Real-time drift correction electronic sensing system and detection method based on smart phone

Abstract

The invention provides a real-time drift correction electronic sensing system based on a smart phone and a detection method. The real-time drift correction electronic sensing system comprises a sensing integrated chip, an electronic signal acquisition circuit and terminal equipment, the sensing integrated chip is in communication connection with the terminal equipment through the electronic signal acquisition circuit; the sensing integrated chip is an AuNPs / MXene modified working electrode and is used for sensing and detecting a target myocardial marker in whole blood; the electronic signal acquisition circuit is used for connecting the sensing integrated chip and terminal equipment to realize signal acquisition and transmission; and the terminal equipment receives, processes and displays the sensing signal, and gives an alarm when the detected concentration exceeds a normal range. According to the invention, a double-signal real-time drift correction mechanism is adopted, so that the stability is improved. And full-process detection and intelligent early warning can be completed within 5 minutes. The integrated design realizes rapid home detection, does not need professional operation, and provides an efficient and portable scheme for early diagnosis of myocardial infarction.

Description

Technical Field

[0001] This invention relates to the field of myocardial biomarker detection technology, and more particularly to a real-time drift-corrected electronic sensing system and detection method based on a smartphone. Background Technology

[0002] Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide, posing a significant threat to patients' lives and health, and imposing a heavy economic burden on society and individuals. Statistics show that millions of people die from AMI globally each year. The out-of-hospital mortality rate for AMI patients is significantly higher than the in-hospital mortality rate. This indicates that many AMI patients lose their lives outside of hospitals before receiving timely professional treatment. Against this backdrop, the development and application of rapid home-based diagnostic technologies for AMI are particularly important. Promoting home monitoring technologies, enhancing public awareness and understanding of AMI, and improving emergency medical services are crucial ways to reduce out-of-hospital mortality.

[0003] Currently, clinical diagnosis and screening for acute myocardial infarction (AMI) primarily utilize electrocardiography (ECG) and imaging methods. Patients showing ST-segment elevation on ECG can be directly diagnosed with acute ST-segment elevation AMI. Imaging examinations also have some value in the diagnosis of AMI. Commonly used imaging methods include echocardiography (UCG), coronary angiography (CAG), and nuclear magnetic resonance imaging (NMRI). These methods can provide information on the morphology, structure, and function of the heart, helping doctors determine the presence of AMI and the location and extent of the infarction. However, both of these methods rely on specialized equipment and the doctor's interpretation of the results. This limits home-based self-diagnosis of AMI. Summary of the Invention

[0004] Therefore, it is necessary to provide a real-time drift correction electronic sensing system and detection method based on smartphones to address the aforementioned technical problems.

[0005] A smartphone-based real-time drift correction electronic sensing system includes:

[0006] The sensor integrated chip, the electronic signal acquisition circuit, and the terminal device are communicatively connected through the electronic signal acquisition circuit.

[0007] The sensing integrated chip is an AuNPs / MXene modified working electrode used for sensing and detecting target myocardial biomarkers in whole blood.

[0008] The electronic signal acquisition circuit is used to connect the sensor integrated chip and the terminal device to realize the acquisition and transmission of sensor signals.

[0009] The terminal device receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range.

[0010] In one embodiment, the sensor integrated chip is manufactured through the following steps:

[0011] Ti3C2 Mxene was prepared by hydrofluoric acid etching.

[0012] The Ti3C2 Mxene was mixed with Nafion solution and then modified onto the electrode surface. After thiolization with MPTMS, AuNPs particles were added dropwise. After standing, AuNPs / MXene@AuE modified electrode was formed.

[0013] A dual-signal drift correction and capture probe was prepared and fixed on the AuNPs / MXene@AuE modified electrode to obtain a sensor integrated chip.

[0014] In one embodiment, the preparation of Ti3C2 Mxene by hydrofluoric acid etching includes:

[0015] Let 15-20 mL of HF stand at 0-4℃ for 30-60 min; weigh 1-1.1 g of MAX Ti3AlC2 powder and slowly add it to the container containing HF while stirring to obtain the first mixture;

[0016] The first mixture was placed on a stirrer at 40-50℃ and stirred continuously for 20-24 hours; after stirring was completed and cooled to room temperature, the second mixture was obtained.

[0017] Centrifuge the second mixture at 3200-3500 rpm for 10-15 min, remove the supernatant, and repeat washing until the supernatant is neutral to obtain the precipitate;

[0018] The precipitate was dried at 45-50℃ for 10-12 hours to obtain a dry powder;

[0019] The dried powder was dispersed in 100-110 mL of deionized water and ultrasonically treated for 10-12 h to obtain a suspension.

[0020] The suspension was centrifuged at 3200-3500 rpm for 1-1.5 h, and the supernatant was used as Ti3C2 MXene.

[0021] In one embodiment, Ti3C2 Mxene was mixed with Nafion solution and then applied to the electrode surface. After thiolization with MPTMS, AuNPs particles were added dropwise. After standing, an AuNPs / MXene@AuE modified electrode was formed, comprising:

[0022] Take an equal volume of the Ti3C2 Mxene and mix it with a 0.15-0.3% Nafion aqueous solution, and sonicate for 1-2 hours to obtain the first mixture;

[0023] Take 10-15 μL of the first mixture and drop it onto the surface of the working electrode of the screen-printed electrode, and dry it at room temperature to obtain the first electrode;

[0024] The first electrode is immersed in 2-10 mL of 1 mM MPTMS in ethanol solution and left to stand at room temperature for 2-3 hours to thiolize MXene, thus obtaining the second electrode.

[0025] 10-15 μL of 8 nm AuNPs solution was dropped onto the second electrode and allowed to stand at 0-4 °C for 10-12 hours to obtain the third electrode;

[0026] The third electrode was rinsed with deionized water and stored in an environment of 0-4°C to obtain an AuNPs / MXene@AuE modified electrode.

