Method for detecting concentration of components in tissue fluid and related device

Abstract

The invention discloses a tissue fluid component concentration detection method and a related device, and belongs to the technical field of biomedicine. The method comprises the following steps: irradiating detection light to one side of an object to be detected, collecting a photoacoustic signal generated after the detection light is scattered by tissue fluid in the object to be detected on the other side, and determining the concentration of a target component in the tissue fluid based on the photoacoustic signal without invading a detection object and causing no injury to the detection object. Wherein in order to reduce the forward reflection of the tissue fluid to the detection light, the forward compensation plate is used for performing forward transmission compensation on the detection light, so that most energy of the detection light is used for forward irradiation, the detection efficiency is improved, and meanwhile, the detection accuracy is ensured. In addition, the forward compensation plate performs forward transmission compensation on the detection light in a modulation mode, so that forward transmission compensation on different to-be-detected media can be realized, namely, the device can adapt to any media, the detection cost is reduced, and the detection requirements of various application fields are met.

Description

Technical Field

[0001] The present application relates to the field of biomedical technology, and in particular to a method and device for detecting the concentration of tissue fluid components. Background Art

[0002] At present, people's living standards are constantly improving, and health issues are receiving more and more attention. In medicine, the diagnosis, monitoring and treatment of diseases can be achieved through quantitative or qualitative analysis of biological samples. In addition to using blood as a test substance, modern medical diagnostic methods take into account that tissue fluid is a medium for material exchange between blood and tissue cells. The remaining components of tissue fluid except protein are basically the same as blood. Therefore, tissue fluid can also be used as a test substance, and certain biological indicators can be detected by detecting the concentration of components in tissue fluid. In related technologies, it is usually necessary to extract the tissue fluid of the test object to detect the concentration of tissue fluid components, which inevitably causes certain trauma or discomfort to the test object. How to ensure the accuracy of tissue fluid component concentration detection without invading the body of the test object is a research hotspot in related fields. Summary of the invention

[0003] The present application provides a method and a related device for detecting the concentration of tissue fluid components, which can ensure the accuracy of the detection of the concentration of tissue fluid components without invading the body of the detected object. The technical solution is as follows:

[0004] In a first aspect, a method for detecting the concentration of tissue fluid components is provided, which is applied to a detection device, wherein the detection device includes a host and a photoacoustic probe, wherein the photoacoustic probe includes a forward compensation plate, a focusing lens, and an ultrasonic transducer, and the photoacoustic probe is used to clamp an object to be detected through a fixture, wherein the object to be detected is located between the focusing lens and the ultrasonic transducer; the method includes:

[0005] The host generates detection light and transmits the detection light to the forward compensation plate; the forward compensation plate performs forward transmission compensation on the detection light by modulating the detection light to reduce the forward reflection of the detection light by the tissue fluid in the object to be measured; the focusing lens irradiates the detection light after the forward transmission compensation onto the object to be measured; the ultrasonic transducer collects the photoacoustic signal generated after the detection light is scattered by the tissue fluid, converts the photoacoustic signal into an electrical signal, and transmits it to the host; the host determines the concentration of the target component in the tissue fluid based on the electrical signal.

[0006] That is, the detection device irradiates the detection light to one side of the object to be detected, and collects the photoacoustic signal generated by the tissue fluid in the object to be detected after scattering the detection light on the other side, and determines the concentration of the target component in the tissue fluid based on the photoacoustic signal, without invading the detection object, and will not cause trauma to the detection object. Among them, in order to reduce the forward reflection of the detection light by the tissue fluid in the object to be detected, the forward compensation plate in the detection device is used to perform forward transmission compensation on the detection light before irradiating it to the object to be detected, so that most of the energy of the detection light is used for forward irradiation, which improves the detection efficiency of the incident light (i.e., the detection light) and ensures the accuracy of the detection of the concentration of the tissue fluid component. In addition, because the forward compensation plate performs forward transmission compensation on the detection light by modulation, it can realize forward transmission compensation for different media to be tested, that is, it can adapt to any medium, reduce the cost of detection, and meet the detection needs of various application fields.

[0007] The forward compensation plate performs forward transmission compensation on the detection light by modulating the detection light, including: the forward compensation plate modulates the detection light based on a forward transmission compensation matrix to perform forward transmission compensation on the detection light, and the forward transmission compensation matrix is ​​determined based on the forward reflection light of the detection light by the tissue fluid in the object to be tested when the photoacoustic probe does not include the forward compensation plate. That is, the forward transmission compensation matrix is ​​determined based on the forward reflection light without forward transmission compensation, and then the forward transmission compensation of the detection light is completed based on the forward transmission compensation matrix.

[0008] Optionally, the forward transmission compensation matrix is ​​determined by a machine learning model based on a forward reflection matrix, and the forward reflection matrix represents information of the forward reflected light. That is, the forward transmission compensation matrix is ​​inferred by a machine learning model to improve accuracy.

[0009] Wherein, the forward reflection matrix is ​​determined based on holographic measurement technology.

[0010] Optionally, the forward reflection matrix is ​​a matrix in complex form, and the forward reflection matrix represents amplitude information and phase information of the forward reflected light.

[0011] Optionally, the forward transmission compensation matrix is ​​a matrix in complex form, and the modulation includes phase modulation and intensity modulation.

[0012] Optionally, the forward compensation plate comprises one or more spatial modulators.

[0013] The host includes a first laser, a second laser, a coupler, a phase-locked amplifier, a control module and a data processing module; the host generates a detection light, including: the first laser generates a first laser signal, the second laser generates a second laser signal, and the coupler couples the first laser signal and the second laser signal into the detection light; the host determines the concentration of the target component in the tissue fluid based on the electrical signal, including: the phase-locked amplifier determines the amplitude information of the photoacoustic signal based on the electrical signal to obtain a phase-locked signal; the control module controls the power of the first laser to change within a first power range, and determines the power of the first laser when the energy of the photoacoustic signal is minimized to obtain a first laser power; the data processing module determines the concentration of the target component based on the phase-locked signal and the first laser power. That is, the accuracy of determining the concentration of tissue fluid components based on the photoacoustic signal is improved by scanning the power of the first laser by the control module.

