Method and system for detecting trace heavy metal ions in bulk drug based on microfluidic chip

Abstract

The application discloses a raw material medicine trace heavy metal ion detection method and system based on a micro-fluidic chip, relates to the technical field of micro-fluidic detection and electrochemical analysis, and comprises the following steps: weighing, constant volume, clarification of the raw material medicine sample, solidifying target ions, standard calibration and peak interval / scanning parameters into a detection parameter table; according to the detection parameter table, the flow and valve control are controlled to complete liquid preparation, muSPE enrichment, washing, elution and constant volume loading on the chip; blank, no standard addition, one-time standard addition and numbered archiving are sequentially measured; baseline is made according to the solidified parameters, integration and blank deduction are carried out, the solution concentration is calculated combined with standard addition measurement, and the content is output. The method disclosed by the application can constrain micro-fluidic liquid preparation, enrichment, elution and constant volume loading, so that blank, no standard addition and standard addition three rounds are measured under the same source condition; the curve and standard addition measurement are numbered and archived, integral, blank deduction and concentration are solved simultaneously, and the quantitative consistency, traceability and calculation reliability are improved.

Description

Technical Field

[0001] This invention relates to the field of microfluidic detection and electrochemical analysis technology, specifically to a method and system for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips. Background Technology

[0002] Trace heavy metal ion control in active pharmaceutical ingredients (APIs) is a crucial aspect of drug quality and safety evaluation. Related detection technologies have evolved from traditional methods such as wet chemical colorimetry and atomic absorption / atomic fluorescence to high-sensitivity instrumental analysis like inductively coupled plasma mass spectrometry (ICP-MS). In recent years, with the development of microfabrication and microfluidics technologies, microfluidic chips have been increasingly applied to sample pretreatment, online solution preparation, micro-solid phase enrichment, and micro-electrochemical detection, enabling small-volume, integrated, and automated detection pathways. Simultaneously, software algorithms combining standard addition, curve processing, and parameterized control have deepened research into quantitative analysis under complex drug matrix conditions, providing a technological foundation for establishing portable and traceable detection solutions for pharmaceutical testing scenarios.

[0003] Current methods for detecting trace heavy metals in active pharmaceutical ingredients (APIs) still suffer from fragmented processes and insufficient quantitative consistency at the engineering implementation level. On the one hand, while large-scale instruments such as ICP-MS offer high sensitivity, sample preparation, matrix matching, and spectral interference correction rely on experience, and they often employ offline preprocessing and batch measurement modes. This makes it difficult to solidify and record key quantities such as weighing, volume adjustment, spiking, enrichment, and detection in a unified structure and form a coherent metrological chain. Furthermore, for multiple batches and rounds of testing, operational differences can easily introduce systematic biases. On the other hand, while microfluidic-electrochemical solutions possess miniaturization potential, common approaches focus on the detection unit itself, lacking structured and consistent constraints across batches on process parameters such as online solution flow rate, valve control timing, and μSPE enrichment-elution-volume determination. This makes it difficult to ensure strict homogeneity of blank, unspecified, and spiked sequence measurements when the sample enters the detection cell, thus weakening the precondition for standard quantification. Furthermore, peak interval selection, baseline processing, and integral calculation often rely on manual experience or discrete software operations, with curve data and spiked measurement records stored separately, making it difficult to bind them with the same number. Consequently, it is difficult to obtain a verifiable solution combining the blank subtraction integral and the equivalent incremental concentration. These shortcomings make it difficult for existing technologies to simultaneously achieve the unified requirements of process traceability, consistent conditions across batches, and closed-loop quantitative calculation under micro-sample conditions. Summary of the Invention

[0004] In view of the above-mentioned problems, the present invention is proposed.

[0005] Therefore, the technical problem solved by this invention is that existing methods for detecting trace heavy metal ions in active pharmaceutical ingredients suffer from scattered detection parameters and metrological elements, making it difficult to form unified and traceable records. The process control of online solution preparation, enrichment, elution, and volume adjustment lacks consistency constraints across rounds, resulting in unstable quantitative premises for standard addition. Curve processing and spiking metrological records are not bound to the same number, and blank subtraction and concentration calculation are difficult to verify in a closed loop. The invention also addresses how to achieve a closed-loop quantitative detection system on a microfluidic chip platform that solidifies process parameters, ensures consistent measurement sequences, and combines curve integration and spiking conversion.

[0006] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a method for detecting trace heavy metal ions in active pharmaceutical ingredients (APIs) based on a microfluidic chip, comprising weighing, volume adjustment, and clarification of the API sample; solidifying the weighed mass, volume adjustment, target ion set, standard solution calibration information, peak intervals, and scanning parameter fields in the same detection parameter table; under the constraints of the detection parameter table, connecting the sample and reagents to the chip and completing online solution preparation, μSPE enrichment, washing, elution, and detection cell volume adjustment according to the flow rate and valve control sequence specified in the detection parameter table, ensuring that the sample state and process record remain consistent across different measurement rounds; and sequentially performing blank... Three electrochemical measurements were performed, one with and one with spikes. The curve data generated from each measurement and the corresponding flow rate and volume spike record were bound and archived with the same measurement number. The solidified peak intervals and scanning parameters were directly called to perform baseline processing and peak interval integration calculation on the three archived curves, outputting blank integral, unspiked integral, and spiked integral. Blank subtraction was performed in the same record structure to obtain the subtracted integral of the two sample measurements. The archived spiked metering records were converted into equivalent incremental concentrations, and the incremental concentration and the two subtracted integrals were combined to output the original sample solution concentration. The content conversion was completed by combining the recorded weighing mass and the fixed volume and outputting the result.

[0007] As a preferred embodiment of the microfluidic chip-based method for detecting trace heavy metal ions in active pharmaceutical ingredients (APIs) according to the present invention, the following steps are included: weighing, volume-adjusting, and clarifying the API sample: weighing the API sample using an analytical balance and recording the mass; adding the sample to a solvent system to dissolve or disperse it and then adjusting the volume to the specified volume, recording the container specifications and the adjusted volume; clarifying the mother liquor after volume adjustment to obtain the injection solution, and recording the filter membrane pore size, centrifugation speed, and time parameters; writing the target ion set, standard solution number, and calibration concentration information into the detection parameter table, and storing the upper and lower limit potentials of the peak interval and the scanning step parameters in a field format.