[0027] In one embodiment, a dual-signal drift correction and capture probe is fabricated, and the dual-signal drift correction and capture probe is fixed on the AuNPs / MXene@AuE modified electrode to obtain a sensor integrated chip comprising:

[0028] Mix 10-15 μM thiol and AQ-labeled aptamers with an equal volume of 10 mM triphosphine hydrochloride solution, and let stand at room temperature in the dark for 1-2 hours to cleave the disulfide bonds of the reduced thiol groups to obtain a mixed aptamer solution.

[0029] Add 5-8 μM of MB-labeled cDNA to the aptamer mixture, heat to 90-95℃ for 5-10 minutes, and then cool to room temperature to prepare a dual-signal drift-corrected capture probe.

[0030] The dual-signal drift correction and capture probe was dropped onto AuNPs / MXene@AuE, incubated at 0-4°C for 10-12 hours, fixed by gold-sulfur bonds, and passivated with 1-1.5 mM 6-mercapto-1-hexanol for 1-2 hours to obtain the sensor integrated chip.

[0031] In one embodiment, the electronic signal acquisition circuit includes: a power supply module, a voltage follower, a positive and negative voltage conversion circuit, an analog switch, a current conversion and acquisition circuit, a wireless transmission module, a microcontroller, and an SPE sensor socket module.

[0032] The power module is connected to the voltage follower, the positive and negative voltage conversion circuit, the analog switch, the microcontroller, and the wireless transmission module to provide power to the entire circuit.

[0033] The voltage follower is connected to the power module, the sensing integrated chip, the positive and negative voltage conversion circuit and the analog switch to provide a stable reference voltage signal;

[0034] The positive and negative voltage conversion circuit is connected to the power module, the voltage follower, and the analog switch to provide switchable positive and negative voltage signals.

[0035] The analog switch is connected to the power module, the sensing integrated chip, the positive and negative voltage conversion circuit and the microcontroller to provide the voltage signal required for detection.

[0036] The current conversion and acquisition circuit is connected to the sensing integrated chip and the microcontroller, and is used to convert analog voltage signals into digital signals.

[0037] The wireless transmission module is connected to the power module, the microcontroller, and the terminal device, and is used to receive processed data and send the processed data to the terminal device;

[0038] The microcontroller is connected to the power module, the analog switch, the positive and negative voltage conversion circuit, the current conversion and acquisition circuit, and the wireless transmission module, and is used to generate processed data and send the processed data to the terminal device through the wireless transmission module.

[0039] The SPE sensor socket module is connected to the sensor integrated chip, the analog switch, the voltage follower, and the current conversion and acquisition circuit, and the sensor integrated chip is communicatively connected to the analog switch, the voltage follower, and the current conversion and acquisition circuit.

[0040] In one embodiment, the terminal device receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range, including:

[0041] Receives sensor signals sent by the electronic signal acquisition circuit;

[0042] The sensing signals are processed and quantitatively analyzed to obtain quantitative results for cTnI, Mb, and CK-MB.

[0043] An alarm signal is sent in response to the quantitative result exceeding the preset normal range.

[0044] A detection method for a smartphone-based real-time drift correction electronic sensing system, used in the smartphone-based real-time drift correction electronic sensing system as described above, includes:

[0045] When the sensor integrated chip is exposed to the whole blood sample to be tested, the target and aptamer compete for binding, resulting in the release of MB-cDNA.

[0046] The electronic signal acquisition circuit acquires the synchronous drifting MB and AQ electrical signals, corrects the MB signal with the AQ signal, obtains the sensing signal, and sends the sensing signal to the terminal device.

[0047] The terminal device receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range.

[0048] Compared to existing technologies, the advantages and beneficial effects of this invention are as follows: This invention can construct a real-time drift correction mechanism through the dual signal molecules of anthraquinone (AQ) and methylene blue (MB), simultaneously compensating for signal fluctuations caused by matrix effects in whole blood testing, thereby improving detection stability. The sensor integrated chip uses AuNPs / MXene composite material modified electrodes, combined with the aptamer competitive binding principle, reducing the detection limit to the pg / mL level and covering the key clinical concentration range. Combined with modular electronic circuitry and a smartphone APP, it achieves fully automated processing from sample addition to abnormal alarm within 5 minutes, enabling rapid home testing without professional operation. This provides an innovative solution for the early diagnosis of acute myocardial infarction that combines accuracy, portability, and intelligence. Attached Figure Description

[0049] Figure 1 This is a schematic diagram of the structure of a real-time drift correction electronic sensing system based on a smartphone in one embodiment;

[0050] Figure 2 This is a schematic diagram of the components and microscopic detection principle of a real-time drift correction electronic sensing system based on a smartphone in one embodiment;

[0051] Figure 3 This is a schematic diagram of an electronic signal acquisition circuit in one embodiment;

[0052] Figure 4 This is a schematic diagram of the main user interface of a terminal device in one embodiment;

[0053] Figure 5 This is a schematic diagram illustrating the detection performance evaluation of the sensing IC in PBS in one embodiment;

[0054] Figure 6 This is a schematic diagram illustrating the performance evaluation of sensing ICs in whole blood in one embodiment;

[0055] Figure 7 This is a schematic diagram illustrating the specificity evaluation of sensing ICs in one embodiment;

[0056] Figure 8This is a schematic diagram of linear regression analysis between analyzer measurements and actual target concentration in one embodiment. Detailed Implementation

[0057] Before describing the specific embodiments of the present invention, the overall concept of the present invention will be explained as follows:

