Impedance flow type sensing system based on parallel double microchannels, detection method and application

Abstract

The invention provides an electrical impedance flow type sensing system based on parallel double micro-channels, which comprises a micro-fluidic chip and a detection mechanism, the micro-fluidic chip comprises two parallel micro-channels which are respectively suitable for feeding a target sample and a reference sample, each micro-channel comprises a buffer area and a detection area, the micro-channel of the buffer area is arranged in an S-shaped bending manner, and the detection area is arranged in the buffer area. The middle section of the micro-channel of the detection area is arranged to be a contraction structure, the two micro-channels in front of the contraction structure are provided with a common signal applying electrode, and the two micro-channels behind the contraction structure are respectively provided with a first signal receiving electrode and a second signal receiving electrode; the detection mechanism comprises an I / V amplifier, a differential arithmetic unit, a lock-in amplifier, a filter processor and a computer which are connected in sequence; the input end of the I / V amplifier is connected with the first signal receiving electrode and the second signal receiving electrode; the system is simple to operate, small in reaction system, high in integration level and capable of meeting the requirement for real-time detection of pathogenic bacteria.

Description

Technical Field

[0001] The present invention relates to the technical field of sensor detection, and particularly to a parallel dual-microchannel impedance flow sensing system, a detection method, and an application thereof. Background Art

[0002] A large amount of water is required for human life, and the safety of water quality is closely related to food safety. In the field of water quality detection, Escherichia coli is one of the microbial indicators for water hygiene detection. Common detection methods include traditional plate culture method, polymerase chain reaction, and enzyme-linked immunosorbent assay, etc. Although these methods have their own advantages, they generally have the disadvantages of being time-consuming and complex, and it is difficult to meet the requirements for simple, rapid, and sensitive detection of Escherichia coli.

[0003] An impedance biosensor combining microfluidic technology with label-free impedance detection is expected to solve this problem, and flow impedance detection also has the advantage of high throughput. However, flow impedance detection generally requires a long and complex calibration to eliminate the adverse effects brought by the detection circuit. For example, when determining the dielectric properties of single cells by conventional impedance detection, a reference bead is added to the suspension of cells to be detected, and the original impedance signals from the two objects are mixed together in the time series, which usually requires a long processing time for calibration after the experiment and benchmarking according to the co-flowing reference target. All the original data must be post-processed and calibrated to eliminate the influence of the detection circuit. For the above problems, there is currently no widely used miniaturized and rapid high-sensitivity detection device for Escherichia coli in the industry. Summary of the Invention

[0004] In view of the above-mentioned disadvantages of the prior art, the purpose of the present invention is to provide a parallel dual-microchannel impedance flow sensing system, a detection method, and an application thereof, which are used to solve the problems of complex sensor operation, long detection time, complex data processing, large volume of detection instruments, and low throughput in the prior art.

[0005] To achieve the above object and other related objects, the present invention provides a parallel dual-microchannel impedance flow sensing system, including a microfluidic chip and a detection mechanism. The microfluidic chip includes two parallel microchannels, and the two microchannels are respectively adapted to introduce a target sample and a reference sample. The microchannel includes a buffer zone and a detection zone. The microchannel in the buffer zone is arranged in an S-shaped bend, which is adapted to make the microfluidic sample tend to be stable before reaching the detection zone. The middle section of the microchannel in the detection zone is set as a contraction structure. Taking the flow direction of the microfluidic sample as a reference, a common signal application electrode is provided on the two microchannels before the contraction structure, which is adapted to apply an electric signal to the two microchannels. A first signal receiving electrode and a second signal receiving electrode are respectively provided on the two microchannels after the contraction structure;

[0006] The detection mechanism includes an I / V amplifier, a differential arithmetic unit, a lock-in amplifier, a filtering processor, and a computer that are connected in sequence. The input end of the I / V amplifier is connected to a first signal receiving electrode and a second signal receiving electrode.

[0007] The present invention also provides an application of the impedance flow cytometry sensing system based on parallel double microchannels as described above in the fields of water quality detection and single-cell impedance detection.

[0008] The present invention also provides a detection method based on the impedance flow cytometry sensing system based on parallel double microchannels as described above, including the following steps:

[0009] S1. Respectively inject a target sample and a reference sample into two microchannels. The samples tend to be stable in the buffer area set in an S shape, and then sequentially inertial focus on a straight line and reach the detection area.

[0010] S2. After the samples pass through the constriction structure in the detection area, a current signal is applied to the two microchannels by a signal application electrode, and the current signals of the target sample and the reference sample are respectively received by a first signal receiving electrode and a second signal receiving electrode.

