A multi-bias potential pulse response fingerprinting and cross-interference intercepting method and device for non-invasive liquid sample electrochemical detection

Abstract

This invention discloses a multi-bias potential pulse response fingerprinting and cross-interference interception method and device for non-invasive electrochemical detection of liquid samples, belonging to the field of electrochemical detection technology. The method sequentially applies a background retention segment, a target response segment, an interference identification segment, a recovery observation segment, and an end-verification segment within the same liquid detection chamber. It collects the current response of each segment and extracts features such as peak current, steady-state current, rise slope, decay slope, and residual current to generate a response fingerprint for the same detection. Cross-interference is judged based on background residue, interference response, recovery sufficiency, and end-verification parameters. The result is locked when the locking condition is met, and the detection result is output after background subtraction and interference removal when the correction condition is met. This scheme is applicable to the electrochemical detection of non-invasive liquid samples such as saliva, oral fluid, tears, sweat, or exhaled breath condensate.

Description

Technical Field

[0001] This invention relates to the fields of electrochemical detection and non-invasive liquid sample detection technology, and in particular to a method and apparatus for multi-bias potential pulse response fingerprinting and cross-interference interception of non-invasive liquid samples such as saliva, oral fluid, tears, sweat or exhaled breath condensate. Background Technology

[0002] Electrochemical detection features compact structure, fast response speed, ease of miniaturization, and low cost, making it suitable for home health monitoring, primary care screening, and portable testing devices. For non-invasive liquid samples, sample sources can include saliva, oral fluid, tears, sweat, and exhaled breath condensate, offering advantages over blood collection such as convenient sampling, high user acceptance, and suitability for continuous or repeated testing.

[0003] However, non-invasive liquid samples have a complex composition. Salinity, pH, proteins, mucins, surfactants, ascorbic acid, uric acid, lactic acid, hydrogen peroxide, and other reducing or oxidizing components in the sample can all affect the electrode response. If the current value is read under a single bias potential, the current change may simultaneously originate from the target analyte, background current, electrode surface adsorption, changes in the sample matrix, or redox reactions of non-target substances, which can easily lead to erroneous output, response drift, or decreased repeatability.

[0004] In existing detection methods, common approaches involve filtering, averaging, or subtracting background from the response current at a single potential. While these methods can reduce random noise, they struggle to distinguish between the target analyte response and the response of interfering substances, and are particularly difficult to determine whether cross-interference, unrecovered response, or abnormal terminal response exist during the same sample detection process. For home use scenarios and multi-index extended platforms, detection systems need to perform more specific technical assessments of the reliability of the sample's electrochemical response before outputting results, rather than relying solely on general data fusion or post-processing algorithms.

[0005] Therefore, it is necessary to provide a technical solution that is directly coupled with the electrochemical detection process. By using multi-segment bias potential, segmented response feature extraction, response fingerprint generation, and cross-interference interception, the device can identify target response, interference response, background residue, and insufficient recovery within the same detection chamber, thereby improving the reliability of non-invasive liquid sample detection results. Summary of the Invention

[0006] The technical problem this invention aims to solve is that non-invasive liquid samples have complex compositions and large differences in sample matrices. Single bias potential readings can easily mix the target analyte response with the response of interfering substances, background current, or insufficient electrode recovery, resulting in insufficient stability and interpretability of the detection results.

[0007] To address the aforementioned technical problems, this invention provides a multi-bias potential pulse response fingerprinting and cross-interference interception method for non-invasive liquid sample electrochemical detection. Within the same liquid electrochemical detection chamber, the method first confirms that the working electrode group, reference electrode, and auxiliary electrode are effectively wetted. Then, it applies a background maintenance segment, a target reaction segment, an interference identification segment, a recovery observation segment, and an end-verification segment in a preset sequence. The device collects current response data within each potential segment, extracting features such as peak current, steady-state current, rise slope, decay slope, and residual current to form a response fingerprint corresponding to the same detection.

[0008] After the response fingerprint is formed, the system generates background residual parameters based on the background preservation segment, interference response parameters based on the response relationship between the interference identification segment and the target response segment, recovery sufficient parameters based on the recovery observation segment, and end verification parameters based on the end verification segment. When at least two parameters meet the preset locking conditions, the system outputs a cross-interference marker and locks the detection result; when the locking conditions are not met but the preset correction conditions are satisfied, the system performs background subtraction and interference removal on the effective response window of the target response segment and then outputs the detection result.