[0058] This invention primarily focuses on the development of a process for detecting myocardial biomarkers. The ischemic necrosis of myocardial cells caused by acute myocardial infarction (AMI) results in the release of certain myocardial biomarkers into the bloodstream. Detecting these biomarkers is a crucial method for diagnosing AMI. These biomarkers mainly include type I cardiac troponin I (cTnI), myoglobin (Mb), and creatine kinase isoenzyme (CK-MB). During AMI, these biomarkers rapidly increase in blood levels, reaching peak levels within a certain timeframe. By detecting changes in the concentration of these biomarkers, the presence, degree, and extent of myocardial damage can be determined. Therefore, combining the detection of myocardial biomarker concentrations in the patient's blood can achieve a comprehensive and accurate diagnosis of AMI. cTnI, a protein specific to myocardial cells, reflects the degree of myocardial cell damage and has high specificity in the early clinical diagnosis of AMI. A cTnI level greater than 1.5 ng / mL suggests the possible presence of AMI. However, its short half-life limits its ability to be detected alone. Mycobacterium hydroxyl (Mb) is an oxygen-binding protein found in cardiac and skeletal muscle. When cardiac cells are damaged, Mb levels rise sharply within 1-2 hours. Therefore, changes in Mb concentration can serve as an early indicator for diagnosing acute myocardial infarction (AMI). However, Mb testing alone cannot rule out other factors such as skeletal muscle damage. Chromosomal infarction-metabolite (CK-MB) is mainly found in cardiac cells. When cardiac cells are damaged, CK-MB is released into the bloodstream. Its concentration changes have high sensitivity for diagnosing AMI. However, similar skeletal muscle diseases and nervous system injuries can also cause elevated CK-MB levels, thus CK-MB testing alone has low specificity. In summary, cTnI, Mb, and CK-MB, three cardiac biomarkers, exhibit different time windows and concentration changes after the onset of AMI, demonstrating complementarity. Therefore, combined detection can not only detect AMI earlier and improve diagnostic accuracy, but also rule out interference from other diseases, improving diagnostic specificity and sensitivity, and reducing misdiagnosis and missed diagnosis. Furthermore, the combined detection of cardiac markers in whole blood enables rapid diagnosis while minimizing errors in sample pretreatment (such as centrifugation, dilution, separation, and transportation), thereby improving the accuracy and efficiency of diagnosis.

[0059] Currently, products used for detecting cardiac biomarkers are still primarily based on traditional enzyme-linked immunosorbent assay (ELISA) kits. ELISA is a commonly used biochemical detection tool with high specificity and sensitivity to avoid false positive results. However, it still has some limitations. For example, the reproducibility of ELISA experiments can be affected by various factors, such as inconsistent experimental conditions, differences in operating techniques, and batch-to-batch variations in reagents. These factors can lead to significant fluctuations in experimental results, affecting the reliability and accuracy of the data. Secondly, the ELISA detection process is relatively complex, requiring multiple steps, including sample pretreatment, antibody binding, enzymatic reaction, and color reading. These steps require precise operation and strict time control, increasing the complexity and time consumption of the experiment. In addition, ELISA detection requires specialized equipment and reagents, increasing the cost and difficulty of the experiment. Therefore, in practical applications, various factors need to be comprehensively considered, limiting its application in rapid on-site testing.

[0060] To address the shortcomings of existing methods, future detection of myocardial biomarkers will combine portable devices, artificial intelligence, and novel materials to develop precise, automated, highly sensitive, and highly integrated technologies for the joint detection and early warning of myocardial biomarkers. Furthermore, it is essential to minimize errors in sample pretreatment (such as centrifugation, dilution, separation, and transportation), for example, by directly detecting myocardial biomarker levels in whole blood, thereby improving diagnostic accuracy and efficiency. This will provide new solutions for the early diagnosis and timely intervention of myocardial infarction in the absence of specialized equipment. Therefore, this invention aims to develop a real-time drift-corrected electronic sensing system based on a smartphone for the intelligent joint detection of myocardial biomarkers in whole blood.

[0061] After introducing the overall concept of the present invention, in order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below through specific embodiments and in conjunction with the accompanying drawings.

[0062] It should be noted that, unless otherwise defined, the technical or scientific terms used in one or more embodiments of this specification should have the ordinary meaning understood by one of ordinary skill in the art to which this invention pertains. The terms "first," "second," and similar terms used in one or more embodiments of this specification do not indicate any order, quantity, or importance, but are merely used to distinguish different components. Terms such as "comprising" or "including" mean that the element or object preceding the word covers the element or object listed following the word and its equivalents, without excluding other elements or objects. Terms such as "connected" or "linked" are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. Terms such as "upper," "lower," "left," and "right" are used only to indicate relative positional relationships; when the absolute position of the described object changes, the relative positional relationship may also change accordingly.

[0063] In one embodiment, such as Figure 1 As shown, a real-time drift correction electronic sensing system based on a smartphone is provided, including: a sensing integrated chip 10, an electronic signal acquisition circuit 11, and a terminal device 12.

[0064] The sensor integrated chip 10 is communicatively connected to the terminal device 12 through the electronic signal acquisition circuit 11.

[0065] The sensor integrated chip 10 is an AuNPs / MXene modified working electrode used for sensing and detecting target myocardial biomarkers in whole blood.

[0066] The electronic signal acquisition circuit 11 is used to connect the sensor integrated chip 10 and the terminal device 12 to realize the acquisition and transmission of sensor signals.

[0067] Terminal device 12 receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range. In some embodiments, terminal device 12 may be a mobile terminal, such as a mobile phone, tablet computer (PAD), etc.

[0068] A smartphone-based real-time drift-corrected electronic sensing system is specifically designed for rapid and accurate automated combined POCT detection of whole blood myocardial biomarkers. The components and microscopic detection principle diagram of this sensing system are shown below. Figure 2 As shown, when the sensor integrated chip is exposed to blood, MB and AQ undergo synchronized signal drift. When the target is present, the target and aptamer competitively bind, causing MB-cDNA to be released from the interface, while the position of AQ-Apt remains relatively unchanged. At this time, the analyzer of the joint terminal device receives, processes, and displays the AQ-corrected MB redox signal on the terminal device through data transmission, enabling sensitive and on-site quantification of whole blood targets within 5 minutes.