[0008] As a preferred embodiment of the microfluidic chip-based method for detecting trace heavy metal ions in pharmaceutical raw materials according to the present invention, the following steps are included: The weighing mass, final volume, target ion set, standard solution calibration information, peak intervals, and scanning parameter fields are solidified in a single detection parameter table. This includes sampling the target ion standard solution for dissolution scanning under an electrode system and scanning program consistent with the sample measurement, obtaining potential and current sequence curve data; based on the curve data, the lower and upper limits of the peak interval corresponding to each target ion are determined, and the lower and upper limits of the peak interval, along with the scan start and end potentials, potential step, deposition potential, and deposition time, are solidified as fields in the detection parameter table; the solidification also includes establishing an association record between the electrode system number, scanning program version number, and standard solution number.

[0009] As a preferred embodiment of the microfluidic chip-based method for detecting trace heavy metal ions in pharmaceutical raw materials according to the present invention, the following steps are included: Connecting the sample and reagents to the chip and completing online solution preparation, μSPE enrichment, washing, elution, and detection cell volume loading according to the flow rate and valve control sequence specified in the detection parameter table. This includes connecting the sample injection solution, buffer solution, washing solution, and elution solution to the chip inlet port and establishing a mapping between the port and the reagent pump channel; performing online solution preparation in the micromixer section according to the inlet flow rate ratio set in the detection parameter table, controlling the mixture to pass through the μSPE enrichment bed at an enrichment flow rate and enrichment time; completing washing according to the washing flow rate and washing time, and switching the elution solution to introduce the components into the detection cell pathway at an elution flow rate and elution time; completing the fixed-volume loading of the detection cell using a fixed-volume chamber or a valve-controlled quantitative strategy, and recording the flow rate, duration, and valve control switching time at each stage in the operation record.

[0010] As a preferred embodiment of the microfluidic chip-based method for detecting trace heavy metal ions in pharmaceutical raw materials according to the present invention, the method for ensuring consistency between the sample state and process records entering the detection cell across different measurement rounds includes setting the flow path switching logic for blank measurement, unspecified measurement, and single-spiked measurement to the same valve control sequence, and setting the enrichment time, washing time, elution time, detection cell volume, deposition potential, deposition time, scan start and end potentials, and potential step to the same set of fixed parameters; wherein the single-spiked measurement only introduces the standard solution channel metering parameters during the online solution preparation stage, and the remaining flow path operating parameters and electrochemical parameters remain consistent with those of the unspecified measurement; for each measurement round, the inlet flow rate or quantitative volume, valve control switching log, and detection cell hold mode parameters are recorded to ensure that the field structure of the operation record is consistent across rounds.

[0011] As a preferred embodiment of the microfluidic chip-based method for detecting trace heavy metal ions in active pharmaceutical ingredients according to the present invention, the method of binding and archiving the curve data generated by each measurement with the corresponding flow rate and volume spiked record using the same measurement number includes assigning measurement numbers to the three measurements respectively, and writing the potential sequence, corresponding current sequence, number of sampling points and scan step output by the electrochemical workstation as curve data fields into the archived record; establishing an association between the measurement number and the current sample inlet flow rate, standard solution inlet flow rate or quantitative addition volume, sample volume involved in mixing, standard solution number and its calibration concentration fields; the archived structure uses the measurement number as the primary key index, so that the curve data field and the spiked measurement field are called in the same record object, and the field naming is consistent between blank, unspecified and single-spiked measurements.

[0012] As a preferred embodiment of the microfluidic chip-based method for detecting trace heavy metal ions in active pharmaceutical ingredients (APIs) according to the present invention, the following steps are included: baseline processing and peak interval integration calculation of the three archived curves: reading the upper and lower limit potentials of the target ion peak interval from the detection parameter table, and determining the peak interval endpoint sampling points in the curve sampling data; using linear interpolation of the peak interval endpoints to output the baseline sequence; discretely integrating the baseline subtracted current within the peak interval according to the potential step to obtain the blank integral, the unspecified integral, and the spiked integral; subtracting the blank integral from the unspecified and spiked integrals to obtain the subtracted integral from the two sample measurements; converting the equivalent incremental concentration based on the archived flow rate or volume spiked metering field, calculating the original sample solution concentration, and combining the weighed mass and fixed volume in the detection parameter table to obtain the API content result.

[0013] Another objective of this invention is to provide a microfluidic chip-based system for detecting trace heavy metal ions in active pharmaceutical ingredients (APIs). This system can convert archived spiking records into equivalent incremental concentrations, and output the original solution concentration by combining the incremental concentration with the integral amount after two subtractions. It also combines the recorded weighing mass and the fixed volume to complete the content conversion and output the result. This solves the problem that current methods for detecting trace heavy metal ions in APIs have blank subtraction and difficulty in closed-loop verification of concentration calculation.

[0014] As a preferred embodiment of the microfluidic chip-based trace heavy metal ion detection system for pharmaceutical raw materials described in this invention, the system includes: a parameter table solidification module, a chip process execution module, and a measurement calculation output module. The parameter table solidification module is used to weigh, dilute, and clarify the pharmaceutical raw material sample; configure and record the target ion set and standard solution calibration information; calibrate and write the peak interval and scanning parameter fields, solidify the data into a single detection parameter table, and output the task configuration record. The chip process execution module is used to connect the sample and reagents to the microfluidic chip under the constraints of the detection parameter table. The sample is prepared and the online solution preparation, μSPE enrichment, washing, elution, and volume loading of the detection cell are completed sequentially according to the flow rate and valve control sequence specified in the detection parameter table. At the same time, the operating parameters and valve control switching logs of each stage are recorded. The measurement calculation output module is used to perform three electrochemical measurements in sequence: blank, unspecified, and one-spiked. The curve data and spiking records are archived. The peak interval and scanning parameters in the detection parameter table are called to perform baseline processing and peak interval integration and blank subtraction on the curve. The spiking is then converted into an equivalent incremental concentration. The concentration of the original sample solution is calculated simultaneously, and the conversion result of the active pharmaceutical ingredient content is output.