[0009] The present invention also provides an apparatus for performing the above-described method, comprising a liquid electrochemical detection chamber, a working electrode assembly, a reference electrode, an auxiliary electrode, a potential application module, a current acquisition module, a main control module, and a result output module. The potential application module is used to generate multiple bias potential pulses, the current acquisition module is used to acquire response data for each segment, and the main control module is used to generate a response fingerprint, determine cross-interference, and control the result output module to release or lock the detection result.

[0010] Compared with existing technologies, the advantages of this invention are as follows: First, it confines the detection and control process to a specific electrochemical multi-bias potential pulse sequence, without relying on general data fusion or simple filtering; Second, it distinguishes between target response, interference response, and insufficient recovery through interference identification segment, recovery observation segment, and end verification segment; Third, it uses response fingerprint as a structured feature object for the same detection, making the detection results have a traceable electrochemical process basis; Fourth, it can perform cross-interference interception, result locking, or interference removal before sample output, improving the reliability of non-invasive liquid sample detection and the consistency of batch applications. Attached Figure Description

[0011] Figure 1 This is a schematic diagram of the detection device of the present invention; Figure 2 This is a schematic diagram of the multi-bias potential pulse sequence of the present invention; Figure 3 This is a schematic diagram illustrating the response fingerprint generation and cross-interference determination of the present invention; Figure 4This is a schematic diagram of the detection result release and locking process of the present invention. Detailed Implementation

[0012] The specific embodiments of the present invention will now be described with reference to the accompanying drawings. These embodiments are used to explain the present invention and are not intended to limit the scope of protection of the present invention. Where there is no conflict, the technical features in the following embodiments can be combined with each other.

[0013] See Figure 1 The detection device of the present invention may include a detector 100, a main control module 101, a potential application module 102, a current acquisition module 103, a liquid electrochemical detection chamber 104, a working electrode assembly 105, a reference electrode 106, an auxiliary electrode 107, a sample status acquisition module 108, a result output module 109, and a disposable liquid detection cartridge 110. The disposable liquid detection cartridge 110 is used to hold non-invasive liquid samples, and the liquid electrochemical detection chamber 104 is used to ensure that the sample covers the working electrode assembly 105, the reference electrode 106, and the auxiliary electrode 107. The main control module 101 controls the potential application module 102 to apply a potential to the working electrode assembly 105 and controls the current acquisition module 103 to acquire the current response corresponding to each potential segment.

[0014] The working electrode assembly 105 may include a target working electrode and an interference recognition working electrode. The target working electrode is used to detect the primary response of the target analyte, while the interference recognition working electrode is used to enhance or expose non-target responses. Both can share the reference electrode 106 and the auxiliary electrode 107, or can be configured as multiple working electrodes depending on the detection parameters. The surface of the working electrode may be provided with an enzyme layer, mediator layer, catalytic layer, or selective membrane layer suitable for the target analyte, such as an electrochemically sensitive layer for analytes like glucose, lactic acid, uric acid, nitrite, or hydrogen peroxide.

[0015] See Figure 2 The multi-bias potential pulse sequence is triggered by the potential pulse control unit 201 and includes at least a background hold segment 202, a target reaction segment 203, an interference identification segment 204, a recovery observation segment 205, and an end verification segment 206. The background hold segment 202 is used to read the background current and initial electrode stability after the sample enters the detection chamber; the target reaction segment 203 is used to induce the target analyte to produce a major redox response; the interference identification segment 204 uses a bias potential different from that of the target reaction segment 203 to induce interfering substances or non-target components to produce a distinct response; the recovery observation segment 205 is used to read the degree of current decline and electrode recovery; and the end verification segment 206 is used to verify the response of the target reaction segment 203. The effective response window 207 is selected from the target reaction segment 203, and the blank verification segment 208 can be used for background verification after the detection is completed.

[0016] In one embodiment, relative to the reference electrode, the potential of the background hold section 202 is -0.10V to 0.10V, lasting 0.5s to 10s; the potential of the target reaction section 203 is 0.20V to 0.75V, lasting 1s to 30s; the potential of the interference identification section 204 is -0.30V to 0.95V, lasting 0.2s to 20s; the potential of the recovery observation section 205 is -0.10V to 0.20V, lasting 0.5s to 15s; and the potential of the end verification section 206 is the same as or no more than 0.15V different from that of the target reaction section 203, lasting 0.5s to 15s. The above potential ranges can be equivalently adjusted according to different reference electrode systems and target analytes.