[0014] In a second aspect, a photoacoustic probe is provided, the photoacoustic probe comprising a forward compensation plate, a focusing lens and an ultrasonic transducer, the photoacoustic probe being used to clamp an object to be tested through a fixture to detect the concentration of a target component in the tissue fluid of the object to be tested, the object to be tested being located between the focusing lens and the ultrasonic transducer;

[0015] The forward compensation plate is used to perform forward transmission compensation on the detection light incident on the photoacoustic probe by modulating the detection light, so as to reduce the forward reflection of the detection light by the tissue fluid in the object to be detected;

[0016] The focusing lens is used to irradiate the detection light after the forward transmission compensation onto the object to be measured;

[0017] The ultrasonic transducer is used to collect the photoacoustic signal generated after the detection light is scattered by the tissue fluid, and convert the photoacoustic signal into an electrical signal, and the electrical signal is used to determine the concentration of the target component.

[0018] The photoacoustic probe further includes a collimator, which is used to collimate the detection light and transmit it to the forward compensation plate; and / or the photoacoustic probe further includes an incident optical fiber and a light window, the incident optical fiber is used to transmit the detection light, and the light window is used to transmit the light signal from the focusing lens to the object to be measured.

[0019] In a third aspect, a device for detecting the concentration of tissue fluid components is provided, wherein the device has the function of implementing the method for detecting the concentration of tissue fluid components in the first aspect. The device includes one or more modules, wherein the one or more modules are used to implement the method for detecting the concentration of tissue fluid components provided in the first aspect.

[0020] That is, a device for detecting the concentration of tissue fluid components is provided, the detection device comprising a main unit and a photoacoustic probe, the photoacoustic probe comprising a forward compensation plate, a focusing lens and an ultrasonic transducer, the photoacoustic probe being used to clamp an object to be detected through a fixture, the object to be detected being located between the focusing lens and the ultrasonic transducer;

[0021] The host is used to generate detection light and transmit the detection light to the forward compensation plate;

[0022] The forward compensation plate is used to perform forward transmission compensation on the detection light by modulating the detection light, so as to reduce the forward reflection of the detection light by the tissue fluid in the object to be detected;

[0023] The focusing lens is used to irradiate the detection light after the forward transmission compensation onto the object to be measured;

[0024] The ultrasonic transducer is used to collect the photoacoustic signal generated after the detection light is scattered by the tissue fluid, convert the photoacoustic signal into an electrical signal and transmit it to the host;

[0025] The host is also used to determine the concentration of the target component in the tissue fluid based on the electrical signal.

[0026] Wherein, the host comprises a first laser, a second laser, a coupler, a lock-in amplifier, a control module and a data processing module;

[0027] The first laser is used to generate a first laser signal, the second laser is used to generate a second laser signal, and the coupler is used to couple the first laser signal and the second laser signal into the detection light;

[0028] The control module is used to control the first laser to change its power, and determine the power of the first laser when the energy of the photoacoustic signal is minimum during the power change process to obtain a first laser power;

[0029] The phase-locked amplifier is used to obtain a phase-locked signal after determining the amplitude information of the photoacoustic signal based on the electrical signal;

[0030] The data processing module is used to determine the concentration of the target component based on the phase-locked signal and the first laser power.

[0031] In a fourth aspect, a device for detecting the concentration of tissue fluid components is provided, the device comprising a processor and a memory, the memory being used to store a program for executing the method for detecting the concentration of tissue fluid components provided in the first aspect, and storing data involved in implementing the method for detecting the concentration of tissue fluid components provided in the first aspect. The processor is configured to execute the program stored in the memory. The device may also include a communication bus, which is used to establish a connection between the processor and the memory.

[0032] In a fifth aspect, a computer-readable storage medium is provided, wherein instructions are stored in the computer-readable storage medium, and when the computer-readable storage medium is run on a computer, the computer executes the method for detecting the concentration of tissue fluid components described in the first aspect.

[0033] In a sixth aspect, a computer program product comprising instructions is provided, which, when executed on a computer, enables the computer to execute the method for detecting the concentration of tissue fluid components as described in the first aspect.

[0034] The technical effects obtained by the above-mentioned second, third, fourth, fifth and sixth aspects are similar to the technical effects obtained by the corresponding technical means in the first aspect, and will not be repeated here. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 is a structural schematic diagram of a detection device provided in an embodiment of the present application;

[0036] Figure 2 is a schematic diagram of another detection device provided in an embodiment of the present application;

[0037] Figure 3 is a schematic diagram of the structure of a photoacoustic probe mentioned in an embodiment of the present application;

[0038] Figure 4 is a schematic diagram of another detection device provided in an embodiment of the present application;

[0039] Figure 5 It is a flow chart of a method for detecting the concentration of tissue fluid components provided in an embodiment of the present application;

[0040] Figure 6 is a structural schematic diagram of a holographic measurement system provided in an embodiment of the present application;

[0041] Figure 7 It is a flow chart of a forward transmission compensation method provided in an embodiment of the present application. DETAILED DESCRIPTION

[0042] In order to make the objectives, technical solutions and advantages of the embodiments of the present application clearer, the implementation methods of the present application will be further described in detail below in conjunction with the accompanying drawings.

[0043] First, the relevant background involved in the embodiments of the present application is introduced.

[0044] At present, the living standards of the Chinese people are constantly improving, and health issues are receiving more and more attention. In medicine, diseases can be diagnosed, monitored and treated by quantitative or qualitative analysis of biological samples. Due to the high efficiency and low cost of blood sampling, modern medical diagnostic methods usually use blood as the test substance. Blood sampling is usually invasive, and the testing process is not only painful but also accompanied by the risk of infection.

[0045] Interstitial fluid is the medium for the exchange of substances between blood and tissue cells. Except for proteins, the other components in interstitial fluid are basically the same as those in blood. Therefore, the detection of certain biological indicators can be achieved through the detection of interstitial fluid. The development of advanced interstitial fluid component detection systems can obtain the in vivo levels of multiple biomarkers so that doctors can obtain the patient's disease progression in a timely manner and carry out timely treatment, which is of great significance.

