Wearable multi-index sweat patch for post-liver transplantation monitoring and application thereof
Patent Information
- Application Number
- CN202611188777.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-08-06
- Publication Date
- 2026-09-25
AI Technical Summary
[0005]为解决现有技术中现有可穿戴汗液传感产品多集中于单一指标检测,且未能将胆红素、谷丙转氨酶、乳酸和pH四种关键指标的检测单元集成于单一可穿戴汗液贴片,无法实现肝移植术后多指标的高灵敏同步检测及实时无线传输的问题,本发明提供了一种制备方法可行、结构集成度高、适合批量化生产并具有临床应用前景的可穿戴汗液监测平台,提供了一种肝移植术后监测的可穿戴多指标汗液贴片及其应用
1、本发明提供了肝移植术后监测的可穿戴多指标汗液贴片,通过微流控芯片微流控汗液采集模块实现汗液采集和分流,通过多通道电化学传感器(电化学传感单元)实现胆红素、谷丙转氨酶、乳酸和pH四种关键指标的同步检测,并通过无线传输模块将检测结果实时上传至终端设备,为肝移植术后护理提供一种新型的无创动态监测技术手段。具体地,所述可穿戴多指标汗液贴片整体贴附于人体皮肤表面,自靠近皮肤的一侧至远离皮肤的一侧依次包括微流控汗液采集模块、多指标电化学传感电极、信号处理电路和无线传输模块。电化学传感单元包括分别对应设置于不同独立检测腔的胆红素检测单元、谷丙转氨酶检测单元、乳酸检测单元和pH检测单元,胆红素检测单元采用金气凝胶作为敏感元件,谷丙转氨酶检测单元以铂镍气凝胶作为敏感元件,乳酸检测单元以氧化铜气凝胶作为敏感元件,pH检测单元以聚苯胺作为敏感元件,各检测单元分别用于将对应待测指标转化为电化学检测信号;信号处理电路与所述电化学传感单元电连接,用于对各路电化学检测信号进行放大、滤波、模数转换和数字分析;无线传输模块与所述信号处理电路电连接,用于将经处理后的实时检测数据向外传输至外部终端。
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Figure CN122805258A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of wearable sensor technology, specifically relating to a wearable multi-index sweat patch for post-liver transplant monitoring and its application. Background Technology
[0002] Liver transplantation is an important treatment for end-stage liver disease, acute liver failure, and some complex hepatobiliary diseases. After liver transplantation, patients may experience problems such as graft function fluctuations, ischemia-reperfusion injury, biliary complications, infection, inadequate perfusion, and metabolic abnormalities during the perioperative period and early recovery. Therefore, continuous, dynamic, and timely biochemical monitoring of postoperative patients is of great significance.
[0003] Clinically, existing monitoring methods mostly rely on blood analysis and laboratory tests. Although they are highly accurate, they have problems such as being highly invasive, having limited sampling frequency, difficulty in achieving continuous real-time monitoring, poor patient comfort, and a heavy nursing burden, making it difficult to meet the needs of high-frequency dynamic monitoring after liver transplantation.
[0004] With the development of wearable technology and electrochemical biosensing technology, sweat, as a non-invasive bodily fluid, has been widely used for dynamic monitoring of biochemical indicators such as glucose, lactic acid, and electrolytes due to its advantages of convenient sampling, minimal irritation to patients, suitability for long-term wear, and continuous monitoring. However, existing wearable sweat sensor products mostly focus on single-indicator detection and have failed to integrate the detection units of four key indicators—bilirubin, alanine aminotransferase, lactic acid, and pH—into a single wearable sweat patch. This makes it impossible to achieve highly sensitive simultaneous detection and real-time wireless transmission of multiple indicators after liver transplantation. Summary of the Invention
[0005] To address the shortcomings of existing wearable sweat sensor products, which primarily focus on single-indicator detection and fail to integrate detection units for four key indicators—bilirubin, alanine aminotransferase (ALT), lactate, and pH—into a single wearable sweat patch, thus hindering high-sensitivity simultaneous detection and real-time wireless transmission of multiple indicators after liver transplantation, this invention provides a wearable sweat monitoring platform with a feasible preparation method, high structural integration, suitability for mass production, and promising clinical applications. It also provides a wearable multi-indicator sweat patch for post-liver transplantation monitoring and its application. To achieve the above objectives, this invention adopts the following technical solution:
[0006] This invention provides a wearable multi-index sweat patch for post-liver transplant monitoring, comprising: The microfluidic sweat collection module is used to attach to the patient's skin surface and collect and transport sweat that seeps from the skin surface.
[0007] An electrochemical sensing unit is disposed on the microfluidic sweat collection module and connected to the sweat output terminal of the microfluidic sweat collection module. The electrochemical sensing unit includes multiple detection units, each of which is used to conduct an electrochemical reaction with a corresponding target component in the sweat and output a corresponding electrochemical detection signal. The multiple detection units include at least a bilirubin detection unit for detecting bilirubin in sweat, an alanine aminotransferase (ALT) detection unit for detecting ALT in sweat, a lactic acid detection unit for detecting ALT in sweat, and a pH detection unit for detecting the pH (acidity / alkalinity) of sweat. The bilirubin detection unit uses gold aerogel as the sensitive element, the ALT detection unit uses platinum-nickel aerogel as the sensitive element, the lactic acid detection unit uses copper oxide aerogel as the sensitive element, and the pH detection unit uses polyaniline as the sensitive element.
[0008] The signal processing circuit, electrically connected to the electrochemical sensing unit, is used to receive and process the electrochemical detection signal and generate corresponding real-time detection data.
[0009] The wireless transmission module is electrically connected to the signal processing circuit and is used to transmit the real-time detection data to the terminal device.
[0010] This invention proposes a wearable multi-index sweat patch for post-liver transplant monitoring. It integrates a microfluidic sweat collection module, an electrochemical sensing unit, a signal processing circuit, and a wireless transmission module into a single patch. The electrochemical sensing unit simultaneously incorporates four detection units for bilirubin, alanine aminotransferase (ALT), lactate, and pH. Each detection unit uses gold aerogel, platinum-nickel aerogel, copper oxide aerogel, and polyaniline as sensing elements, respectively. These detection units are embedded within independent detection chambers of the microfluidic sweat collection module, allowing for the directional diversion of sweat samples to each independent detection area for synchronous electrochemical reactions during the same collection period, achieving high levels of four key indicators. This device features sensitive and highly selective parallel detection. Simultaneously, it utilizes signal processing circuitry to amplify, filter, convert analog-to-digital, and perform digital analysis on multiple electrochemical signals. Real-time detection values and trends are then synchronously transmitted to an external terminal via a wireless transmission module. This addresses the limitations of existing wearable sweat sensor products, which often focus on single-indicator detection and fail to integrate detection units for four key indicators—bilirubin, alanine aminotransferase (ALT), lactate, and pH—into a single wearable sweat patch. This prevents highly sensitive, simultaneous detection and real-time wireless transmission of multiple indicators after liver transplantation. The device provides a compact, multi-dimensional, and real-time visualized integrated non-invasive monitoring method for post-liver transplant care.
