Noninvasive AGEs concentration monitoring method and system, storage medium and watch
By integrating different wavelength excitation light sources and contact pressure correction technology into the watch, combined with Bayesian optimization, non-invasive, convenient, and real-time monitoring of AGEs concentration is achieved, solving the problems of invasiveness and operational complexity of existing detection methods, and providing an efficient health monitoring and chronic disease management solution.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HAINAN UNIV
- Filing Date
- 2024-10-21
- Publication Date
- 2026-04-21
AI Technical Summary
Existing AGEs detection methods are highly invasive, complex to operate, costly, time-consuming, and easily affected by ambient light sources, making it difficult to achieve portable and easy-to-use continuous monitoring.
The system uses different wavelengths of light to excite the fluorescence of skin tissue, and combines contact pressure correction and Bayesian optimization techniques to establish a discrete three-dimensional fluorescence spectrum. The concentration of AGEs is monitored by optical sensors and intelligent algorithms. The system is integrated into a watch using a low-power design and a long-lasting battery.
It enables non-invasive, convenient, and real-time monitoring of AGEs concentration, improves data accuracy and user experience, reduces maintenance costs, enhances the device's adaptability to various environments, and supports early diagnosis and timely intervention.
Smart Images
Figure CN121890938A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biosensing and spectral analysis technology. It relates to a non-invasive method, system, storage medium and watch for monitoring AGEs concentration, which is suitable for clinical label-free monitoring. Background Technology
[0002] Advanced glycation end products (AGEs) are complex molecules formed through non-enzymatic reactions. Studies have shown that the accumulation of AGEs may lead to inflammation and immune dysfunction, thereby promoting the occurrence and development of various diseases, including diabetes, kidney disease, cardiovascular disease, and neurological disorders.
[0003] Currently, methods for detecting advanced glycation end products (AGEs) mainly fall into two categories: biochemical methods and non-destructive optical methods. Biochemical methods involve the collection of blood or urine samples. While biochemical methods offer high detection accuracy, the process is relatively complex. Especially for blood samples, invasive methods are required for collection, causing discomfort to the test subjects. This type of biochemical test is not only costly but also time-consuming, taking 8-9 hours. Developing non-invasive, convenient, and painless detection methods is crucial for the practical and continuous measurement of AGEs in human blood and tissues, and is fundamental for long-term monitoring and research on their role in chronic diseases.
[0004] On the other hand, while optical non-destructive testing methods offer a detection approach that eliminates the need for direct biological sample collection, they face challenges in practical applications, such as weak autofluorescence signals and susceptibility to interference from ambient light sources. Current equipment is typically bulky and difficult to operate, requiring specific experimental setups, which significantly limits its practicality in everyday life. Therefore, there is an urgent need for a new type of monitoring device that is portable, easy to use, capable of continuous monitoring, and requires no invasive procedures. Summary of the Invention
[0005] The purpose of this invention is to provide a non-invasive method, system, storage medium, and watch for monitoring AGEs concentration. The algorithm can improve the accuracy and real-time performance of the data.
[0006] The technical solution to achieve the purpose of this invention is as follows:
[0007] A non-invasive method for monitoring AGEs concentration includes the following steps:
[0008] S01: Excitation light sources of different wavelengths are used to excite fluorescence inside the skin tissue;
[0009] S02: Obtain the intensity of spontaneous fluorescence at different wavelengths;
[0010] S03: The concentration of AGEs is obtained from discrete three-dimensional fluorescence spectra established based on different excitation wavelengths.
[0011] In the preferred technical solution, the wavelengths of the excitation light source in step S01 are λ1nm, λ2nm, and λ3nm, and the values of λ1, λ2, and λ3 are rational numbers ranging from 200 to 450.
[0012] In the preferred technical solution, step S02 further includes simultaneously acquiring the spontaneous fluorescence intensity under different contact pressures;
[0013] A power function fitting formula for "contact pressure - fluorescence intensity" was established to quantify the relationship between contact pressure and detected autofluorescence intensity.