[0015] A computer device includes a memory and a processor, the memory storing a computer program, and the processor executing the computer program to implement a method for detecting trace heavy metal ions in a drug substance based on a microfluidic chip.

[0016] A computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the steps of a method for detecting trace heavy metal ions in a drug substance based on a microfluidic chip.

[0017] The beneficial effects of this invention are as follows: The microfluidic chip-based method for detecting trace heavy metal ions in active pharmaceutical ingredients (APIs) provides a unified detection parameter table that consolidates the weighing mass, volumetric volume, target ion set, standard solution calibration information, peak intervals, and scanning parameters of the API sample. This achieves structured aggregation of key metrological elements and algorithm boundary conditions for the detection task, establishing a directly callable and traceable parameter benchmark at the initial detection stage, thereby reducing the risk of traceability disruptions caused by information dispersion and parameter drift. By executing online solution preparation, μSPE enrichment, washing, elution, and detection cell volumetric loading under the constraints of the detection parameter table, the flow rate and valve control timing are standardized and fixed, ensuring that the processing path and loading state before entering the detection cell are consistent for different measurement rounds, thus reducing the differences caused by human intervention during switching. The system bias introduced by inconsistent loading is addressed by sequentially performing blank, unspecified, and single-specified measurements and binding curve data with flow / volume spiking records using measurement numbers. This achieves a one-to-one correspondence between electrochemical data and metrological inputs, preventing mismatches between curves and spiking parameters and thus improving the accuracy of data attribution and the convenience of verification. By calling the solidified peak interval and scanning parameters to complete baseline processing, peak interval integration, and blank subtraction, the rules for generating integral quantities are made consistent and verifiable, allowing for comparable input of subtracted integral quantities and thus suppressing background drift and subjective peak selection errors. By converting spiking measurements to equivalent incremental concentrations and solving for the original sample concentration by combining them with subtracted integral quantities, and then combining weighing and volume-dilution records to complete content conversion, the consistency of trace detection calculations and the feasibility of engineering implementation are improved. Attached Figure Description

[0018] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 The first embodiment of the present invention provides an overall flowchart of a method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips. Detailed Implementation

[0020] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the protection scope of the present invention.

[0021] Example 1, referring to Figure 1 As an embodiment of the present invention, a method for detecting trace heavy metal ions in a pharmaceutical raw material based on a microfluidic chip is provided, comprising: S1: Complete the weighing, volume adjustment and clarification of the active pharmaceutical ingredient sample, and solidify the weighing mass, volume adjustment, target ion set, standard solution calibration information, peak range and scanning parameter fields in the same detection parameter table.

[0022] Furthermore, the batch information and testing task information of the active pharmaceutical ingredient to be tested are obtained, and the target heavy metal ion type index is determined under this task. For the determined target ion, the corresponding metal ion standard solution is prepared and its calibrated concentration is recorded. The standard solution is prepared using calibrated volumetric instruments. During the preparation process, the source information of the standard substance, the concentration calculation record, the volume adjustment record, and the preparation date are recorded. When a certified standard substance is used, the nominal concentration on the certificate is recorded as the source record item, and the correspondence between the standard solution number and the target ion index is linked in the testing record.

[0023] Weigh the active pharmaceutical ingredient (API) sample using an analytical balance, recording the weighing reading and time. Add the weighed API sample to a solvent system for dissolution or dispersion, forming a sample stock solution. The solvent system should be prepared according to established experimental procedures, clearly recording the solvent composition, acidifying reagent name and volume fraction, addition order, and stirring conditions. After dissolution or dispersion, bring the sample stock solution to a fixed volume, controlled by the nominal value and graduation mark of the volumetric caliper, recording the actual caliper specifications and serial number. After volume adjustment, clarify the sample stock solution to obtain a sample solution suitable for chip loading. Clarification should be performed using either filtration or centrifugation: in filtration, record the filter membrane pore size and filter media type, and the solution volumes before and after filtration; in centrifugation, record the centrifugation speed, centrifugation time, and sampling location, recording the supernatant volume. The weighed mass and adjusted volume are recorded as fixed inputs for this testing task in the testing record and linked to the sample batch information.

[0024] It should be noted that the same electrode system and electrochemical scanning program as the detection system were used to perform peak calibration on the standard solution of the target ion. The electrode system includes the material types and on-chip layout information of the working electrode, reference electrode, and counter electrode. The scanning program includes the scanning mode, start and end potential range, and potential step. Parameters such as deposition potential and deposition time are all recorded in a parameter table format. During the calibration process, the electrochemical workstation outputs a discrete sampling dataset. ,in For sampling potential sequence, To correspond to the sampling current sequence, and according to the target ion Data is archived using the standard solution numbering system. The peak boundaries of the ions are determined based on this calibration curve. and will and The data is written and saved as a field in the parameter table, and the saved items include the target ion. The upper and lower limit potential values ​​of the peak interval, the corresponding scan parameter version number and electrode system version number.

[0025] In this testing task, a process control parameter table was set and solidified. The parameter table should include at least: enrichment time, flow rate setpoint for the enrichment stage, flow rate setpoint for the washing stage, flow rate setpoint for the elution stage, volume control strategy parameters for the test cell, deposition potential and deposition time, and the start and end potential range and potential step for the dissolution scan. And the data sampling frequency or equivalent number of sampling points. Synchronous solidification spiking strategy parameters: When using an online mixing method with two inlet flow rates, record the sample inlet flow rate. With standard solution inlet flow rate The set value field and its traceable recording method; when using the quantitative volume addition method, record the volume of standard solution added. With the volume of the sample involved in the mixing The source fields and their measurement methods are listed. The above parameter table is numbered in relation to the sample batch information, standard solution number, and peak range parameters. The weighing mass and the volume determination are bound together and archived to form a complete test task configuration record.

[0026] S2: Under the constraints of the detection parameter table, the sample and reagent are connected to the chip and online solution preparation, μSPE enrichment, washing, elution and detection cell volume adjustment are completed according to the flow rate and valve control sequence specified in the detection parameter table, so that the sample state and process record entering the detection cell remain consistent between different measurement rounds.