[0017] See Figure 3 The system first obtains the raw current response data 301, and then extracts peak current features 302, steady-state current features 303, rising slope features 304, decay slope features 305, and residual current features 306 from different potential segments. The main control module 101 combines the above features into a response fingerprint vector 307. The response fingerprint vector 307 can contain both raw feature values ​​and normalized ratio features, such as the difference between the peak current of the target segment and the background current, the ratio of the peak current of the interference segment to the peak current of the target segment, the ratio of the residual current of the recovery segment to the steady-state current of the target segment, and the deviation between the end verification response and the target segment response. The cross-interference determination module 308 determines whether cross-interference exists based on the response fingerprint vector 307.

[0018] In one implementation, the background residual parameter Rb is determined by the ratio of the end current of the background holding section 202 to the steady-state current of the target response section 203; the interference response parameter Ri is determined by the ratio of the response amplitude of the interference identification section 204 to the response amplitude of the target response section 203; the recovery sufficiency parameter Rr is determined by the ratio of the residual current of the recovery observation section 205 to the steady-state current of the target response section 203; and the end verification parameter Rv is determined by the relative deviation between the response of the end verification section 206 and the response of the target response section 203. The system determines that there is a risk of cross-interference when at least two of the following conditions are met: Ri is greater than a first threshold, Rr is greater than a second threshold, Rv is greater than a third threshold, the rising slope of the target response section 203 is lower than a fourth threshold, or Rb is greater than a fifth threshold.

[0019] For glucose detection in saliva samples, the target reaction segment 203 can be set in a potential range suitable for indirect electrochemical reading of the glucose oxidation reaction, and the interference identification segment 204 can be set in a potential range that more easily excites the response of ascorbic acid, uric acid, or other reducing components. If the response of the interference identification segment 204 is significantly higher than the expected proportion of the target reaction segment 203, and the residual current of the recovery observation segment 205 decreases insufficiently, the main control module 101 will not directly output the glucose concentration, but will instead generate a cross-interference marker and enter the result lockout 407 or prompt for retesting.

[0020] For the detection of lactic acid, uric acid, or electrolytes in tears or sweat, the system can configure corresponding target reaction segments 203 and interference identification segments 204 according to different target analytes. Since tears and sweat have significant differences in conductivity, salinity, and protein content, the response fingerprint vector 307 can further include temperature or conductivity parameters provided by the sample state acquisition module 108, but the core judgment of cross-interference is still formed by the electrochemical response characteristics under multiple bias potentials.

[0021] See Figure 4 The detection process can include sample entry 401, admission check 402, multi-bias detection 403, fingerprint calculation 404, background correction 405, interference interception 406, result locking 407, and result release 408. After sample entry 401, the system confirms that the sample has covered the electrode by inter-electrode impedance or initial current; after admission check 402 is passed, multi-bias detection 403 is performed; fingerprint calculation 404 forms a response fingerprint vector; if the background residual parameters meet the correction conditions, background correction 405 is performed; if the cross-interference determination meets the locking conditions, interference interception 406 is performed and result locking 407 is performed; if the locking conditions are not met but the correction conditions are met, the result release 408 is performed after background correction 405 and interference interception 406.

[0022] In result release 408, the system selects the time interval within the target response segment 203 where the slope is stable, the noise is below the threshold, and it is not affected by the synchronous changes in the interference identification segment 204 as the effective response window 207. The concentration of the target analyte can be determined based on the steady-state current, integrated charge, or the response value converted from the calibration curve within the effective response window 207. If there is slight interference and the interference removal condition is met but the result locking condition is not met, the system can remove the response component that changes synchronously with the interference identification segment 204 from the effective response window 207, and then output the detection result based on the remaining response.

[0023] This invention can be deployed in non-invasive liquid electrochemical detectors for home use, as well as in hospitals, primary care facilities, or health management devices. The device output can include target analyte concentration, response level, retest prompt, cross-interference flag, or result lock flag. For health monitoring or risk alert applications, the output is used for sample status indication and retest assessment, and is not considered a disease diagnosis.

[0024] The above-described embodiments of the present invention combine multiple bias potential pulse sequences, response fingerprint construction, and cross-interference interception into the same electrochemical detection process, providing specific technical solutions for the complex matrix and cross-reaction problems of non-invasive liquid samples.