[0014] The contact pressure P is acquired in real time, and the autofluorescence intensity after contact pressure correction is obtained based on the fitting formula of "contact pressure-fluorescence intensity".
[0015] In the preferred technical solution, the fitting formula for "contact pressure - fluorescence intensity" is:
[0016]
[0017] Among them, I AGEs (λ) represents the intensity of autofluorescence, P represents the contact pressure, and λ represents different wavelengths. λ (P) is a correction function used to quantify the effect of contact pressure on the detected autofluorescence intensity.
[0018] In the preferred technical solution, step S02 further includes detecting the backscattering spectrum of different individuals at a wavelength of λ4nm, and using this as a reference, correcting the influence of different optical absorption and scattering coefficients on the autofluorescence spectrum, where λ4 is a rational number ranging from 450 to 1000.
[0019] The normalized autofluorescence intensity is expressed as follows: The backscattering spectrum at wavelength λ4 nm, corrected for contact pressure, is then normalized.
[0020]
[0021] Among them, I AGEs (λ4) is the intensity of the reflected light at λ4 nm, F λ4 (P) is a correction function used to quantify the effect of contact pressure on the intensity of the detected λ4nm reflected light.
[0022] In the preferred technical solution, the discrete three-dimensional fluorescence spectrum established in step S03 based on different excitation wavelengths is as follows:
[0023] C1*A j I AGEs (λ)+C2*B j I AGEs (λ)+C3*Cj I AGEs (λ)
[0024] Among them, A j B j C j C1, C2, and C3 represent the product of the quantum efficiency and the concentration of the three autofluorescent substances under the j-th wavelength, respectively, and are the discrete coefficients.
[0025] AGEs concentration C AGEs :
[0026] C AGEs =C1*A j I AGEs (λ)+C2*B j I AGEs (λ)+C3*C j I AGEs (λ).
[0027] In the preferred technical solution, Bayesian optimization technology is used to perform linear optimization combination of the discrete coefficients, with the AGEs concentration test value of the blood or urine of the corresponding volunteers as the constraint condition, and the discrete coefficients C1, C2 and C3 are obtained by optimization calculation.
[0028] This invention also discloses a non-invasive AGEs concentration monitoring system, comprising:
[0029] The excitation light source emission module uses excitation light sources of different wavelengths to excite fluorescence inside the skin tissue;
[0030] The spectral detection module acquires the intensity of spontaneous fluorescence light at different wavelengths;
[0031] The data processing module obtains the AGEs concentration based on discrete three-dimensional fluorescence spectra established by different excitation wavelengths.
[0032] The present invention also discloses a watch, including a watch case, wherein a control processing module is provided inside the watch case, and the control processing module implements the above-mentioned non-invasive AGEs concentration monitoring method when executed.
[0033] The present invention also discloses a computer storage medium storing a computer program, which, when executed, implements the above-described non-invasive AGEs concentration monitoring method.
[0034] Compared with the prior art, the significant advantages of this invention are:
[0035] By virtue of its non-invasive nature, this invention significantly enhances the comfort and convenience of monitoring, enabling users to continuously monitor their health status without disruption during daily activities. The combination of a highly sensitive optical sensor and intelligent algorithms not only ensures the accuracy and real-time nature of the data but also provides a reliable basis for early diagnosis and timely intervention. Furthermore, the low-power design and long-lasting battery significantly reduce maintenance costs and enhance the device's environmental adaptability, making it reliable and effective in various environments. These combined advantages make this invention uniquely valuable in the fields of health monitoring and chronic disease management. Attached Figure Description
[0036] Figure 1 This is a flowchart of the non-invasive AGEs concentration monitoring method in this embodiment;
[0037] Figure 2 A schematic diagram of a wrist-worn, low-power, ultra-sensitive, non-invasive AGEs concentration monitoring watch;
[0038] Figure 3 This is a schematic diagram of the light source structure. Detailed Implementation
[0039] The principle of this invention is that this method can extract the main fluorescent components of AGEs and counteract the fluorescence crosstalk of non-AGEs substances, and correct the autofluorescence intensity, thereby improving the accuracy and real-time performance of the data.