[0011] S3. The received current signal is converted into a voltage signal by an I / V amplifier, and then the differential voltage signal between the first signal receiving electrode 13 and the second signal receiving electrode 14 is calculated through a differential amplifier, and the fluctuation of the differential voltage is detected. Then, after being processed by a lock-in amplifier and a filtering processor in sequence, it is recorded in the computer.

[0012] The present invention also provides a computer-readable storage medium storing a computer program, and when the computer program runs, it realizes the data analysis, processing, and control steps in the detection method as described above.

[0013] The present invention also provides a terminal including a memory and a processor. The memory includes a computer program, and when the computer program is run by the processor, it executes the data analysis, processing, and control steps in the detection method as described above.

[0014] The present invention also provides a computer program product including a computer program, and when the computer program is executed by a processor, it realizes the data analysis, processing, and control steps in the detection method as described above.

[0015] As described above, the impedance flow cytometry sensing system based on parallel double microchannels, the detection method, and the application of the present invention have the following beneficial effects:

[0016] The impedance flow sensing system based on parallel dual microchannels of the present invention designs two parallel microchannels for separately injecting a target sample and a reference sample, eliminating the need to mix the reference sample with the target sample, thereby avoiding sample contamination and time-consuming post-processing, and enabling easy calibration and evaluation of cell dielectric properties; simplifies the calibration process, enhances sensitivity, and maintains rapid and high-throughput operation.

[0017] The impedance flow sensing system based on parallel dual microchannels of the present invention forms a sensing region with parallel dual microchannels and a special electrode layout, and constructs an impedance detection system in cooperation with a detection circuit. It reduces the calibration and post-processing processes, improves the sensitivity, detection speed, etc. of the flow impedance sensing system, and can provide a new platform for high-throughput and real-time single-cell characterization. At the same time, it brings greater application potential to the field of impedance detection methods in the detection of pathogenic bacteria in microfluidics.

[0018] The impedance flow sensing system based on parallel dual microchannels of the present invention is small in size and easy to operate, without the need for complex operations by professional personnel; and the small-volume unit detection can improve the detection efficiency and greatly reduce the detection time; at the same time, the impedance method is used for detection without any labeling, reducing the detection cost; it is low in cost, strong in stability, high in detection sensitivity, and of great practical application value. By introducing a small amount of sample into the microfluidic chip, sensitive detection of pathogenic bacteria in water can be achieved. The operation is simple, the reaction system is small, and the integration degree is high, which can meet the needs of real-time detection of pathogenic bacteria. Brief Description of the Drawings

[0019] Figure 1 It is a schematic structural diagram of the microfluidic chip of the present invention.

[0020] Figure 2 It is a schematic structural diagram of the detection area of the microfluidic chip of the present invention.

[0021] Figure 3 It is a working block diagram of the detection mechanism of the present invention.

[0022] Figure 4 It is a comparison diagram of the pulse signals of the target sample and the reference sample in Example 1 of the present invention.

[0023] Description of the Reference Numerals in the Drawings

[0024] 11 Microchannel

[0025] 12 Signal Application Electrode

[0026] 13 First Signal Receiving Electrode

[0027] 14 Second Signal Receiving Electrode

[0028] 21 I / V Amplifier

[0029] 22 Differential Amplifier

[0030] 23 Phase-Locked Amplifier

[0031] 24 Filter Processor

[0032] 25 Computer

[0033] 26 Voltage Amplifier

[0034] 111 Buffer

[0035] 112 Detection Area

[0036] 113 Shrink Structure

[0037] 114 Liquid Inlet Detailed Implementation Modes

[0038] The following uses specific specific examples to illustrate the implementation modes of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific implementation modes. Various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0039] In the present invention, unless otherwise clearly specified and defined, terms such as "installation", "connection", "connection", "fixation", etc. should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral one; it can be a mechanical connection, an electrical connection, or a communication connection; it can be a direct connection, or an indirect connection through an intermediate medium, which can be the internal connection of two components or the interaction relationship between two components, unless otherwise clearly defined. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0040] In the present invention, the terms "first" and "second" are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the quantity of the indicated technical features. Thus, the features defined with "first" and "second" can explicitly or implicitly include one or more of such features. The orientation or positional relationship indicated by terms such as "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the present invention.

