System for improving micro-fluidic electrical impedance signal analysis precision

Abstract

The invention discloses a system for improving micro-fluidic electrical impedance signal analysis precision, the system comprises a circuit board and a signal processing operation button mechanism, the circuit board is welded and fixed with a gold electrode of a micro-fluidic chip, and the circuit board is used for collecting an impedance signal detected by the micro-fluidic chip and transmitting the impedance signal to the signal processing operation button mechanism. The beneficial effects of the invention are that the welding between the circuit board and the gold electrode does not fall off; button processing can be simplified, and the learning signal processing time and knowledge cost are reduced; interference factors are eliminated through multi-dimensional pretreatment, and the precise characterization requirements of single cells and micron-sized particles are met; a complex impedance signal is represented through a complex variable function, data structuring is achieved through matrix operation, the processing precision is guaranteed through integration and convolution operation, it is guaranteed that no information is lost in the whole process from signal collection to analysis, and reliable data support is provided for biophysical characteristic backstepping.

Description

Technical Field

[0001] This invention relates to the field of biomedical engineering technology, specifically to a system for improving the accuracy of microfluidic impedance signal analysis. Background Technology

[0002] Microfluidic impedance cytometry is a cutting-edge analytical method that integrates microfluidics and electrical impedance tomography (EIT) techniques, enabling real-time, high-throughput, and precise analysis of the biophysical properties and functional state of individual living cells. This technology allows researchers to perform detailed measurements of cells at the micrometer scale, providing crucial technical support for biomedical research and possessing significant application value. In the EIT measurement stage, the industry typically employs a coplanar dual-differential seven-electrode structure to achieve precise size analysis of micrometer-scale particles and maintain high signal-to-noise ratio performance over a wide frequency range. This design significantly improves the accuracy and reliability of the analytical results.

[0003] However, many technical bottlenecks remain in promoting the application and large-scale development of this advanced technology. For example, the connection stability between the impedance meter and the microfluidic chip is particularly prominent in impedance flow cytometry experiments. Specifically, the fixing strength of commonly used conductive tape is limited, which can easily lead to the connection detaching, causing the impedance signal to be interrupted and affecting the continuity of the experiment. At the same time, due to the extremely small size of the seven electrodes, the cutting of conductive tape is extremely difficult, placing stringent requirements on the precision of the assembly process. In addition, the analysis and processing of impedance signals is relatively complex, further raising the threshold for experimental operation and limiting the popularization and efficient application of the technology.

[0004] Therefore, in order to address the above-mentioned technical problems, it is necessary to provide a system that improves the accuracy of microfluidic impedance signal analysis. Summary of the Invention

[0005] To address the shortcomings of the existing technology, the purpose of this invention is to provide a system for improving the accuracy of microfluidic impedance signal analysis, thereby solving the problems mentioned in the background art.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: This invention provides a system for improving the accuracy of microfluidic impedance signal analysis, including a circuit board and a signal processing operation button mechanism. The circuit board is welded and fixed to the gold electrode of the microfluidic chip, and is used to collect the impedance signal detected by the microfluidic chip and transmit it to the signal processing operation button mechanism. The signal processing operation button mechanism performs preprocessing, feature extraction, and result export on the received impedance signal in sequence, and outputs high-precision impedance signal analysis results.

[0007] In one or more embodiments of the present invention, the circuit board includes a central hollow observation area, a symmetrical electrode welding area, an SMA RF socket, and a symmetrically distributed pin header interface; the central hollow observation area has a rectangular structure for adapting to the light transmission observation of an optical microscope; the symmetrical electrode welding area has welding points, which are welded one-to-one with the gold electrodes of the microfluidic chip; the SMA RF socket is symmetrically distributed on both sides of the circuit board for connecting SMA RF lines to transmit impedance signals; the symmetrically distributed pin header interface has pin headers for connecting pin header lines as alternative signal transmission paths for SMA RF lines.

[0008] In one or more embodiments of the present invention, the circuit board is made of FR-4 epoxy fiberglass board with a thickness of 1-2mm, the length of the central hollow observation area is 80-95mm and the width is 10-15mm, and the distance between the edge of the central hollow observation area and the welding point is 10-30mm.

[0009] In one or more embodiments of the present invention, each of the SMA RF sockets is an SMA-K type RF socket, which is electrically connected to the corresponding soldering point through pins, and each row of pins of the symmetrically distributed pin header is a single row of through-hole pins, which is electrically connected to the corresponding soldering point through wires.

[0010] In one or more embodiments of the present invention, the signal processing operation button mechanism includes an import file button, a time zeroing button, a baseline correction button, a signal filtering button, an event extraction button, a feature point extraction button, a data export button, and a signal visualization area; the import file button is used to receive impedance signal data transmitted by the circuit board and import it into the operating system; the signal visualization area is used to display the impedance signal waveform and data results after each button operation in real time.

