Wearable flexible coagulation monitoring sensor

Abstract

The present application relates to a kind of wearable flexible coagulation monitoring sensor, which is by flexible sensing base, integrated detection circuit, display unit, man-machine interaction unit and wireless communication unit, flexible sensing base is the biocompatibility flexible elastomer base with force-induced color change ability, for carrying each functional unit and feedback sensor's deformation state and fit degree;Integrated detection circuit is wholly prepared on flexible sensing base, through quantum tunneling detection unit gathers blood impedance / reactance change signal, after signal conditioning, analog-digital conversion is transmitted to microcontroller, extracts coagulation monitoring core index, simultaneously realizes data display, man-machine interaction and wireless transmission, its advantage is in that it has the flexible sensor product with high biocompatibility, good flexibility, high degree of integration and self-indication function, it is suitable for long-term wearing or short-term implantation, for the technical effect of in-vivo coagulation monitoring.

Description

Technical Field

[0001] This invention relates to the field of medical information technology applications, and in particular to a wearable flexible coagulation monitoring sensor. Background Technology

[0002] Existing implantable coagulation monitoring devices (such as MXene-based terahertz platforms) typically have a rigid structure, require surgical implantation, and are incompatible with the mechanical properties of human tissue, easily causing rejection, local blood flow disturbance, or thrombosis risks. Terahertz platform systems are usually discrete, with sensors and control circuits separated, resulting in a large overall size, low reliability, and unsuitability for long-term wear or implantation monitoring.

[0003] Currently, no effective solution has been proposed to address the problems of large overall size, low reliability, and unsuitability for long-term wear or implantation monitoring in existing technologies. Summary of the Invention

[0004] The purpose of this invention is to address the shortcomings of existing technologies by providing a wearable flexible coagulation monitoring sensor, thereby solving the technical problems of large overall size, low reliability, and unsuitability for long-term wear or implantation monitoring in existing technologies.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: This invention provides a wearable flexible coagulation monitoring sensor, comprising: a flexible sensing substrate, an integrated detection circuit, a display unit, a human-computer interaction unit, and a wireless communication unit; wherein, the flexible sensing substrate is a biocompatible flexible elastomer substrate with force-sensitive color-changing capability, used to support the integrated detection circuit, display unit, human-computer interaction unit, and wireless communication unit, and simultaneously providing feedback on the sensor's deformation state and fit through its own force-sensitive color-changing characteristics; the integrated detection circuit is integrally fabricated on the flexible sensing substrate, and includes a power management module, a quantum tunneling detection unit, a signal conditioning unit, an analog-to-digital converter unit, and a microcontroller unit; wherein, the output terminal of the power management module is connected to the power supply terminals of the quantum tunneling detection unit, signal conditioning unit, analog-to-digital converter unit, microcontroller unit, display unit, human-computer interaction unit, and wireless communication unit respectively, providing stable power supply for the entire system; the signal output terminal of the quantum tunneling detection unit is connected to the signal input terminal of the signal conditioning unit, used to collect the impedance / ... The signal conditioning unit output is connected to the analog-to-digital converter input for filtering and baseline calibration of the acquired signal. The analog-to-digital converter communicates with the microcontroller unit to convert the conditioned analog signal into a digital signal and transmit it to the microcontroller unit. The microcontroller unit output is connected to the display unit and the wireless communication unit input. The microcontroller unit control unit is connected to the human-machine interface unit (HMI) for algorithmic processing of the received digital signal, extraction of core coagulation monitoring indicators, and control of the display unit, wireless communication unit, and HMI to perform corresponding functions. The display unit displays real-time coagulation monitoring data and coagulation progress curves. The HMI unit provides system function control and status prompts. The wireless communication unit enables wireless transmission of detection data.

[0006] Optionally, the flexible sensing substrate is composed of a biodegradable thermoplastic polyurethane elastomer. Spiropyran derivatives are covalently grafted into the polymer chains of the flexible sensing substrate, giving it the ability to change color upon stretching and fade upon rebound. The flexible sensing substrate is a thin film structure of a preset thickness. The spiropyran derivatives are introduced into the main chain and side chain of the thermoplastic polyurethane elastomer through physical blending, and the flexible sensing substrate undergoes reversible color development and fading within the stretching range.

[0007] Optionally, the quantum tunneling detection unit consists of a pair of parallel-arranged micro-gap gold electrodes, which are fabricated on the surface of a flexible sensing substrate. The micro-gap gold electrodes have a continuous linear structure, a serpentine structure, or a comb-shaped structure. A biological probe that specifically recognizes thrombin is immobilized on the surface of the micro-gap gold electrodes to form a sensing interface. The biological probe is a DNA aptamer or an antibody.

[0008] Optionally, the signal conditioning unit includes: a filter network and a zero-point offset calibration circuit; wherein, the input terminal of the filter network is electrically connected to the output terminal of the quantum tunneling detection unit, and the output terminal of the filter network is electrically connected to the input terminal of the zero-point offset calibration circuit; the zero-point offset calibration circuit completes the zero-point shift setting by acquiring half of the voltage of the negative terminal feed-out power supply, and the output terminal of the zero-point offset calibration circuit is electrically connected to the analog input terminal of the analog-to-digital conversion unit.

[0009] Optionally, the analog-to-digital conversion unit uses an analog-to-digital converter. The analog-to-digital conversion unit is electrically connected to the microcontroller unit via an SPI bus, and the microcontroller unit sends control commands to the analog-to-digital conversion unit via the SPI bus.

[0010] Optionally, the power management module includes a low dropout linear regulator, and outputs a 3.3V digital power supply and a 3.3V-AV analog power supply, forming a power supply closed loop with GND as the common ground.

[0011] Optionally, the human-machine interaction unit includes surface-mount buttons, status indicator lights, a speaker, and a driver transistor. The control terminals of the surface-mount buttons, status indicator lights, speaker, and driver transistor are all electrically connected to the I / O ports of the microcontroller unit.

