CN115137298B - Signal collection device, system and method for subcutaneous biomarker - Google Patents
Signal collection device, system and method for subcutaneous biomarker Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
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Abstract
The invention provides a signal collecting device of a subcutaneous biomarker, which comprises an excitation light source, a wave front control module and a focusing module, wherein the excitation light source is arranged along a light path and 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 by the wavefront analyzer based on a neural network convolution algorithm, calculates an optimized wavefront and controls the emergent light wavefront of the spatial light modulator. Simple structure, low cost, improved wave front distortion condition, high-efficiency excitation of subcutaneous specific position and high collection efficiency. The signal collecting system and the signal collecting method have corresponding advantages due to the adoption of the signal collecting device, and are favorable for further popularization and application of the noninvasive optical detection technology.
Description
Technical Field
The invention belongs to the technical field of optical detection, and particularly relates to a signal collection device, a signal collection system and a signal collection 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 to be taken as an admission of prior art as including in this section.
The application of optical detection technology has been promoted to various fields in life, and has been widely used in medical examination related to human health, and there is a further in-depth and popular demand. Biological characteristics can be reflected through the characteristics of the optical information, and the analysis can be carried out to strongly support treatment and daily health monitoring.
For example, the measurement method based on near infrared spectrum analysis has the characteristics of painless, noninvasive, simple, quick and the like, can improve the problems of the conventional inspection method, and is one of potential methods for obtaining application of blood noninvasive biochemical analysis. 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 biomedical field, and is a novel technology for early 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 theoretical basis for clinical diagnosis. The prediction can be used for judging whether the disease is caused or not according to the characteristic peak intensity of the blood sample in the Raman spectrum.
Taking a Raman detection device as an example, the Raman signal light is collected and transmitted to a detection module, and the Raman signal intensities at different wavelengths are detected. Thus how to collect signals efficiently and sufficiently in optical detection is a prominent problem of the design of the optical path in optical detection devices is also one of the key designs in the current art that need to be optimized. On the other hand, the problem before collection is how accurately the excitation light is focused to the location to be detected, which is related to the ease of sample preparation and whether it can be generalized outside the laboratory. If the excitation light is accurately focused on a specific position on the sample, a sample holder or a sample table is obviously required to be reasonably designed under the condition that the design of an optical path is unchanged, and possible pretreatment is performed on the surface of the sample, so that the test efficiency is affected, the sample is regulated each time, the efficiency is low, and the cost is possibly increased. While the testing conditions are limited for applications outside the laboratory, the medium between the sample to be tested and the light source is an unavoidable problem affecting the concentration of excitation light to a specific location and subsequent signal collection.
Particularly in subcutaneous biomarker detection applications. Skin is the largest and most useful organ of the human body surface area, the total weight is approximately eight percent of the human body weight, it contains 25% -30% of water of the whole circulating blood of the human body, and skin tissue is basically composed of epidermis, dermis, subcutaneous fat. The interstitial fluid or blood under the skin contains many biospecific markers which are closely related to the health condition and disease level of the human body. However, many current medical techniques have difficulty in noninvasive detection of biomarkers through the skin, such as blood glucose detection requiring blood sampling assays, or finger prick blood sampling. 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 individuals in places other than the medical laboratory. Skin is a turbid scattering medium that scatters incident light, resulting in a large deviation in the wavefront of photons entering the skin, and focusing to a specific subcutaneous location is greatly compromised, resulting in a need for improved collection efficiency. Therefore, it is necessary to develop a signal collecting device, a system and a method thereof, which can accurately focus on a specific detection position, is beneficial to improving the collection efficiency and has reliable detection results.
The above information disclosed in the background section is only for enhancement of understanding of the background of the disclosure and therefore it may include information that does not form the prior art that is already known to a person of ordinary skill in the art. The matters in the background section are only those known to the public and do not, of course, represent prior art in the field.