[0069] Specifically, the aptamer sequences are shown in Table 1 below.

[0070] Table 1 Aptamer Sequences

[0071]

[0072]

[0073] Based on this, the sensor integrated chip 12 is manufactured through the following steps:

[0074] Step a: Ti3C2 Mxene is prepared by hydrofluoric acid etching.

[0075] Step b: Ti3C2 Mxene is mixed with Nafion solution and then modified onto the electrode surface. After thiolization with MPTMS, AuNPs particles are added dropwise. After standing, AuNPs / MXene@AuE modified electrode is formed.

[0076] Step c: Prepare a dual-signal drift correction and capture probe, fix the dual-signal drift correction and capture probe on an AuNPs / MXene@AuE modified electrode, and prepare a sensor integrated chip.

[0077] Step a specifically includes:

[0078] Place 15-20 mL of HF and a polytetrafluoroethylene (PTFE) conical flask at 0-4℃ for 30-60 min; weigh 1-1.1 g of MAX Ti3AlC2 powder and slowly add it to the container containing HF while stirring to obtain the first mixture.

[0079] The first mixture was placed on a stirrer at 40-50℃ and stirred continuously for 20-24 hours. After stirring was completed and the mixture was cooled to room temperature, the second mixture was obtained.

[0080] Centrifuge the second mixture at 3200-3500 rpm for 10-15 min, remove the supernatant, and repeat washing until the supernatant is neutral to obtain the precipitate.

[0081] The precipitate was dried at 45-50℃ for 10-12 hours to obtain a dry powder.

[0082] Disperse the dried powder in 100-110 mL of deionized water and sonicate for 10-12 h to obtain a suspension.

[0083] Centrifuge the suspension at 3200-3500 rpm for 1-1.5 h, and use the supernatant as Ti3C2 MXene.

[0084] Step b specifically includes:

[0085] Take an equal volume of Ti3C2 Mxene nanosheet suspension and mix it with 0.15-0.3% Nafion aqueous solution. Sonicate for 1-2 hours to obtain the first mixture.

[0086] Take 10-15 μL of the first mixture and add it dropwise to the surface of the working electrode of the screen-printed electrode. Dry it at room temperature to obtain the first electrode.

[0087] The first electrode is immersed in 2-10 mL of 1 mM (3-mercaptopropyl)trimethoxysilane (MPTMS) ethanol solution and left to stand at room temperature for 2-3 hours to thiolize MXene, thus obtaining the second electrode.

[0088] A solution of 10-15 μL of 8 nm gold nanoparticles (AuNPs) was dropped onto the second electrode and allowed to stand at 0-4 °C for 10-12 hours to obtain the third electrode.

[0089] The third electrode was rinsed with deionized water and stored at 0-4℃ to obtain the AuNPs / MXene@AuE modified electrode.

[0090] Step c specifically includes:

[0091] Mix 10-15 μM thiol and AQ-labeled aptamers with an equal volume of 10 mM tris(2-carboxyethyl)phosphonic acid hydrochloride (TCEP) solution, and let stand at room temperature in the dark for 1-2 hours to cleave the disulfide bonds of the reduced thiol groups, thus obtaining a mixed solution of aptamers.

[0092] Add 5-8 μM of MB-labeled cDNA to the aptamer mixture, heat to 90-95℃ for 5-10 minutes, and then cool to room temperature to prepare the dual signal drift correction capture probe (Apt(AQ)-cDNA(MB)).

[0093] The dual-signal drift correction capture probe was dropped onto AuNPs / MXene@AuE and incubated at 0-4℃ for 10-12 hours to fix it through gold-sulfur bonds. It was then passivated with 1-1.5mM 6-mercapto-1-hexanol (MCH) for 1-2 hours to obtain the sensor integrated chip.

[0094] like Figure 3 As shown, the electronic signal acquisition circuit 11 includes: a power supply module, a voltage follower, a positive and negative voltage conversion circuit, an analog switch, a current conversion and acquisition circuit, a wireless transmission module, a microcontroller, and an SPE sensor socket module.

[0095] The power module connects to a voltage follower, a positive-to-negative voltage conversion circuit, an analog switch, a microcontroller, and a wireless transmission module to provide power to the entire circuit.

[0096] The voltage follower is connected to the power module, sensor integrated chip, positive and negative voltage conversion circuit and analog switch to provide a stable reference voltage signal.

[0097] The positive and negative voltage conversion circuit is connected to the power supply module, voltage follower, and analog switch to provide switchable positive and negative voltage signals.

[0098] The analog switch is connected to the sensor integrated chip, positive / negative voltage conversion circuit, microcontroller, and power module to provide the voltage signal required for detection. In this embodiment, the analog switch is a 2-to-1 analog switch.

[0099] The current conversion and acquisition circuit is connected to the sensor integrated chip and microcontroller to convert analog voltage signals into digital signals.

[0100] The wireless transmission module connects to the microcontroller, power module, and terminal device to receive processed data and send the processed data to the terminal device.

[0101] The microcontroller is connected to an analog switch, a positive and negative voltage conversion circuit, a current conversion and acquisition circuit, a power supply module, and a wireless transmission module to generate processed data and send the processed data to the terminal device via the wireless transmission module.

[0102] The SPE sensor socket module connects to the sensor integrated chip, analog switch, voltage follower, and current conversion and acquisition circuit, enabling communication between the sensor integrated chip and the analog switch, voltage follower, and current conversion and acquisition circuit.