[0012] Optionally, the flexible sensing substrate has a pre-set correspondence table between color parameters and strain and bending radius, and the correspondence table is written into the microcontroller unit. The microcontroller unit determines the fit of the sensor and the risk of overload based on the color parameters of the flexible sensing substrate. When the color parameters exceed the preset threshold, the microcontroller unit triggers a measurement pause, recalibration, or status prompt command.

[0013] Optionally, the microcontroller unit performs filtering, drift compensation, and feature point detection on the received digital signal, and outputs a coagulation process curve as a phase change curve over time, a loss tangent change curve over time, or an impedance amplitude change curve over time; the microcontroller unit synchronously extracts and outputs the core coagulation monitoring indicators including coagulation initiation time, coagulation rate, stable plateau value, and stabilization time.

[0014] Optionally, the wearable flexible coagulation monitoring sensor has an integrated hierarchical structure, which, from bottom to top, includes: a flexible sensing substrate, an electrode and wiring layer, a circuit mounting area, a packaging and window layer, and an external power supply interface. The electrode and wiring layer is a thin metal film formed on the surface of the flexible sensing substrate, with micro-pitch gold electrodes and flexible wiring formed by photolithography, laser etching, or template transfer. The circuit mounting area is a locally thickened area or a locally reinforced layer reserved in the flexible sensing substrate for mounting corresponding components of the integrated detection circuit. The packaging and window layer is a biocompatible packaging layer covering the circuit area, with a window in the electrode sensing area allowing blood to contact the electrodes. The external power supply interface uses a flexible battery connector, a button battery connector, or an induction coil to provide power input to the system.

[0015] This invention employs the above technical solution, comprising a flexible sensing substrate, an integrated detection circuit, a display unit, a human-computer interaction unit, and a wireless communication unit. The flexible sensing substrate is a biocompatible flexible elastomer substrate with force-induced color change capability, used to support the integrated detection circuit, display unit, human-computer interaction unit, and wireless communication unit. Simultaneously, its force-induced color change characteristics provide feedback on the sensor's deformation state and fit. The integrated detection circuit is fabricated entirely on the flexible sensing substrate and includes a power management module, a quantum tunneling detection unit, a signal conditioning unit, an analog-to-digital converter (ADC), and a microcontroller unit. The output of the power management module is connected to the power supply terminals of the quantum tunneling detection unit, signal conditioning unit, ADC, microcontroller unit, display unit, human-computer interaction unit, and wireless communication unit, providing stable power to the entire system. The signal output of the quantum tunneling detection unit is connected to the signal input of the signal conditioning unit for collecting blood impedance / ... The signal conditioning unit output is connected to the analog-to-digital converter input for filtering and baseline calibration of the acquired signal. The analog-to-digital converter communicates with the microcontroller unit to convert the conditioned analog signal into a digital signal and transmit it to the microcontroller unit. The microcontroller unit output is connected to the display unit and the wireless communication unit input, respectively. The microcontroller unit control unit is connected to the human-machine interface unit. The microcontroller unit processes the received digital signal using algorithms, extracts core coagulation monitoring indicators, and controls the display unit, wireless communication unit, and human-machine interface unit to perform corresponding functions. The display unit displays real-time coagulation monitoring data and coagulation progress curves. The human-machine interface unit provides system function control and status prompts. The wireless communication unit enables wireless transmission of detection data. Compared with existing technologies, this technology offers the following advantages: it features a flexible sensor product with high biocompatibility, good flexibility, high integration, and self-indicating function, suitable for long-term wear or short-term implantation for in vivo coagulation monitoring. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention; Figure 2 This is a schematic diagram of a microcontroller unit in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention; Figure 3 This is a schematic diagram of an analog-to-digital conversion unit in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention; Figure 4 This is a schematic diagram of a power management module in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention; Figure 5 This is a schematic diagram of a display unit in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention; Figure 6 This is a schematic diagram of a human-computer interaction unit in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention; Figure 7 This is a schematic diagram of the internal structure of a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention; Figure 8 This is a schematic diagram of the flexible substrate structure in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention. Detailed Implementation

[0017] To make the objectives, technical solutions, and advantages of this application clearer, the application is described and illustrated below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application. All other embodiments obtained by those skilled in the art based on the embodiments provided in this application without inventive effort are within the scope of protection of this application.

[0018] Obviously, the accompanying drawings described below are merely some examples or embodiments of this application. Those skilled in the art can apply this application to other similar scenarios based on these drawings without any inventive effort. Furthermore, it is understood that although the efforts made in this development process may be complex and lengthy, for those skilled in the art related to the content disclosed in this application, any changes to design, manufacturing, or production based on the technical content disclosed in this application are merely conventional technical means and should not be construed as insufficient disclosure of the content of this application.

[0019] In this application, the reference to "embodiment" means that a specific feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment that is mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described in this application may be combined with other embodiments without conflict.

[0020] Unless otherwise defined, the technical or scientific terms used in this application shall have the ordinary meaning understood by one of ordinary skill in the art to which this application pertains. The terms “a,” “an,” “an,” “the,” and similar words used in this application do not indicate quantity limitation and may indicate singular or plural. The terms “comprising,” “including,” “having,” and any variations thereof used in this application are intended to cover non-exclusive inclusion; for example, a process, method, system, product, or device that includes a series of steps or units (elements) is not limited to the listed steps or units, but may also include steps or units not listed, or may include other steps or units inherent to these processes, methods, products, or devices. The terms “connected,” “linked,” “coupled,” and similar words used in this application are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. The terms “multiple” / “several” used in this application refer to two or more. “And / or” describes the relationship between related objects, indicating that three relationships may exist; for example, “A and / or B” can indicate: A alone, A and B simultaneously, or B alone. The character " / " generally indicates that the preceding and following objects are in an "or" relationship. The terms "first," "second," and "third" used in this application are merely to distinguish similar objects and do not represent a specific ordering of the objects.

