CN-121987148-A - Intelligent collagen monitoring method and system integrated with microsensor

CN121987148ACN 121987148 ACN121987148 ACN 121987148ACN-121987148-A

Abstract

The invention relates to the technical field of intelligent monitoring of collagen, and particularly discloses an intelligent collagen monitoring method and system of an integrated microsensor, wherein a state-switchable enzyme response hydrogel is anchored to skin through a microneedle array, and a high-frequency acoustic impedance analysis module is utilized to continuously probe acoustic impedance change of the hydrogel so as to identify a collagen degradation event; once collagen degradation is detected, the system activates the micro regeneration unit, the micro regeneration unit conveys cleaning fluid and regeneration fluid through the microfluidic channel, the broken peptide chain is removed, the hydrogel crosslinked network is reconstructed, the functional regeneration of the sensing unit is realized, the system further comprises a regeneration state confirmation and cycle reset mechanism, the reliability of each monitoring cycle and the consistency of a data reference are ensured, the limitation of the traditional monitoring method is overcome, the repeated cyclic use of a single sensor is realized, the reliability and the consistency of long-term monitoring data are improved, and the method has important significance for skin health management and aging research.

Inventors

PAN RUILUN
LIU XIN
ZHANG XIAOLONG
ZHANG JING

Assignees

派能生物科技（深圳）有限公司

Dates

Publication Date: 20260508
Application Date: 20260128

Claims (10)