[0027] Furthermore, the sample injection solution, buffer solution, and washing and elution solutions corresponding to the configuration of this procedure are respectively connected to the corresponding inlet channels of the microfluidic chip, and the tubing and interface are sealed. For each inlet channel, the name, batch number, container number, and inlet port number of the connected reagent are recorded, and a mapping table of inlet port, reagent type, and pump channel is established in the control system. The chip flow path includes a micromixer section, a μSPE enrichment unit, a washing section, an elution section, and a detection cell loading path; the above structure is executed using the same set of flow path switching logic, and the flow path switching is completed by a valve control module or an equivalent fluid switching mechanism. The switching action record includes the switching time, the target channel being switched, and the corresponding flow rate setpoint.

[0028] During the online solution preparation and conditioning stage, the sample injection solution and buffer solution are input into the micromixer section at set flow rates, allowing the two liquids to form a stable mixed flow within the mixer. The sample inlet flow rate is denoted as... The inlet flow rate of the buffer solution is denoted as Both are supplied by an injection pump, peristaltic pump, or pneumatic drive module, and the setpoints and real-time output values ​​are recorded in the control system. The micromixer uses serpentine channels, herringbone trenches, or equivalent microstructures to achieve mixing, executing the channel flow path corresponding to the predetermined chip structure without changing the channel morphology parameters. Before the mixed solution enters the enrichment unit, it is continuously supplied according to the conditioning time window fixed in the parameter table to allow the flow field, flow resistance, and mixing ratio within the chip to reach a stable state; this stabilization process is recorded as a fixed-duration running segment, and the recorded items include the start and end times of the running segment, the setpoints of each inlet flow rate, and the real-time value sampling records.

[0029] It should be noted that after online solution preparation, the mixed sample flow is controlled to enter the μSPE enrichment unit for enrichment. The μSPE enrichment unit is a solid-phase bed region within the chip, and its filler type, bed length, and packing method are fixed as chip structural parameters. The enrichment flow rate is maintained during the enrichment stage. With enrichment time The solidification values ​​are recorded in the parameter table, and the start and end times of the enrichment stage and the corresponding pump output data are recorded. After the enrichment stage, a washing operation is performed: the washing liquid is introduced into the enrichment unit through valve-controlled switching, and the inlet flow rate of the washing liquid is recorded as... Washing time is recorded as All operations are performed using the fixed values ​​in the parameter table; the washing process record includes the washing liquid name, washing flow rate setpoint, washing time, and switching action log. After washing, the elution operation is performed: the eluent is switched via valve control to allow the eluent to enter the enrichment unit and the bound ionic components in the bed are migrated out with the eluent; the eluent inlet flow rate is recorded as... Washout time is recorded as All operations are executed according to the parameter table and generate continuous running records.

[0030] When the eluent carrying the target component enters the detection cell pathway, a volume-controlled loading operation is performed. In-chip detection cell loading is achieved using a volume-controlled chamber or an equivalent valve-controlled quantification strategy; the volume-controlled volume is denoted as [missing information]. This volume is determined by the chip geometry or quantitative chamber structure and is fixed in the chip design parameters. Valve-controlled logic allows the eluent to enter the volume-fixing chamber until a fixed volume is reached. After reaching the fixed volume, the flow path is switched to bring the detection cell into a stable loading state. Corresponding record items include the volume-fixing strategy type, nominal volume value, loading stage start and end times, loading stage flow rate setting, and valve-controlled switching log. After loading, the flow state of the detection cell is switched to the hold mode (static hold or microfluidic hold) fixed in the parameter table. The flow rate setting corresponding to the hold mode is recorded as follows: The values ​​and durations are executed and recorded according to the parameter table.

[0031] When this testing task includes a spiking measurement sequence, the connection and metering configuration of the spiking input channel are performed simultaneously during the online solution preparation stage, and the spiking method is fixed to one of two types. When using online mixed spiking with two inlet flow rates, the standard solution inlet flow rate is recorded as follows: and the sample inlet flow rate Record this information in the operation log; when using quantitative volumetric spiking, the volume of standard solution added is recorded as follows: The volume of the sample involved in the mixing is denoted as Both are derived from the geometric volume of the metering chamber or the calibration volume of the metering pump stroke, and the corresponding volume parameters are recorded in the system configuration. The spiking-related channel number, valve control switching time, flow rate or volume measurement parameters, and standard solution concentration are also included. The parameters are uniformly recorded in this operation log to form a closed-loop record consistent with the chip's online solution preparation, enrichment, washing, elution, and volume loading processes.

[0032] S3: Perform three electrochemical measurements in sequence: blank, unspecified, and spiked. Then, bind and archive the curve data generated from each measurement with the corresponding flow rate and volume spiked record using the same measurement number.

[0033] Furthermore, after completing the switching between constant-volume loading and holding modes, the electrochemical workstation is activated to execute a measurement sequence on the three-electrode system within the chip detection cell. The three-electrode system includes a working electrode, a reference electrode, and a counter electrode. The electrode material type, geometry, on-chip placement, and electrical connection method with the external workstation are written as fixed information into the detection record. The electrochemical workstation loads the scan parameter configuration file for this detection task. The configuration file includes at least the deposition potential, deposition time, and settings for whether the deposition stage is static or maintains a holding flow rate, as well as the scan mode, start and end potential range, potential step, sampling frequency or number of sampling points, and pulse / square wave parameters corresponding to the scan mode for the dissolution scan stage.

[0034] During blank measurements, the blank solution is connected to the sample inlet and operated using the same flow path switching and loading strategy as the sample, ensuring the detection cell reaches the same loading state as the sample measurement. The name, batch number, acidity, or buffer system composition of the blank solution are recorded. Blank measurements are performed at the electrochemical workstation according to a predetermined measurement sequence, completing deposition and dissolution scans, and the workstation outputs a discrete sampling dataset. ,in For the first Potential value at each sampling point This corresponds to the sampled current value. This blank dataset is marked as a blank curve in the data management module and compared with the peak interval parameters of this detection task. Scanning Steps The electrode system number used in this study is bound to the archive, and the start and end times of the blank measurement and the parameters of the detection cell hold mode are specified in the record.