[0021] An illustrative embodiment of the present invention, such as Figure 1 As shown, Figure 1 This is a schematic diagram of a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention. The wearable flexible coagulation monitoring sensor provided in this application includes: The system comprises a flexible sensing substrate 10, an integrated detection circuit 12, a display unit 14, a human-computer interaction unit 16, and a wireless communication unit 18. The flexible sensing substrate 10 is a biocompatible flexible elastomer substrate with force-induced color-changing capabilities, used to support the integrated detection circuit 12, display unit 14, human-computer interaction unit 16, and wireless communication unit 18. It also uses its force-induced color-changing characteristics to provide feedback on the sensor's deformation state and fit. The integrated detection circuit 12 is integrally fabricated on the flexible sensing substrate 10 and includes a power management module 121 and a quantum... The system comprises a quantum tunneling detection unit 122, a signal conditioning unit 123, an analog-to-digital converter 124, and a microcontroller unit 125. The output of the power management module 121 is connected to the power supply terminals of the quantum tunneling detection unit 122, signal conditioning unit 123, analog-to-digital converter 124, microcontroller unit 125, display unit 14, human-computer interaction unit 16, and wireless communication unit 18, providing stable power to the entire system. The signal output of the quantum tunneling detection unit 122 is connected to the signal input of the signal conditioning unit 123 for collecting blood impedance / ... The signal conditioner unit 123 is connected to the signal input of the analog-to-digital converter unit 124 to filter and calibrate the acquired signal. The analog-to-digital converter unit 124 is connected to the microcontroller unit 125 to convert the conditioned analog electrical signal into a digital signal and transmit it to the microcontroller unit 125. The output of the microcontroller unit 125 is connected to the input of the display unit 14 and the wireless communication unit 18. The control of the microcontroller unit 125 is connected to the human-machine interface unit 16 to process the received digital signal using algorithms, extract the core indicators of coagulation monitoring, and control the display unit 14, the wireless communication unit 18, and the human-machine interface unit 16 to complete the corresponding functions. The display unit 14 is used to display coagulation monitoring data and coagulation process curves in real time. The human-machine interface unit 16 is used to realize system function control and working status prompts. The wireless communication unit 18 is used to realize wireless transmission of detection data.

[0022] In this embodiment, the display unit 14 is used to display coagulation monitoring data and coagulation progress curves in real time. The display unit 14 uses a flexible OLED screen, which can be integrated with a flexible sensing substrate to display core coagulation monitoring indicators, coagulation progress curves, device operating status, sensor fitment prompts, and other information in real time, allowing users to directly view the monitoring results.

[0023] In this embodiment, the wireless communication unit 18 is used to realize the wireless transmission of detection data. In this embodiment, the wireless communication unit adopts a low-power Bluetooth module, which can transmit the coagulation monitoring data and device status data output by the microcontroller unit to external devices such as mobile phones, tablets, and medical monitoring terminals in real time, so as to realize remote viewing, storage and traceability analysis of data.

[0024] Optionally, the flexible sensing substrate 10 is composed of a biodegradable thermoplastic polyurethane elastomer. Spiropyran derivatives are covalently grafted into the polymer chain of the flexible sensing substrate 10, enabling the flexible sensing substrate 10 to exhibit force-induced color change capability when stretched and faded when rebounded. The flexible sensing substrate 10 is a thin film structure of a preset thickness. The spiropyran derivatives are introduced into the main chain and side chain of the thermoplastic polyurethane elastomer through physical blending, and the flexible sensing substrate 10 undergoes reversible color development and fading within the stretching range.

[0025] Specifically, in this embodiment, the flexible sensing substrate 10 is composed of a biodegradable thermoplastic polyurethane elastomer. Spiropyran derivatives are covalently grafted into the polymer chain of the flexible sensing substrate 10, enabling the flexible sensing substrate to exhibit force-induced color change capability when stretched and faded when rebounded. The flexible sensing substrate 10 is a thin film structure with a preset thickness, preferably 50–300 μm (i.e., the preset thickness in this embodiment), which can be flexibly adjusted according to the fit requirements of the wearable scenario. The spiropyran derivatives are introduced into the main chain and side chain of the thermoplastic polyurethane elastomer through physical blending. By controlling the grafting density of the spiropyran derivatives and the film curing process, the flexible sensing substrate can reversibly exhibit color change and fade within a preset stretching range of 5–50% (i.e., the stretching range in this embodiment), ensuring the sensitivity and repeatability of deformation feedback.

[0026] Furthermore, the flexible sensing substrate 10 has a pre-set correspondence table between color parameters and strain and bending radius. This correspondence table is calibrated through a standardized tensile test before the wearable flexible coagulation monitoring sensor provided in this application embodiment leaves the factory and is written into the microcontroller unit 125. During the operation of the wearable flexible coagulation monitoring sensor provided in this application embodiment, the microcontroller unit 125 determines the fit and overload risk of the sensor based on the real-time color parameters of the flexible sensing substrate. When the color parameters exceed the preset threshold, the microcontroller unit 125 triggers a measurement pause, recalibration, or status prompt command to avoid measurement artifacts caused by sensor debonding or excessive stretching, thereby improving the reliability of the monitoring results.

[0027] It should be noted that when the sensor deforms with human tissue (such as pulse or muscle movement), the TPU substrate is stretched, and the spiropyran molecules inside undergo a ring-opening reaction, resulting in a change in the substrate color, which directly reflects the sensor's working status and fit.

[0028] In this embodiment, the integrated detection circuit 12 is fabricated on the flexible sensing substrate 10. The integrated detection circuit 12 includes a power management module 121, a quantum tunneling detection unit 122, a signal conditioning unit 123, an analog-to-digital conversion unit 124, and a microcontroller unit 125. Each unit is electrically connected through patterned traces on the flexible sensing substrate to form a complete closed loop for signal acquisition and processing.

[0029] Optionally, the quantum tunneling detection unit 122 consists of a pair of parallel-arranged micro-gap gold electrodes, which are fabricated on the surface of the flexible sensing substrate 10. The micro-gap gold electrodes have a continuous linear structure, a serpentine structure, or a comb-shaped structure. A biological probe that specifically recognizes thrombin is fixed on the surface of the micro-gap gold electrodes to form a sensing interface. The biological probe is a DNA aptamer or an antibody.