[0011] Preferably, the bilirubin detection unit, alanine aminotransferase detection unit, lactate detection unit, and pH detection unit all adopt a three-electrode system, each including three sensing elements: a working electrode, a reference electrode, and a counter electrode. The working electrode surface of each detection unit is sequentially modified with gold aerogel, platinum-nickel aerogel, copper oxide aerogel, and polyaniline. The reference electrode is an Ag / AgCl electrode, and the counter electrode is a carbon electrode. The patterns of the working electrode, reference electrode, and counter electrode are formed on the flexible substrate by screen printing, and the sensing area of each electrode is defined by an insulating layer.
[0012] Preferably, the gold aerogel is a three-dimensional porous aerogel material prepared by reduction reaction of chloroauric acid precursor salt, gelation induced by p-toluenesulfonic acid and freeze drying, and is modified on the working electrode surface of the bilirubin detection unit in the form of a dispersion by drop coating.
[0013] Preferably, the alanine aminotransferase (ALT) detection unit utilizes the electrocatalytic response of platinum-nickel aerogel to hydrogen peroxide to achieve indirect quantitative detection of ALT.
[0014] The platinum-nickel aerogel was prepared by liquid-phase reduction-self-assembly in a water-ethanol mixed solvent using chloroplatinic acid and nickel chloride as metal precursors and sodium borohydride as a reducing agent. It was then modified onto the working electrode surface of the alanine aminotransferase detection unit by drop coating.
[0015] Preferably, the copper oxide aerogel is prepared by one-step gelation and heat treatment with sodium borohydride, and then modified onto the working electrode surface of the lactic acid detection unit by drop coating.
[0016] Preferably, the polyaniline is formed on the surface of the working electrode of the pH detection unit by electrochemical deposition, for detecting H+ in sweat. + Changes in concentration generate a potential response, which in turn causes the pH detection unit to generate an electrochemical signal.
[0017] Preferably, the microfluidic sweat collection module includes a microfluidic chip, which comprises a flexible substrate, a sweat inlet layer (inlet layer), a microfluidic channel network, and four independent detection chambers. The sweat inlet layer is located on the side of the flexible substrate facing the patient's skin surface and has multiple sweat collection holes with a pore size of 0.5 mm for collecting sweat from the skin surface. The microfluidic channel network is located inside the flexible substrate and is connected to the four independent detection chambers for diverting and delivering the collected sweat to the four independent detection chambers. The four independent detection chambers correspond to the bilirubin detection unit, the alanine aminotransferase (ALT) detection unit, the lactate detection unit, and the pH detection unit, respectively, for partitioning and storing the collected sweat, so that the sweat in each detection chamber comes into contact with the corresponding detection unit and undergoes a specific reaction, thereby achieving simultaneous and independent detection of bilirubin, ALT, lactate, and pH.
[0018] Preferably, the microfluidic channel network is a parallel channel network, and each of the four independent detection chambers is directly connected to the corresponding sweat collection hole through an independent microfluidic channel.
[0019] Preferably, the microfluidic sweat collection module further includes a PI encapsulation film, which is located between the flexible substrate and the electrochemical sensing unit, or disposed on the side of the electrochemical sensing unit away from the flexible substrate, for encapsulating and protecting the electrochemical sensing unit, signal processing circuit and wireless transmission module.
[0020] Preferably, the flexible substrate is made of polydimethylsiloxane and constitutes the main support structure of the microfluidic sweat collection module; the inner wall of the microfluidic channel network is hydrophilicated to enhance the transport capacity of sweat in the microchannels.
[0021] Preferably, the signal processing circuit includes four independent preamplifier circuits, a multi-channel filter circuit, an analog-to-digital converter (ADC), and a microprocessor. The input terminals of the four independent preamplifier circuits are electrically connected to the signal output terminals of the bilirubin detection unit, the alanine aminotransferase (ALT) detection unit, the lactate detection unit, and the pH detection unit, respectively. The output terminals of the four independent preamplifier circuits are electrically connected to the corresponding input channels of the multi-channel filter circuit. The output terminal of the multi-channel filter circuit is electrically connected to the analog input terminal of the ADC. The digital output terminal of the ADC is electrically connected to the I / O port of the microprocessor. The microprocessor is connected to an external terminal via a data bus for outputting detection values. Simultaneously, the four independent preamplifier circuits, the multi-channel filter circuit, the ADC, and the microprocessor are all mounted on the same flexible circuit board and arranged sequentially along the signal transmission direction. The flexible circuit board is attached to the side of the flexible substrate facing away from the patient's skin surface, forming a stacked structure with the microfluidic chip.
[0022] The four independent preamplifier circuits correspond to the bilirubin detection unit, alanine aminotransferase detection unit, lactate detection unit, and pH detection unit, respectively. Each preamplifier circuit is composed of an operational amplifier and is used to initially amplify the weak electrochemical signals output by the corresponding detection unit.
[0023] The multi-channel filtering circuit is composed of a low-pass filter, which is used to filter out high-frequency noise interference in each channel.
[0024] The analog-to-digital converter is integrated into the microprocessor and is used to convert the analog electrochemical signal, after preliminary amplification and high-frequency noise interference filtering, into a digital signal.
[0025] The microprocessor is used to analyze, process, and convert the digital signal to concentration, and extract the real-time detection values (real-time detection values of bilirubin, alanine aminotransferase, lactate and pH) corresponding to the bilirubin detection unit, alanine aminotransferase detection unit, lactate detection unit and pH detection unit.
[0026] Preferably, the wireless transmission module is a Bluetooth module, used to realize the real-time wireless transmission of the real-time detection values (bilirubin, alanine aminotransferase, lactic acid and sweat pH detection data) corresponding to the bilirubin detection unit, alanine aminotransferase detection unit, lactic acid detection unit and pH detection unit.
[0027] The external terminal is a mobile terminal used for data reception, storage, visualization, trend analysis, and joint trend indication of real-time detection values (four indicators) of the bilirubin detection unit, alanine aminotransferase detection unit, lactate detection unit, and pH detection unit during the same collection period.
[0028] The Bluetooth module uses the Bluetooth Low Energy protocol to transmit the multi-index detection data processed by the signal processing circuit to the mobile terminal in real time, so that the mobile terminal can simultaneously display the real-time detection values (four indicators) of the bilirubin detection unit, alanine aminotransferase detection unit, lactate detection unit and pH detection unit, the real-time values, changing trends and joint trend prompts.