[0046] The existing tissue fluid component detection methods usually require the extraction of tissue fluid from the test object, which will undoubtedly cause irritation to the skin and cause discomfort. Therefore, there is an urgent need for a non-invasive and painless tissue fluid component detection device in the market.

[0047] Currently, photoacoustic technology has been proven to be a potential non-invasive solution for tissue fluid composition detection. Since it collects acoustic signals instead of optical signals, it can effectively avoid interference caused by reflection, refraction, and scattering in tissues, showing great advantages. In today's biomedical field, related technologies of optical detection such as photoacoustic detection have been widely used. For example, photoacoustic technology is used to measure blood sugar and blood pressure through laser.

[0048] However, there is a problem that cannot be ignored in these detection technologies using light. Due to the complex composition and irregular shape of biological tissue, biological tissue is usually regarded as a strong chaotic scatterer in optics. This type of strong scatterer has a strong forward and backward scattering effect on the incident light. In technologies that do not use reflected light to complete detection, the strong backscattering generated by biological tissue often reduces the detection depth of forward scattered light, resulting in a decrease in light detection efficiency. Especially for some technologies that use the absorption of light by biological tissue to complete detection, the backscattered light generated by the medium will significantly reduce the detection efficiency and interfere with the detection results.

[0049] In response to this problem, scientists and technicians have proposed some solutions. The core of these solutions is to reduce the backscattering of light waves in biological tissues by modulating light waves in specific bands. One of the technologies requires measuring the transmission matrix of biological tissues. However, for most non-ex vivo biological tissues, their transmission matrix is ​​usually not available, so this type of technology cannot be widely used for information detection of biological tissues. In addition, there is a technology that places a device called a "guide star" into the biological tissue in advance to complete the detection, but this technology requires invasive detection of biological tissues. There is also a method for designing complementary media, which requires the generation of specific materials to complement the medium to be tested, thereby eliminating the backscattering of light waves (including forward reflection), but not all media can find actual complementary materials, and this method is too expensive and not easy to popularize.

[0050] This application proposes an adaptive wavefront shaping system for biological tissues. The system uses a forward compensation plate to complete the generation of a virtual complementary medium. The system will not cause physical and chemical damage to the medium to be tested during application, and only needs to measure the reflection matrix of the biological tissue. This application uses photoacoustic technology to detect the concentration of specific components of tissue fluid, which has the following significant innovations: there is no need to extract tissue fluid from the human body, which is safer and achieves non-invasive detection; the effect of detecting multiple substances can be achieved by selecting different laser wavelengths; the detection accuracy can be improved through a dual-wavelength differential experimental system; based on a machine learning algorithm, a prediction model for the concentration of specific components of human tissue fluid is established to eliminate the influence of uncertain factors. This will be introduced in detail below.

[0051] In order to achieve the above effects, the present application provides a device for detecting the concentration of tissue fluid components. The structure of the detection device will be introduced below.

[0052] Figure 1 is a schematic diagram of the structure of a detection device provided in an embodiment of the present application. Figure 1 The detection device includes a host and a photoacoustic probe (also called a photoacoustic detector), and the photoacoustic probe includes a forward compensation plate, a focusing lens and an ultrasonic transducer. The photoacoustic probe is used to clamp the object to be tested through a fixing device, and the object to be tested is located between the focusing lens and the ultrasonic transducer.

[0053] The host is used to generate detection light and transmit the detection light to the forward compensation plate. The forward compensation plate is used to perform forward transmission compensation on the detection light by modulating the detection light to reduce the forward reflection of the detection light by the tissue fluid in the object to be measured. The focusing lens is used to irradiate the detection light after forward transmission compensation onto the object to be measured. The ultrasonic transducer is used to collect the photoacoustic signal generated after the detection light is scattered by the tissue fluid, and the photoacoustic signal is converted into an electrical signal and transmitted to the host. The host is also used to determine the concentration of the target component in the tissue fluid based on the electrical signal.

[0054] That is to say, the detection light passes through the forward compensation plate and the focusing lens in sequence and then irradiates one side of the object to be measured, and the ultrasonic transducer collects the photoacoustic signal on the other side of the object to be measured, thereby realizing the detection of tissue fluid component concentration based on the photoacoustic signal.

[0055] In order to reduce the forward reflection of the detection light by the tissue fluid in the object to be tested, a forward compensation plate in the detection device is used to perform forward transmission compensation on the detection light before irradiating it to the object to be tested, so that most of the energy of the detection light is used for forward irradiation, thereby improving the detection efficiency of the incident light (i.e., the detection light).

[0056] The forward compensation plate can be implemented using a spatial modulator (also called a spatial light modulator). For example, the forward compensation plate includes one or more spatial modulators, and the number of spatial modulators can be determined according to the size of the forward transmission compensation matrix required to be loaded on the forward compensation plate and whether it is in complex form. For example, if the forward transmission compensation matrix is ​​a complex matrix, then the forward compensation plate may include multiple spatial modulators. The multiple spatial modulators can be arranged on a plane to form a forward compensation plate.

[0057] Figure 2 is a schematic diagram of another detection device provided in an embodiment of the present application. Figure 2 , relative to Figure 1 The photoacoustic probe shown, Figure 2 The photoacoustic probe also includes a collimator, which is used to collimate the detection light and transmit it to the forward compensation plate. In addition, Figure 2 The photoacoustic probe further includes an incident optical fiber and an optical window, wherein the incident optical fiber is used to transmit the detection light, that is, to transmit the detection light generated by the host to the collimator. The optical window is used to transmit the optical signal from the focusing lens to the object to be measured.

[0058] That is to say, the detection light passes through the incident optical fiber, the collimator, the forward compensation plate, the focusing lens and the light window in sequence and then irradiates the object to be measured.

[0059] The collimator may include two collimating lenses, which may be beam expanding collimating lenses.

[0060] Figure 3Schematic diagram of the structure of a photoacoustic probe mentioned in the embodiment of the present application. Figure 3 The photoacoustic probe includes an incident optical fiber, a collimator, a forward compensation plate, a focusing lens, an optical window, an acoustic detector and a signal line. The acoustic detector and the signal line can be Figure 1 or Figure 2 The photoacoustic probe further includes a torsion spring and a clamp. The torsion spring and the clamp may become part or all of the fixing device. In other words, the photoacoustic probe further includes a fixing device. Of course, in some other embodiments, the photoacoustic probe and the fixing device are independent of each other, and the photoacoustic probe may not include the fixing device, but the photoacoustic probe can be assembled with the fixing device to clamp the object to be measured.