[0030] Specifically, in this embodiment, the signal output terminal of the quantum tunneling detection unit 122 is connected to the signal input terminal of the signal conditioning unit 123 to collect the impedance / capacitive reactance change signal of blood. The quantum tunneling detection unit 122 consists of a pair of parallel-arranged micro-pitch gold electrodes, which are fabricated on the surface of the flexible sensing substrate 10. The electrode spacing is preferably 1-5 micrometers, and the effective sensing length of a single electrode is preferably 3 centimeters. The micro-pitch gold electrodes can be in the form of a continuous linear structure, a serpentine structure, or a comb-like structure, allowing for adjustment of the electrode shape according to the spatial requirements of the monitoring scenario, balancing flexibility and bending tolerance with effective sensing area. Furthermore, a biological probe that specifically recognizes thrombin is immobilized on the surface of the micro-pitch gold electrodes, forming a sensing interface. The biological probe is a DNA aptamer or antibody, which can achieve specific enrichment of target markers during the coagulation process, improving detection sensitivity and anti-interference capability.

[0031] Optionally, the signal conditioning unit 123 includes a filter network and a zero-point offset calibration circuit; wherein, the input terminal of the filter network is electrically connected to the output terminal of the quantum tunneling detection unit 122, and the output terminal of the filter network is electrically connected to the input terminal of the zero-point offset calibration circuit; the zero-point offset calibration circuit completes the zero-point shift setting by acquiring half the voltage of the negative terminal of the power supply, and the output terminal of the zero-point offset calibration circuit is electrically connected to the analog input terminal of the analog-to-digital conversion unit 124.

[0032] Specifically, in this embodiment, the signal conditioning unit 123 includes a filter network and a zero-point offset calibration circuit. The input of the filter network is electrically connected to the output of the quantum tunneling detection unit, and the output of the filter network is electrically connected to the input of the zero-point offset calibration circuit. This is used to filter out power frequency interference, high-frequency noise, and baseline jitter in the acquired signal, ensuring the purity of the signal to be processed. The zero-point offset calibration circuit completes the zero-point shift setting by feeding half the voltage of the power supply from the negative terminal of the acquisition system. The output of the zero-point offset calibration circuit is electrically connected to the analog input of the analog-to-digital conversion unit, used to eliminate baseline drift caused by electrode polarization and non-specific protein adsorption, establish a stable zero-point reference for the acquisition system, and ensure the consistency of multiple measurement results.

[0033] In this system, micro-pitch electrodes are placed in the blood. When a small AC signal is applied, a sensitive electric field is formed between the electrodes. The change in dielectric properties caused by blood coagulation (from predominantly capacitive in liquids to predominantly resistive in solids) drastically affects the quantum tunneling current or equivalent impedance between the electrodes. This change is captured by the back-end circuitry. At the circuit level, the "blood-electrode interface-micro-pitch electrode gap" is considered as an equivalent impedance network that dynamically evolves with coagulation: initially, it is dominated by dielectric polarization / double-layer capacitance (equivalent to C-dominant). As fibrin networks form and cells / proteins deposit, ion migration is restricted and conductive channels are reconstructed. The system gradually shifts to being dominated by leakage conduction and charge transport loss (equivalent to R-dominant), resulting in a significant transition in the amplitude and phase of the total impedance Z(ω,t). After a small AC signal of fixed frequency / amplitude is applied to the electrodes at the front end, the sensing end maps this change in Z(ω,t) as a change in current amplitude and phase shift. The back-end circuit amplifies and demodulates the current signal through transimpedance amplification / locked-loop amplification (or synchronous detection), extracting the in-phase component III (corresponding to the resistance channel) and the quadrature component Q (corresponding to the capacitance channel), and further calculates the equivalent resistance R(t), equivalent capacitance C(t), or the ratio of the loss tangent tanδ(t) = R to C as it changes with time. The final system output is a "coagulation process curve" (such as tanδ(t), phase...). The trajectory of (t) or R / C ratio over time is used to define repeatable key indicators from the curve: coagulation initiation time (CT / coagulation point), coagulation rate (slope / growth constant), plateau / endpoint (complete coagulation), etc., to achieve quantitative coagulation time, assessment of the effects of anticoagulant / procoagulant drugs, rapid bedside screening, and individualized medication monitoring.

[0034] Optionally, the analog-to-digital conversion unit 124 is an analog-to-digital converter. The analog-to-digital conversion unit 124 is electrically connected to the microcontroller unit 125 via the SPI bus. The microcontroller unit 125 sends control commands to the analog-to-digital conversion unit 124 via the SPI bus.

[0035] Specifically, in this embodiment, the analog-to-digital conversion unit 124 adopts a high-precision analog-to-digital converter to meet the requirements of weak bioelectrical signal acquisition; the analog-to-digital conversion unit 124 is electrically connected to the microcontroller unit 125 through the SPI bus, and the microcontroller unit 125 sends control commands to the analog-to-digital conversion unit 124 through the SPI bus to complete the configuration of acquisition parameters, acquisition start and stop control, and readback of acquisition data.

[0036] Optionally, the power management module 121 includes a low dropout linear regulator. The power management module 121 outputs a 3.3V digital power supply and a 3.3V-AV analog power supply, forming a power supply closed loop with GND as the common ground.

[0037] Specifically, in this embodiment, the power management module 121 outputs a 3.3V digital power supply and a 3.3V-AV analog power supply, forming a closed-loop power supply with GND as the common ground. Through the separate design of the digital and analog power supplies, the interference of digital circuit switching noise on the analog acquisition front end is reduced, ensuring the acquisition accuracy of weak bioelectrical signals. Simultaneously, the power management module 121 is equipped with reverse connection protection, overvoltage surge protection, and ripple suppression circuits to improve the stability and safety of the system power supply.