[0029] The present invention also provides the application of the wearable multi-index sweat patch in postoperative nursing monitoring after liver transplantation.
[0030] Preferably, the application is used for dynamic, continuous, and non-invasive monitoring of bilirubin, alanine aminotransferase, lactic acid, and sweat pH levels in patients after liver transplantation. The synchronous trends of these four indicators provide nursing staff with information on changes in graft function, changes in hepatocyte injury-related enzyme activity, perfusion metabolic status, and acid-base status, as well as trend indicators.
[0031] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention provides a wearable multi-index sweat patch for post-liver transplant monitoring. It utilizes a microfluidic chip-based microfluidic sweat collection module to collect and divert sweat, and a multi-channel electrochemical sensor (electrochemical sensing unit) to simultaneously detect four key indicators: bilirubin, alanine aminotransferase (ALT), lactate, and pH. The detection results are then wirelessly transmitted to a terminal device in real time, providing a novel non-invasive dynamic monitoring technology for post-liver transplant care. Specifically, the wearable multi-index sweat patch is attached to the surface of the skin and, from the side closest to the skin to the side furthest away, sequentially includes a microfluidic sweat collection module, multi-index electrochemical sensing electrodes, a signal processing circuit, and a wireless transmission module. The electrochemical sensing unit includes a bilirubin detection unit, an alanine aminotransferase (ALT) detection unit, a lactate detection unit, and a pH detection unit, each located in a separate detection chamber. The bilirubin detection unit uses gold aerogel as the sensing element, the ALT detection unit uses platinum-nickel aerogel, the lactate detection unit uses copper oxide aerogel, and the pH detection unit uses polyaniline. Each detection unit converts the corresponding analyte into an electrochemical detection signal. The signal processing circuit is electrically connected to the electrochemical sensing unit and is used to amplify, filter, perform analog-to-digital conversion, and perform digital analysis on the various electrochemical detection signals. The wireless transmission module is electrically connected to the signal processing circuit and is used to transmit the processed real-time detection data to an external terminal.
[0032] With the above-described structure, sweat on the skin surface is first collected and directed by the microfluidic sweat collection module, and then distributed to independent detection chambers via the sweat output end of the microfluidic sweat collection module. Subsequently, the bilirubin detection unit, alanine aminotransferase detection unit, lactic acid detection unit, and pH detection unit in each detection chamber use gold aerogel, platinum-nickel aerogel, copper oxide aerogel, and polyaniline sensitive elements to simultaneously detect bilirubin, alanine aminotransferase, lactic acid, and sweat pH, forming four independent electrochemical response signals. The signal processing circuit then processes, analyzes, and converts the above four signals in a unified manner, and uploads them to an external terminal in real time via a wireless transmission module. Therefore, this invention enables non-invasive sweat collection, simultaneous multi-indicator detection, real-time signal processing, and wireless transmission on a single wearable patch platform. Simultaneously, the structural design, with each detection unit independently positioned in a different detection chamber, reduces sweat cross-contamination, sample evaporation, and signal interference during multi-indicator detection. Furthermore, the high specific surface area and high catalytic activity of the aerogel sensing element enhance the detection sensitivity and selectivity for low-concentration biomarkers, thereby improving the stability, accuracy, and continuity of the detection results. This provides a dynamic, continuous, and non-invasive method for collecting multi-indicator information for post-liver transplant nursing monitoring and recovery assessment.
[0033] 2. Compared with existing wearable sweat sensor products, the present invention also has the following advantages: (1) Synergistic integration of aerogel sensing elements enhances the ability to detect multiple indicators simultaneously: This invention employs gold aerogel, platinum-nickel aerogel, and copper oxide aerogel as key sensitive elements for bilirubin, alanine aminotransferase (ALT), and lactate, respectively. All three types of aerogel possess a three-dimensional porous structure and a large specific surface area, providing abundant active sites and enhancing interfacial electron transport capabilities, thereby improving detection sensitivity, stability, and anti-interference ability. By integrating these four types of detection units on a single flexible platform, simultaneous monitoring of key biochemical indicators after liver transplantation is achieved.
[0034] (2) The microfluidic sweat collection module enables efficient sweat collection and independent diversion, improving detection accuracy: This invention integrates a microfluidic sweat collection module into a patch system, enabling precise guidance, efficient distribution, and transport of sweat. Through optimized microfluidic channels and a multi-detection chamber structure, sample collection and diversion can be completed even with minimal sweat volume, reducing sweat evaporation, contamination, and mixing during transport, thereby improving the accuracy and reproducibility of multi-index detection.
[0035] (3) Epidermal sweat patches enable continuous dynamic non-invasive monitoring of key indicators after liver transplantation: Unlike traditional blood analysis methods that rely on static, point-based detection, this invention enables dynamic, continuous, and non-invasive monitoring of bilirubin, alanine aminotransferase (ALT), lactate, and pH levels. Simultaneous monitoring of these four indicators provides more complete dynamic information for postoperative care, offering greater overall value than individual testing of any single indicator. The skin patch can be worn for extended periods and is suitable for various scenarios, including ICUs, general wards, postoperative recovery periods, and home follow-ups.
[0036] (4) It has a clear product transformation path and clinical application prospects: The patch structure of this invention has a high degree of integration and the manufacturing process is operable, making it suitable for standardized and mass production. In addition to serving post-liver transplant nursing monitoring, it can also be extended to scenarios such as follow-up of hepatobiliary diseases, perioperative monitoring, and monitoring of drug-induced liver injury, and has high clinical translational value.
[0037] More importantly, the technical features of this invention work synergistically around the same technical problem. First, the microfluidic sweat collection module diverts samples from the same sweat collection period to four independent detection chambers, ensuring that the four indicators have the same or similar sampling time basis, while reducing liquid cross-contamination and signal interference. Second, gold aerogel, platinum-nickel aerogel, and copper oxide aerogel are respectively matched with the electrocatalytic detection of bilirubin oxidation, alanine aminotransferase transamination-coupling product hydrogen peroxide, and lactic acid electrochemical detection. The selection of these three materials is determined by the target reaction pathway, not by arbitrary material substitution. Third, although the polyaniline pH unit can be considered a mature pH-responsive material, it works synchronously with the other three detections in this invention, providing both an acid-base metabolism dimension and a reference for the acid-base state of the sweat matrix, thereby improving the reliability of the joint trend interpretation of the four indicators. Fourth, the four-channel signal processing and wireless transmission module uniformly converts the above signals into real-time values and trend curves, enabling caregivers to simultaneously observe hepatocyte damage, bile excretion, perfusion metabolism, and acid-base state changes on a continuous time axis.