[0061] In the embodiment of the present application, the fixing device is not limited to Figure 3 The torsion spring and the clamp shown are implemented, but can also be implemented by other types of components. The object to be tested can be such as Figure 3 The earlobe shown may also be other objects, such as other parts of the human body, or the earlobe or other parts of an animal, and this embodiment of the present application is not limited to this.

[0062] In addition, the photoacoustic probe may further include other components, such as a spatial filter, for filtering out noise signals in the detection light before irradiating the object to be detected. Figure 3 It is only used as an exemplary introduction to the photoacoustic probe and is not used to limit the structure of the photoacoustic probe.

[0063] Figure 4 This is a schematic diagram of another detection device provided in the embodiment of the present application. Figure 4 The host provided in the embodiment of the present application is described in detail. The host can be Figure 1 or Figure 2 The host shown.

[0064] The host comprises a first laser, a second laser, a coupler, a phase-locked amplifier, a control module and a data processing module.

[0065] The first laser is used to generate a first laser signal, the second laser is used to generate a second laser signal, and the coupler is used to couple the first laser signal and the second laser signal into a detection light. The control module is used to control the power change of the first laser, and determine the power of the first laser when the energy of the photoacoustic signal is minimum during the power change to obtain the first laser power. The phase-locked amplifier is used to determine the amplitude information of the photoacoustic signal based on the electrical signal output by the ultrasonic transducer to obtain a phase-locked signal. The data processing module is used to determine the concentration of the target component based on the phase-locked signal and the first laser power.

[0066] See also Figure 4The host also includes a signal generator and a laser driver. The signal generator is used to generate a first modulation signal and a second modulation signal, and the laser driver is used to perform signal modulation on the first laser using the first modulation signal so that the first laser outputs a first laser signal, and to perform signal modulation on the second laser using the second modulation signal so that the second laser outputs a second laser signal.

[0067] Optionally, the first modulation signal and the second modulation signal are both square wave signals with a duty cycle not exceeding 50%, and there is a certain phase difference between the first modulation signal and the second modulation signal. Figure 4 As shown, the first modulation signal and the second modulation signal are both square wave signals with a duty cycle of 50%, and the phase difference is π.

[0068] In the embodiment of the present application, the laser driver can use the first modulation signal and the second modulation signal to adjust the intensity of the first laser and the second laser respectively without phase modulation. In this way, the first laser signal and the second laser signal also have the above-mentioned phase difference. The first laser signal and the second laser signal are combined into a beam of detection light after passing through the coupler, and the detection light concentrates the energy of the first laser signal and the second laser signal.

[0069] In addition, the second modulated signal is also input to the reference terminal of the lock-in amplifier as the reference signal of the lock-in amplifier, and the electrical signal output by the ultrasonic transducer is transmitted to the measurement terminal of the lock-in amplifier as the measurement signal of the lock-in amplifier.

[0070] It is worth noting that the control module is used to control the power change of the first laser by using the optical power balance displacement method, that is, the power of the first laser is scanned within a certain range, but the power of the second laser is not scanned, that is, the power of the second laser remains unchanged. During the power change process, the control module determines the power of the first laser when the energy of the photoacoustic signal is minimum, and obtains the first laser power, so as to use the first laser power at this time to determine the concentration of the target component in the tissue fluid, thereby improving the accuracy.

[0071] The control module has another function in some embodiments. For example, when the power and wavelength of the optical signal emitted by the first laser drift due to temperature changes of the first laser, the control signal can also avoid the influence of the surrounding environment and laser temperature changes by scanning the power of the first laser.

[0072] In the embodiment of the present application, the first laser can select a wavelength-adjustable laser to achieve detection of different media, that is, the first laser can generate laser signals of multiple wavelengths, and the multiple wavelengths correspond to multiple components in the tissue fluid, and the laser signals of different wavelengths are used to detect different components in the tissue fluid. For example, the first laser can generate laser signals of 4 wavelengths, and these 4 wavelengths refer to the characteristic wavelengths of light absorption of the four components in the tissue fluid. The second laser can select a wavelength-adjustable laser or a non-adjustable laser. The wavelength of the laser signal generated by the second laser is equal to the characteristic wavelength of light absorption of the background substance in the tissue fluid. For example, the background substance in the tissue fluid is water, and the laser signal generated by the second laser signal is the characteristic wavelength of light absorption by water.

[0073] Exemplarily, the adjustable wavelength range of the first laser covers 1300nm (nanometers) to 1700nm. In a concentration detection of four components of tissue fluid in a human earlobe, the first laser generated laser signals with four wavelengths of 1392nm, 1560nm, 1580nm, and 1610nm. The laser signals with these four wavelengths are used to detect the concentrations of the four components, respectively.

[0074] In order to improve the detection accuracy, the sensitivity of the ultrasonic transducer is as high as possible, and under the premise of ensuring the sensitivity, the size and weight of the ultrasonic transducer are as small as possible so as to be firmly attached to the surface of the object to be detected. In addition, the first laser and the second laser can also be selected to be compact and small in size.

[0075] The device structure and business scenarios described in the embodiments of the present application are intended to more clearly illustrate the technical solutions of the embodiments of the present application, and do not constitute a limitation on the technical solutions provided in the embodiments of the present application. Ordinary technicians in this field can know that with the evolution of the device structure and the emergence of new business scenarios, the technical solutions provided in the embodiments of the present application are also applicable to similar technical problems.

[0076] It should be noted that: the detection device provided in the above embodiment only uses the division of the above functional modules as an example to illustrate when detecting the concentration of tissue fluid components. In actual applications, the above functions can be assigned to different functional modules as needed, that is, the internal structure of the device is divided into different functional modules to complete all or part of the functions described above. In addition, the detection device provided in the above embodiment and the detection method embodiment of the tissue fluid component concentration belong to the same concept, and the specific implementation process is detailed in the method embodiment below, which will not be repeated here.