[0038] Optionally, the human-machine interaction unit 16 includes a surface-mount button, a status indicator light, a speaker, and a driver transistor. The control terminals of the surface-mount button, the status indicator light, the speaker, and the driver transistor are all electrically connected to the I / O ports of the microcontroller unit 125.

[0039] Specifically, the human-machine interface unit 16 is used to realize system function control and working status prompts. The human-machine interface unit 16 includes surface-mount buttons, status indicator lights, a speaker, and a driver transistor. The control terminals of the surface-mount buttons, status indicator lights, speaker, and driver transistor are all electrically connected to the I / O ports of the microcontroller unit 125. The surface-mount buttons are used to realize functions such as start / stop data acquisition, parameter setting, data saving, and system reset. The status indicator lights are used to display information such as power on / off, running status, data transmission status, and abnormal alarms. The speaker and driver transistor work together to realize audio feedback functions such as system abnormal alarms and operation success prompts.

[0040] Optionally, the flexible sensing substrate 10 has a preset correspondence table between color parameters and strain and bending radius, and the correspondence table is written into the microcontroller unit 125. The microcontroller unit 125 determines the fit of the sensor and the risk of overload based on the color parameters of the flexible sensing substrate 10. When the color parameters exceed the preset threshold, the microcontroller unit 125 triggers a measurement pause, recalibration or status prompt command.

[0041] Optionally, the microcontroller unit 125 performs filtering, drift compensation, and feature point detection on the received digital signal, and outputs a coagulation process curve as a phase change curve over time, a loss tangent change curve over time, or an impedance amplitude change curve over time; the microcontroller unit 125 synchronously extracts and outputs the core coagulation monitoring indicators including coagulation initiation time, coagulation rate, stable plateau value, and stabilization time.

[0042] Specifically, in this embodiment, the microcontroller unit 125 filters, compensates for drift, and detects feature points on the received digital signal. The output coagulation process curve is a phase change curve over time, a loss tangent change curve over time, or an impedance amplitude change curve over time. The microcontroller unit 125 synchronously extracts and outputs core coagulation monitoring indicators including coagulation initiation time, coagulation rate, stable plateau value, and stabilization time, realizing quantitative monitoring of the coagulation process. It can be adapted to multiple application scenarios such as anticoagulant drug efficacy evaluation, bedside coagulation screening, and long-term home coagulation indicator monitoring.

[0043] Optionally, in this embodiment, the wearable flexible coagulation monitoring sensor has an integrated hierarchical structure, which includes, from bottom to top: a flexible sensing substrate 10, an electrode and wiring layer, a circuit mounting area, a packaging and window layer, and an external connection power supply interface; wherein, the electrode and wiring layer is a metal thin film formed on the surface of the flexible sensing substrate 10, and micro-pitch gold electrodes and flexible wiring are formed by photolithography, laser etching or template transfer; the circuit mounting area is a locally thickened area or a locally reinforced layer reserved in the flexible sensing substrate 10, used to mount the corresponding components of the integrated detection circuit 12; the packaging and window layer is a biocompatible packaging layer covering the circuit area, and a window is opened in the electrode sensing area to allow blood to contact the electrode; the external connection power supply interface adopts a flexible battery connector, a button battery connector or an induction coil to provide power input to the system.

[0044] Specifically, in this embodiment, the wearable flexible coagulation monitoring sensor has an integrated hierarchical structure, which, from bottom to top, includes: a flexible sensing substrate 10, an electrode and wiring layer, a circuit mounting area, a packaging and window layer, and an external connection power interface. The specific application methods of each layer are as follows: Flexible sensing substrate: It is the bottom layer of the sensor, serving as the supporting substrate for the entire sensor, and also has a deformation self-indication function that changes color due to force. Electrode and wiring layer: A metal thin film formed on the surface of the flexible sensing substrate, through photolithography, laser etching or template transfer to form micro-pitch gold electrodes and flexible wiring, to realize electrical connection between the sensing front end and the back end circuit. Circuit mounting area: A locally thickened area or a locally reinforced layer reserved in the flexible sensing substrate, used to mount corresponding components of the integrated detection circuit, thereby improving the reliability of component mounting and the stability of circuit connection under sensor bending conditions. Encapsulation and window layer: This is a biocompatible encapsulation layer covering the circuit area, and a window is opened in the electrode sensing area to allow blood to come into contact with the electrode; the encapsulation layer provides the circuit with protection against moisture, insulation and antibody liquid erosion, and the electrode sensing window can control the effective contact area between the blood sample and the sensing electrode to prevent liquid from creeping into the circuit area. External power supply interface: Located at the edge of the flexible sensing substrate, it uses a flexible battery connector, button battery connector or induction coil to provide power input to the system, while reserving a connection channel for program download and function expansion.

[0045] It should be noted that the preparation steps of the key components in the embodiments of this application are as follows: Step 1, substrate film formation and mechanochromic construction: TPU solution containing spiropyran grafted monomer / prepolymer is cast or extruded to form a film, and uniform film is obtained by controlling the curing conditions; through stretch-springback cycle pretreatment, the color development threshold and recovery time are stabilized and repeatable, and a color-strain calibration curve is established (for subsequent self-indication interpretation).

[0046] Step 2, Metal Deposition and Patterning: An adhesion layer / gold layer (e.g., 5–20 nm Ti + 50–200 nm Au) is deposited on the TPU surface, and then micro-pitch electrodes and traces are formed by photolithography-wet / dry etching or laser patterning; the micro-pitch is 1–5 μm, and the effective sensing length of the electrode is about 3 cm (which can be a continuous straight line, serpentine or comb-tooth structure to balance flexibility and effective length).

[0047] Step 3, rigid-flexible composite mounting enhancement: Locally laminate PI islands or thicken TPU in the component mounting area to form a "hard island" load-bearing area; use serpentine interconnects in the routing bend transition area to reduce strain concentration.

[0048] Step 4, Component integration and electrical connection: The ADC (Σ-Δ type), MCU, LDO, BLE module and passive devices are fixed in the hard island area by conductive silver paste printing, anisotropic conductive film (ACF) or low temperature soldering / mounting, and electrically connected to the electrode traces; after completion, continuity, impedance and noise floor tests are performed.