[0038] Therefore, the inventiveness of this invention lies in the overall technical solution of "specific clinical nursing scenarios, specific combination of four indicators, specific aerogel / polyaniline functional allocation, specific microfluidic independent compartments, and four-channel synchronous trend display". Generally, multi-channel sensors do not naturally derive the combination of four indicators (bilirubin, alanine aminotransferase, lactate, and pH) and corresponding material configurations for post-liver transplant nursing monitoring.
[0039] The monitoring described in this invention is used for nursing monitoring, recovery assessment information collection, and trend indication, without directly providing disease diagnosis or treatment conclusions. For clinical translation, an individual baseline and trend consistency model can be further established based on the patient's initial postoperative time window or paired blood test results; this model is an application calibration method for the detection data of this invention and does not change the core structure and detection principle of the patch of this invention. Attached Figure Description
[0040] Figure 1 This is a schematic diagram of the overall structure of the wearable multi-index sweat patch for post-liver transplant monitoring in this invention.
[0041] Figure 2 This is a schematic diagram of the microfluidic chip structure provided in an embodiment of the present invention.
[0042] Figure 3 This is a schematic diagram of the microfluidic chip fabrication process provided in the embodiments of the present invention.
[0043] Figure 4 This is a schematic diagram of the preparation process of gold aerogel for bilirubin detection provided in an embodiment of the present invention.
[0044] Figure 5This is a schematic diagram of the preparation process of PtNi aerogel for alanine aminotransferase detection provided in an embodiment of the present invention.
[0045] Figure 6 This is a schematic diagram of the preparation process of CuO aerogel for lactic acid detection provided in an embodiment of the present invention.
[0046] Figure 7 This is an electrochemical response curve of the bilirubin detection unit provided in an embodiment of the present invention; wherein: A shows the differential pulse voltammetry curves of the gold aerogel sensing electrode in bilirubin at concentrations of 1 µmol / L, 10 µmol / L, 100 µmol / L, 2000 µmol / L and 5000 µmol / L. B is the calibration curve of the gold aerogel sensing electrode at the above bilirubin concentration. C represents the it response curve of the gold aerogel sensing electrode in the presence of bilirubin and interfering substances.
[0047] Figure 8 This is an electrochemical response curve of the alanine aminotransferase (ALT) detection unit provided in an embodiment of the present invention; wherein: A shows the differential pulse voltammetry curves of the platinum-nickel aerogel sensing electrode in alanine aminotransferase at concentrations of 1 mM, 10 mM, 100 mM, 1000 mM, and 2000 mM. B is the calibration curve of the platinum-nickel aerogel sensing electrode at the above-mentioned alanine aminotransferase concentration. C is the it response curve of the platinum-nickel aerogel sensing electrode in the presence of alanine aminotransferase and interfering substances.
[0048] Figure 9 This is an electrochemical response curve of the lactic acid detection unit provided in an embodiment of the present invention; wherein: A shows the it response curves of the copper oxide aerogel sensing electrode in lactic acid at concentrations of 0, 1 mM, 5 mM, 10 mM, 20 mM, 30 mM and 40 mM. B is the calibration curve of the copper oxide aerogel sensing electrode at the above lactic acid concentration. C represents the it response curve of the copper oxide aerogel sensing electrode in the presence of lactic acid and interfering substances.
[0049] Figure 10 This is an electrochemical response curve of the pH detection unit provided in an embodiment of the present invention; wherein: A shows the OCP-t response curves of the polyaniline sensing electrode in PBS at pH 3, 4, 5, 6, 7, 8, and 9. B is the calibration curve of the polyaniline sensing electrode at the above pH; C represents the OCP-t response curve of the polyaniline sensing electrode under pH and in the presence of interfering substances.
[0050] Figure 11 This is a schematic diagram of the mobile terminal display interface and trend analysis provided in an embodiment of the present invention. Detailed Implementation
[0051] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments, but this should not be construed as limiting the invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following embodiments are commercially available unless otherwise specified.
[0052] Example 1 This invention provides a wearable multi-index sweat patch (epidermal sweat patch) for post-liver transplant monitoring, the structure of which is as follows: Figure 1 As shown, it includes a microfluidic sweat collection module, an electrochemical sensing unit, a signal processing circuit, and a wireless transmission module that are sequentially stacked and electrically connected, enabling continuous monitoring and remote display of bilirubin, alanine aminotransferase, lactic acid, and pH concentrations.
[0053] The microfluidic sweat collection module serves as the bottom layer of the patch, including a microfluidic chip. The microfluidic chip uses a flexible circular PDMS substrate with a diameter of 20mm and a thickness of 1mm. Eight fixed adhesive wings are evenly distributed along the circumference for adhering to the skin. A sweat inlet layer is provided on the side of the substrate facing the skin. This inlet layer has a double-row staggered array of circular sweat collection holes with a pore size of 0.5mm and a spacing of 0.2mm, which is used to guide sweat from the skin surface to the collection area. The substrate contains a parallel microfluidic channel network and four independent detection chambers. Each detection chamber has a diameter of 6mm and a depth of 4mm. Each chamber is directly connected to the corresponding sweat collection hole through an independent microfluidic channel, which is used to divert and deliver the collected sweat to each detection chamber.
[0054] The electrochemical sensing unit is located on the side of the microfluidic chip away from the skin and includes a bilirubin detection unit, an alanine aminotransferase detection unit, a lactate detection unit, and a pH detection unit. The four detection units are respectively located in four independent detection chambers, and each detection unit includes a working electrode, a reference electrode, and a counter electrode. The working electrode of the bilirubin detection unit is coated with a gold aerogel sensitive material, which is prepared by reduction reaction of chloroauric acid precursor salt, gelation induced by p-toluenesulfonic acid, and freeze-drying. The working electrode of the alanine aminotransferase (ALT) detection unit is coated with a platinum-nickel aerogel, which is prepared by one-step gelation with sodium borohydride using chloroplatinic acid and nickel chloride as precursor salts. The aerogel is used to achieve indirect quantitative detection of ALT by utilizing its electrocatalytic response to hydrogen peroxide. The working electrode of the lactate detection unit is coated with a copper oxide aerogel, which is prepared by one-step gelation with sodium borohydride and heat treatment. The working electrode of the pH detection unit is coated with a polyaniline sensitive film formed by electrochemical deposition, which is used to generate a potential response to changes in H⁺ concentration in sweat.
[0055] The signal processing circuit is located on the side of the electrochemical sensing unit away from the microfluidic chip, and includes four independent preamplifier circuits, a multi-channel filter circuit, an analog-to-digital converter, and a microprocessor. The four preamplifier circuits correspond to the four detection units, each consisting of an operational amplifier, and are used to initially amplify the weak electrochemical signals. The multi-channel filter circuit consists of a low-pass filter, used to filter out high-frequency noise. The analog-to-digital converter is integrated into the microcontroller unit to convert analog signals into digital signals. The microprocessor analyzes, processes, and converts the digital signals to concentration, and extracts the real-time detection values of the four indicators.