Disclosure of Invention
The invention aims to solve all or part of the problems in the prior art, and provides a signal collecting device of subcutaneous biomarkers, a corresponding system and a corresponding method, so that the wave front of excitation light is matched with the wave front in skin, and tissue fluid or blood below the skin can be efficiently detected, so that information of some biomarkers can be obtained, and diseases or health conditions can be accurately and efficiently reflected.
The following description of some of the principles and concepts that may be pursued are provided for purposes of illustrating the invention and are not to be construed as limiting the scope of the invention.
The curved surface of an equiphase plane where a wave propagates to a certain position is called a wavefront. The wavefront is a wave front, or wavefront. The invention uses the spatial light modulator to regulate and control the wave front phase of the incident light of the random medium, so that the light beam transmitted through the random medium is coherently enhanced at the target point, and wave front modulation focusing is realized. The signal collection device of the invention adjusts and controls the wave front signal fed back based on the wave front adjustment focusing design, thereby realizing higher quality, faster speed and more accurate focusing of the specific position of light passing through the random medium. The basic principle of the signal collection device of the invention is to optimize the incident wavefront, and at a specific position behind the scattering medium, the optical phases of the wavelets (which are initially randomly distributed) become matched, so that constructive interference is formed by the linear relationship between the two, i.e. 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.
Wavefront analyzers are mainly used to measure optical aberrations at pupil plane positions.
A spatial light Modulator (SLM, spatial Light) has a Digital Micromirror Device (DMD) therein, comprising an array of individually addressable and controllable elements, each of which is independently controllable by an optical or electrical signal to deflect and change its optical properties in response to a control signal to modulate certain characteristics of an incoming light wave in accordance with the form of an electric field of the controlled voltage. Under active control, the purpose of light wave modulation is achieved by modulating the phase through the refractive index.
The artificial neural network algorithm simulates a biological neural network and is a pattern matching algorithm. Typically to solve classification and regression problems. Artificial neural networks are a vast branch of machine learning, where deep learning is one type of algorithm.
The invention provides a signal collection device of a subcutaneous biomarker, which comprises a signal excitation light path and a signal collection light path; an excitation light source, a wave front control module and a focusing module are arranged along a signal excitation light path, wherein 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 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 wavefront control module comprises a wavefront analyzer, a control unit and a spatial light modulator which are sequentially in communication connection; the excitation light of the excitation light source enters the spatial light modulator after being collimated, and the modulated emergent light enters the focusing module and is focused subcutaneously through the focusing module; the control unit comprises a processor, and the processor learns the feedback received by the wavefront analyzer based on a neural network convolution algorithm, calculates an optimized wavefront and controls the emergent light wavefront of the spatial light modulator.
In a specific case, the 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 fiber coupler to which the excitation light source is connected 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 is used for splitting the emergent light of the spatial light modulator into beams which respectively enter the wavefront analyzer and the focusing module; the wavefront analyzer compares the received wavefront information of photons in the skin with the current wavefront information of the emergent light, and then feeds back the result to the control unit. The emergent light beam modulated by the spatial light modulator can be received by the wavefront analyzer through the arrangement of the first beam splitting unit, so that the control unit can continuously realize iterative optimization of the wavefront according to acquired feedback.
The first beam splitting unit includes, but is not limited to, a half mirror, a laser beam splitter, a beam splitting prism, or a thin film beam splitter.
The first beam splitting unit divides the 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, at least 2 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 direction of the light path, and the size of the aperture diaphragm is matched with the numerical aperture of the focusing lens group. The wavefront signal at and near the center excitation point is shielded by the light shield, which is beneficial to subsequent signal light collection and reduction of fluorescence interference.
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 adoption of the focusing optical fiber matched with the optical fiber coupler for realizing the optical path connection is beneficial to the more flexible optical path design of the signal collecting device, the optical path turning can be realized according to the actual structural design requirement, and the miniaturization requirement of the device design is met.
The detection module comprises a detector and a collection optical fiber bundle, and a condensing lens 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 condensing lens and the focusing module form a conjugate optical device, and the incident end face of the collecting optical fiber bundle is the receiving face of the detecting module. The dichroic second beam splitting unit is adopted, so that partial coincidence of the signal excitation light path and the signal collection light path is realized, and 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, a 785nm semiconductor laser, 830nm semiconductor laser.