[0035] It should be noted that measurements without calibration are performed. At that time, the obtained sample injection solution is connected to the sample inlet, and the online solution preparation, enrichment, washing, elution, and volume adjustment are performed. The electrochemical measurement sequence is initiated after the detection cell reaches the loading state. During the measurement process, the electrochemical workstation also outputs... A discrete sampling dataset in the form of a sample-unspecified curve is generated and labeled as such in the data management module, with its measurement sequence number recorded. The operation log entries archived along with the curve data include: sample inlet flow rate, buffer inlet flow rate, enrichment stage flow rate and enrichment time, washing stage flow rate and washing time, elution stage flow rate and elution time, detection cell volume parameters, hold mode flow rate, deposition potential and deposition time, and the start and end potentials and potential steps of the dissolution scan. These operation log entries are associated with a unique identifier for this curve data.

[0036] Perform a single spiking measurement At the same time, while keeping the chip flow path structure and electrochemical workstation scanning parameter configuration file unchanged, the standard addition operation is incorporated into the metering configuration of the online solution preparation stage. When using the online mixed spiking method with two inlet flow rates, the standard solution inlet and the sample inlet are supplied simultaneously, and the standard solution inlet flow rate is recorded as follows: The sample inlet flow rate is denoted as The set values ​​and real-time output values ​​of both were recorded during this measurement; the concentration of the standard solution was also recorded. The value is determined by the standard solution preparation record or certificate and is linked to the measurement using the standard solution number. When using the quantitative volume addition method, the volume of standard solution added is recorded as follows: The volume of the sample involved in the mixing is denoted as Both are derived from the geometric volume of the quantitative chamber or the calibration volume of the metering pump stroke, and the corresponding volume parameters and metering methods are recorded in the configuration record of this measurement. After completing the spiking configuration, online solution preparation, enrichment, washing, elution, and volume adjustment are completed, and the electrochemical measurement sequence is initiated after the detection cell reaches the loading state; the workstation output... The dataset is labeled as the single-spiking curve of the sample, and its measurement sequence number is recorded. .

[0037] The three sets of curve data—blank curve, unspecified sample curve, and single-specified sample curve—along with their corresponding operation records, are archived together. The archive structure retains the number of sampling points, potential sequence, current sequence, scan step, peak interval parameters, and the associated flow or volume parameters for each set of curves.

[0038] S4: Directly call the fixed peak interval and scanning parameters, perform baseline processing and peak interval integration calculation on the three archived curves, output blank integral, unspecified integral and spiked integral, and complete blank subtraction in the same record structure to obtain the subtracted integral of the two sample measurements.

[0039] Furthermore, after data archiving is completed, the discrete sampling datasets of the three sets of curve data are read and processed according to the same field structure. The three sets of curve data are: blank measurement curve dataset, unspecified sample measurement curve dataset (measurement sequence number) ), Sample single-spiking measurement curve dataset (measurement sequence number) For any curve dataset, it includes the number of sampling points, potential sequence, current sequence, and potential step consistent with the current scan.

[0040] For each target ion type index, the peak interval boundary corresponding to that ion is read from the solidified parameter table, and the set of sampling points within the peak interval is determined in the read potential sequence. In practice, the potential sequence is filtered to meet the criteria... The set of all sampling point indices, denoted as Meanwhile, to ensure that the current values ​​at both ends of the peak interval have a definite source, the sampling point numbers at both ends are defined as follows: :satisfy The smallest sequence number; :satisfy The maximum sequence number. Based on this, the terminal potential and current are denoted as... and .

[0041] In the peak range Inside, for each sampling point Constructing endpoint linear baseline current The baseline sequence is then aligned with the original current sequence and stored according to the sampling point number. The baseline current is determined by the following formula:

[0042] in, Indicates the sampling point number; For the first The potential value at each sampling point; For the first The current at each sampling point; Indicates the target ion Lower limit potential and upper limit potential of the peak interval; This indicates the sampling sequence number corresponding to the lower limit endpoint of the peak interval, satisfying... And the sequence number is the smallest; This indicates the sampling sequence number corresponding to the upper limit endpoint of the peak interval, satisfying... And the serial number is the largest; Indicates the sampling potential at the peak interval endpoint; This indicates the sampling current at the peak interval endpoints; Indicates at potential The linear baseline current at the endpoint.

[0043] In baseline sequence Once determined, for each target ion Calculate the discrete integral within the peak interval. The integration operation is performed on the selected set of sampling points. Execution is performed using potential stepping and baseline subtraction of current. Summation is performed, and the integral is calculated using the following formula:

[0044] in, Indicates the target ion Discrete integral quantities in the peak interval of this curve dataset.

[0045] It should be noted that, following the same calculation process described above, the integral quantities of the three sets of curve data were calculated separately and stored using measurement sequence numbers: the integral quantity corresponding to the blank curve was denoted as... The integral quantity corresponding to the unspecified sample curve is denoted as . The integral quantity corresponding to the single-spiking curve of the sample is denoted as . The subscript "blank" indicates a blank dataset identifier, and subscripts 0 and 1 indicate the fixed measurement sequence number. , .

[0046] After completing the calculation of the three sets of integrals, perform the blank subtraction operation and output the integral after blank subtraction. and Blank subtraction on the same target ion The following steps are performed, calculated using the following formula:

[0047] in, Indicates the target ion In the measurement sequence number The discrete integral quantity after blank subtraction.

[0048] The completed data record includes: each target ion Corresponding peak interval boundary Endpoint sampling sequence number Peak interval sampling point set Baseline sequence Values ​​within the peak interval, and three sets of integrals And the points after deducting blanks The above record items are archived with unique identifiers for the corresponding curve datasets, and the field names are in... and The measurements of the two sets of samples remained consistent.

[0049] S5: Convert the archived spiking measurement records into equivalent incremental concentrations, and output the original sample solution concentration by combining the incremental concentration with the integral amount after two subtractions. Combine the recorded weighing mass and the fixed volume to complete the content conversion and output the result.