[0056] The wireless transmission module is a Bluetooth Low Energy module, located on the side of the signal processing circuit away from the electrochemical sensing unit. It is used to wirelessly transmit the processed multi-index detection data to the mobile terminal in real time. After receiving the data, the mobile terminal stores, visualizes, analyzes the trend of change, and provides joint trend prompts for the four indicators under the same collection period. It simultaneously displays the real-time values and trend curves of bilirubin, alanine aminotransferase, lactate, and pH.
[0057] When the wearable multi-index sweat patch provided by this invention is used, the sweat is applied to the skin surface of the patient's upper arm. The sweat enters the microfluidic channel network through the collection hole of the microfluidic chip entry layer and is directionally diverted to four independent detection chambers. It comes into contact with the sensitive material on the working electrode surface of each detection unit and undergoes an electrochemical reaction to generate an electrochemical signal. After the signal is pre-amplified, filtered, converted from analog to digital and analyzed digitally, it is transmitted to a mobile terminal in real time via Bluetooth module, realizing continuous, synchronous and non-invasive monitoring of four key indicators: bilirubin, alanine aminotransferase, lactate and pH after liver transplantation.
[0058] The working process of the wearable multi-index sweat patch provided by this invention is as follows: First, a microfluidic device (microfluidic sweat collection module) guides and collects sweat from the skin surface and diverts it to the bilirubin electrochemical sensing detection chamber, the alanine aminotransferase (ALT) electrochemical sensing detection chamber, the lactate electrochemical sensing detection chamber, and the pH electrochemical sensing detection chamber. After receiving the current / potential signals output by the corresponding sensors of each electrochemical sensing unit, an analog circuit with an amplifier amplifies the acquired signals, and a low-pass filter removes interference signals and environmental noise, thereby extracting the effective response signals. Next, a microcontroller-based analog-to-digital converter converts the analog current signals into digital signals. After further analysis and processing, the digital signals yield real-time bilirubin, ALT, lactate, and pH concentration data. Subsequently, a Bluetooth module, as a wireless communication unit, transmits the processed digital data to a mobile terminal in real time. Finally, users can intuitively view the real-time detection results on a mobile phone interface or nursing platform and analyze the trends of the above indicators, assisting postoperative care personnel in dynamic monitoring.
[0059] Example 2: Fabrication of a microfluidic chip The microfluidic chip (microfluidic structure) in this embodiment includes six sweat inlets, six flow channels, four independent detection chambers, and four connected outlets.
[0060] Furthermore, the microfluidic structure consists of a liquid inlet with a diameter of 0.5 mm and four detection chambers corresponding to the electrochemical sensing and detection chambers for bilirubin, alanine aminotransferase, lactate, and pH, respectively.
[0061] The bilirubin electrochemical sensing chamber has a major axis diameter of 8 mm and a minor axis diameter of 6 mm; the alanine aminotransferase (ALT), lactate, and pH electrochemical sensing chambers all have a major axis diameter of 8 mm and a minor axis diameter of 4 mm. The depth of each channel and all four sensing chambers is 0.2 mm.
[0062] The specific steps for fabricating microfluidic chips using molding technology are as follows: (1) Based on the structural dimensions of the above six sweat inlets, six flow channels, four independent detection chambers and four outlets, a microfluidic mold with corresponding raised patterns was prepared (Anhui Chixin Biotechnology Co., Ltd.); wherein, the raised patterns correspond to the inlet connection area, flow channel, bilirubin electrochemical sensing detection chamber, alanine aminotransferase electrochemical sensing detection chamber, lactic acid electrochemical sensing detection chamber, pH electrochemical sensing detection chamber and outlet connection area in the microfluidic chip respectively.
[0063] (2) Prepare PDMS slurry (Hangzhou Weisicheng Technology Co., Ltd.) at a mass ratio of PDMS monomer to curing agent of 10:1. After thorough mixing, place the resulting PDMS slurry in a vacuum environment and let it stand for 30 minutes to remove air bubbles generated during the mixing process. After the air bubbles are removed, slowly pour the PDMS slurry onto the surface of the pre-prepared microfluidic mold, so that the PDMS slurry fully covers the microchannels and detection cavity protrusions on the mold, and avoids leaving air bubbles in the microstructure area.
[0064] (3) The microfluidic mold containing the PDMS slurry is heated and cured at 60°C to allow the PDMS to fully cross-link and form. After curing, the formed PDMS layer is peeled off from the microfluidic mold to obtain the PDMS microfluidic chip layer.
[0065] (4) The obtained PDMS microfluidic chip layer is cleaned and dried, and the side that is attached to the sensing electrode is subjected to plasma hydrophilic treatment to improve the hydrophilicity of the inner wall of the microfluidic channel and the sweat transport capacity. After hydrophilic treatment, the PDMS microfluidic chip layer is aligned and attached to the pre-prepared multi-index electrochemical sensing electrode, so that the bilirubin electrochemical sensing detection cavity corresponds to the working electrode area of the bilirubin detection unit, the alanine aminotransferase electrochemical sensing detection cavity corresponds to the working electrode area of the alanine aminotransferase detection unit, the lactate electrochemical sensing detection cavity corresponds to the working electrode area of the lactate detection unit, and the pH electrochemical sensing detection cavity corresponds to the working electrode area of the pH detection unit.
[0066] (5) During use, sweat from the skin surface enters the microfluidic chip through six sweat inlets. Guided by the flow channel, it is diverted and transported to four independent detection chambers, which then contact the corresponding bilirubin detection unit, alanine aminotransferase detection unit, lactate detection unit, and pH detection unit, respectively, thereby achieving simultaneous detection of four indicators within the same sweat collection period. The above structure can improve the efficiency of collection and transport of trace amounts of sweat, reduce cross-contamination between different detection areas, and provide a stable supply of sweat samples for subsequent multi-indicator electrochemical detection.
[0067] Example 3: Preparation of gold aerogel sensing working electrode Chloroauric acid (25.6 µL, 10 wt%) was used as a precursor salt, sodium citrate (256 mg) was added as a protecting ligand, and ascorbic acid (1 M, 1 mL) was used as a reducing agent to prepare a gold nanoparticle solution via a one-pot wet chemical method. Subsequently, p-toluenesulfonic acid (0.1 M, 50 µL) was used as a destabilizing agent to induce the controlled assembly of gold nanoparticles to form a gold gel. After freeze-drying, a three-dimensional porous gold aerogel material was obtained.