[0049] Step 5, Biocompatible Encapsulation and Windowing: The entire circuit area is encapsulated with a film, and windows are opened only in the electrode sensing area; if necessary, hydrophobic / hydrophilic patterns are formed at the window boundaries to control sample wetting and positioning, and to prevent liquid from creeping into the circuit area.

[0050] Step 6, Sterilization and Pre-calibration: The finished product is sterilized (e.g., ethylene oxide or low-temperature plasma; the process should not damage the spiropyran colorimetric and electrode interfaces), and zero-point and gain calibration is completed using a standard medium and written into the MCU parameters.

[0051] In this embodiment, the operation adopts a fixed timing sequence of "interface gating (DC) → reset → linear readout (AC) → I / Q demodulation → index extraction", and the steps are as follows: Step 1, Interface Gating: Negative Bias Binding / Enrichment; Apply a negative DC bias Vbind to the micro-pitch electrode for continuous tbind to enable thrombin to bind / enrich rapidly at the electrode interface and establish a controllable initial state; the purpose of this step is to improve the detectability of interface-related events and shorten the response time of the coagulation phase.

[0052] Step 2, Interface Reset: Positive bias dissociation / desorption; then apply a positive DC bias Vreleas continuously treleaset to promote the dissociation and desorption of the bound thrombin and "zero" the interface state, so as to reduce the memory effect and batch drift caused by protein adsorption and double layer polarization, and ensure the consistency of long-term multiple measurements.

[0053] Step 3, AC small-signal readout: impedance shift from C-dominant to R-dominant; after removing the DC bias, apply a small AC excitation VCV (fixed frequency or narrow band) and acquire the current response. The coagulation process causes the system to gradually shift from capacitance-dominant to resistance-dominant, resulting in a identifiable transition in the amplitude and phase of the complex impedance Z(ω,t).

[0054] Step 4, Circuit Processing: Transimpedance Amplification and Synchronous Detection / Phase-Locked Loop; The current signal is first converted into voltage by transimpedance amplification, and then the in-phase component I(t) and quadrature component Q(t) are obtained by synchronous detection / phase-locked loop demodulation, and then calculated: phase (t) = arctan(Q / I) (reflects C→R transfer) Or loss factor / equivalent ratio (such as tanδ(t) or monotonic characterization of R / C). The MCU performs filtering, drift compensation, and feature point detection on the above curve.

[0055] The output of this embodiment is a coagulation process curve ( (t), tanδ(t)\tan\delta(t)tanδ(t) or |Z(t)|), and automatically provides: coagulation time CT, coagulation rate (threshold slope), endpoint plateau value / stabilization time; used for in vivo / surface coagulation monitoring, anticoagulant / procoagulant efficacy assessment, bedside screening and personalized medication monitoring.

[0056] To make the "visualization of deformation state" feasible in engineering, the embodiments of this application further specify: Color-Strain Calibration: Each device is stretched and calibrated at the factory stage to establish a correspondence table between color parameters (such as RGB or spectral peaks) and strain / bending radius, and write it into the MCU or APP to determine the fit and overload risk.

[0057] Self-indicating linkage protection: When the color indication exceeds the preset threshold (corresponding to overstretching or delamination), the system can automatically trigger measurement pause, re-gating, or prompt re-attachment to avoid electrical artifacts caused by abnormal mechanical conditions.

[0058] Consistency enhancement mechanism: A dual stabilization mechanism is formed through "positive and negative gating reset + mechanical self-indication error correction": on the one hand, it suppresses interface memory drift, and on the other hand, it eliminates false signals introduced by deformation.

[0059] In a preferred embodiment, the wearable coagulation monitoring patch is packaged as a skin patch. The electrode window interfaces with a microfluidic / blood collection needle structure to collect a small blood sample, which enters the electrode window. The device is attached to the wrist, forearm, or other areas. After attachment, a gating reset procedure is performed to establish a baseline. Subsequently, it enters AC readout mode, outputting coagulation curves and CT parameters in real time, which are then transmitted to a mobile phone via Bluetooth. When the patch undergoes slight deformation due to pulse and muscle movement, spiropyran colorimetry provides a visual indication of the adhesion status. When colorimetry indicates detachment / overstretching, the system prompts for re-attachment or automatic recalibration.

[0060] In summary, as Figure 2 As shown, Figure 2 This is a schematic diagram of a microcontroller unit in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention. In this embodiment, the microcontroller unit consists of an STM32F103C8T6, a 5032 active surface-mount crystal oscillator, a 32768Hz passive crystal oscillator, a W25Q16, and a ULN2803. like Figure 2As shown, the STM32F103C8T6, designated U2, serves as the main control chip. It includes a complete GPIO interface and clock circuit. During operation, the STM32F103C8T6 is a 32-bit ARM-based MCU with 64kB Flash and 20kB internal RAM. Its operating temperature range is -40℃ to +85℃, making it the control core of the entire circuit and fully realizing all the functions of the microcontroller unit. In terms of connectivity, it connects to the analog-to-digital converter unit 124, Flash memory, and display unit via the SPI bus (SCLK, DIN, CS, D / C pins). It connects to the acquisition electrodes, buttons, and indicator lights of the human-machine interface unit 16 via I / O ports such as PA05 / PA07. It connects to the wireless communication unit via the USART interface, along with the RX1 / TX1 status indicator lights. The ULN2803 driver chip enhances its high-current driving capability, adapting to peripherals such as speakers and relays.

[0061] The 5032 active surface mount crystal oscillator, designated Y1, provides the main clock reference for the STM32F103C8T6 core, ensuring the stability of program execution and communication timing.

[0062] The 32768Hz passive crystal oscillator, designated Y2 and packaged in 3215, provides a clock source for the STM32F103C8T6's built-in RTC real-time clock. It is used for timestamp recording of acquired data, adapting to the data traceability requirements for long-term monitoring.