[0040] Example 1:
[0041] like Figure 1 As shown, a non-invasive method for monitoring AGEs concentration includes the following steps:
[0042] S01: Excitation light sources of different wavelengths are used to excite fluorescence inside the skin tissue;
[0043] S02: Obtain the intensity of spontaneous fluorescence at different wavelengths;
[0044] S03: The concentration of AGEs is obtained from discrete three-dimensional fluorescence spectra established based on different excitation wavelengths.
[0045] In a preferred embodiment, the wavelengths of the excitation light source in step S01 are λ1nm, λ2nm, and λ3nm, and the values of λ1, λ2, and λ3 are rational numbers ranging from 200 to 450.
[0046] In a preferred embodiment, step S02 further includes simultaneously acquiring the autofluorescence intensity under different contact pressures;
[0047] A power function fitting formula for "contact pressure - fluorescence intensity" was established to quantify the relationship between contact pressure and detected autofluorescence intensity.
[0048] The contact pressure P is acquired in real time, and the autofluorescence intensity after contact pressure correction is obtained based on the fitting formula of "contact pressure-fluorescence intensity".
[0049] In a preferred embodiment, the fitting formula for "contact pressure - fluorescence intensity" is:
[0050]
[0051] Among them, I AGEs (λ) represents the intensity of autofluorescence, P represents the contact pressure, and λ represents different wavelengths. λ (P) is a correction function used to quantify the effect of contact pressure on the detected autofluorescence intensity.
[0052] In a preferred embodiment, step S02 further includes detecting the backscattering spectra of different individuals at a wavelength of λ4nm, and using this as a reference, correcting the influence of different optical absorption and scattering coefficients on the autofluorescence spectrum, wherein λ4 is a rational number ranging from 450 to 1000.
[0053] The normalized autofluorescence intensity is expressed as follows: The backscattering spectrum at wavelength λ4 nm, corrected for contact pressure, is then normalized.
[0054]
[0055] Among them, I AGEs (λ4) is the intensity of the reflected light at λ4 nm, F λ4 (P) is a correction function used to quantify the effect of contact pressure on the intensity of the detected λ4nm reflected light.
[0056] In a preferred embodiment, the discrete three-dimensional fluorescence spectrum established in step S03 based on different excitation wavelengths is as follows:
[0057] C1*A j I AGEs (λ)+C2*B j I AGEs (λ)+C3*C j I AGEs (λ)
[0058] Among them, A j B j C j C1, C2, and C3 represent the product of the quantum efficiency and the concentration of the three autofluorescent substances under the j-th wavelength, respectively, and are the discrete coefficients.
[0059] AGEs concentration C AGEs :
[0060] CAGEs =C1*A j I AGEs (λ)+C2*B j I AGEs (λ)+C3*C j I AGEs (λ).
[0061] In a preferred embodiment, the discrete coefficients are linearly optimized using Bayesian optimization techniques, with the AGEs concentration test value of the corresponding volunteers' blood or urine as a constraint, and the discrete coefficients C1, C2 and C3 are obtained by optimization calculation.
[0062] In another embodiment, a computer storage medium stores a computer program that, when executed, implements the above-described non-invasive AGEs concentration monitoring method.
[0063] The specific methods used are the monitoring methods described above, and will not be repeated here.
[0064] In another embodiment, a non-invasive AGEs concentration monitoring system includes:
[0065] The excitation light source emission module uses excitation light sources of different wavelengths to excite fluorescence inside the skin tissue;
[0066] The spectral detection module acquires the intensity of spontaneous fluorescence light at different wavelengths;
[0067] The data processing module obtains the AGEs concentration based on discrete three-dimensional fluorescence spectra established by different excitation wavelengths.