[0050] Furthermore, each target ion was obtained. Blank subtraction integral in two sample measurements and And obtain the blank integral. and the peak interval parameters corresponding to each curve With potential step ΔE\Delta EΔE. Based on reading the archived spiking method field, flow rate or volume measurement field, and standard solution concentration field, determine the equivalent incremental concentration corresponding to one spiking. Based on this, the target ions in the original sample solution are calculated. concentration The concentration of the solution was then converted into the ion content of the active pharmaceutical ingredient. .

[0051] When the recorded spiking method field indicates online mixing of two continuous inlet streams, the equivalent incremental concentration formed at the chip inlet by a single spiking is determined based on the inlet flow rates of the two streams and the standard solution concentration. The calculation formula is:

[0052] in, This indicates the equivalent incremental concentration formed at the chip entry point by a single spiking.

[0053] When the recorded spiking method field indicates addition by quantitative volume, the equivalent incremental concentration is determined based on the quantitative volume and the standard solution concentration. The calculation formula is as follows:

[0054] in, This indicates the volume of standard solution added in a single spiking operation. This indicates the volume of the sample that participated in the mixing.

[0055] Under the premise of using the same flow path control and electrochemical scan parameters for both spiked and unspiked measurements, blank subtraction integral was used. , Equivalent incremental concentration of spiking Calculate the target ion in the original solution concentration The calculation formula is:

[0056] in, Indicates the target ion in the original solution The concentration.

[0057] For each target ion Perform the above calculations separately, and then use the results... Write the results to the results field table, which includes the standard solution number, spiking method field, flow rate or volume record field, and the corresponding... , Maintain associated archives.

[0058] It should be noted that the concentration of the original solution was... Converted to target ions in active pharmaceutical ingredients content The calculation formula is:

[0059] in, Indicates the target ion in the active pharmaceutical ingredient The content of.

[0060] The unit system is also recorded in the output field: when use , use , use hour, The result unit is And write it into the results field table in that unit. For each target ion Repeat the above calculation process to form the corresponding ion. , and The three types of fields are linked and archived with the unique identifiers of the curve data, parameter table numbers, standard liquid numbers, flow or volume measurement records, and weighing and volume determination records of this testing task.

[0061] Example 2, one embodiment of the present invention, provides a method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips. To verify the beneficial effects of the present invention, scientific demonstration is carried out through economic benefit calculations and simulation experiments.

[0062] First, a synthetic active pharmaceutical ingredient sample was selected as the matrix, and the target ion was set as Pb. 2+ For demonstration purposes. The standard solution uses metrically traceable Pb. 2+ Single-element standard stock solutions were prepared, and the standard solution number and calibration concentration were recorded after preparation. These were then entered into the detection parameter table as experimental input fields. For sample preparation, the specified mass of the active pharmaceutical ingredient was weighed using an analytical balance, placed in a volumetric flask, and dissolved completely in a pre-set solvent system. The solution was then diluted to the specified volume to form the sample stock solution. Subsequently, a clear injection solution was obtained by filtration using a fixed-pore-size membrane. The filter media specifications and operation records were entered into the detection parameter table. After sample preparation was completed, Pb was measured using the same electrode system and scanning program as the sample measurement. 2+ The standard solution is used for calibration measurement, and Pb is determined based on the calibration curve. 2+ The upper and lower limits of the peak range potential are determined, and parameters such as scan start and end potential, potential step, deposition potential, and deposition time are fixed into the detection parameter table as fields to ensure that the blank, unspecified, and single-specified tests of the same batch of tests all use the same set of fixed parameters.

[0063] The microfluidic chip integrates a micromixer, a μSPE enrichment unit, a washing / elution channel, and a volumetric detection chamber. The chip inlets are connected to the sample injection solution, buffer solution, washing solution, elution solution, and standard solution, respectively. The mapping relationship between each inlet and the pump channel is registered before the experiment begins. During the execution process, online solution preparation is performed according to the flow ratio set in the parameter table and the process is stabilized. Then, the μSPE enrichment stage is initiated. After enrichment, the washing solution is switched to complete a fixed-duration washing process. Next, the elution solution is switched to introduce the enriched components into the detection chamber pathway, and the volumetric detection chamber is used to achieve a fixed volume loading. The valve switching times, flow setpoints for each stage, and start and end times of each running segment are recorded as operation records and archived with the same numbering as the curve data. The measurement sequence is executed in the order of blank, unspecified, and single-specified: Blank measurement uses a blank solution to complete a full measurement using the same flow path and electrochemical parameters; unspecified measurement repeats the above chip process without introducing a standard solution to complete the electrochemical measurement; single-specified measurement introduces the standard solution channel during the online solution preparation stage, with the standard solution flow rate or quantitative volume added fixed according to the parameter table and written into the spiking record, while the remaining flow path and electrochemical parameters remain unchanged. The potential and current sequences from the three measurements are output from the electrochemical workstation, and together with the flow / volume spiking record for each measurement, are bound and archived with a unified measurement number, forming a raw data package that can be directly used for subsequent baseline processing, peak interval integration, and blank subtraction.