[0011] In one or more embodiments of the present invention, the operation process of the time zeroing button is as follows: starting from the first valid signal acquisition time point in the imported impedance signal data, the first valid signal acquisition time point is set as the time zero point by the operating system, and the timestamps of all impedance signal data are calibrated to obtain the time-standardized impedance signal data.

[0012] In one or more embodiments of the present invention, the operation process of the baseline correction button is as follows: starting with the time-normalized impedance signal data, the operating system identifies the stable period in the data where no particles pass through the microfluidic chip detection channel, calculates the average signal value of the stable period as the baseline value, and subtracts the baseline value from each data point in the time-normalized impedance signal data to obtain the baseline-corrected impedance signal data.

[0013] In one or more embodiments of the present invention, the operation process of the signal filtering button is as follows: starting with the baseline-corrected impedance signal data, the operating system uses a low-pass filtering algorithm to filter noise from the baseline-corrected impedance signal data. The cutoff frequency of the low-pass filtering algorithm can be adjusted within the range of 100Hz-1MHz to obtain filtered impedance signal data. The operation process of the event extraction button is as follows: starting with the filtered impedance signal data, the operating system sets a customizable signal amplitude threshold, identifies continuous signal segments in the filtered impedance signal data whose amplitude exceeds the threshold as valid events, marks the start time and end time of each valid event, and obtains an event dataset containing at least one valid event signal.

[0014] In one or more embodiments of the present invention, the operation process of the feature point extraction button is as follows: starting with the event dataset, the operating system extracts five core feature parameters—peak value, valley value, amplitude, rise time, and fall time—for each valid event signal in the event dataset. The five core feature parameters of each valid event signal constitute a feature parameter set, and the feature parameter sets of all valid event signals are summarized to form a feature parameter set.

[0015] In one or more embodiments of the present invention, the operation process of the data export button is as follows: starting with the feature parameter set and the signal waveform data of each step displayed in the signal visualization area, the feature parameter set is organized in CSV or Excel format by the operating system, and an analysis report is generated by combining the impedance signal data and signal waveform images after each step, and the analysis report is exported to a preset storage path.

[0016] The beneficial effects of this invention are as follows: 1) The circuit board replaces the conductive tape, and the soldering between the circuit board and the gold electrode will not fall off. The SMA RF connection used further increases the reliability of the connection, and the pin header interface provides a fault tolerance option for possible damage to the RF line during the experiment. 2) It can be simplified to button processing, reducing the time and knowledge cost of learning signal processing, and the signal visualization area can provide timely feedback on the processing results of each step; 3) Time standardization eliminates invalid time redundancy, baseline correction eliminates system drift, and multi-dimensional preprocessing eliminates interference factors to meet the precise characterization needs of single cells and micron-sized particles. 4) By characterizing complex impedance signals through complex variable functions, structuring data through matrix operations, and ensuring processing accuracy through integral and convolution operations, we can ensure that there is no information loss throughout the entire process from signal acquisition to analysis, and provide reliable data support for the inference of biophysical characteristics. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the 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.

[0018] Figure 1 This is a schematic diagram of the circuit board structure of a system for improving the accuracy of microfluidic impedance signal analysis according to an embodiment of the present invention; Figure 2 The following is a logic flow diagram of a system for improving the accuracy of microfluidic impedance signal analysis in one embodiment of the present invention. Figure 1 ; Figure 3 The following is a logic flow diagram of a system for improving the accuracy of microfluidic impedance signal analysis in one embodiment of the present invention. Figure 2 ; Figure 4 The following is a logic flow diagram of a system for improving the accuracy of microfluidic impedance signal analysis in one embodiment of the present invention. Figure 3 ; Figure 5 The following is a logic flow diagram of a system for improving the accuracy of microfluidic impedance signal analysis in one embodiment of the present invention. Figure 4 ; Figure 6 The following is a logic flow diagram of a system for improving the accuracy of microfluidic impedance signal analysis in one embodiment of the present invention. Figure 5 .

[0019] Explanation of reference numerals in the attached figures: 1. Circuit board. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] like Figures 1 to 6As shown, a system for improving the accuracy of microfluidic impedance signal analysis according to an embodiment of the present invention includes a circuit board 1 and a signal processing operation button mechanism. The interfaces of the circuit board 1 are symmetrically arranged, and the circuit board 1 is welded and fixed to the gold electrodes of the microfluidic chip. The impedance signal detected by the microfluidic chip is acquired through an impedance signal transmission model characterized by a complex variable function and transmitted to the signal processing operation button mechanism. The signal processing operation button mechanism uses a fixed data flow of "data import → time calibration → baseline correction → noise filtering → event recognition → feature extraction → result export" to sequentially preprocess the received impedance signal, extract features, and export results, outputting high-precision impedance signal analysis results.