[0068] In another embodiment, a watch includes a case, and a control processing module is disposed inside the case. When the control processing module is executed, it implements the above-described non-invasive AGEs concentration monitoring method.
[0069] Specifically, let's take a watch as an example:
[0070] A smartwatch for monitoring AGEs concentration includes the following key components: a watchband 1, a watch case 2, a micro development board 3, a micro CMOS camera 4, Bluetooth 5, a module integrating a light source and pressure device 6, a micro light source driver board 7, and a button battery 8. In use, the user wears the watch and presses the surface with the light source and pressure device against their arm, then opens a mobile app, which automatically connects to the watch.
[0071] In operation, the excitation light source (LED light source) illuminates sequentially and shines on the skin tissue. AGEs within the skin fluoresce under laser excitation and escape through the arm, subsequently being captured by the detection window on the back of the watch and transmitted to the miniature CMOS camera 4. The signal is processed by the miniature development board 3 and then transmitted via Bluetooth 5 to a mobile app for display and analysis.
[0072] like Figure 2 As shown, the probe is a key component of this invention, designed as an embedded light source with a large fluorescence collection window. Located on the back of the watch, the probe is equipped with three short-wavelength laser LEDs: LED602 (365nm), LED603 (395nm), LED604 (415nm), and LED605 (520nm). The 520nm LED605 is used to eliminate interference from human skin tissue parameters on the fluorescence signal. When these LEDs are lit, they excite fluorescence within the skin tissue. The fluorescence signal is then captured through the fluorescence collection window and transmitted to a CMOS camera for analysis.
[0073] In addition, a pressure sensor 601 is mounted on the back of the watch. This sensor monitors the pressure between the skin tissue and the watch in real time, connects to the micro-development board 3 via a serial port, and sends the converted pressure data to a mobile app. This design enables the watch to accurately collect and analyze skin fluorescence signals, thereby effectively monitoring AGEs concentration.
[0074] The data acquisition process of this invention will be further explained below.
[0075] To ensure effective coordination and cooperation among the various modules, a dedicated control module was designed for the system. This control module, primarily comprised of the miniature light source driver board 7, is responsible for establishing connections with the biological tissue spectral detection module, the LED light source and its driver module, and the pressure sensor module. This design allows the miniature light source driver board 7 to precisely control the workflow of each module, ensuring they operate at the appropriate time and under suitable conditions, thereby effectively capturing and processing fluorescence signals.
[0076] The system control module is responsible for setting the exposure time of the biological tissue spectral detection module, controlling the lighting timing of the LED light source and its driving module, and processing the pressure sensor signals received by the data acquisition card. The specific operation is as follows:
[0077] First, the exposure time for each LED is set via the host computer: 1000ms for 365nm, 395nm, and 415nm LEDs, and 100ms for the 520nm LED. Before capturing the fluorescence signal, the host computer sends a command to light up the LEDs via a serial port connection with the STM32 microcontroller. Upon receiving the command, the STM32 microcontroller lights up the corresponding wavelength LED according to the preset lighting conditions. The microcontroller is programmed in C language using Keil5 software and the program is burned into the microcontroller. Its core logic is to wait for serial port information from the host computer, confirm the information using the Uart_Getflag function, and compare it with the preset LED lighting condition strings (e.g., "LED1", "LED2", "LED3", and "LED4" correspond to 365nm, 395nm, 415nm, and 520nm LEDs respectively) to determine and execute the lighting operation. The serial port is set to a baud rate of 115200, no parity bit, 8 data bits, and 1 stop bit. The LED's illumination time is set to 1.5 seconds to ensure sufficient time to capture the fluorescence signal.