[0068] The gold aerogel material was thoroughly dispersed in ultrapure water to obtain a concentration of 1 mg / mL.‒1 A gold aerogel dispersion was prepared. Using a physical adsorption method, 5 µL of the gold aerogel dispersion was pipetted onto the surface of a blank working electrode, followed by a layer of chitosan (0.5 wt%, 3 µL) to prevent material detachment. The modified gold aerogel was in the microgram range. No functionalization was performed on the electrode or the reference electrode, resulting in a gold aerogel-modified bilirubin sensing working electrode.
[0069] Among them, the gold aerogel sensing working electrode is the working electrode of the bilirubin detection unit.
[0070] Example 4: Fabrication of PtNi aerogel sensing working electrode Using chloroplatinic acid (46.8 µL, 10 wt%) and nickel chloride (100 µL, 0.1 M) as precursor salts, the mixture was prepared by passing sodium borohydride (1 mL, 20 mg / mL). ‒1 PtNi gel was prepared by a one-step reduction method; PtNi aerogel material (platinum-nickel aerogel) was further prepared by freeze drying.
[0071] The PtNi aerogel material was thoroughly dispersed in ultrapure water to obtain a concentration of 1 mg / mL. ‒1 A PtNi aerogel dispersion was prepared. Using a physical adsorption method, 5 µL of the PtNi aerogel dispersion was pipetted onto the surface of a blank working electrode to obtain a platinum-nickel aerogel sensing working electrode. This PtNi aerogel sensing working electrode is the working electrode of the alanine aminotransferase (ALT) detection unit.
[0072] Subsequently, a layer of pyruvate oxidase (1 mg / mL) was modified onto the surface of the platinum-nickel aerogel working electrode. ‒1 (5µL) to complete the construction of the cascade enzyme reaction system.
[0073] The alanine aminotransferase (ALT) detection unit also includes a pre-set substrate system and a coupling reaction system. The substrate system comprises alanine and α-ketoglutarate. After the target ALT enters the detection chamber, it undergoes a transamination reaction to produce pyruvate and glutamate. Subsequently, the coupling reaction system further generates hydrogen peroxide from the reaction products. Because PtNi aerogel exhibits excellent electrocatalytic performance for hydrogen peroxide, the content of pyruvate oxidase can be indirectly characterized by the electrochemical response signal of the generated hydrogen peroxide.
[0074] Example 5: Preparation of copper oxide aerogel sensing working electrode Using copper chloride (100 µL, 0.1 M) as the precursor salt, the solution was prepared by reacting sodium borohydride (1 mL, 20 mg / mL). ‒1 Copper gel was prepared by a one-step reduction method; copper aerogel was further prepared by freeze-drying. After pyrolysis treatment (air atmosphere, 5℃ min)... ‒1The heating rate was increased to 300℃ and calcined for 3 hours to obtain CuO aerogel material (copper oxide aerogel).
[0075] The copper oxide aerogel material was thoroughly dispersed in ultrapure water to obtain a concentration of 1 mg / mL. ‒1 A CuO aerogel dispersion was prepared. Using a physical adsorption method, 5 µL of the CuO aerogel dispersion was pipetted onto the surface of a blank working electrode to obtain a CuO aerogel-modified lactic acid sensing working electrode. This CuO aerogel sensing working electrode serves as the working electrode for the lactic acid detection unit.
[0076] Subsequently, a layer of Nafion was applied to the surface of the copper oxide aerogel electrode to prevent material detachment. The mass of the modified CuO aerogel was in the microgram range, and neither the electrode nor the reference electrode underwent functionalization modification.
[0077] Example 6: Preparation of polyaniline pH sensing working electrode A polyaniline film was formed on the surface of a blank sensing working electrode by electrochemical deposition in a solution containing aniline (0.1M) and hydrochloric acid (1M). The polyaniline film can react with H... + Changes in concentration trigger a proton doping / dedoping process, resulting in a stable potential response.
[0078] Among them, the polyaniline pH sensing working electrode is the working electrode of the pH detection unit.
[0079] Example 7: Performance Verification of the Bilirubin Detection Unit (1) Differential pulse voltammetry was performed on bilirubin at different concentrations using a gold aerogel-modified bilirubin detection unit (hereinafter referred to as the bilirubin detection unit). Specifically, a bilirubin stock solution (10 mM) was prepared and stored under light-protected conditions. Before use, the bilirubin stock solution was serially diluted with PBS buffer to prepare bilirubin standard solutions of different concentrations. The concentration range of the bilirubin standard solutions was 1 μM to 5000 μM, and the preferred concentration gradients included 1 μM, 10 μM, 50 μM, 100 μM, 500 μM, 1000 μM, 2000 μM, and 5000 μM. Differential pulse voltammetry was performed using an electrochemical workstation. Preferably, the potential scan range of the differential pulse voltammetry was 0 V to 0.6 V, the pulse amplitude was 50 mV, the pulse width was 50 ms, and the potential step was 4 mV. Each concentration of bilirubin standard solution was tested at least three times, and the bilirubin oxidation peak current value was recorded.
[0080] Experimental results show that the bilirubin oxidation peak current gradually increases with increasing bilirubin concentration; within the range of 1 μM to 5000 μM, the bilirubin concentration and the response current exhibit a good linear relationship, and the linear correlation coefficient R of the calibration curve is [value missing]. 2=0.998.
[0081] (2) Further, the chronoamperometry method was used to analyze glucose, lactic acid, urea, uric acid, ascorbic acid, and sodium. + K + NH 4+ and Cl - Common sweat interfering agents were tested for their response. Glucose, lactic acid, urea, uric acid, and ascorbic acid were prepared using appropriate standards; Na+, K+, NH4+, and Cl- were provided by sodium chloride, potassium chloride, and ammonium chloride, respectively. The electrochemical responses of blank artificial sweat, bilirubin standard solution, and test solutions containing the aforementioned interfering agents were tested using a chronoamperometry method. Preferably, the bilirubin standard solution concentration was 100 μM, and the interfering agent concentration was set according to a range higher than common concentrations in human sweat to evaluate the detection unit's anti-interference ability in the complex sweat matrix.
[0082] The results showed that the current change caused by the aforementioned interfering substances was significantly lower than the response caused by bilirubin, indicating that the bilirubin detection unit has the advantage of target response and anti-interference capability.