[0022] The complex variable function characterization model for impedance signals is as follows: in, The complex impedance signal acquired by circuit board 1. Angular frequency, The signal frequency ranges from 1 kHz to 10 MHz. For signal acquisition time, The resistance component, measured in Ω, represents the resistance encountered when current passes through cells in a microfluidic chip due to the directional movement of charges, which is the energy consumption characteristic. Its physical meaning is consistent with that of a conventional resistor, with no phase shift. This refers to the reactance component, with the unit of reactance being Ω; The imaginary unit. Satisfy the equation The complex number is the basic unit for constructing complex number systems. It is used to characterize physical quantities that have a 90° phase difference with the real number part, such as reactance and phase shift.

[0023] In use, the signal transmission triggering condition between circuit board 1 and the signal processing operation button mechanism is: the port impedance of circuit board 1 and the input impedance of the signal processing operation button mechanism meet the matching condition, that is: in, The reflection coefficient, The input impedance of the signal processing operation button mechanism, measured in Ω. The characteristic impedance of circuit board 1 is given.

[0024] Circuit board 1 includes a central hollow observation area, a symmetrical electrode welding area, an SMA RF socket, and a pin array symmetrically distributed interface; the central hollow observation area has a rectangular structure for adapting to the light transmission observation of an optical microscope, and its size meets the requirements for unobstructed optical imaging. in, The length of the central openwork observation area. The width of the central open observation area. The wavelength of the illumination light for an optical microscope. This refers to the numerical aperture of the microscope objective.

[0025] The electrode welding symmetrical area has welding points, which are welded one-to-one with the gold electrodes of the microfluidic chip using a soldering process. SMA RF sockets are symmetrically distributed on both sides of the circuit board 1 for connecting SMA RF lines to transmit impedance signals.

[0026] The pin header symmetrically distributed interface has pin headers for connecting pin header cables as alternative signal transmission paths for SMA RF cables. The trigger condition is an interruption in SMA RF cable transmission, i.e., the transmitted signal amplitude... Automatic switching.

[0027] Furthermore, the circuit board 1 is made of FR-4 epoxy fiberglass board with a thickness of 1-2mm. The length of the central hollow observation area is 80-95mm and the width is 10-15mm. The distance between the edge of the central hollow observation area and the soldering point is 10-30mm.

[0028] To further enhance connection stability and ensure experimental continuity, each SMA RF socket is an SMA-K type RF socket, which is electrically connected to the corresponding soldering point through pins. Each row of pins in the symmetrically distributed interface is a single row of through-hole pins, which is electrically connected to the corresponding soldering point through wires.

[0029] The signal processing operation button mechanism includes an import file button, a time zeroing button, a baseline correction button, a signal filtering button, an event extraction button, a feature point extraction button, a data export button, and a signal visualization area. The import file button is used to receive impedance signal data transmitted from circuit board 1 and import it into the operating system. The trigger condition is that the signal data transmitted from circuit board 1 is in TXT or CSV format. After importing, the original data matrix is ​​generated. in, Number of signal frequency channels The number of sampling points for each frequency channel. For the first The frequency channel, the first Complex impedance signal at each sampling time point.

[0030] The signal visualization area is used to display the impedance signal waveform and data results after each button operation in real time. The trigger condition is that the corresponding button operation is completed and the output data matrix dimension meets the visualization requirements.

[0031] Further, the first valid signal acquisition time point in the imported impedance signal data was used. To begin, set the effective signal amplitude threshold. .

[0032] The operating system sets the first valid signal acquisition time point as time zero, and calibrates the timestamps of all impedance signal data to obtain time-normalized impedance signal data. Starting with the time-normalized impedance signal data, the operating system identifies stable periods in the data where no particles pass through the microfluidic chip detection channel. The average signal value of these stable periods is calculated as the baseline value. The baseline value is then subtracted from each data point in the time-normalized impedance signal data to obtain baseline-corrected impedance signal data.

[0033] Starting with baseline-corrected impedance signal data, the operating system employs a low-pass filtering algorithm to filter noise from the baseline-corrected impedance signal data. The cutoff frequency of the low-pass filtering algorithm can be adjusted within the range of 100Hz-1MHz, resulting in filtered impedance signal data. Using this filtered impedance signal data as a starting point, a customizable signal amplitude threshold is set through the operating system. Continuous signal segments in the filtered impedance signal data whose amplitude exceeds the threshold are identified as valid events. The start and end times of each valid event are marked, resulting in an event dataset containing at least one valid event signal. .