[0063] The W25Q16 device, designated U3, uses a 16Mbit SPI serial Flash memory to store system programs, acquisition calibration parameters, and historical coagulation monitoring data, thus meeting the offline data storage requirements of this embodiment.

[0064] The ULN2803 device, designated U4, uses an 8-channel NPN Darlington transistor array to enhance the high-current drive capability of the main control I / O port, adapting to the driving requirements of peripherals such as speakers and relays, corresponding to the drive circuit of the human-machine interaction unit 16 in this embodiment.

[0065] In addition, the STM32F103C8T6 includes a reset circuit (NRST) and a BOOT0 configuration pin.

[0066] like Figure 3 As shown, Figure 3This is a schematic diagram of an analog-to-digital converter (ADC) unit in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention. In this embodiment, the ADC unit 124 can be an AD7793BRUZ, a high-precision Σ-Δ type ADC designed specifically for low-noise, weak bioelectrical signals. In terms of circuit connections, the analog input terminal is connected to the front-end micro-pitch gold electrode (i.e., the quantum tunneling detection unit in this embodiment), the SPI communication interface (CS, SCLK, DIN) is connected to the main control STM32, and the power supply terminal is connected to a 3.3V-AV analog power supply. Strict digital ground / analog ground separation design is implemented to reduce noise interference and achieve high-precision digital conversion of analog signals. The AD7793 needs to be added for acquisition below 100mV. An internal zero-point offset setting is set; after zero-point shift, half the power supply voltage is fed back from the negative acquisition terminal, requiring a capacitor for voltage stabilization. Furthermore, by setting a 560KΩ matching resistor, the front-end gain adjustment and impedance matching resistor of the ADC, in conjunction with the zero-point offset calibration circuit, achieve baseline stability.

[0067] The analog-to-digital conversion unit 124 includes a precision resistor network (R22 150K) and filter capacitors (C25-C26) to ensure signal quality; the electrode input channel is connected to pins such as PA05, PA06, and PA07.

[0068] like Figure 4 As shown, Figure 4 This is a schematic diagram of the power management module in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention. In this embodiment, the power management module 121 can be a REG1117-3, 800mA low dropout positive linear regulator (LDO), with a fixed output voltage of 3.3V. It is the core component of the power management module 121, providing a stable 3.3V digital power supply and a 3.3V-AV analog power supply for the entire system. Specifically, this embodiment uses separate 3.3V digital power supply / 3.3V-AV analog power supply and digital GND / analog GND to reduce the interference of digital circuit switching noise on the analog acquisition front end, ensuring the acquisition accuracy of weak signals and fully meeting the coagulation signal acquisition requirements of this embodiment.

[0069] In this embodiment, the REG1117-3 / SOT223 regulator (U1) converts the input voltage to a stable 3.3V; multiple filter capacitors (C1-C5, 10μF) ensure power supply stability; the power management module 121 also includes a TVS protection diode (D1 SMBJ6.8CA) and a rectifier diode (D2 SS34).

[0070] like Figure 5 As shown, Figure 5This is a schematic diagram of a display unit in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention. In this embodiment, the display unit 14 is a 1.29-inch OLED, which is connected to the main controller via the SPI bus through the RES, D / C, SCLK, DIN, and CS control pins. It is used to display the coagulation process curve, acquisition parameters, and system status in real time, which fully matches the display requirements of this embodiment.

[0071] like Figure 6 As shown, Figure 6 This is a schematic diagram of a human-machine interface unit in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention. In this embodiment, the patch button of the human-machine interface unit can be a YTSD003A0502504B6*6 patch button, used to control functions such as start / stop data acquisition, parameter setting, and data saving. Furthermore, the status indicator light of the human-machine interface unit can be a 0603 patch LED, corresponding to working states such as power supply, operation, serial port transmission / reception, and data saving.

[0072] like Figure 7 and Figure 8 As shown, Figure 7 This is a schematic diagram of the internal structure of a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention. Figure 8 This is a schematic diagram of the flexible substrate structure in a wearable flexible coagulation monitoring sensor according to an embodiment of the present invention.

[0073] This invention employs the above technical solution, comprising a flexible sensing substrate, an integrated detection circuit, a display unit, a human-computer interaction unit, and a wireless communication unit. The flexible sensing substrate is a biocompatible flexible elastomer substrate with force-induced color change capability, used to support the integrated detection circuit, display unit, human-computer interaction unit, and wireless communication unit. Simultaneously, its force-induced color change characteristics provide feedback on the sensor's deformation state and fit. The integrated detection circuit is integrally fabricated on the flexible sensing substrate and includes a power management module, a quantum tunneling detection unit, a signal conditioning unit, an analog-to-digital converter unit, and a microcontroller unit. The output terminal of the power management module is connected to the power supply terminals of the quantum tunneling detection unit, signal conditioning unit, analog-to-digital converter unit, microcontroller unit, display unit, human-computer interaction unit, and wireless communication unit, providing stable power to the entire system. The signal output terminal of the quantum tunneling detection unit is connected to the signal input terminal of the signal conditioning unit for collecting blood impedance / The signal conditioning unit output is connected to the analog-to-digital converter input for filtering and baseline calibration of the acquired signal. The analog-to-digital converter communicates with the microcontroller unit to convert the conditioned analog signal into a digital signal and transmit it to the microcontroller unit. The microcontroller unit output is connected to the display unit and the wireless communication unit input. The microcontroller unit control unit is connected to the human-machine interface unit. The microcontroller unit processes the received digital signal using algorithms, extracts core coagulation monitoring indicators, and controls the display unit, wireless communication unit, and human-machine interface unit to perform corresponding functions. The display unit displays real-time coagulation monitoring data and coagulation progress curves. The human-machine interface unit provides system function control and status prompts. The wireless communication unit enables wireless transmission of detection data. Compared with existing technologies, this technology offers the following advantages: it features a flexible sensor product with high biocompatibility, good flexibility, high integration, and self-indicating function, suitable for long-term wear or short-term implantation for in vivo coagulation monitoring.