[0077] Next, the method for detecting the concentration of tissue fluid components provided in the embodiments of the present application is introduced.

[0078] Figure 5: is a flow chart of a method for detecting the concentration of tissue fluid components provided in an embodiment of the present application. The method is applied to a detection device, the structure of which is as follows: Figures 1 to 4 That is, the detection device includes a host and a photoacoustic probe, the photoacoustic probe includes a forward compensation plate, a focusing lens and an ultrasonic transducer, the photoacoustic probe is used to clamp the object to be tested through a fixture, and the object to be tested is located between the focusing lens and the ultrasonic transducer. Please refer to Figure 5 , the method comprises the following steps.

[0079] Step 501: The host generates detection light and transmits the detection light to the forward compensation plate.

[0080] Among them, the detection light generated by the host is a laser signal.

[0081] In an embodiment of the present application, the host includes a first laser, a second laser and a coupler. One implementation of the host generating the detection light is: the first laser generates a first laser signal, the second laser generates a second laser signal, and the coupler couples the first laser signal and the second laser signal into the detection light.

[0082] The host also includes a signal generator and a laser driver. The signal generator is used to generate a first modulation signal and a second modulation signal, and the laser driver is used to perform signal modulation on the first laser using the first modulation signal so that the first laser outputs a first laser signal, and to perform signal modulation on the second laser using the second modulation signal so that the second laser outputs a second laser signal.

[0083] Optionally, the first modulation signal and the second modulation signal are both square wave signals with a duty cycle not exceeding 50%, and there is a certain phase difference between the first modulation signal and the second modulation signal. For example, the first modulation signal and the second modulation signal are both square wave signals with a duty cycle of 50%, and the phase difference is π. For another example, the first modulation signal and the second modulation signal are both square wave signals with a duty cycle of 40%, and the phase difference is π.

[0084] In an embodiment of the present application, the laser driver may use the first modulation signal and the second modulation signal to adjust the intensity of the first laser and the second laser respectively without phase modulation. In this way, the first laser signal and the second laser signal also have the above-mentioned phase difference. The first laser signal and the second laser signal are combined into a beam of detection light after passing through the coupler, and the detection light concentrates the energy of the first laser signal and the second laser signal. In a specific implementation, the phase difference should make the energy of the detection light equal to the sum of the energy of the first laser signal and the second laser signal as much as possible, thereby reducing energy loss.

[0085] As can be seen from the above, the photoacoustic probe also includes an incident optical fiber and a collimator. The detection light generated by the host first passes through the incident optical fiber to reach the collimator, and then is irradiated onto the forward compensation plate after being collimated by the collimator.

[0086] Step 502: The forward compensation plate performs forward transmission compensation on the detection light by modulating the detection light, so as to reduce the forward reflection of the detection light by the tissue fluid in the object to be detected.

[0087] In order to use most of the energy of the detection light for forward irradiation and improve the detection efficiency of the incident light (ie, the detection light), a forward compensation plate is used to perform forward transmission compensation on the detection light to reduce the forward reflection of the detection light.

[0088] The forward compensation plate modulates the detection light based on the forward transmission compensation matrix to perform forward transmission compensation on the detection light, and the forward transmission compensation matrix is ​​determined based on the forward reflection light of the detection light by the tissue fluid in the object to be measured when the photoacoustic probe does not include the forward compensation plate. In other words, in the absence of forward transmission compensation, the forward reflection light of the detection light by the tissue fluid in the object to be measured is measured, and the forward transmission compensation matrix is ​​determined based on the forward reflection light.

[0089] In one implementation, the forward transmission compensation matrix is ​​determined by a machine learning model based on a forward reflection matrix, wherein the forward reflection matrix represents information of the forward reflected light. In other words, the forward reflection matrix corresponding to the forward reflected light of the tissue fluid in the object to be measured to the detection light is measured, and the forward reflection matrix is ​​input into the machine learning model to infer the forward transmission compensation matrix.

[0090] The forward reflection matrix is ​​determined based on holographic measurement technology. In holographic measurement technology, light waves are regarded as complex functions composed of amplitude and phase, and the forward compensation matrix plate can modulate the amplitude and phase of light respectively. Therefore, the use of holographic measurement technology can perfectly match the modulation method of the forward compensation plate in this solution.

[0091] Based on this, the forward reflection matrix can be a matrix in complex form, and the forward reflection matrix represents the amplitude information and phase information of the forward reflected light. Similarly, the forward transmission compensation matrix can also be a matrix in complex form, and the modulation performed by the forward compensation plate includes phase modulation and intensity modulation. In order to represent the forward transmission compensation matrix in complex form, the forward compensation plate can be implemented by multiple spatial modulators.

[0092] Next, the specific implementation method of determining the forward reflection matrix based on holographic measurement technology is introduced.

[0093] Figure 6is a schematic diagram of the structure of a holographic measurement system provided in an embodiment of the present application. The holographic measurement system is used to measure the forward reflection matrix of tissue fluid. Figure 6 In this measurement system, the laser light emitted by the laser first passes through the collimator lens 1, the spatial filter 2 (optionally, the spatial filter 2 may not be included) and the collimator lens 3 in sequence to complete the collimation and denoising of the laser light, wherein the collimator lens 1 and the collimator lens 3 form a collimator to complete the collimation process, and the spatial filter 2 completes the denoising process. The laser light after passing through the collimator lens 3 can be regarded as a plane wave. After passing through the beam splitter 4, the laser light obtains a beam of detection light and a beam of reference light, wherein the detection light is injected into the spatial modulator controlled by the computer to complete the phase modulation, and the detection light emitted by the spatial modulator passes through the collimator lens 5 and the collimator lens 6 in sequence and reaches the beam splitter 7, and the detection light passes through the beam splitter 7 and is transmitted to the focusing lens 8, and enters the objective lens 9 after passing through the focusing lens 8, and then irradiates the medium to be measured. The reflected light (as shown by the dotted arrow in the figure) after the detection light is scattered by the tissue fluid in the medium to be measured will return to the original path, that is, the reflected light passes through the objective lens 9 and the focusing lens 8 in sequence to reach the beam splitter 7. The reference light emitted from the beam splitter 4 is reflected by the plane mirror (i.e., reflector) 10 and the plane mirror 11 in turn and then reaches the beam splitter 7. The interference fringes generated by the interference between the reference light incident on the beam splitter 7 and the reflected light are irradiated onto the CCD (Charge Coupled Device) camera and recorded by the CCD camera. The recorded interference fringes contain the amplitude and phase information of the above-mentioned reflected light (i.e., forward reflected light). The amplitude and phase information of the reflected light is transmitted to the computer, and the computer obtains the forward reflection matrix based on the amplitude and phase information.

