal collection device employing the subcutaneous biomarkers of any of claims 1-5 comprising:
s1, implanting a biocompatible and degradable fluorescence inducer below skin;
s2, irradiating the fluorescence inducer by exciting light, detecting fluorescence by a wavefront analyzer, and analyzing wavefront information of photons in the skin; feeding wavefront information back to the control unit;
s3, the control unit controls the spatial light modulator to remodulate the wavefront of the exciting light;
step S2 and step S3 are carried out in an iterative manner;
s4, focusing the excitation light subjected to wavefront optimization to a specific position under the skin through the focusing module to generate signal light;
and S5, the detection module collects the signal light through the signal collection light path to perform subsequent signal analysis.
9. A signal collection method according to claim 8, wherein: in the step S2, the method further includes detecting current wavefront information of light emitted by the spatial modulator by a wavefront analyzer, comparing the current wavefront information with wavefront information of photons inside the skin, and feeding back a comparison result to the control unit.
10. A signal collection method according to claim 8 or 9, wherein: before the step S3, the control unit performs deep learning on the feedback information of the wavefront analyzer, trains a self-adaptive optimal algorithm, and performs iterative computation to obtain an optimal wavefront.
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