[0078] The host computer's logic involves cyclically sending serial port information to illuminate the LEDs, waiting 100ms for the microcontroller to process, and then capturing and acquiring fluorescence data. The host computer also reads and saves the pressure sensor's output data each time an LED illuminates. Three pressure values are saved for each LED band, averaged, and converted into a pressure value representing the contact pressure applied by the subject during that LED detection period.
[0079] Each time the laser illuminates, the collected fluorescence signal is displayed on the CMOS sensor. The entire photosensitive chip receives electrical signals, which are summed to obtain the current intensity, recorded as the fluorescence signal. During the autofluorescence spectroscopy detection process, the system relies on an integrated pressure sensor to synchronously acquire the autofluorescence intensity variation characteristics under different contact pressures. A power function fitting formula for "contact pressure - fluorescence intensity" is established to quantify the relationship between contact pressure and the detected autofluorescence intensity.
[0080]
[0081] F λ (P) is a correction function used to quantify the effect of contact pressure on the detected autofluorescence intensity. This function shows the relationship between contact pressure and fluorescence intensity, derived through an experimental model.
[0082] I AGEs (λ) is the uncorrected autofluorescence spectrum as a function of wavelength λ. It is the spectral data obtained from actual measurements during clinical testing.
[0083] In obtaining clinical autofluorescence spectra I AGEsDuring (λ) the contact pressure P is acquired in real time, and the autofluorescence spectrum I after contact pressure correction is obtained based on the fitting formula of "contact pressure-fluorescence intensity". AGEs (λ) / F λ (P). This ratio provides more accurate fluorescence spectral information, eliminating errors caused by contact pressure.
[0084] Because different individuals have different skin colors, their optical absorption and scattering coefficients also differ. Therefore, this invention incorporates the use of a 520nm LED to irradiate the skin, while simultaneously detecting the backscattering spectrum of the 520nm LED under different individuals. Based on this, the influence of different optical absorption and scattering coefficients on the autofluorescence spectrum is corrected.
[0085] The backscattering spectrum at 520 nm, corrected for contact pressure, was normalized. Therefore, the final normalized AGEs fluorescence intensity can be expressed as:
[0086]
[0087] During the excitation of AGEs to produce autofluorescence, other substances in skin tissue (such as collagen and NADH) are also excited in the 420 nm to 600 nm range, leading to fluorescence crosstalk. To extract the main fluorescent components of AGEs and counteract the fluorescence crosstalk of non-AGEs, this study obtained discrete three-dimensional fluorescence spectral data using three excitation wavelengths.
[0088] Specifically, the test area is sequentially illuminated using LEDs at wavelengths of 365nm, 395nm, and 415nm. When the first wavelength LED is lit, the detector records the fluorescence spectrum of the skin under this excitation condition, while the other two wavelengths are turned off. Subsequently, the LED of the current wavelength is turned off, and the LED of the next wavelength is turned on for measurement. This yields the skin fluorescence spectrum in three wavelength bands. Let the three spectra be I, I, and I, respectively. AGEs (λ), where λ is 365nm, 395nm, and 415nm respectively. Where A j B j C j These represent the product of the quantum efficiency and the concentration of the three autofluorescent substances under the j-th wavelength, respectively, and are known and readily available parameters. The data structure for discrete three-dimensional fluorescence spectroscopy is: C1*A j I AGEs (λ)+C2*B j I AGEs (λ)+C3*C j I AGEs (λ).
[0089] Bayesian optimization techniques were used to linearly optimize the discrete coefficients, with the AGEs concentration test values from the blood or urine of the corresponding volunteers as constraints. Specifically, the data structure in the above formula was set to equal the AGEs concentration in the volunteer's urine. Parameters C1, C2, and C3 were then obtained through optimization calculations. Therefore, after determining the coefficients, the target's spectrum was acquired in three bands, and the results were substituted into the formula to solve for C. AGEs This represents the volunteers' actual AGEs concentration.
[0090] C AGEs =C1*A j I AGEs (λ)+C2*B j I AGEs (λ)+C3*C j I AGEs (λ).
[0091] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.