In another aspect, the present invention also provides a signal collection method, and a signal collection device using the subcutaneous biomarker of the present invention, including: s1, implanting a biocompatible and degradable fluorescence inducer under the skin; s2, irradiating the fluorescence inducer by excitation light, detecting fluorescence by a wavefront analyzer, scattering light, and analyzing the 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 excitation light; iteratively performing step S2 and step S3; s4, focusing the excitation light subjected to wavefront optimization to excitation signal light under the skin through the focusing module; and S5, collecting the signal light by the detection module through the signal collection light path for subsequent signal analysis.
In step S2, the method further includes that the wavefront analyzer detects current wavefront information of the light emitted by the spatial light modulator, compares the current wavefront information with the wavefront information of photons inside the skin in real time, and feeds back a comparison result to the control unit.
Before the step S3, the control unit performs deep learning on feedback information of the wavefront analyzer, trains a self-adaptive optimal algorithm, and performs iterative computation to obtain an optimal wavefront. In a specific embodiment, according to the intensity of characteristic signals of intravascular or subcutaneous characteristic molecules, artificial intelligence technology is used for deep learning, a self-adaptive optimal algorithm is trained, and parameters of a spatial light modulator are intelligently adjusted to obtain optimal subcutaneous wave fronts.
The invention also provides a signal collection system for noninvasively detecting nail bed blood biomarker information, comprising an optical bin and a support, wherein the optical bin and the support form a finger or toe end placement bin for accommodating fingers or toes; the support piece is movably connected with the optical bin; the optical bin is used for integrating the parts of the signal collecting device except the excitation light source, the control unit and the detector; an optical window is formed in one surface of the optical bin, facing the supporting piece, 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 nail bed blood is detected, and the reflected or refracted signal light is collected, so that the information of the biological marker in the nail bed blood is obtained.
The optical bin provides excitation light and collects returned signal light, the excitation light is emitted through the optical window, and the returned signal light is collected. The support piece is used for supporting the finger or toe end of the organism to be detected. The signal collection system is used for collecting the characteristic signals of the nail bed of the biological finger or toe end in a noninvasive manner. 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 obtained through detection, and the disease or health condition of the nail bed is accurately reflected.
The optical bin is connected with the support piece through a rotating piece, and a biological finger or toe end placing bin is formed between the optical bin and the support 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 is rotatable counterclockwise by the hinge or bearing, preferably by 90 ° counterclockwise, to facilitate inspection of the optical window for light transmission, and to facilitate replacement when the optical window is damaged.
The detachable rubber ring is arranged at the inlet of the biological finger or toe end placing bin. The rubber ring is used for fixing the biological finger or toe end to be detected and can be replaced according to the size of the biological finger or toe end to be detected. The diameter of the rubber ring is preferably 10mm to 20mm.
The optical bin and the support member can be connected in a sliding manner. The optical bin is provided with a sliding groove, and the support piece is provided with a sliding rail; the support piece is fixed, the optical bin slides towards the direction away from the support piece, and a biological finger or toe end placing bin is formed between the optical bin and the support piece according to the size of the biological finger or toe end to be detected.
Or the optical bin is provided with a sliding 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 bin and the support member can slide simultaneously, and the biological finger or toe end placing bin is formed between the optical bin and the support member.
The optical window is of a sheet-like structure. The thickness of the optical window is in the range of 0.5mm-10mm, preferably 1mm; when the optical window is of a circular sheet structure, the diameter of the optical window is in the range of 0.5mm to 25mm, preferably 5mm.
The optical window is made of transparent resin or quartz glass. The optical window should be selected to have a high transmittance and to allow transmission of excitation light having a wavelength of preferably 785nm or 830 nm.