[0094] In the case where the medium to be measured includes tissue fluid in the substance to be measured, the forward reflection matrix measured by the holographic measurement system is the forward reflection matrix of the tissue fluid to the detection light in the absence of forward transmission compensation.

[0095] It can be seen that this scheme uses digital holography to complete the wavefront reconstruction of the medium reflected light. In the holographic measurement system, the interference of the reference light and the reflected light can be regarded as occurring in the near field range. Therefore, the Fresnel diffraction principle and the phase shift method can be used to complete the reconstruction of the amplitude and phase information of the medium reflected light wave in the computer, and store it in the form of a complex matrix as a forward reflection matrix.

[0096] Since this solution uses a forward compensation plate instead of a real complementary medium, we can regard the complementary medium of the medium to be tested as a symmetric medium, that is, the forward and reverse propagation processes of light are exactly the same, that is, the reflection matrix during forward propagation is equal to the reflection matrix during reverse propagation. Related research has shown that in random scattering theory, there is a strong correlation between the reflection matrix and the transmission matrix in the same direction, so the relationship between the two can be modeled using a deep learning network, so as to infer the transmission matrix in the corresponding direction from the reflection matrix.

[0097] Generally speaking, light intensity is a linear unit, so the light intensity of any incident light wave can be expressed as a multiple of the light intensity used in the above-mentioned holographic measurement system. This means that for an incident light wave of known light intensity, by linearly changing the amplitude of the forward transmission compensation matrix of the complementary medium loaded by the forward compensation plate, the full transparency of the medium to be measured to the incident light wave can be achieved by modulating the forward compensation plate. In summary, in this scheme, for any medium to be measured, in principle, it is only necessary to measure the forward reflection matrix of the medium to be measured once in advance, and then use the above-mentioned method to obtain the forward transmission compensation matrix of the corresponding complementary medium, and use the forward compensation plate to modulate the incident light wave accordingly, so that the incident light wave can propagate in the medium to be measured without backscattering.

[0098] In addition, since this solution uses a forward compensation plate instead of a real complementary medium, this makes the solution effective for any medium, especially those to be tested that cannot find a corresponding complementary medium in reality. This solution can still achieve the purpose of eliminating the backscattering of the incident light wave.

[0099] The machine learning model for determining the forward transmission compensation matrix can be implemented based on any machine learning algorithm or deep learning algorithm, that is, the machine learning model can be a traditional machine learning model or a deep learning model, such as a convolutional neural network model. In addition, the embodiments of the present application do not limit the framework, structure, training method, etc. of the machine learning model.

[0100] Figure 7 is a flow chart of a forward transmission compensation method provided in an embodiment of the present application. Figure 7 The above-mentioned holographic measurement technology is used to obtain the reflection matrix of the medium to be measured, that is, the forward reflection matrix, and the transmission matrix of the complementary medium, that is, the forward transmission compensation matrix, is obtained through a deep learning network. The forward transmission compensation matrix is ​​loaded onto a forward compensation plate implemented by a spatial light modulator to obtain the outgoing light of the complementary medium, that is, the forward compensated transmitted light, thereby achieving full transparency of the medium to be measured to the incident light that satisfies the random scattering theory.

[0101] Step 503: The focusing lens irradiates the detection light after forward transmission compensation onto the object to be measured.

[0102] In this solution, the detection light emitted from the forward compensation plate is irradiated onto the focusing lens, and then the detection light is irradiated onto the object to be measured after passing through the focusing lens.

[0103] Optionally, when the photoacoustic probe further includes a light window, the detection light passes through the focusing lens and then irradiates the object to be measured through the light window.

[0104] Step 504: The ultrasonic transducer collects the photoacoustic signal generated after the detection light is scattered by the tissue fluid, converts the photoacoustic signal into an electrical signal, and transmits it to the host.

[0105] After the detection light is irradiated onto the object to be tested, it will be scattered by the tissue fluid in the object to be tested, and the scattering includes transmission and reflection. During the propagation of the detection light in the tissue fluid, it is converted into ultrasonic waves, which are collected by the ultrasonic transducer to obtain photoacoustic signals. The ultrasonic transducer converts the photoacoustic signals into electrical signals and transmits them to the host. In other words, after the detection light is irradiated onto the surface of the object to be tested, the tissue fluid absorbs heat and undergoes thermoelastic expansion. If the modulation frequency of the laser is high enough, the thermoelastic expansion is fast enough, and the tissue fluid will continue to expand and contract, thereby radiating ultrasonic waves.

[0106] Exemplarily, the ultrasonic transducer includes an acoustic detector and a signal line. The acoustic detector collects the photoacoustic signal and converts it into an electrical signal, which is transmitted to the host through the signal line.

[0107] Step 505: The host determines the concentration of the target component in the tissue fluid based on the electrical signal.

[0108] In essence, the electrical signal represents the above-mentioned photoacoustic signal, and the host determines the concentration of the target component in the tissue fluid based on the electrical signal, that is, determines the concentration of the target component in the tissue fluid based on the above-mentioned photoacoustic signal.

[0109] As can be seen from the above, the host includes a first laser, a second laser, a coupler, a phase-locked amplifier, a control module and a data processing module. Among them, the first laser generates a first laser signal, the second laser generates a second laser signal, and the coupler couples the first laser signal and the second laser signal into a detection light. In addition, the control module controls the power of the first laser to change within a first power range, and determines the power of the first laser when the energy of the photoacoustic signal is minimized to obtain a first laser power. The phase-locked amplifier receives the above-mentioned electrical signal, and obtains a phase-locked signal after determining the amplitude information of the above-mentioned photoacoustic signal based on the electrical signal. The data processing module determines the concentration of the target component based on the phase-locked signal and the first laser power.