[0034] With event dataset Starting with the operating system, for each valid event signal in the event dataset, five core feature parameters are extracted: peak value, valley value, amplitude, rise time, and fall time. The five core feature parameters of each valid event signal constitute a feature parameter set. The feature parameter sets of all valid event signals are summarized to form a feature parameter set. The operating system organizes the feature parameter set in CSV or Excel format. Combined with the impedance signal data and signal waveform images processed in each step, an analysis report is generated and exported to a preset storage path.

[0035] Obviously, the above-described embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention also intends to include these modifications and variations.

Claims

1. A system for improving the accuracy of microfluidic impedance signal analysis, characterized in that, It includes a circuit board (1) and a signal processing operation button mechanism. The circuit board (1) is welded and fixed to the gold electrode of the microfluidic chip and is used to collect the impedance signal detected by the microfluidic chip and transmit it to the signal processing operation button mechanism. The signal processing operation button mechanism performs preprocessing, feature extraction, and result export on the received impedance signal in sequence, and outputs high-precision impedance signal analysis results.

2. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 1, characterized in that, The circuit board (1) includes a central hollow observation area, an electrode welding symmetrical area, an SMA RF socket, and pin-shaped symmetrically distributed interfaces; The central hollow observation area has a rectangular structure, which is used to adapt to the light transmission observation of an optical microscope; The electrode welding symmetrical region is provided with welding sites, and the welding sites are welded one-to-one with the gold electrodes of the microfluidic chip; The SMA RF sockets are symmetrically distributed on both sides of the circuit board (1) and are used to connect the SMA RF lines to transmit impedance signals. The pin header symmetrically distributed interface is equipped with pin headers for connecting pin header lines as alternative signal transmission paths for SMA RF lines.

3. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 2, characterized in that, The circuit board (1) is made of FR-4 epoxy fiberglass board with a thickness of 1-2mm. The length of the central hollow observation area is 80-95mm and the width is 10-15mm. The distance between the edge of the central hollow observation area and the welding point is 10-30mm.

4. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 2, characterized in that, Each of the SMA RF sockets is an SMA-K type RF socket, which is electrically connected to the corresponding soldering point through pins. Each row of pins of the symmetrically distributed interface is a single row of through-hole pins, which is electrically connected to the corresponding soldering point through wires.

5. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 1, characterized in that, The signal processing operation button mechanism includes an import file button, a time zeroing button, a baseline correction button, a signal filtering button, an event extraction button, a feature point extraction button, a data export button, and a signal visualization area; The import file button is used to receive impedance signal data transmitted by the circuit board (1) and import it into the operating system; The signal visualization area is used to display the impedance signal waveform and data results after each button operation in real time.

6. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 5, characterized in that, The operation process of the time reset button is as follows: Starting with the first valid signal acquisition time point in the imported impedance signal data, the operating system sets the first valid signal acquisition time point as the time zero point, and calibrates the timestamps of all impedance signal data to obtain time-standardized impedance signal data.

7. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 1, characterized in that, The operation process of the baseline correction button is as follows: Starting with the time-normalized impedance signal data, the operating system identifies stable periods in the data where no particles pass through the microfluidic chip detection channel. The average signal value of these stable periods is calculated as a baseline value. The baseline value is then subtracted from each data point in the time-normalized impedance signal data to obtain the baseline-corrected impedance signal data.

8. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 7, characterized in that, The operation process of the signal filtering button is as follows: Starting with the baseline-corrected impedance signal data, the operating system uses a low-pass filtering algorithm to filter noise from the baseline-corrected impedance signal data. The cutoff frequency of the low-pass filtering algorithm can be adjusted in the range of 100Hz-1MHz to obtain the filtered impedance signal data. The operation process of the event extraction button is as follows: starting with the filtered impedance signal data, a customizable signal amplitude threshold is set through the operating system. Continuous signal segments in the filtered impedance signal data whose amplitude exceeds the threshold are identified as valid events. The start and end times of each valid event are marked to obtain an event dataset containing at least one valid event signal.

9. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 8, characterized in that, The operation process of the feature point extraction button is as follows: Starting with the event dataset, the operating system extracts five core feature parameters—peak value, valley value, amplitude, rise time, and fall time—from each valid event signal in the event dataset. The five core feature parameters of each valid event signal constitute a feature parameter set, and the feature parameter sets of all valid event signals are summarized to form a feature parameter set.

10. The system for improving the accuracy of microfluidic impedance signal analysis as described in claim 9, characterized in that, The operation process of the data export button is as follows: Starting with the set of feature parameters and the signal waveform data of each step displayed in the signal visualization area, the set of feature parameters is organized in CSV or Excel format by the operating system. An analysis report is generated by combining the impedance signal data and signal waveform images processed in each step, and the analysis report is exported to a preset storage path.

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