[0041] In addition, it should be understood that the combined connection relationship between one or more devices / apparatuses mentioned in the present invention does not exclude the existence of other devices / apparatuses before and after the combined device / apparatus, or the insertion of other devices / apparatuses between the two explicitly mentioned devices / apparatuses, unless otherwise specified. Moreover, unless otherwise specified, the numbering of each method step is only a convenient tool for identifying each method step, rather than restricting the arrangement order of each method step or limiting the scope of implementation of the present invention. The change or adjustment of their relative relationship, without substantial change in technical content, should also be regarded as the scope of implementation of the present invention.

[0042] Please refer to the accompanying drawings. It should be noted that the illustrations provided in this embodiment only schematically illustrate the basic concept of the present invention. Therefore, only the components related to the present invention are shown in the drawings, rather than being drawn according to the number, shape, and size of the components in actual implementation. The type, quantity, and proportion of each component in actual implementation can be arbitrarily changed, and the component layout type may also be more complex.

[0043] As Figures 1 to 3 shown, a parallel dual-microchannel impedance flow sensing system is provided in the first aspect of the present invention, including a microfluidic chip and a detection mechanism. The microfluidic chip includes two parallel microchannels 11, and the two microchannels 11 are respectively adapted to introduce a target sample and a reference sample. The microchannel 11 includes a buffer zone 111 and a detection zone 112. The microchannel in the buffer zone 111 is arranged in an S-shaped bend, which is adapted to make the microfluidic sample tend to be stable before reaching the detection zone. The middle section of the microchannel in the detection zone 112 is set as a constriction structure 113. According to the flow direction of the microfluidic sample, a common signal application electrode 12 is provided on the two microchannels before the constriction structure 113, which is adapted to apply an electrical signal to the two microchannels. A first signal receiving electrode 13 and a second signal receiving electrode 14 are respectively provided on the two microchannels after the constriction structure 113;

[0044] The detection mechanism 20 includes an I / V amplifier 21, a differential operator 22, a lock-in amplifier 23, a filter processor 24, and a computer 25 connected in sequence. The input end of the I / V amplifier 21 is connected to the first signal receiving electrode 13 and the second signal receiving electrode 14.

[0045] Among them, as Figure 2 shown, the two microchannels are powered by the same electrode connected to an external power supply, and there are two independent detection electrodes respectively. The symmetric electrode layout on the two parallel microchannels 11 can ensure that the circuit losses in the two channels are equivalent.

[0046] The contraction structure 113 can be set with appropriate dimensions to increase the detection sensitivity and improve the signal-to-noise ratio. If detecting deformable cells, physical compression can also be applied to the cells to characterize the mechanical properties and viability of the cells, etc.

[0047] In some embodiments of the present invention, the detection mechanism further includes a voltage amplifier 26, and the voltage amplifier 26 is respectively connected to the lock-in amplifier 23 and the signal application electrode 12. The lock-in amplifier 23 outputs a specific excitation signal (i.e., excitation voltage S t , S t = A cos(w n t); where A is the amplitude of the applied excitation voltage; W n is the frequency of the output excitation signal; t is the time when the excitation voltage is applied), and then the voltage amplifier 26 amplifies the voltage and can apply it to the signal application electrode 12 as an excitation signal to meet the requirements of characterizing multiple indicators of a single cell.

[0048] In some embodiments of the present invention, the length of the cross-section of the microchannel 11 is 18 - 25 μm, 18 - 20 μm, 20 - 22 μm, or 22 - 25 μm, and the width is 18 - 25 μm, 18 - 20 μm, 20 - 22 μm, or 22 - 25 μm. In a preferred embodiment of the present invention, the length of the cross-section of the microchannel 11 is 20 μm and the width is 20 μm.

[0049] In some embodiments of the present invention, the length of the cross-section of the channel at the contraction structure 113 is 8 - 12 μm, 8 - 10 μm, or 0 - 12 μm, and the width is 8 - 12 μm, 8 - 10 μm, or 0 - 12 μm.

[0050] In the present invention, the "cross-section" refers to the cross-section of the pipeline perpendicular to the sample flow direction.

[0051] In some embodiments of the present invention, both of the two microchannels 11 are further provided with liquid inlets 114 in the buffer area.

[0052] The second aspect of the present invention provides an application of the impedance flow cytometry sensing system based on parallel dual microchannels as described above in the field of water quality detection and the field of single-cell impedance detection. Among them, the field of single-cell impedance detection can be fields such as circulating tumor cell detection and cell counting that require rapid and simple detection.

[0053] The third aspect of the present invention provides a detection method based on the impedance flow cytometry sensing system based on parallel dual microchannels as described above, including the following steps:

[0054] S1. Inject the target sample and the reference sample into two microchannels 11 respectively. The samples tend to stabilize in the buffer area 111 with an S-shaped bend and then reach the detection area 112 after inertial focusing on a straight line in sequence.