[0110] In addition, the host also includes a signal generator and a laser driver. The signal generator is used to generate a first modulation signal and a second modulation signal, and the laser driver is used to modulate the first laser using the first modulation signal so that the first laser outputs a first laser signal, and to modulate the second laser using the second modulation signal so that the second laser outputs a second laser signal. The second modulation signal also serves as a reference signal for a lock-in amplifier, and the lock-in amplifier determines the amplitude information of the above-mentioned photoacoustic signal based on the reference signal.

[0111] Optionally, the data processing module determines the concentration of the target component through a prediction model based on the above-mentioned phase-locked signal and the first laser power. The prediction model is also implemented based on a machine learning algorithm or a deep learning algorithm. That is, the data processing model uses the prediction model to infer the concentration of the target component.

[0112] As can be seen from the above, the target component in the tissue fluid can be one or more than one, so the prediction model can have the function of predicting the concentration of multiple components at the same time, so that the concentration of multiple components can be measured through one measurement. It should be understood that, as can be seen from the above, the wavelength of the first laser is adjustable, and each wavelength corresponds to a component. In a measurement process, the wavelength of the first laser is adjusted to the wavelength corresponding to the above-mentioned multiple components, thereby obtaining multiple photoacoustic signals corresponding to the multiple components. The phase-locked signals, corresponding wavelengths and first laser powers obtained based on the multiple photoacoustic signals are input into the prediction model to obtain the concentration of each component in the multiple components.

[0113] Of course, the prediction model can also only have the function of predicting the concentration of one component. During the measurement process, the wavelength of the first laser can be fixed to the wavelength corresponding to the component. In order to achieve the concentration measurement of multiple components, multiple prediction models can be deployed in the host, each prediction model is used to predict the concentration of one component. In this case, there is no need to enter the wavelength of the first laser in the prediction model.

[0114] The embodiments of the present application do not limit the framework, structure and training method of the above prediction model. For example, the above prediction model can be an SVR (Support Vector Regression) model, a BP (Back Propagation) neural network model, a decision tree model or an integrated regression algorithm model.

[0115] The training data of the prediction model includes the real values ​​of the target components of the tissue fluid of m subjects and the phase-locked signals obtained by measuring the photoacoustic signals of the m subjects using the detection device in this solution at n different powers of the first laser. The prediction accuracy of the trained prediction model can be guaranteed by the training data.

[0116] In summary, in the embodiment of the present application, the detection device irradiates the detection light to one side of the object to be detected, collects the photoacoustic signal generated by the tissue fluid in the object to be detected after scattering the detection light on the other side, and determines the concentration of the target component in the tissue fluid based on the photoacoustic signal, without invading the detection object, and will not cause trauma to the detection object. Among them, in order to reduce the forward reflection of the detection light by the tissue fluid in the object to be detected, the forward compensation plate in the detection device is used to perform forward transmission compensation on the detection light before irradiating it to the object to be detected, so that most of the energy of the detection light is used for forward irradiation, thereby improving the detection efficiency of the incident light (i.e., the detection light) and ensuring the accuracy of the detection of the concentration of the tissue fluid component. In addition, because the forward compensation plate performs forward transmission compensation on the detection light by modulation, it can realize forward transmission compensation for different media to be tested, that is, it can adapt to any medium, reduce the cost of detection, and meet the detection needs of various application fields.

[0117] Specifically, this solution uses photoacoustic technology, which has higher safety. The light source energy meets safety requirements and the photoacoustic detection method is completely non-invasive, avoiding problems such as wound infection and allergies. This solution uses a dual-wavelength differential photoacoustic system to detect the concentration of tissue fluid components, which is more accurate. The first laser selects the characteristic wavelength of light absorption by the detection substance, and the second laser selects the characteristic wavelength of light absorption by the background component (such as water) in the tissue fluid. The optical power balance displacement method can be used to accurately detect the concentration of the component to be tested. This solution uses a modulated laser light source, which can control the penetration depth of light to adapt to individual differences, and uses a phase-locked amplifier with a high signal-to-noise ratio. This solution post-processes the collected photoacoustic signals based on a machine learning algorithm to improve the prediction accuracy.

[0118] In the above embodiments, it can be implemented in whole or in part by software, hardware, firmware or any combination thereof. When implemented using software, it can be implemented in whole or in part in the form of a computer program product. The computer program product includes one or more computer instructions. When the computer instructions are loaded and executed on a computer, the process or function described in the embodiment of the present application is generated in whole or in part. The computer can be a general-purpose computer, a special-purpose computer, a computer network or other programmable device. The computer instructions can be stored in a computer-readable storage medium, or transmitted from one computer-readable storage medium to another computer-readable storage medium. For example, the computer instructions can be transmitted from a website site, computer, server or data center by wired (e.g., coaxial cable, optical fiber, digital subscriber line (DSL)) or wireless (e.g., infrared, wireless, microwave, etc.) mode to another website site, computer, server or data center. The computer-readable storage medium can be any available medium that a computer can access, or a data storage device such as a server or data center that includes one or more available media integrated. The available medium may be a magnetic medium (e.g., a floppy disk, a hard disk, a magnetic tape), an optical medium (e.g., a digital versatile disc (DVD)), or a semiconductor medium (e.g., a solid state disk (SSD)). It is worth noting that the computer-readable storage medium mentioned in the embodiment of the present application may be a non-volatile storage medium, in other words, a non-transient storage medium.

[0119] It should be understood that the "at least one" mentioned herein refers to one or more, and "multiple" refers to two or more. In the description of the embodiments of the present application, unless otherwise specified, " / " means or, for example, A / B can mean A or B; "and / or" in this article is only a description of the association relationship of the associated objects, indicating that there can be three relationships, for example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone. In addition, in order to facilitate the clear description of the technical solutions of the embodiments of the present application, in the embodiments of the present application, the words "first", "second" and the like are used to distinguish the same items or similar items with basically the same functions and effects. Those skilled in the art can understand that the words "first", "second" and the like do not limit the quantity and execution order, and the words "first", "second" and the like do not limit them to be necessarily different.