[0064] Table 1 Experimental Data

[0065] As shown in Table 1, the three groups of samples in this invention maintain strict consistency in key process fields, especially the constant volume, peak range upper and lower limits, potential step, enrichment time, and constant volume of the detection cell, all of which are fixed values. Furthermore, the flow rate settings are stable (sample inlet flow rate is 8.0 µL / min, standard solution inlet flow rate is 1.0 µL / min). This ensures that the fluid state and electrochemical acquisition boundary conditions before the sample enters the detection cell are within the same recording system for the blank, unspecified, and spiked measurements. Correspondingly, the blank integral of this invention is in the range of 0.11–0.12 au, with little difference among the three groups of samples, indicating that background items can be consistently included and subtracted at the recording level. In contrast, in Comparison 2, without changing the scan step and peak range, the blank integral increases to 0.25 au, reflecting a significant increase in background items when process control is inconsistent, which amplifies the uncertainty after subtraction. Further observation of the spiked recovery rates revealed that the three sample groups of this invention achieved recoveries of 99.2%, 100.6%, and 98.7%, respectively, concentrated within a narrow range close to 100%, with a repeatability RSD of 2.3%–2.8%. This indicates that the curve data bound with the same number and the spiked measurement records can support stable closed-loop quantification of standard addition. While Comparison 1 also yielded spiked results, the recovery rate reached 111.3% with an RSD of 6.9%. Furthermore, there were deviations between the peak interval parameters and the weighing / volume field (m=0.198g, V=49.2mL, and the upper and lower limits of the peak interval were inconsistent with those of this invention). This data demonstrates that when key fields are recorded separately and peak interval boundaries are not fixed, the integration interval and measurement input are prone to non-homogeneity, resulting in systematic overestimation and decreased repeatability. Compared with the external standard method in Comparison 3, which did not add any standard (the inlet flow rate of the standard solution was 0), the calculated solution concentration and content were significantly higher (C0=16.0µg / L, w=4.00µg / g). At the same time, the recalculation of the results was only partial. This indicates that under the complex raw material matrix conditions, the lack of spiking records along the same path as the sample and the data structure of the three rounds under the same conditions can easily lead to decoupling between calibration and curve processing. In summary, the inventiveness of this invention lies in: unifying weighing / volume determination, peak interval and scanning parameters, flow path flow rate and valve control timing, curve data and spiking metering records into the same detection parameter table and numbered archiving structure. This allows blank subtraction, peak interval integration, and equivalent incremental concentration calculation to be completed within the same data object, ensuring the closed-loop consistency of the quantitative chain from a data perspective. As can be seen from the table comparison results, this structured closed loop brings a spike recovery rate closer to 100%, a lower RSD, and a more stable blank background level. Thus, it demonstrates a substantial improvement over the existing technology's scattered parameters, inconsistent cycles, and insufficient decoupling between curves and metering in the microfluidic chip trace heavy metal detection scenario.

[0066] Example 3, an embodiment of the present invention, provides a trace heavy metal ion detection system in active pharmaceutical ingredients based on a microfluidic chip, including a parameter table solidification module, a chip process execution module, and a measurement calculation output module.

[0067] The parameter table solidification module is used to weigh, dilute, and clarify the active pharmaceutical ingredient (API) sample; configure and record the target ion set and standard solution calibration information; calibrate and write the peak interval and scanning parameter fields, solidify the data into the same detection parameter table, and output the task configuration record; the chip process execution module is used to connect the sample and reagent to the microfluidic chip under the constraints of the detection parameter table, and sequentially complete online solution preparation, μSPE enrichment, washing, elution, and detection cell dilution loading according to the flow rate and valve control sequence specified in the detection parameter table, while recording the operating parameters and valve control switching logs at each stage; the measurement calculation output module is used to perform three electrochemical measurements in sequence: blank, unspecified, and one-spiked, and archive the curve data and spiking records, call the peak interval and scanning parameters in the detection parameter table to perform baseline processing and peak interval integration on the curve, blank subtraction, and then convert the spiking measurement into an equivalent incremental concentration, calculate the original sample solution concentration, and output the API content conversion result.

[0068] If a function is implemented as a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of this invention, or the part that contributes to the prior art, or a part of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods of the various embodiments of this invention. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.

[0069] The logic and / or steps represented in the flowchart or otherwise described herein, for example, can be considered as a sequenced list of executable instructions for implementing logical functions, and can be embodied in any computer-readable medium for use by, or in conjunction with, an instruction execution system, apparatus, or device (such as a computer-based system, a processor-including system, or other system that can fetch and execute instructions from, an instruction execution system, apparatus, or device). For the purposes of this specification, "computer-readable medium" can be any means that can contain, store, communicate, propagate, or transmit programs for use by, or in conjunction with, an instruction execution system, apparatus, or device.

[0070] More specific examples (a non-exhaustive list) of computer-readable media include: electrical connections (electronic devices) having one or more wires, portable computer disk drives (magnetic devices), random access memory (RAM), read-only memory (ROM), erasable and editable read-only memory (EPROM or flash memory), fiber optic devices, and portable optical disc read-only memory (CDROM). Furthermore, computer-readable media can even be paper or other suitable media on which programs can be printed, because programs can be obtained electronically, for example, by optically scanning the paper or other medium, followed by editing, interpreting, or otherwise processing as necessary, and then stored in computer memory.

[0071] It should be understood that various parts of the present invention can be implemented using hardware, software, firmware, or a combination thereof. In the above embodiments, multiple steps or methods can be implemented using software or firmware stored in memory and executed by a suitable instruction execution system. For example, if implemented in hardware, as in another embodiment, it can be implemented using any one or a combination of the following techniques known in the art: discrete logic circuits having logic gates for implementing logical functions on data signals, application-specific integrated circuits (ASICs) having suitable combinational logic gates, programmable gate arrays (PGAs), field-programmable gate arrays (FPGAs), etc. It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

[0072] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A method for detecting trace heavy metal ions in pharmaceutical raw materials based on microfluidic chips, characterized in that, include: Complete the weighing, volume adjustment and clarification of the active pharmaceutical ingredient sample, and solidify the weighing mass, volume adjustment volume, target ion set, standard solution calibration information, peak range and scanning parameter fields in the same detection parameter table; Under the constraints of the detection parameter table, the sample and reagent are connected to the chip and online solution preparation, μSPE enrichment, washing, elution and detection cell volume adjustment are completed according to the flow rate and valve control sequence specified in the detection parameter table, so that the sample state and process record entering the detection cell remain consistent between different measurement rounds; Perform three electrochemical measurements in sequence: blank, unspecified, and spiked. Then, bind and archive the curve data generated from each measurement with the corresponding flow rate and volume spiked record using the same measurement number. The system directly calls the fixed peak intervals and scanning parameters to perform baseline processing and peak interval integration calculation on the three archived curves, outputting blank integral, unspecified integral, and spiked integral, and completes blank subtraction in the same record structure to obtain the subtracted integral of the two sample measurements. The archived spiking records are converted into equivalent incremental concentrations. The incremental concentration is then combined with the integral after two subtractions to output the original sample solution concentration. The content conversion is completed by combining the recorded weighing mass and the final volume, and the result is output.