1. An intelligent collagen monitoring method of an integrated microsensor is characterized by comprising the following steps: S1, acquiring sensor feedback data attached to a target skin area, establishing signal characteristics of acoustic impedance of a response hydrogel of a characterization enzyme and an analysis module within a preset deviation range, and generating an initial acoustic impedance reference; S2, calling an initial acoustic impedance reference and controlling a high-frequency acoustic impedance analysis module, performing continuous exploration in a preset time interval, and processing echo signals in real time to generate continuous real-time acoustic impedance signal streams; S3, comparing the real-time acoustic impedance signal flow with an initial acoustic impedance reference, and judging that a collagen degradation event occurs and generating a collagen degradation event signal when detecting that the signal is suddenly reduced in signal amplitude which represents collagen degradation and exceeds a preset threshold; S4, responding to the collagen degradation event signal, generating a regeneration control instruction to activate the micro regeneration unit, controlling the microfluidic channel to convey cleaning liquid to flush the enzyme response hydrogel converted into liquid-like state, and controlling the waste liquid recovery channel to remove the waste liquid containing the broken peptide chain fragments so as to generate a clean gel matrix; S5, transferring the regeneration liquid containing the active peptide chain with complete structure to a clean gel matrix, so that the active peptide chain with complete structure reforms a crosslinked network in the gel matrix, and the enzyme response hydrogel is promoted to recover to an initial solid-like state with high acoustic impedance, so that the functional regeneration of the sensing unit is completed; S6, the regenerated acoustic impedance signal is updated to be a new steady-state reference and the monitoring cycle is reset through acquiring the regenerated acoustic impedance signal and comparing the regenerated acoustic impedance signal with the initial acoustic impedance reference to confirm consistency.
2. The method for intelligent collagen monitoring integrated with a microsensor according to claim 1, wherein the establishing a signal characteristic that characterizes the acoustic impedance of the enzyme-responsive hydrogel and the analysis module within a preset deviation range, generating an initial acoustic impedance reference, comprises: anchoring a sensor patch integrated with a microneedle array, a state-switchable enzyme-responsive hydrogel, a high-frequency acoustic impedance analysis module, and a micro-regeneration unit to a target skin region; Controlling the high-frequency acoustic impedance analysis module to emit high-frequency sound waves, penetrating the enzyme response hydrogel which is in an initial solid-like state and is switchable, and receiving reflected echo signals; based on the intensity and morphology of the echo signals, analyzing and recording initial acoustic impedance signals representing that the acoustic impedance difference between the enzyme response hydrogel and the high-frequency acoustic impedance analysis module is smaller than a preset matching threshold.
3. The method of claim 1, wherein the real-time processing of echo signals to generate a continuous stream of real-time acoustic impedance signals comprises: setting a preset time interval, and periodically triggering high-frequency sound wave transmitting and receiving operation; Amplifying, filtering and analog-to-digital converting the received analog echo signal to remove environmental noise; and extracting the intensity characteristics and the morphological characteristics of the echo signals at each time point, marking a time stamp, and generating a discrete recorded data packet sequence as a real-time acoustic impedance signal stream.
4. The intelligent collagen monitoring method of the integrated microsensor according to claim 1, wherein said determining that a collagen degradation event has occurred comprises: Extracting the signal amplitude of the initial acoustic impedance reference from the initial acoustic impedance reference, naming the initial reference signal amplitude, and comparing the ratio of the real-time signal amplitude to the initial reference signal amplitude with a preset signal dip judgment threshold; When the ratio of the real-time signal amplitude to the initial reference signal amplitude falls from being greater than a preset signal dip judgment threshold value to being less than the preset signal dip judgment threshold value in N continuous exploration time points, judging that signal amplitude dip exceeding the preset threshold value occurs; The sudden drop of the signal amplitude exceeding the preset threshold value represents that the enzyme responds that the hydrogel is converted from a quasi-solid state to a quasi-liquid state due to the cutting of the peptide chain crosslinking point, so that acoustic impedance mismatch is caused, and accordingly, the occurrence of collagen degradation event is judged.
5. The method for intelligent collagen monitoring integrated with a microsensor of claim 4, wherein the generating the collagen degradation event signal comprises immediately packaging the determination result into a standardized digital command packet, wherein the digital command packet comprises a collagen degradation event type identifier, an accurate occurrence timestamp and signal attenuation amplitude information, and the digital command packet is used as the collagen degradation event signal.
6. The method of claim 1, wherein the controlling the waste recovery channel to remove waste containing broken peptide chain fragments to produce a clean gel matrix comprises: Responding to the collagen degradation event signal or the external regeneration instruction, and driving the micropump to pump out the cleaning fluid from the liquid storage bag; directionally conveying the cleaning liquid to the area where the enzyme response hydrogel converted into the liquid-like state is located through the microfluidic channel; The broken peptide chain fragments dispersed in the matrix are moved into a waste liquid collecting cavity through a negative pressure waste liquid recycling channel by utilizing the fluid flushing effect, and a polymer main chain network which is not cut off by enzyme is reserved, so that the clean gel matrix is obtained.
7. The method for intelligent collagen monitoring integrated with a microsensor according to claim 1, wherein the functional regeneration of the sensing unit is completed, comprising: controlling the miniature regeneration unit to pump the regeneration liquid dissolved with the active peptide chain with complete structure from the liquid preparation liquid storage bag; Fully infiltrating the regenerated liquid into the clean gel matrix, adjusting the pH value of the microenvironment to adapt to the crosslinking reaction condition, and carrying out covalent bonding reaction by utilizing a chemical reaction group at the tail end of the active peptide chain with complete structure and a functional site on the gel polymer skeleton; by reestablishing the chemical connection in situ inside the gel, the elastic modulus of the gel material is raised back to the original solid-like state with high acoustic impedance, thereby completing the functional regeneration of the sensing unit.
8. The method for intelligent collagen monitoring integrated with a microsensor according to claim 1, wherein the specific steps of confirming consistency by acquiring the regenerated acoustic impedance signal and comparing the regenerated acoustic impedance signal with an initial acoustic impedance reference comprise: the high-frequency acoustic impedance analysis module is controlled again to emit high-frequency sound waves and receive echoes, and a regenerated acoustic impedance signal is generated; Calculating the consistency ratio of the amplitude of the regenerated acoustic impedance signal and the amplitude of the initial reference signal; Comparing the consistency ratio with a preset threshold, if the consistency ratio is larger than or equal to the preset threshold, judging that the consistency of the regenerated acoustic impedance signal and the initial acoustic impedance reference reaches the preset threshold, verifying to pass, and confirming that the sensor successfully recovers the monitoring capability, otherwise, judging that the consistency of the regenerated acoustic impedance signal and the initial acoustic impedance reference does not reach the preset threshold, and verifying to fail.
9. The method of intelligent collagen monitoring integrated with a microsensor of claim 8 wherein updating the regenerated acoustic impedance signal to a new steady state reference and resetting the monitoring cycle comprises: covering and updating the data of the verified regenerated acoustic impedance signal with the original stored initial acoustic impedance reference to make the original acoustic impedance reference a new steady state reference; the system automatically jumps, calls a new steady state reference and re-performs the continuous acoustic impedance probing when the next preset time interval has arrived.
10. An intelligent collagen monitoring system integrated with a microsensor, comprising: The initial acoustic impedance reference generation module is used for acquiring sensor feedback data attached to a target skin area, establishing signal characteristics of the acoustic impedance of the characterization enzyme response hydrogel and the analysis module within a preset deviation range, and generating an initial acoustic impedance reference; the real-time acoustic impedance signal flow generating module is used for calling an initial acoustic impedance reference and controlling the high-frequency acoustic impedance analyzing module, performing continuous exploration in a preset time interval, and processing echo signals in real time to generate continuous real-time acoustic impedance signal flows; The collagen degradation event signal generation module is used for comparing the real-time acoustic impedance signal flow with an initial acoustic impedance reference, and judging that a collagen degradation event occurs and generating a collagen degradation event signal when detecting that the signal is suddenly reduced in signal amplitude which represents collagen degradation and exceeds a preset threshold value; The cleaned gel matrix generation module responds to the collagen degradation event signal, generates a regeneration control instruction to activate the micro regeneration unit, controls the microfluidic channel to convey cleaning liquid to flush the enzyme response hydrogel converted into a liquid-like state, and controls the waste liquid recovery channel to remove waste liquid containing broken peptide chain fragments so as to generate a cleaned gel matrix; the functional regeneration module of the sensing unit calls the regeneration liquid containing the active peptide chain with complete structure to be conveyed into the clean gel matrix, so that the active peptide chain with complete structure reforms a crosslinked network in the gel matrix, and the enzyme is promoted to respond the hydrogel to recover to the initial quasi-solid state with high acoustic impedance, thereby completing the functional regeneration of the sensing unit; The regeneration state confirmation and cycle reset module updates the regenerated acoustic impedance signal to a new steady state reference and resets the monitoring cycle by acquiring the regenerated acoustic impedance signal and comparing the regenerated acoustic impedance signal to the initial acoustic impedance reference to confirm consistency.