[0074] The above description is merely a preferred embodiment of the present invention and does not limit the implementation and protection scope of the present invention. Those skilled in the art should realize that any equivalent substitutions and obvious changes made based on the description and illustrations of the present invention should be included within the protection scope of the present invention.

Claims

1. A wearable flexible coagulation monitoring sensor, characterized in that, include: The system comprises a flexible sensing substrate, integrated detection circuitry, a display unit, a human-computer interaction unit, and a wireless communication unit; among which, The flexible sensing substrate is a biocompatible flexible elastomer substrate with force-induced color change capability, used to support the integrated detection circuit, the display unit, the human-computer interaction unit and the wireless communication unit, and at the same time, it uses its own force-induced color change characteristics to provide feedback on the deformation state and fit of the sensor. The integrated detection circuit is fabricated entirely on the flexible sensing substrate, and includes a power management module, a quantum tunneling detection unit, a signal conditioning unit, an analog-to-digital converter unit, and a microcontroller unit; wherein... The output of the power management module is connected to the power supply terminals of the quantum tunneling detection unit, the signal conditioning unit, the analog-to-digital conversion unit, the microcontroller unit, the display unit, the human-computer interaction unit, and the wireless communication unit, respectively, to provide a stable power supply for the entire system. The signal output terminal of the quantum tunneling detection unit is connected to the signal input terminal of the signal conditioning unit, and is used to collect the impedance / capacitive reactance change signal of the blood. The signal output terminal of the signal conditioning unit is connected to the signal input terminal of the analog-to-digital conversion unit, and is used to perform filtering and baseline calibration processing on the acquired signal. The analog-to-digital conversion unit is communicatively connected to the microcontroller unit and is used to convert the conditioned analog electrical signal into a digital signal and transmit it to the microcontroller unit. The output terminal of the microcontroller unit is connected to the input terminal of the display unit and the wireless communication unit respectively. The control terminal of the microcontroller unit is connected to the human-computer interaction unit, which is used to perform algorithm processing on the received digital signal, extract the core indicators of coagulation monitoring, and control the display unit, the wireless communication unit, and the human-computer interaction unit to complete the corresponding functions. The display unit is used to display coagulation monitoring data and coagulation process curves in real time. The human-computer interaction unit is used to realize system function control and work status prompts; The wireless communication unit is used to realize the wireless transmission of detection data.

2. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The flexible sensing substrate is composed of a biodegradable thermoplastic polyurethane elastomer. Spiropyran derivatives are covalently grafted into the polymer chains of the flexible sensing substrate, giving it the ability to change color upon stretching and fade upon rebound. The flexible sensing substrate is a thin film structure of a predetermined thickness. The spiropyran derivatives are introduced into the main chain and side chains of the thermoplastic polyurethane elastomer through physical blending. The flexible sensing substrate undergoes reversible color development and fading within the stretching range.

3. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The quantum tunneling detection unit consists of a pair of parallel-arranged micro-gap gold electrodes, which are fabricated on the surface of the flexible sensing substrate. The micro-gap gold electrodes have a continuous linear structure, a serpentine structure, or a comb-like structure. A biological probe that specifically recognizes thrombin is fixed on the surface of the micro-gap gold electrodes to form a sensing interface. The biological probe is a DNA aptamer or an antibody.

4. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The signal conditioning unit includes: a filter network and a zero-point offset calibration circuit; wherein... The input terminal of the filter network is electrically connected to the output terminal of the quantum tunneling detection unit, and the output terminal of the filter network is electrically connected to the input terminal of the zero-point offset calibration circuit. The zero-point offset calibration circuit completes the zero-point translation setting by acquiring half the voltage of the negative terminal power supply. The output terminal of the zero-point offset calibration circuit is electrically connected to the analog input terminal of the analog-to-digital conversion unit.

5. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The analog-to-digital conversion unit is an analog-to-digital converter. The analog-to-digital conversion unit is electrically connected to the microcontroller unit via an SPI bus. The microcontroller unit sends control commands to the analog-to-digital conversion unit via the SPI bus.

6. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The power management module includes a low dropout linear regulator. The power management module outputs a 3.3V digital power supply and a 3.3V-AV analog power supply, forming a power supply closed loop with GND as the common ground.

7. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The human-computer interaction unit includes a surface-mount button, a status indicator light, a speaker, and a driver transistor. The control terminals of the surface-mount button, the status indicator light, the speaker, and the driver transistor are all electrically connected to the I / O ports of the microcontroller unit.

8. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The flexible sensing substrate has a preset correspondence table between color parameters and strain and bending radius, and the correspondence table is written into the microcontroller unit. The microcontroller unit determines the fit and overload risk of the sensor based on the color parameters of the flexible sensing substrate. When the color parameters exceed the preset threshold, the microcontroller unit triggers a measurement pause, recalibration, or status prompt command.

9. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The microcontroller unit filters, compensates for drift, and detects feature points on the received digital signal. The output coagulation process curve is a phase change curve over time, a loss tangent change curve over time, or an impedance amplitude change curve over time. The core coagulation monitoring indicators extracted and output by the microcontroller unit simultaneously include coagulation initiation time, coagulation rate, stable plateau value, and stabilization time.

10. The wearable flexible coagulation monitoring sensor according to claim 1, characterized in that, The wearable flexible coagulation monitoring sensor has an integrated hierarchical structure, which, from bottom to top, includes: a flexible sensing substrate, an electrode and wiring layer, a circuit mounting area, a packaging and window layer, and an external connection power interface; wherein... The electrode and wiring layer are metal thin films formed on the surface of the flexible sensing substrate, and micro-pitch gold electrodes and flexible wiring are formed by photolithography, laser etching or template transfer. The circuit mounting area is a locally thickened area or a locally reinforced layer reserved in the flexible sensing substrate, used to mount the corresponding components of the integrated detection circuit; the encapsulation and window layer is a biocompatible encapsulation layer covering the circuit area, and a window is opened in the electrode sensing area to allow blood to contact the electrode. The external power supply interface uses a flexible battery connector, a button battery connector, or an induction coil to provide power input to the system.

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