[0103] The power module supplies power to the entire circuit. The microcontroller controls the positive and negative voltage conversion circuit to generate the required detection voltage through the DAC output. The microcontroller controls the analog switch to switch and apply the detection voltage to the working electrode (WE). The voltage of the reference electrode (RE) is stabilized by a voltage follower and used as a reference. When the detection voltage is applied to the working electrode, the myocardial markers in whole blood react with the sensor integrated chip to generate an electrode current. The electrode current is transmitted to the current conversion and acquisition circuit through the auxiliary electrode (CE). The current conversion and acquisition circuit converts the current signal into a voltage signal and transmits it to the microcontroller. The microcontroller converts the analog voltage signal into a digital signal for processing. The processed data is sent to the APP on the terminal device through the 4G wireless transmission module. The APP receives the data and displays and analyzes it. When the detection value exceeds the normal range, an alarm is issued.

[0104] The working electrode (WE), reference electrode (RE), and auxiliary electrode (CE) are all part of the sensing integrated circuit (SIC). The working electrode (WE) is the key interface for detecting target myocardial biomarkers. It is connected to the output of a 2-to-1 analog switch in the signal acquisition electronics via the SPE sensor socket module to receive the detection voltage signal. The reference electrode (RE) provides a stable potential reference and is connected to the input of the voltage follower in the signal acquisition electronics via the SPE sensor socket module to ensure the stability of the reference voltage. The auxiliary electrode (CE) forms a current loop with the working electrode and is connected to the input of the current conversion and acquisition circuit in the signal acquisition electronics via the SPE sensor socket module to acquire the electrode current signal.

[0105] The integrated voltage regulator module provides +5V and -5V voltages, which are the positive and negative power supplies for the integrated operational amplifier (ADA4610-4ARZ, Analog Devices Inc.) and the 4-channel 2-to-1 analog switch (ADG1434YRUZ, Analog Devices Inc.) in the current conversion and acquisition circuit, respectively. The +5V voltage is converted to 3.3V output by a 3.3V integrated voltage regulator (KIA1117-3.3, KIA Semicon Tech), serving two purposes: first, as the power supply for the microcontroller (STM32F103RCT6, STMicroelectronics); and second, as the reference voltage for the three-electrode electronic signal acquisition circuit.

[0106] exist Figure 3 In the above, the integrated operational amplifier U29.2 constitutes an inverting proportional amplifier, and the relationship between its output voltage and input voltage is as follows:

[0107]

[0108] In the formula, U O1 To adjust the output voltage of the integrated operational amplifier U29.2, R33 is an adjustable resistor. A resistor R34 (100Ω) is connected in series with R33 for current limiting and protection. Adjusting resistor R33 makes the voltage at pin 7 of U29.2 -0.58V. Similarly, the integrated operational amplifier U29.3 also forms an inverting proportional amplifier; adjusting resistor R38 makes the voltage at pin 7 of U29.3 -0.30V.

[0109] The ADG1434 chip is a 4-channel 2-to-1 analog switch. When SW is high, the output voltage of D1 is -0.58V; when SW is low, the output voltage of D1 is -0.30V. SW is controlled by the STM32 processor, with a sampling time of 1ms. RE1, CE1, and WE1 are the three pins of the first channel's three electrodes; RE2, CE2, and WE2 are the three pins of the third channel's three electrodes; and RE3, CE3, and WE3 are the three pins of the third channel's three electrodes. The integrated operational amplifier U32.1 converts the current I of the WE electrode into a voltage output UO, with the following conversion relationship:

[0110] U O = I × [R42 + R49]

[0111] Where I represents the current of the three-electrode signal acquisition circuit, resistors R47 (30KΩ) and R49 (1MΩ) are adjustable resistors used to adjust the dynamic range of the test current. Voltage output U... O The voltage follower is formed by the integrated operational amplifier U32.2 and then input to the analog-to-digital (A / D) converter port of the STM32 processor. This circuit uses the 12-bit A / D function built into the STM32 processor.

[0112] Terminal device 12 receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range, including:

[0113] It receives sensor signals sent by the electronic signal acquisition circuit.

[0114] Signal processing and quantitative analysis were performed on the sensor signals to obtain quantitative results for cTnI, Mb, and CK-MB.

[0115] An alarm signal is sent when the quantitative result exceeds the preset normal range.

[0116] Specifically, such as Figure 4 As shown, this is the main user interface during the operation of the mini-program in terminal device 12.

[0117] To comprehensively evaluate the detection efficiency of sensing IC, the spiked concentrations of the target analytes were assessed and compared in PBS and whole blood. First, in differential pulse voltammetry (DPV) mode, the sensing ability of sensing IC for three myocardial infarction biomarkers (cTnI, Mb, and CK-MB) in PBS buffer was investigated by detecting the oxidation current of myocardial infarction (MB). Figure 5 As can be seen from a series of DPV curves, the oxidation current of MB decreases with increasing target concentration, while the oxidation current of AQ remains almost unchanged. Figure 5As shown in EG, the changes in MB oxidative current increased with increasing concentrations of the three myocardial infarction markers, exhibiting a good linear correlation. The sensing IC demonstrated good analytical performance, an acceptable dynamic range (cTnI, 0.1 pg / mL–100 ng / mL; Mb, 1 pg / mL–1000 ng / mL; CK-MB, 0.1 pg / mL–100 ng / mL), and low detection limits (cTnI, 0.0295 pg / mL; Mb, 0.245 pg / mL; CK-MB, 0.0229 pg / mL).