The invention also provides another signal collection system for detecting biomarker information under limb skin, comprising an optical bin, an optical fiber transmission structure and a binding band, wherein the optical fiber transmission structure is used for optically connecting the optical bin and the binding band, and the binding band is used for circumferentially accommodating limbs; the surface of the optical bin is provided with a light passing hole, and the optical bin is used for collecting 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 and an optical fiber coupling system, wherein the optical fiber coupling system is connected with a first optical fiber coupling system and a second optical fiber coupling system at two ends of the optical fiber bundle, the first optical fiber coupling system is used for guiding the excitation light out of the optical bin, the excitation light is sequentially guided into the binding band along the optical fiber bundle and the second optical fiber coupling system, the signal light is emitted after being reflected or refracted by a biomarker under limb skin, and the signal light is sequentially guided into the optical bin along the second optical fiber coupling system, the optical fiber bundle and the first optical fiber coupling system; the optical fiber bundle is connected with the light through hole through the optical fiber coupling system. Transmitting the excitation light provided in the optical bin to the surface of the limb to be measured through the optical fiber transmission structure; and re-couples the signal light returned from the surface back into the optical bin. The optical fiber bundle is beneficial to being suitable for different scenes, the length of the optical fiber bundle is changed to meet different spatial positions of the optical bin and the limb to be tested, 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 collection device of the subcutaneous biomarker, provided by the invention, the spatial light modulator is combined with the wavefront analyzer, so that the excitation light wave front entering the skin can be optimized, the accurate convergence of a subcutaneous specific position is realized, the excitation efficiency is improved, and the signal collection efficiency in optical detection is also improved; the control unit can obtain the optimal subcutaneous wave front by adopting a convolutional neural network algorithm, and the spatial light modulator is controlled by the optimal subcutaneous wave front, so that the optimal excitation light wave front is obtained, the optical detection efficiency is improved, and the reliability and the accuracy of the optical detection are greatly improved. The signal collecting system has the corresponding advantages due to the integration of the signal collecting device, is suitable for specific application scenes, is convenient to use, has high structural integration level, is convenient to produce, and is beneficial to application and popularization of noninvasive detection in home scenes. The two signal collecting systems are suitable for application requirements of specific scenes due to the fact that the signal collecting device of the subcutaneous biomarker is integrated, and the signal collecting system is good in portability, simple in structure and convenient to use.
2. The signal collecting method provided by the invention has the corresponding advantages due to the adoption of the signal collecting device, the spatial light modulator can be intelligently controlled through deep learning, and the artificial intelligence technology is applied to the field of optical detection, so that the method is very beneficial to further popularization and application of the noninvasive optical detection technology.
Drawings
Fig. 1 is a schematic diagram of a signal excitation optical path and related structures according to a first embodiment of the present invention.
Fig. 2 (a) is a schematic diagram of a signal collecting device according to a second embodiment of the invention.
Fig. 2 (b) is a schematic diagram of a focusing module according to a second embodiment of the 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 invention.
Fig. 5 is a schematic diagram of a signal collection system according to a fourth embodiment of the invention.
Fig. 6 is a schematic diagram illustrating rotation of an optical pickup in accordance with a fourth embodiment of the present invention.
Fig. 7 is a schematic diagram of a signal collection system and related structures according to a fifth embodiment of the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully, and it is apparent that the embodiments described are only some, but not all, of the embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The foregoing and/or additional aspects and advantages of the present invention will be 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 illustrated parts are denoted by the associated reference numerals throughout the figures, if necessary, for the sake of clarity.
Example 1
The signal collection device of the subcutaneous biomarker is integrated through an optical bin I-1, and the optical bin I-1 is provided with a light transmission 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 emits signal light after being reflected 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 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 in communication connection; the excitation light of the excitation light source 1 enters the spatial light modulator 23 after being collimated, and the modulated outgoing light enters the focusing module 3, and is focused under the skin 4 by the focusing module 3, and in this embodiment, the position to be focused is taken as an example of a blood vessel 40. The initial wavefront of the excitation light is illustrated as 1w in fig. 1. The control unit 22 comprises a processor, which in 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 outgoing light wavefront of the spatial light modulator 23 accordingly. In this embodiment, the excitation light source 1 adopts a semiconductor laser with 830nm wavelength, and the collimation fiber 101 is matched with the fiber coupler 102 to collimate the excitation light and then make the collimated excitation light enter 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 be used to implement optical path connection with the wavefront control module through an 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 light path are integrated in the optical bin I-1.