[0083] Example 8: Performance Verification of Alanine Aminotransferase Detection Unit A PtNi aerogel-modified alanine aminotransferase (ALT) detection unit (hereinafter referred to as ALT detection unit) was used for ALT concentration gradient testing. First, an ALT stock solution containing alanine and α-ketoglutarate was prepared using phosphate buffer as a solvent. Subsequently, the ALT stock solution was serially diluted to prepare ALT standard solutions of 1 U / L, 10 U / L, 50 U / L, 100 U / L, 500 U / L, 1000 U / L, and 2000 U / L. During detection, ALT standard solutions of different concentrations were added to the ALT detection unit. ALT catalyzes the transamination reaction between alanine and α-ketoglutarate to produce pyruvate and glutamate. The generated pyruvate is further converted into hydrogen peroxide by pyruvate oxidase. The electrocatalytic response signal of the PtNi aerogel-modified working electrode to hydrogen peroxide was detected using an electrochemical workstation. Experimental results showed that the alanine aminotransferase (ALT) detection unit exhibited a concentration-dependent response to different ALT concentrations; within the range of 1 U / L to 2000 U / L, the ALT concentration showed a good linear relationship with the response signal, R0. 2 =0.999.
[0084] Further differential pulse voltammetry was used to analyze glucose, lactic acid, bilirubin, urea, uric acid, ascorbic acid, and sodium. + K + Mg 2+ and Cl -Common sweat interfering agents were used for response testing. The interfering agent preparation was described in Example 7. The differential pulse voltammetry method was employed to test the electrochemical responses of the alanine aminotransferase standard solution and the test solution containing the aforementioned interfering agents, in order to evaluate the detection unit's anti-interference capability in the complex sweat matrix.
[0085] In the anti-interference experiment, glucose, lactic acid, bilirubin, urea, uric acid, ascorbic acid, and sodium were used. + K + Mg 2+ and Cl - The components had little impact on the alanine aminotransferase (ALT) detection signal, while the corresponding response of ALT was significantly enhanced, demonstrating that the ALT detection unit can achieve target detection in the context of complex sweat components.
[0086] Example 9: Performance Verification of Lactic Acid Detection Unit A CuO aerogel-modified lactate detection unit (hereinafter referred to as the lactate detection unit) was used for lactate gradient response and concentration calibration tests. Specifically, a 100 mM lactate stock solution was prepared and stored under light-protected conditions. Before use, the lactate stock solution was serially diluted with PBS buffer to prepare lactate standard solutions of different concentrations. The concentration range of the lactate standard solutions was 0–40 mM, with preferred concentration gradients including 0 mM, 1 mM, 5 mM, 10 mM, 20 mM, 30 mM, and 40 mM. Chronoamperometry was performed using an electrochemical workstation. Preferably, the detection potential for chronoamperometry was 0.2 V.
[0087] Experimental results show that the current signal increases stepwise with increasing lactic acid concentration; within the range of 0–40 mM, the lactic acid concentration and the response current exhibit a good linear relationship, R0 2 =0.992. Further analysis was conducted using a chronoamperometry method to determine the levels of glucose, urea, uric acid, ascorbic acid, bilirubin, and sodium. + K + and Cl - Common sweat interfering agents were used for response testing. The interfering agent preparation was described in Example 7. In the interfering agent test, the baseline current of blank artificial sweat was first recorded, and then the aforementioned interfering agents and lactic acid standard solutions were added separately. The changes in current caused by each component were compared.
[0088] In selective testing, glucose, urea, uric acid, ascorbic acid, bilirubin, and sodium were tested. + K + and Cl - The response caused by interfering substances is low, while the response caused by lactic acid is significantly stronger, indicating that the CuO aerogel lactic acid detection unit has good target response and anti-interference ability.
[0089] Example 10: Performance Verification of pH Detection Unit A polyaniline-modified pH sensing unit was used to test the potential response under different pH conditions. Experimental results showed that pH changes induced stable stepwise potential changes; within the pH range of 3-9, pH value and potential response exhibited a good linear relationship, R0. 2 =0.985. In the interference test, sweat components such as glucose, lactic acid, urea, ascorbic acid, and common ions had little impact on the pH detection potential, demonstrating that the pH detection unit can maintain a stable response in complex sweat environments.
[0090] Example 11 The portable electrochemical workstation comprises electrode connection terminals, four independent preamplifier circuits, a multi-channel low-pass filter circuit, an analog-to-digital converter (ADC), a microcontroller unit, a Bluetooth wireless transmission module, and a power supply module. The electrode connection terminals are electrically connected to the electrode leads of the bilirubin, alanine aminotransferase (ALT), lactate, and pH detection units, respectively, to receive the electrochemical signals output from these four units. The four independent preamplifier circuits correspond to the bilirubin, ALT, lactate, and pH detection channels, respectively, and are used to initially amplify the weak current or potential signals output by each detection unit. The multi-channel low-pass filter circuit filters out high-frequency noise and environmental interference in each detection channel. The ADC converts the amplified and filtered analog signals into digital signals. The microcontroller unit acquires, analyzes, and converts the four digital signals, and obtains real-time detection values for bilirubin, ALT, lactate, and pH based on pre-established calibration curves.
[0091] The Bluetooth wireless transmission module is electrically connected to the microcontroller unit and uses Bluetooth Low Energy communication. The microcontroller unit encapsulates the data for four tests—bilirubin, alanine aminotransferase (ALT), lactate, and pH—according to channel number and acquisition time, and then transmits the data to the mobile terminal via the Bluetooth wireless transmission module. Upon receiving the data, the mobile terminal displays and stores it as real-time values, change curves, or combined trend indicators.
[0092] The power supply module provides operating power to the four-channel preamplifier circuit, multi-channel low-pass filter circuit, analog-to-digital converter, microcontroller unit, and Bluetooth wireless transmission module. The power supply module is an external low-voltage power supply module and includes a voltage regulator circuit to ensure power stability during signal acquisition and wireless transmission.
[0093] Example 12: Simultaneous Detection and Application of Multiple Indicators The wearable multi-index sweat patch prepared according to this invention was attached to the forearm, upper arm, chest, or other suitable sweat-collecting sites of subjects (patients in the Surgical ICU of the First Affiliated Hospital of Xi'an Jiaotong University. Informed consent was obtained from both patients and their families before the trial, and the trial process strictly followed the regulations of the Ethics Committee of Xi'an Jiaotong University). After the wearable multi-index sweat patch was in operation, the microfluidic chip continuously collected and diverted sweat, and the bilirubin detection unit, alanine aminotransferase detection unit, lactate detection unit, and pH detection unit simultaneously generated electrochemical response signals. The signal processing circuit processed the four signals in real time, and the Bluetooth module uploaded the detection results to the terminal. Figure 11 The mobile terminal can simultaneously display the real-time values of four indicators: bilirubin, alanine aminotransferase, lactate, and pH, and present their corresponding trend curves.
[0094] The above experimental results demonstrate that this invention does not simply list multiple detection elements, but rather achieves simultaneous monitoring of multiple indicators through microfluidic shunt, independent response of multiple detection chambers, four-channel electrochemical signal processing, and wireless terminal display. In post-liver transplant care, nurses can observe changes in graft function, hepatocyte damage, and perfusion metabolic status by combining dynamic changes in bilirubin, alanine aminotransferase, lactate, and pH, providing auxiliary evidence for post-operative observation and nursing assessment.