[0120] It should be noted that the information (including but not limited to user device information, user personal information, etc.), data (including but not limited to data used for analysis, stored data, displayed data, etc.) and signals involved in the embodiments of the present application are all authorized by the user or fully authorized by all parties, and the collection, use and processing of relevant data need to comply with relevant laws, regulations and standards of relevant countries and regions.

[0121] The above-mentioned embodiments are provided for the present application and are not intended to limit the present application. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A method for detecting the concentration of tissue fluid components, characterized in that: The invention is applied to a detection device, the detection device comprises a host and a photoacoustic probe, the photoacoustic probe comprises a forward compensation plate, a focusing lens and an ultrasonic transducer, the photoacoustic probe is used to clamp an object to be detected through a fixture, and the object to be detected is located between the focusing lens and the ultrasonic transducer; the method comprises: The host generates detection light and transmits the detection light to the forward compensation plate; The forward compensation plate performs forward transmission compensation on the detection light by modulating the detection light, so as to reduce the forward reflection of the detection light by the tissue fluid in the object to be detected; The focusing lens irradiates the detection light after the forward transmission compensation onto the object to be measured; The ultrasonic transducer collects the photoacoustic signal generated after the detection light is scattered by the tissue fluid, converts the photoacoustic signal into an electrical signal and transmits it to the host; The host determines the concentration of a target component in the tissue fluid based on the electrical signal.

2. The method according to claim 1, characterized in that The forward compensation plate performs forward transmission compensation on the detection light by modulating the detection light, including: The forward compensation plate modulates the detection light based on a forward transmission compensation matrix to perform forward transmission compensation on the detection light. The forward transmission compensation matrix is ​​determined based on the forward reflected light of the detection light by the tissue fluid in the object to be measured when the photoacoustic probe does not include the forward compensation plate.

3. The method according to claim 2, characterized in that The forward transmission compensation matrix is ​​determined by a machine learning model based on a forward reflection matrix, and the forward reflection matrix represents information of the forward reflected light.

4. The method according to claim 3, characterized in that The forward reflection matrix is ​​determined based on holographic measurement technology.

5. The method according to claim 3 or 4, characterized in that The forward reflection matrix is ​​a matrix in complex form, and the forward reflection matrix represents the amplitude information and phase information of the forward reflected light.

6. The method according to any one of claims 2 to 5, characterized in that: The forward transmission compensation matrix is ​​a matrix in complex form, and the modulation includes phase modulation and intensity modulation.

7. The method according to any one of claims 1 to 6, characterized in that: The forward compensation plate includes one or more spatial modulators.

8. The method according to any one of claims 1 to 7, characterized in that: The host comprises a first laser, a second laser, a coupler, a lock-in amplifier, a control module and a data processing module; The host generates a detection light, including: The first laser generates a first laser signal, the second laser generates a second laser signal, and the coupler couples the first laser signal and the second laser signal into the detection light; The host determines the concentration of the target component in the tissue fluid based on the electrical signal, including: The phase-locked amplifier determines the amplitude information of the photoacoustic signal based on the electrical signal to obtain a phase-locked signal; The control module controls the power of the first laser to change within a first power range, and determines the power of the first laser when the energy of the photoacoustic signal is minimum, to obtain a first laser power; The data processing module determines the concentration of the target component based on the phase-locked signal and the first laser power.

9. A photoacoustic probe, characterized in that: The photoacoustic probe comprises a forward compensation plate, a focusing lens and an ultrasonic transducer, and the photoacoustic probe is used to clamp the object to be tested through a fixture to detect the concentration of the target component in the tissue fluid of the object to be tested, and the object to be tested is located between the focusing lens and the ultrasonic transducer; The forward compensation plate is used to perform forward transmission compensation on the detection light incident on the photoacoustic probe by modulating the detection light, so as to reduce the forward reflection of the detection light by the tissue fluid in the object to be detected; The focusing lens is used to irradiate the detection light after the forward transmission compensation onto the object to be measured; The ultrasonic transducer is used to collect the photoacoustic signal generated after the detection light is scattered by the tissue fluid, and convert the photoacoustic signal into an electrical signal, and the electrical signal is used to determine the concentration of the target component.

10. The photoacoustic probe according to claim 9, characterized in that: The photoacoustic probe further comprises a collimator, which is used to collimate the detection light and then transmit it to the forward compensation plate; and / or, The photoacoustic probe further comprises an incident optical fiber and an optical window, wherein the incident optical fiber is used to transmit the detection light, and the optical window is used to transmit the optical signal from the focusing lens to the object to be detected.

11. A device for detecting the concentration of tissue fluid components, characterized in that: The detection device comprises a host and a photoacoustic probe, wherein the photoacoustic probe comprises a forward compensation plate, a focusing lens and an ultrasonic transducer, and the photoacoustic probe is used to clamp an object to be detected through a fixture, and the object to be detected is located between the focusing lens and the ultrasonic transducer; The host is used to generate detection light and transmit the detection light to the forward compensation plate; The forward compensation plate is used to perform forward transmission compensation on the detection light by modulating the detection light, so as to reduce the forward reflection of the detection light by the tissue fluid in the object to be detected; The focusing lens is used to irradiate the detection light after the forward transmission compensation onto the object to be measured; The ultrasonic transducer is used to collect the photoacoustic signal generated after the detection light is scattered by the tissue fluid, convert the photoacoustic signal into an electrical signal and transmit it to the host; The host is also used to determine the concentration of the target component in the tissue fluid based on the electrical signal.

12. The detection device according to claim 11, characterized in that: The host comprises a first laser, a second laser, a coupler, a lock-in amplifier, a control module and a data processing module; The first laser is used to generate a first laser signal, the second laser is used to generate a second laser signal, and the coupler is used to couple the first laser signal and the second laser signal into the detection light; The control module is used to control the first laser to change its power, and determine the power of the first laser when the energy of the photoacoustic signal is minimum during the power change process to obtain a first laser power; The phase-locked amplifier is used to obtain a phase-locked signal after determining the amplitude information of the photoacoustic signal based on the electrical signal; The data processing module is used to determine the concentration of the target component based on the phase-locked signal and the first laser power.

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