Example two
The main difference between the second embodiment 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 disposed between the spatial light modulator 23 and the optical path of the focusing module 3, and splits the outgoing light of the spatial light modulator 23 into beams that respectively enter the wavefront analyzer 21 and the focusing module 3; the wavefront analyzer 21 compares the received wavefront information of the photons inside the skin 4 with the current wavefront information 23w of the outgoing 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, so that the control unit 22 is more beneficial to continuously realizing iterative optimization of the wavefront according to the acquired feedback. The wavefront after focusing through the skin 4 is illustrated as 4w in fig. 2 (a).
The first beam splitter 24 in this example employs a common dichroic-free beam splitter, and the ratio of transmitted power to reflected power is preferably 90:10. in some implementations, a half mirror, a laser beam splitter, a beam splitting prism, or a thin film beam splitter is used, but the beam splitting structure may be used without changing the wavefront. The first beam splitting unit divides the 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 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 a signal collection optical path L2; the second beam splitting unit 53 has optical dichroism, and is disposed in the signal excitation light 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, and the reflection angle is 45 ° in this embodiment. The condenser 52 and the focusing module 3 form a conjugate optical device, and the incident end face of the optical fiber bundle 51, i.e. the receiving face of the detection module, is collected. 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 in the embodiment, the second dichroic beam splitting unit is a dichroic mirror. Wherein the detector 5 is outside the optical bin I-1 and is connected with a 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 focus-adjustable focusing lens group formed by 2 focusing lenses 30, and more focusing lenses 30 may be set according to the actual application scene, which is not limited. The focusing lens 30 is disposed in a light shield 31, and the light shield 31 is provided with an aperture stop in the direction of the optical path, the size of which matches the numerical aperture of the focusing lens group. The focal length of the focusing module 3 is in the range of 5mm-900mm. In this embodiment, the focal length of the focusing module 3 is preferably 300mm. The exciting light source 1 adopts a semiconductor laser with 785nm wavelength, and the exciting light source can be selected according to the actual application scene.
In this embodiment, as shown in fig. 3, the signal collection method includes: s1, implanting a biocompatible and degradable fluorescence inducer under the skin; in this embodiment, some detectable microspheres or particles are temporarily implanted under the skin as fluorescence inducers, and the microspheres or particles are biocompatible, biodegradable, and can emit fluorescence, and the implantation position is preferably a dermis layer, and is about 200-300 μm subcutaneous. S2, irradiating the fluorescence inducer by excitation light, detecting fluorescence and scattered light by a wavefront analyzer, and analyzing the 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 excitation light; iteratively performing step S2 and step S3; s4, focusing the wave-front optimized excitation light to the skin through the focusing module to generate signal light; and S5, collecting the signal light by the detection module through the signal collection light path for subsequent signal analysis.
In step S2, the method further includes that the wavefront analyzer detects current wavefront information of the light emitted by the spatial light modulator, compares the current wavefront information with the wavefront information of photons inside the skin in real time, and feeds back a comparison result to the control unit. Before the step S3, the control unit performs deep learning on feedback information of the wavefront analyzer, trains a self-adaptive optimal algorithm, and performs iterative computation to obtain an optimal wavefront. In the embodiment, according to the intensity of the characteristic signal of the intravascular or subcutaneous characteristic molecule, the artificial intelligence technology is used for deep learning, the self-adaptive optimal algorithm is trained, and the parameters of the spatial light modulator are intelligently adjusted to obtain the optimal subcutaneous wave front.