[0095] Example 13: Validation of synergistic effect and application in post-liver transplant nursing monitoring In Examples 7 to 10, the four detection units—bilirubin detection unit, alanine aminotransferase detection unit, lactate detection unit, and pH detection unit—each exhibited target analyte concentration-dependent response and anti-interference capability. In Example 12, the four detection units were integrated into the same microfluidic patch, and real-time values and trend curves were synchronously displayed via a mobile terminal. Therefore, this invention is not a mechanical parallel arrangement of multiple individual electrodes, but rather completes diversion, independent detection, four-channel electrical signal processing, and synchronous display within the same sweat sample collection time window.
[0096] In post-liver transplant care, bilirubin readings alone primarily indicate changes in bile excretion and hepatocyte metabolic function; alanine aminotransferase (ALT) readings alone primarily indicate changes in hepatocyte injury-related enzyme activity; and lactate or pH readings alone primarily indicate changes in perfusion and metabolic balance. When all four indicators are obtained simultaneously, the interconnected trends of these different physiological dimensions can be displayed on the same timeline, providing nurses with more complete post-operative dynamic information than a single indicator. In particular, pH signals can serve as a reference for the acid-base state of the same sweat sample, forming a metabolic state dimension together with lactate, and helping to explain the dynamic changes of bilirubin, ALT, and lactate signals in the sweat matrix.
[0097] The mobile terminal (i.e., the mobile app HY-FlexiSens equipped with the portable electrochemical workstation) uses the patient's postoperative set time window or initial test values as an individual baseline to calculate the relative changes of four indicators: bilirubin, alanine aminotransferase (ALT), lactate, and pH, and displays four trend curves or combined trend indicators. These combined trend indicators are only used for nursing monitoring and recovery assessment information collection and do not directly output disease diagnoses or treatment plans.
[0098] For further clinical validation, sweat patch readings and routine blood test results can be collected from the same patient at similar time points to establish trend consistency or individual calibration relationships between sweat readings and blood indicators. Even before a universal absolute conversion relationship is established, this invention can still provide dynamic information as a continuous, non-invasive, homologous sample four-indicator trend monitoring device, and its technical effect differs from traditional offline blood testing and single-indicator sweat sensors.
[0099] The experimental results above show that this invention is not a simple combination of multiple single detection electrodes, but rather a collaborative system that achieves continuous, dynamic, and non-invasive joint monitoring of bile excretion, hepatocyte damage, perfusion metabolism, and acid-base status after liver transplantation through the coordinated use of microfluidic homogeneous flow splitting, independent detection of four indicators, synchronous processing of four signals, and wireless trend display. This significantly improves the synchronicity, completeness, and clinical reference value of postoperative nursing monitoring information.
[0100] It should be noted that when numerical ranges are involved in this invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. To avoid redundancy, this invention describes preferred embodiments.
[0101] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments, all of which fall within the scope of the invention.
Claims
1. A wearable multi-index sweat patch for post-liver transplant monitoring, characterized in that, include: The microfluidic sweat collection module is used to attach to the patient's skin surface and collect and transport sweat that seeps from the skin surface; An electrochemical sensing unit is disposed on the microfluidic sweat collection module and connected to the sweat output terminal of the microfluidic sweat collection module. The electrochemical sensing unit includes multiple detection units, each of which is used to undergo an electrochemical reaction with a corresponding target component in the sweat and output a corresponding electrochemical detection signal. The multiple detection units include at least a bilirubin detection unit for detecting bilirubin in sweat, an alanine aminotransferase (ALT) detection unit for detecting alanine aminotransferase (ALT) in sweat, a lactic acid detection unit for detecting ALT in sweat, and a pH detection unit for detecting the pH of sweat. The bilirubin detection unit uses gold aerogel as the sensing element, the ALT detection unit uses platinum-nickel aerogel as the sensing element, the lactic acid detection unit uses copper oxide aerogel as the sensing element, and the pH detection unit uses polyaniline as the sensing element. A signal processing circuit, electrically connected to the electrochemical sensing unit, is used to receive and process the electrochemical detection signal and generate corresponding real-time detection data. The wireless transmission module is electrically connected to the signal processing circuit and is used to transmit the real-time detection data to the terminal device.
2. The wearable multi-index sweat patch according to claim 1, characterized in that, The gold aerogel is a three-dimensional porous aerogel material prepared by reduction reaction of chloroauric acid precursor salt, gelation induced by p-toluenesulfonic acid and freeze drying, and is modified on the working electrode surface of the bilirubin detection unit in the form of a dispersion by drop coating.
3. The wearable multi-index sweat patch according to claim 1, characterized in that, The platinum-nickel aerogel was prepared by liquid-phase reduction-self-assembly in a water-ethanol mixed solvent using chloroplatinic acid and nickel chloride as metal precursors and sodium borohydride as a reducing agent. It was then modified onto the working electrode surface of the alanine aminotransferase detection unit by drop coating.
4. The wearable multi-index sweat patch according to claim 1, characterized in that, The copper oxide aerogel was prepared by one-step gelation and heat treatment with sodium borohydride, and then modified onto the working electrode surface of the lactic acid detection unit by drop coating.
5. The wearable multi-index sweat patch according to claim 1, characterized in that, The polyaniline is formed on the working electrode surface of the pH detection unit by electrochemical deposition, and is used to detect H in sweat. + Changes in concentration generate a potential response, which in turn causes the pH detection unit to generate an electrochemical signal.
6. The wearable multi-index sweat patch according to claim 1, characterized in that, The microfluidic sweat collection module includes a microfluidic chip, which comprises a flexible substrate, a sweat inlet layer, a microfluidic channel network, and four independent detection chambers. The sweat inlet layer is located on the side of the flexible substrate facing the patient's skin surface and has multiple sweat collection holes for collecting sweat from the skin surface. The microfluidic channel network is located inside the flexible substrate and is connected to the four independent detection chambers, used to divert and transport the collected sweat to the four independent detection chambers. The four independent detection chambers correspond to the bilirubin detection unit, the alanine aminotransferase (ALT) detection unit, the lactate detection unit, and the pH detection unit, respectively, for partitioning and storing the collected sweat, so that the sweat in each detection chamber comes into contact with the corresponding detection unit and undergoes a specific reaction, thereby achieving simultaneous and independent detection of bilirubin, ALT, lactate, and pH.
7. The wearable multi-index sweat patch according to claim 6, characterized in that, The microfluidic channel network is a parallel channel network, and the four independent detection chambers are each directly connected to the corresponding sweat collection hole through an independent microfluidic channel.
8. The application of the wearable multi-index sweat patch as described in claim 1 in postoperative nursing monitoring after liver transplantation.