2. The method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips as described in claim 1, characterized in that: The weighing, volume adjustment and clarification of the active pharmaceutical ingredient sample includes weighing the active pharmaceutical ingredient sample using an analytical balance and recording the weighing mass, adding the sample to a solvent system to dissolve or disperse it, adjusting the volume to the specified volume, and recording the specifications of the container and the adjusted volume. The mother liquor after volume adjustment was clarified to obtain the injection solution. The filter membrane pore size, centrifugation speed and time parameters were recorded. The target ion set, standard solution number, and calibration concentration information are written into the detection parameter table, and the upper and lower limit potentials of the peak interval and the scanning step parameters are stored in the form of fields.

3. The method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips as described in claim 2, characterized in that: The weighing mass, fixed volume, target ion set, standard solution calibration information, peak range and scanning parameter fields are solidified in the same detection parameter table. Under the electrode system and scanning program consistent with the sample measurement, the target ion standard solution is sampled for dissolution scanning to obtain curve data of potential sequence and current sequence. Based on the curve data, the lower limit potential and upper limit potential of the peak interval corresponding to each target ion are determined, and the lower limit potential and upper limit potential of the peak interval, along with the scan start and end potentials, potential step, deposition potential and deposition time, are solidified as fields in the detection parameter table. The curing process also includes establishing a record linking the electrode system number, scanning program version number, and standard solution number.

4. The method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips as described in claim 3, characterized in that: The process of connecting the sample and reagents to the chip and completing online solution preparation, μSPE enrichment, washing, elution, and volume loading of the detection cell according to the flow rate and valve control sequence specified in the detection parameter table includes connecting the sample injection solution, buffer solution, washing solution, and elution solution to the chip inlet port respectively and establishing a mapping of the port reagent pump channel; After online liquid preparation in the micro mixer section according to the inlet flow rate ratio set in the detection parameter table, the mixture is controlled to pass through the μSPE enrichment bed at the enrichment flow rate and enrichment time. Washing is completed according to the washing flow rate and washing time, and the eluent is switched to introduce the components into the detection cell pathway according to the elution flow rate and elution time. A fixed-volume loading of the detection cell is completed using a constant-volume chamber or a valve-controlled quantitative strategy, and the flow rate, duration, and valve-controlled switching time of each stage are written into the operation record.

5. The method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips as described in claim 4, characterized in that: The method of keeping the sample state and process record consistent across different measurement rounds includes setting the flow path switching logic of blank measurement, unspiked measurement and single-spiked measurement to the same valve control sequence, and setting the enrichment time, washing time, elution time, detection cell volume, deposition potential, deposition time, scan start and end potential and potential step to the same set of fixed parameters. One of the spiked measurements only introduced the standard solution channel metering parameters during the online solution preparation stage, while the remaining flow path operating parameters and electrochemical parameters remained consistent with the unspiked measurement. For each measurement cycle, record the inlet flow rate or quantitative volume, valve control switching log, and detection pool hold mode parameters to ensure that the field structure of the operation record is consistent across cycles.

6. The method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips as described in claim 5, characterized in that: The step of binding and archiving the curve data generated by each measurement with the corresponding flow volume spiking record using the same measurement number includes assigning measurement numbers to the three measurements respectively, and writing the potential sequence, corresponding current sequence, number of sampling points and scan step output by the electrochemical workstation as curve data fields into the archived record; Establish a correlation between the measurement number and the current sample inlet flow rate, standard solution inlet flow rate or quantitative addition volume, sample volume involved in mixing, standard solution number and its calibration concentration field; The archive structure uses the measurement number as the primary key index, so that curve data fields and spiked measurement fields are accessed in the same record object, and the field naming is consistent between blank, unspiked, and single-spiked measurements.

7. The method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips as described in claim 6, characterized in that: The baseline processing and peak interval integration calculation for the three archived curves include reading the upper and lower limit potentials of the target ion's peak interval from the detection parameter table and determining the peak interval endpoint sampling points in the curve sampling data. The baseline sequence is output by linear interpolation at the peak interval endpoints. The baseline subtracted current in the peak interval is discretely integrated according to the potential step to obtain blank integral, unspiked integral and spiked integral respectively. The blank integral is subtracted from the unspecified and spiked integrals to obtain the subtracted integrals of the two sample measurements. The equivalent incremental concentration is converted based on the archived flow rate or volume spike metering fields, the concentration of the original sample solution is calculated, and the content of the active pharmaceutical ingredient is obtained by converting the weighed mass and the fixed volume in the detection parameter table.

8. A system for detecting trace heavy metal ions in a pharmaceutical raw material using a microfluidic chip-based method as described in any one of claims 1 to 7, characterized in that: Includes a parameter table fixing module, a chip process execution module, and a measurement calculation output module; The parameter table solidification module is used to complete the weighing, volume adjustment and clarification of the active pharmaceutical ingredient sample; configure and record the target ion set and standard solution calibration information; calibrate and write the peak range and scanning parameter fields, solidify the data into the same detection parameter table, and output the task configuration record; The chip process execution module is used to connect the sample and reagent to the microfluidic chip under the constraints of the detection parameter table, and sequentially complete online solution preparation, μSPE enrichment, washing, elution and volume loading of the detection cell according to the flow rate and valve control sequence specified in the detection parameter table, while recording the operating parameters and valve control switching logs of each stage. The measurement calculation output module is used to perform three electrochemical measurements in sequence: blank, unspecified, and spiked, and archive the curve data and spiking records. It calls the peak interval and scanning parameters in the detection parameter table to perform baseline processing and peak interval integration and blank subtraction on the curve. Then, it converts the spiking measurement into the equivalent incremental concentration, calculates the original sample solution concentration, and completes the conversion of the active pharmaceutical ingredient content output.

9. A computer device comprising a memory and a processor, wherein the memory stores a computer program, characterized in that, When the processor executes the computer program, it implements the steps of the method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips as described in any one of claims 1 to 7.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by the processor, it implements the steps of the method for detecting trace heavy metal ions in active pharmaceutical ingredients based on microfluidic chips as described in any one of claims 1 to 7.

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