Example III
The signal collection system in this embodiment is used for noninvasively detecting biomarkers in the blood of the nail bed under the nail, and referring to fig. 4, the signal collection system comprises an optical bin I-1 and an optical window I-2 arranged on the optical bin I-1. The optical bin I-1 is used for integrating the signal collecting device, providing excitation light and collecting returned signal light, projecting the excitation 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 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 may be configured as an oval, square, rectangle, etc. The material of the optical window I-2 is transparent resin, and the selected material has high transmittance and can allow the excitation light with the wavelength of 785nm or 830nm to pass through. During detection, the nail of the finger to be detected is arranged under the optical window I-2, excitation light provided by the optical bin I-1 is projected to the nail bed to be detected through the optical window I-2, biological markers in the blood of the nail bed are detected, and returned signal light is collected, so that information of the biological markers in the blood of the nail bed is obtained.
Example IV
The signal collecting device of any one of the integrated embodiment one to the embodiment three provides a signal collecting system for noninvasively detecting biomarkers in nail bed blood, and referring to fig. 5, the signal collecting system comprises an optical bin I-1 and a support piece I-5, wherein the optical bin I-1 is movably connected with the support piece I-5, and particularly is connected with the support piece through a rotating piece; a finger or toe end placement bin I-4 is formed between the optical bin I-1 and the support I-5 to accommodate a finger or toe. The optical bin I-1 is used for integrating the optical signal collecting device in any one of the first to third embodiments except the excitation light source, the control unit and the detector, and is externally connected with the excitation light source, the control unit and the detector when in use, so as to provide excitation light, and the optical bin is used for collecting signal light reflected or refracted by skin; the optical bin I-1 is further provided with an optical window I-2, and the optical window I-2 is arranged on one surface of the optical bin I-1, which faces the supporting piece I-5. In this embodiment, the optical window I-2 has a square sheet structure, but is 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 the transmission of excitation light with the wavelength of 785nm or 830 nm. 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 biological marker in the nail bed blood is detected, and the returned signal light is collected, so that the information of the biological marker in the nail bed blood is obtained.
Referring to fig. 6, the optical bin i-1 is connected with the supporting member i-5 through the rotating member i-3, the rotating member i-3 is a hinge, the optical bin i-1 can rotate counterclockwise through the hinge, and the counterclockwise rotation angle of the optical bin i-1 is preferably 90 °, so that the light transmission condition of the optical window i-2 can be checked conveniently, and secondly, when the optical window i-2 is damaged, the replacement is convenient.
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 so as to accommodate fingers or toes, and the finger or toe end placing bin I-4 is used for placing fingers to be detected; the support piece I-5 is used for supporting the finger to be detected. When 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 placed under the optical window I-2. The entrance of finger or toe end place storehouse I-4 is equipped with rubber ring I-6, rubber ring I-6 can dismantle and change for the fixed finger of waiting to detect prevents to wait to detect the unexpected detection error that slides and bring of finger. 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 biological marker in the nail bed blood of the finger needs to be detected, the finger to be detected is placed in a 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, 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 biological marker in the nail bed blood is detected, and returned signal light is collected, so that the information of the biological marker in the nail bed blood is obtained.
Preferably, the optical bin i-1 is used for integrating the signal collecting device according to any one of the first to third embodiments of the present invention, and comprises the excitation light source, the control unit and the controller.
Example five
The present embodiment integrates the signal collection device of any one of the first to third embodiments, providing a signal collection system for detecting biomarker information under the skin of a limb. Referring to fig. 7, the signal collection system includes an optical compartment i-1, an optical fiber transmission structure for optically connecting the optical compartment i-1 and the strap ii-5, and the strap ii-5 for encircling a receiving limb ii-7. The optical bin I-1 is used for integrating the parts of the signal collecting device except the excitation light source, the control unit and the controller in any one of the first to third embodiments 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. The binding belt is provided with a signal collection window II-4. 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 is connected with the light through hole, and the optical fiber bundle II-6 is connected with the first optical fiber coupling system II-2 and the second optical fiber coupling system II-3. The optical fiber transmission structure transmits the excitation light provided in the optical bin I-1 to the skin surface of the limb to be measured; and the signal light returned from the skin surface is transmitted to the optical bin I-1 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 4-15, 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 collecting window II-4 can be correspondingly connected with an optical bin I-1, when detecting biological markers in tissue fluid or blood below the skin of a limb, 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, excitation light in the optical bin I-1 is transmitted to the skin surface of the limb to be detected through an optical fiber transmission structure, and then signals returned by the detected skin are transmitted to the optical bin I-1 through the optical fiber transmission structure and analyzed.