[0118] The stability and drift correction capability of the sensing IC were tested using a blank test in whole blood. Figure 6 B shows that after placing the sensing IC in whole blood for 300 seconds, the current drift of MB and AQ was approximately 8%–11%. The current drift of these two signaling molecules was synchronous. Based on the results obtained, it was verified that the sensing IC also possesses the same stable drift correction capability when detecting targets in whole blood. Figure 6 C). The detection performance of the sensing IC in whole blood for different concentrations of cTnI, Mb, and CK-MB was evaluated. Figure 6 dD-I). The figure shows that the oxidation current of the calibration signal molecule AQ gradually increases due to signal drift. Simultaneously, with increasing target analyte concentration, the oxidation current of the detection signal molecule MB shows a trend of offsetting the increase in current. The change in MB current relative to AQ current increases with increasing concentrations of the three myocardial infarction biomarkers, exhibiting a good linear correlation. Figure 6 The standard curves are: y(cTnI) = 1.11858 + 0.28081x(R). 2 =0.9974);y(Mb)=3.55213+1.01949x(R 2 =0.9917);y(CK-MB)=3.57489+0.94356x(R 2 =0.9947). The sensing IC maintained excellent detection performance in whole blood, with an acceptable dynamic range (cTnI, 1 pg / mL-100 ng / mL; Mb, 10 pg / mL-1000 ng / mL; CK-MB, 1 pg / mL-100 ng / mL) and a low limit of detection (cTnI, 0.245 pg / mL; Mb, 6.607 pg / mL; CK-MB, 0.331 pg / mL).

[0119] To assess the specificity of sensing IC, control experiments were performed for each target, using common post-AMI biomarkers as interfering agents, including cTnI, Mb, CK-MB, heat-bound fatty acid-binding protein (H-FABP), and C-reactive protein (CRP). Figure 7 As shown, when the concentration ratio of interfering substance to target analyte is 10:1, the electrical signal of the sensing IC does not change significantly in the presence of the interfering substance. However, when the corresponding target analyte is present in the system, its electrical signal changes significantly. This confirms that the sensing IC can resist the influence of interfering substances in the matrix and has good specificity.

[0120] To evaluate the performance of the smartphone-based real-time drift correction electronic sensing system, linear regression analysis curves were plotted, and the measured values ​​were compared with the actual target concentration. Figure 8 (A) cTnI, (B) Mb, (C) CK-MB). Linear regression analysis showed that the correlation coefficients (R²) of cTnI, MB, and CK-MB were... 2 The values ​​were 0.9994, 0.9996, and 0.9993, respectively. The results indicate that the system has good accuracy.

[0121] In this embodiment, known amounts of the target substances, namely cTnI, Mb, and CK-MB, were added to whole blood to prepare whole blood samples at concentrations of 0.01, 1, and 50 ng / mL. These samples were used to evaluate the accuracy of the electronic sensing system in detecting real samples, and the results were compared with those obtained by a standard detection method (ELISA). The test data are shown in Table 2. The results indicate that the electronic sensing system demonstrates significant advantages in terms of sensitivity, accuracy, and operating procedures.

[0122] Table 2 Recovery experiments of different concentrations of target analytes in whole blood samples

[0123]

[0124] Each spiked concentration was obtained from three parallel experiments. Nd: Not detected.

[0125] The real-time drift correction electronic sensing system based on a smartphone provided by this invention has significant technical advantages and clinical application value. Firstly, its innovative real-time drift correction mechanism effectively solves the problem of signal drift in whole blood testing through the design of dual-signal molecules, anthraquinone (AQ) and methylene blue (MB). During the 300-second detection process, the signal changes of AQ and MB are monitored simultaneously. Utilizing the similar physical properties but different biological responses of these two molecules, real-time compensation for matrix effects and environmental interference is achieved, improving detection stability by more than 85%. This dual-signal correction strategy is significantly superior to traditional single-signal detection methods, ensuring the system's detection accuracy in complex biological samples. The recoveries of cTnI, Mb, and CK-MB in whole blood reach 92.55%-112.0%, with a relative standard deviation (RSD) of less than 5.77%.

[0126] Secondly, the system's integrated and intelligent design achieves high efficiency and convenience in myocardial biomarker detection. The integrated sensor chip combines AuNPs / MXene composite materials with aptamer technology, greatly improving detection sensitivity, with detection limits as low as pg / mL and a dynamic range covering the key concentration range for clinical diagnosis. The signal acquisition electronic circuit adopts a modular design, wirelessly connecting electrochemical detection to a smartphone. The entire process from sample addition to result output can be completed within 5 minutes, and operation is simple and requires no professional training. The dedicated APP not only displays detection data in real time but also automatically identifies abnormal values ​​and triggers multi-level alarms, providing strong support for the early diagnosis and timely intervention of acute myocardial infarction, especially suitable for home health monitoring and pre-hospital emergency scenarios.

[0127] It should be noted that the above description describes some embodiments of the present invention. Other embodiments are within the scope of the appended claims. In some cases, the actions or steps described in the claims may be performed in a different order than that shown in the above embodiments and still achieve the desired results. Furthermore, the processes depicted in the drawings do not necessarily require a specific or sequential order to achieve the desired results. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.

[0128] Based on the same inventive concept, and corresponding to any of the above embodiments, the present invention also provides a detection method for a real-time drift correction electronic sensing system based on a smartphone.

[0129] include:

[0130] When the sensor integrated chip is exposed to the whole blood sample to be tested, the target and aptamer compete for binding, resulting in the release of MB-cDNA.

[0131] The electronic signal acquisition circuit acquires the synchronous drifting MB and AQ electrical signals, corrects the MB signal with the AQ signal, obtains the sensing signal, and sends the sensing signal to the terminal device.

[0132] The terminal device receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range.

[0133] The system described above is used in the corresponding smartphone-based real-time drift correction electronic sensing system in any of the foregoing embodiments, and has the beneficial effects of the corresponding method embodiments, which will not be repeated here.

[0134] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0135] Example 1

[0136] Preparation of Ti3C2 MXene nanosheets:

[0137] Place 15 mL of HF and PTFE conical flasks in a 4°C refrigerator and let stand for 30 minutes.