Claims

1. A method for intercepting multi-bias potential pulse response fingerprints and cross-interference in non-invasive liquid sample electrochemical detection, applied to a liquid electrochemical detection chamber with a working electrode group, a reference electrode, and an auxiliary electrode, characterized in that, include: Obtain a non-invasive liquid sample that enters the liquid electrochemical detection chamber, and confirm that the working electrode assembly, reference electrode, and auxiliary electrode are in an effective wetted state; A multi-bias potential pulse sequence, including at least a background maintenance segment, a target response segment, an interference identification segment, a recovery observation segment, and an end verification segment, is applied to the working electrode group in a preset order; current response data corresponding to the non-invasive liquid sample is collected within each potential segment; At least the peak current, steady-state current, rise slope, decay slope and residual current features are extracted from the current response data to generate a response fingerprint corresponding to the same detection. Based on the response fingerprint, background residual parameters, interference response parameters, recovery sufficiency parameters, and end verification parameters are calculated. When at least two of the background residual parameters, interference response parameters, recovery sufficiency parameters, and end verification parameters meet the preset locking conditions, a cross-interference marker is generated and the detection result is locked. When the preset locking conditions are not met but the preset correction conditions are met, the target analyte detection result is output after background subtraction and interference removal are performed on the effective response window of the target reaction segment.

2. The method according to claim 1, characterized in that, The background retention section is used to record the background current after the sample enters the detection chamber. The target reaction section is used to induce the target analyte to generate a major redox response. The bias potential of the interference identification section is different from that of the target reaction section and is used to induce a distinguishing response between the interference substance and the non-target reactant. The recovery observation section is used to record the degree of current drop. The end verification section is used to read the verification response again after the target reaction section.

3. The method according to claim 1, characterized in that, In the multi-bias potential pulse sequence, relative to the reference electrode, the potential of the background hold segment is -0.10V to 0.10V and lasts for 0.5s to 10s; the potential of the target reaction segment is 0.20V to 0.75V and lasts for 1s to 30s; the potential of the interference identification segment is -0.30V to 0.95V and lasts for 0.2s to 20s; the potential of the recovery observation segment is -0.10V to 0.20V and lasts for 0.5s to 15s; the potential of the end verification segment is the same as or differs from the potential of the target reaction segment by no more than 0.15V and lasts for 0.5s to 15s.

4. The method according to claim 1, characterized in that, The response fingerprint includes the target segment peak current, the target segment steady-state current, the interference segment peak current, the interference segment steady-state current, the recovery segment residual current, and the end verification segment deviation value. The interference response parameter is determined by the ratio of the interference segment response amplitude to the target segment response amplitude. The recovery sufficiency parameter is determined by the ratio of the recovery segment residual current to the target segment steady-state current. The end verification parameter is determined by the deviation between the end verification segment response and the target segment response.

5. The method according to claim 1, characterized in that, The preset locking conditions include at least two of the following: the interference response parameter is greater than a first threshold, the recovery sufficiency parameter is greater than a second threshold, the end verification parameter is greater than a third threshold, the rise slope of the target reaction segment is less than a fourth threshold, and the background residual parameter is greater than a fifth threshold.

6. The method according to claim 1, characterized in that, When no result locking mark is generated, the time interval with a stable slope and noise below a preset noise threshold in the target response segment is selected as the effective response window, and the concentration of the target analyte is calculated based on the steady-state current or integrated charge within the effective response window. When the result locking condition is not met but the interference removal condition is met, the response component that changes synchronously with the interference identification segment is removed from the effective response window before the concentration of the target analyte is calculated.

7. The method according to any one of claims 1 to 6, characterized in that, The non-invasive liquid sample includes at least one of saliva, oral fluid, tears, sweat, or exhaled condensate, and the target analyte includes at least one of glucose, lactic acid, uric acid, ketone bodies, nitrite, hydrogen peroxide, hydrogen ion activity-related parameters, conductivity, or electrolyte ions.

8. A multi-bias potential pulse response fingerprint and cross-interference interception device for non-invasive liquid sample electrochemical detection, characterized in that, The system includes a liquid electrochemical detection chamber, a working electrode assembly, a reference electrode, an auxiliary electrode, a potential application module, a current acquisition module, a main control module, and a result output module. The potential application module applies background retention, target reaction, interference identification, recovery observation, and end-of-life verification segments to the working electrode assembly. The current acquisition module acquires current response data for each potential segment. The main control module extracts response fingerprints, calculates residual background parameters, interference response parameters, recovery sufficiency parameters, and end-of-life verification parameters, and controls the result output module to output detection results, cross-interference markers, or result lock markers according to preset locking or correction conditions.

9. The apparatus according to claim 8, characterized in that, The working electrode group includes a target working electrode and an interference identification working electrode. The target working electrode and the interference identification working electrode share the same liquid electrochemical detection chamber, reference electrode and auxiliary electrode. The current acquisition module acquires the response data of the target working electrode and the interference identification working electrode respectively.

10. An electronic device, characterized in that, It includes a processor and a memory, wherein the memory stores a computer program that, when executed by the processor, implements the method according to any one of claims 1 to 7.

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