Preferably, the optical bin i-1 is used for integrating the optical signal collecting device according to any one of the first to third embodiments of the present invention, and includes the excitation light source, the control unit and the controller.
The use of certain conventional english terms or letters for the sake of clarity of description of the invention is intended to be exemplary only and not limiting of the interpretation or particular use, and should not be taken to limit the scope of the invention in terms of its possible chinese translations or specific letters. It is further noted that relational terms such as first and second, and the like are 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. Moreover, 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 foregoing has outlined rather broadly the more detailed description of the invention in order that the detailed description of the structure and operation of the invention may be better understood, and in order that the present invention may be better understood. It will be apparent to those skilled in the art that various modifications and variations can be made without departing from the principles of the invention, and such modifications and variations fall within the scope of the appended claims.
Claims (5)
1. A signal collection device for subcutaneous biomarkers, characterized in that: the device comprises a signal excitation light path and a signal collection light path; an excitation light source, a wave front control module and a focusing module are arranged along a signal excitation light path, wherein 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 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 the modulated emergent light enters the focusing module and is focused subcutaneously through the focusing module;
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 is used for splitting the emergent light of the spatial light modulator into beams which respectively enter the wavefront analyzer and the focusing module; the wavefront analyzer compares the received wavefront information of photons in the skin with the current wavefront information of the emergent light and feeds back the comparison result to the control unit;
The detection module comprises a detector and a collection optical fiber bundle, and a condensing lens 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 condensing lens and the focusing module form a conjugate optical device, and the incident end face of the collecting optical fiber bundle is the receiving face of the detecting module;
The control unit comprises a processor, and the processor learns the feedback received by the wavefront analyzer based on a neural network convolution algorithm, calculates an optimized wavefront and controls the emergent light wavefront of the spatial light modulator.
2. The signal collection device of a subcutaneous biomarker according to any of claim 1, wherein: the focusing module comprises a focusing lens; at least 2 focusing lenses are arranged to form a focusing lens group; the focal length of the focusing lens group is adjustable.
3. The signal collection device of a subcutaneous biomarker according to claim 2, 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 direction of the light path, and the size of the aperture diaphragm is matched with the numerical aperture of the focusing lens group.
4. A signal collection system for noninvasively detecting nail bed blood biomarker information, characterized by: comprising an optical bin and a support, the optical bin and the support forming a finger or toe end placement bin to accommodate a finger or toe; the optical bin is used for integrating the parts of the signal collection device of any one of claims 1-3 except the excitation light source, the control unit and the detector; an optical window is formed in one surface of the optical bin, facing the supporting piece, 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 nail bed blood is detected, and the reflected or refracted signal light is collected, so that the information of the biological marker in the nail bed blood is obtained.
5. A signal collection system for detecting biomarker information under the skin of a limb, characterized by: the device comprises an optical bin, an optical fiber transmission structure and a binding belt, wherein the optical fiber transmission structure is used for optically connecting the optical bin and the binding belt, and the binding belt is used for encircling and accommodating limbs; the optical bin is used for integrating the parts of the signal collection device of any one of claims 1-3 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 guiding the excitation light out of the optical bin, the excitation light is sequentially guided into the binding band along the optical fiber bundle and the second optical fiber coupling system, the signal light is emitted after being reflected or refracted by a biomarker under the skin of a limb, and the signal light is sequentially guided into the optical bin along the second optical fiber coupling system, the optical fiber bundle and the first optical fiber coupling system.
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