[0138] Weigh 1g of Ti3AlC2 powder and slowly add it to HF while stirring to obtain the first mixture.

[0139] Place the first mixture on a magnetic stirrer at 45°C and stir continuously for 24 hours.

[0140] After stirring, cool to room temperature, centrifuge at 3500 rpm for 10 minutes, remove the supernatant, and obtain the precipitate.

[0141] The precipitate was repeatedly washed with deionized water until the supernatant was neutral, thus obtaining the precipitate.

[0142] The precipitate was dried at 50°C for 12 hours to obtain a dry powder.

[0143] The dried powder was dispersed in 100 mL of deionized water and sonicated for 10 hours to obtain a suspension.

[0144] Centrifuge at 3500 rpm for 1 hour and collect the supernatant to obtain the Ti3C2 MXene nanosheet solution.

[0145] Example 2

[0146] Fabrication of modified electrodes (AuNPs / MXene@AuE):

[0147] The prepared Ti3C2 MXene nanosheet suspension was mixed with an equal volume of 0.2% Nafion aqueous solution and ultrasonicated for 1 hour to obtain the first mixture.

[0148] Take 10 μL of the first mixture and add it dropwise to the surface of the working electrode of the screen-printed electrode. Dry it at room temperature to obtain the first electrode.

[0149] The first electrode was immersed in 2 mL of 1 mM MPTMS ethanol solution and left to stand at room temperature for 2 hours to thiolize MXene, thus obtaining the second electrode.

[0150] Take 10 μL of 8 nm AuNPs solution and drop it onto the second electrode. Let it stand at 4 °C for 12 hours.

[0151] After rinsing with deionized water, the electrode was stored in a 4°C refrigerator for later use, yielding AuNPs / MXene@AuE modified electrode.

[0152] Example 3

[0153] Fabrication of sensor integrated circuits (ICs):

[0154] The 10 μM thiol and AQ-labeled aptamers were mixed with an equal volume of 10 mM TCEP solution and allowed to stand at room temperature in the dark for 1 hour to cleave the disulfide bonds of the thiol groups, thus obtaining a mixed solution of aptamers.

[0155] Add 5 μM of MB-labeled cDNA to the aptamer mixture, heat to 95 °C for 10 minutes, and then cool to room temperature to prepare the dual signal drift correction capture probe (Apt(AQ)-cDNA(MB)).

[0156] 10 μL of the dual-signal drift correction capture probe was dropped onto AuNPs / MXene@AuE and incubated at 4 °C for 12 hours to fix it via gold-sulfur bonds.

[0157] The electrode was passivated with 1 mM MCH for 1 hour to obtain the sensor integrated chip.

[0158] Example 4

[0159] Detection of cardiac markers in whole blood:

[0160] Fresh whole blood samples were taken and spiked with different concentrations of cTnI, Mb and CK-MB standards.

[0161] Connect the sensor integrated chip to the signal acquisition electronic circuit and insert a whole blood sample.

[0162] Launch the terminal device's APP to control the analyzer to acquire and process signals.

[0163] The app receives the MB redox signal after AQ correction and displays the detection results within 5 minutes.

[0164] When the detected concentration exceeds the normal range, the APP interface will highlight the data in red and issue a vibration and sound alarm.

[0165] Those skilled in the art should understand that the discussion of any of the above embodiments is merely exemplary and is not intended to imply that the scope of the invention (including the claims) is limited to these examples; within the framework of the invention, the technical features of the above embodiments or different embodiments can also be combined, the steps can be implemented in any order, and there are many other variations of different aspects of the embodiments of the invention as described above, which are not provided in the details for the sake of brevity.

[0166] Any process or method description in the flowchart or otherwise herein can be understood as representing a module, segment, or portion of code comprising one or more executable instructions for implementing a particular logical function or process, and the scope of the preferred embodiments of the invention includes additional implementations in which functions may be performed not in the order shown or discussed, including substantially simultaneously or in reverse order depending on the functions involved, as will be understood by those skilled in the art to which embodiments of the invention pertain.

[0167] While specific details have been set forth to describe exemplary embodiments of the invention, it will be apparent to those skilled in the art that embodiments of the invention may be practiced without these specific details or with variations thereof. Therefore, these descriptions should be considered illustrative rather than restrictive. Although the invention has been described in conjunction with specific embodiments thereof, many substitutions, modifications, and variations of these embodiments will be apparent to those skilled in the art based on the foregoing description.

[0168] The embodiments of this invention are intended to cover all such substitutions, modifications, and variations falling within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the embodiments of this invention should be included within the protection scope of this invention.

Claims

1. A real-time drift correction electronic sensing system based on a smartphone, characterized in that, include: The sensor integrated chip, the electronic signal acquisition circuit, and the terminal device are communicatively connected through the electronic signal acquisition circuit. The sensing integrated chip is an AuNPs / MXene modified working electrode used for sensing and detecting target myocardial biomarkers in whole blood. The electronic signal acquisition circuit is used to connect the sensor integrated chip and the terminal device to realize the acquisition and transmission of sensor signals. The terminal device receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range.

2. The real-time drift correction electronic sensing system based on a smartphone according to claim 1, characterized in that, The sensor integrated chip is manufactured through the following steps: Ti3C2 Mxene was prepared by hydrofluoric acid etching. The Ti3C2 Mxene was mixed with Nafion solution and then modified onto the electrode surface. After thiolization with MPTMS, AuNPs particles were added dropwise. After standing, AuNPs / MXene@AuE modified electrode was formed. A dual-signal drift correction and capture probe was prepared and fixed on the AuNPs / MXene@AuE modified electrode to obtain a sensor integrated chip.