Claims
1. A non-invasive method for monitoring AGEs concentration, characterized in that, Includes the following steps: S01: Excitation light sources of different wavelengths are used to excite fluorescence inside the skin tissue; S02: Obtain the intensity of spontaneous fluorescence at different wavelengths; S03: The concentration of AGEs is obtained from discrete three-dimensional fluorescence spectra established based on different excitation wavelengths.
2. The non-invasive AGEs concentration monitoring method according to claim 1, characterized in that, In step S01, the wavelengths of the excitation light source are λ1nm, λ2nm, and λ3nm, and the values of λ1, λ2, and λ3 are rational numbers ranging from 200 to 450.
3. The non-invasive AGEs concentration monitoring method according to claim 1, characterized in that, Step S02 also includes simultaneously acquiring the spontaneous fluorescence intensity under different contact pressures; A power function fitting formula for "contact pressure - fluorescence intensity" was established to quantify the relationship between contact pressure and detected autofluorescence intensity. The contact pressure P is acquired in real time, and the autofluorescence intensity after contact pressure correction is obtained based on the fitting formula of "contact pressure-fluorescence intensity".
4. The non-invasive AGEs concentration monitoring method according to claim 3, characterized in that, The fitting formula for "contact pressure - fluorescence intensity" is: in, Let λ be the intensity of the autofluorescence under contact pressure P, λ be the wavelength, and F be the value of F. λ (P) is a correction function used to quantify the effect of contact pressure on the detected autofluorescence intensity.
5. The non-invasive AGEs concentration monitoring method according to claim 3, characterized in that, Step S02 also includes detecting the backscattering spectra of different individuals at a wavelength of λ4nm, and using this as a benchmark, correcting the influence of different optical absorption and scattering coefficients on the autofluorescence spectrum, where λ4 is a rational number ranging from 450 to 1000. The normalized autofluorescence intensity is expressed as follows: The backscattering spectrum at wavelength λ4 nm, corrected for contact pressure, is then normalized. Among them, I AGEs (λ4) is the intensity of the reflected light at λ4 nm, F λ4 (P) is a correction function used to quantify the effect of contact pressure on the intensity of the detected λ4nm reflected light.
6. The non-invasive AGEs concentration monitoring method according to claim 3, characterized in that, The discrete three-dimensional fluorescence spectra established in step S03 based on different excitation wavelengths are as follows: C1*A j AND AGEs (λ)+C2*B j AND AGEs (λ)+C3*C j AND AGEs (λ) Among them, A j B j C j C1, C2, and C3 represent the product of the quantum efficiency and the concentration of the three autofluorescent substances under the j-th wavelength, respectively, and are the discrete coefficients. AGEs concentration C AGEs : C AGEs =C1*A j AND AGEs (λ)+C2*B j AND AGEs (λ)+C3*C j AND AGEs (λ)。 7. The non-invasive AGEs concentration monitoring method according to claim 6, characterized in that, The discrete coefficients were linearly optimized using Bayesian optimization techniques, with the AGEs concentration test values of the blood or urine of the corresponding volunteers as constraints. The discrete coefficients C1, C2 and C3 were obtained through optimization calculation.
8. A non-invasive AGEs concentration monitoring system, characterized in that, include: The excitation light source emission module uses excitation light sources of different wavelengths to excite fluorescence inside the skin tissue; The spectral detection module acquires the intensity of spontaneous fluorescence light at different wavelengths; The data processing module obtains the AGEs concentration based on discrete three-dimensional fluorescence spectra established by different excitation wavelengths.
9. A watch, comprising a watch case, wherein a control processing module is disposed within the watch case, characterized in that, When the control processing module is executed, it implements the non-invasive AGEs concentration monitoring method according to any one of claims 1-7.
10. A computer storage medium having a computer program stored thereon, characterized in that, When the computer program is executed, it implements the non-invasive AGEs concentration monitoring method according to any one of claims 1-7.