Description

Intelligent collagen monitoring method and system integrated with microsensor Technical Field The invention belongs to the technical field of intelligent collagen monitoring, and relates to an intelligent collagen monitoring method and system integrating a microsensor. Background Currently, real-time, minimally invasive monitoring of the dynamic changes in collagen content in skin tissue is an important challenge in the field of skin health management and aging research. Collagen is the main component of the extracellular matrix of skin, and its equilibrium state of degradation and synthesis is directly related to skin elasticity, firmness and health. Therefore, development of a technology capable of continuously tracking collagenase activity to reflect collagen degradation events has important application value. The patent publication CN106535743B discloses a light-based measurement system and method of collagen denaturation measurement and a skin care system, comprising a measurement system 110 comprising a light source 120, the light source 120 being configured and arranged for emitting a light beam via a polarization modulator 130 to a target location within the skin 160, wherein the polarization modulator 130 is configured and arranged for providing, in use, simultaneously a first and a second region in a cross section of the light beam in the target location, the first and second region being different and having corresponding first and second polarization directions, the first and second polarization directions being different from each other, and the measurement system further comprising a detection unit 150 for simultaneously detecting a first and second intensity of reflected light 145, the first intensity corresponding to light reflected from the first region of the light beam in the target location 160 and the second intensity corresponding to light reflected from the second region of the light beam in the target location 160, and the measurement system further comprising a processor coupled to the detection unit 150 for determining a difference between the first and second intensities. The prior art has the defects that 1) invasive and limiting methods such as tissue biopsy and the like belong to invasive operations, not only bring discomfort and potential risks to users, but also determine that the continuous and dynamic observation of the collagen state cannot be realized by the sampling mode. 2) The equipment and scene limitation is that the method for monitoring large-scale professional equipment such as high-frequency ultrasound is depended on, and the application scene is strictly limited in the professional medical institution due to huge equipment volume and high cost, so that the daily and portable personal health management requirement cannot be met. 3) The sensing signal is irreversible, and the monitoring method based on chemical reactions such as fluorescent probes and the like has the core problem that the sensing mechanism is consumable. The probe molecules are consumed or fluorescence quenched once they react with the target enzyme, resulting in irreversible signaling, making the sensor a disposable device. 4) The function persistence is poor and the data is discontinuous, namely, because of the single-use characteristic of the sensor, the whole sensor is required to be frequently replaced or the probe is required to be reapplied in order to monitor for a long time or repeatedly, so that the operation is inconvenient, the breakpoint of the measured data in time is caused, a continuous trend curve is difficult to form, and the reliability of effectively observing and evaluating the long-term change rule of the collagen is influenced. Disclosure of Invention In view of this, in order to solve the problems set forth in the background art, an intelligent collagen monitoring method and system integrated with a microsensor are now proposed. The invention provides an intelligent collagen monitoring method of an integrated microsensor, which comprises the following steps of S1, acquiring sensor feedback data attached to a target skin area, establishing signal characteristics representing that acoustic impedance of enzyme response hydrogel and an analysis module is in a preset deviation range, and generating an initial acoustic impedance reference. S2, calling an initial acoustic impedance reference and controlling a high-frequency acoustic impedance analysis module, performing continuous exploration in a preset time interval, and processing echo signals in real time to generate continuous real-time acoustic impedance signal streams. S3, comparing the real-time acoustic impedance signal flow with an initial acoustic impedance reference, and judging that a collagen degradation event occurs and generating a collagen degradation event signal when detecting that the signal is suddenly reduced in signal amplitude which represents collagen degradation and exceeds a preset threshold value. And