3. The real-time drift correction electronic sensing system based on a smartphone according to claim 2, characterized in that, The preparation of Ti3C2 Mxene by hydrofluoric acid etching includes: Let 15-20 mL of HF stand at 0-4℃ for 30-60 min; weigh 1-1.1 g of MAX Ti3AlC2 powder and slowly add it to the container containing HF while stirring to obtain the first mixture; The first mixture was placed on a stirrer at 40-50℃ and stirred continuously for 20-24 hours; after stirring was completed and cooled to room temperature, the second mixture was obtained. Centrifuge the second mixture at 3200-3500 rpm for 10-15 min, remove the supernatant, and repeat washing until the supernatant is neutral to obtain the precipitate; The precipitate was dried at 45-50℃ for 10-12 hours to obtain a dry powder; The dried powder was dispersed in 100-110 mL of deionized water and ultrasonically treated for 10-12 h to obtain a suspension. The suspension was centrifuged at 3200-3500 rpm for 1-1.5 h, and the supernatant was used as Ti3C2 MXene.

4. The real-time drift correction electronic sensing system based on a smartphone according to claim 2, characterized in that, The process of mixing Ti3C2 Mxene with Nafion solution and modifying the electrode surface, followed by MPTMS thiolation and dropwise addition of AuNPs particles, and then allowing it to stand to form an AuNPs / MXene@AuE modified electrode includes: Take an equal volume of the Ti3C2 Mxene and mix it with a 0.15-0.3% Nafion aqueous solution, and sonicate for 1-2 hours to obtain the first mixture; Take 10-15 μL of the first mixture and drop it onto the surface of the working electrode of the screen-printed electrode, and dry it at room temperature to obtain the first electrode; The first electrode is immersed in 2-10 mL of 1 mM MPTMS in ethanol solution and left to stand at room temperature for 2-3 hours to thiolize MXene, thus obtaining the second electrode. 10-15 μL of 8 nm AuNPs solution was dropped onto the second electrode and allowed to stand at 0-4 °C for 10-12 hours to obtain the third electrode; The third electrode was rinsed with deionized water and stored in an environment of 0-4°C to obtain an AuNPs / MXene@AuE modified electrode.

5. The real-time drift correction electronic sensing system based on a smartphone according to claim 2, characterized in that, The process of fabricating a dual-signal drift correction and capture probe, and fixing the dual-signal drift correction and capture probe onto the AuNPs / MXene@AuE modified electrode to obtain a sensor integrated chip includes: Mix 10-15 μM thiol and AQ-labeled aptamers with an equal volume of 10 mM triphosphine hydrochloride solution, and let stand at room temperature in the dark for 1-2 hours to cleave the disulfide bonds of the reduced thiol groups to obtain a mixed aptamer solution. Add 5-8 μM of MB-labeled cDNA to the aptamer mixture, heat to 90-95℃ for 5-10 minutes, and then cool to room temperature to prepare a dual-signal drift-corrected capture probe. The dual-signal drift correction and capture probe was dropped onto AuNPs / MXene@AuE, incubated at 0-4°C for 10-12 hours, fixed by gold-sulfur bonds, and passivated with 1-1.5 mM 6-mercapto-1-hexanol for 1-2 hours to obtain the sensor integrated chip.

6. The real-time drift correction electronic sensing system based on a smartphone according to claim 1, characterized in that, The electronic signal acquisition circuit includes: a power supply module, a voltage follower, a positive and negative voltage conversion circuit, an analog switch, a current conversion and acquisition circuit, a wireless transmission module, a microcontroller, and an SPE sensor socket module. The power module is connected to the voltage follower, the positive and negative voltage conversion circuit, the analog switch, the microcontroller, and the wireless transmission module to provide power to the entire circuit. The voltage follower is connected to the power module, the sensor integrated chip, the positive and negative voltage conversion circuit and the analog switch to provide a stable reference voltage signal; The positive and negative voltage conversion circuit is connected to the power module, the voltage follower, and the analog switch to provide switchable positive and negative voltage signals. The analog switch is connected to the power module, the sensing integrated chip, the positive and negative voltage conversion circuit and the microcontroller to provide the voltage signal required for detection. The current conversion and acquisition circuit is connected to the sensing integrated chip and the microcontroller, and is used to convert analog voltage signals into digital signals. The wireless transmission module is connected to the power module, the microcontroller, and the terminal device, and is used to receive processed data and send the processed data to the terminal device; The microcontroller is connected to the power module, the analog switch, the positive and negative voltage conversion circuit, the current conversion and acquisition circuit, and the wireless transmission module, and is used to generate processed data and send the processed data to the terminal device through the wireless transmission module. The SPE sensor socket module is connected to the sensor integrated chip, the analog switch, the voltage follower, and the current conversion and acquisition circuit, and the sensor integrated chip is communicatively connected to the analog switch, the voltage follower, and the current conversion and acquisition circuit.

7. The real-time drift correction electronic sensing system based on a smartphone according to claim 1, characterized in that, The terminal device receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range, including: Receives sensor signals sent by the electronic signal acquisition circuit; The sensing signal is processed and quantitatively analyzed to obtain quantitative results of cTnI, Mb, and CK-MB; An alarm signal is sent in response to the quantitative result exceeding the preset normal range.

8. A detection method for a real-time drift correction electronic sensing system based on a smartphone, characterized in that, For a smartphone-based real-time drift correction electronic sensing system as described in any one of claims 1-7, comprising: When the sensor integrated chip is exposed to the whole blood sample to be tested, the target and aptamer compete for binding, resulting in the release of MB-cDNA. The electronic signal acquisition circuit acquires the synchronous drifting MB and AQ electrical signals, corrects the MB signal with the AQ signal, obtains the sensing signal, and sends the sensing signal to the terminal device. The terminal device receives, processes, and displays sensor signals, and issues an alarm when the detected concentration exceeds the normal range.

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