[0055] S2. After the samples pass through the contraction structure 113 of the detection area 112, a current signal is applied to the two microchannels 11 by the signal application electrode 12, and the current signals of the target sample and the reference sample are received by the first signal receiving electrode 13 and the second signal receiving electrode 14 respectively.

[0056] S3. The received current signal is converted into a voltage signal by the I / V amplifier 21, and then the differential voltage signal between the first signal receiving electrode (13) and the second signal receiving electrode (14) is calculated by the differential amplifier 22, and the fluctuation of the differential voltage is detected. Then, after being processed by the phase-locked amplifier 23 and the filter processor 24 in sequence, it is recorded in the computer 25.

[0057] Among them, the signals output by the first signal receiving electrode 13 and the second signal receiving electrode 14 are: Among them, Z n is the amplitude of the output signal; W n is the frequency of the output excitation signal; is the phase of the output signal.

[0058] In some embodiments of the present invention, step S3 further includes: the phase-locked amplifier 23 outputs an excitation signal according to a set value, and this excitation signal is amplified in voltage by the voltage amplifier 26 and applied to the signal application electrode 12. The phase-locked amplifier 23 can be set with multiple frequencies, such as: a low detection frequency of 500 kHz and a high detection frequency of 6 MHz.

[0059] The operation principle of the phase-locked amplifier is:

[0060] X t =O t cosw n t; Y t =O t sinw n t; where X t is the real part of the impedance amplitude signal; Y t is the imaginary part of the impedance amplitude signal;

[0061] Among them, the phase-locked amplifier 23 demodulates the output signal into the in-phase Xn and the quadrature component Yn; Z t is the amplitude of the impedance feedback response signal; Y, X, that is, Y t , X t .

[0062] Among them, the set values include parameters: frequency, amplitude, and phase.

[0063] In some embodiments of the present invention, the frequency of the phase-locked amplifier 23 is 0.5 - 6 MHz. For example, it is 0.5 - 1 MHz, 1 - 1.5 MHz, 1.5 - 2 MHz, 2 - 2.5 MHz, 2.5 - 3 MHz, 3 - 3.5 MHz, 3.5 - 4 MHz, 4 - 4.5 MHz, 4.5 - 5 MHz, 5 - 5.5 MHz, or 5.5 - 6 MHz.

[0064] A fourth aspect of the present invention provides a computer-readable storage medium storing a computer program, which when run implements the data analysis, processing, and control steps in the detection method described above.

[0065] In the present invention, the computer-readable storage medium may include, but is not limited to, a floppy disk, an optical disk, a CD-ROM (Compact Disc Read-Only Memory), a magneto-optical disk, a ROM (Read-Only Memory), a RAM (Random Access Memory), an EPROM (Erasable Programmable Read-Only Memory), an EEPROM (Electrically Erasable Programmable Read-Only Memory), a magnetic card or an optical card, a flash memory, or other types of media / machine-readable media suitable for storing machine-executable instructions. The computer-readable storage medium may be a product not connected to a computer device or a component already connected to a computer device for use.

[0066] A fifth aspect of the present invention provides a terminal including a memory and a processor, wherein the memory contains a computer program, and is characterized in that when the computer program is run by the processor, it executes the data analysis, processing, and control steps in the detection method described above.

[0067] In the present invention, the number of memories may be one or more, and the number of processors may be one or more.

[0068] In the present invention, the processor will, as Figure 3 shown, load instructions corresponding to one or more application program processes into the memory, and the processor runs the application program stored in the first memory, thereby implementing various functions such as data analysis, processing, and control in the detection method.

[0069] In the present invention, the memory may include, but is not limited to, high-speed random access memory and non-volatile memory. For example, one or more disk storage devices, flash memory devices or other non-volatile solid-state storage devices; the processor may include, but is not limited to, a central processing unit (CPU), a network processor (NP), etc.; it may also be a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components.

[0070] In the present invention, the processor may be a general-purpose processor, including a central processing unit (CPU), a network processor (NP), etc.; it may also be a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components.

[0071] The sixth aspect of the present invention provides a computer program product, including a computer program, and when the computer program is executed by a processor, it implements the data analysis, processing and control steps in the detection method described above.

[0072] Embodiment 1

[0073] As Figures 1 to 3 shown, based on the parallel dual-microchannel impedance flow cytometry sensing system:

[0074] It includes a microfluidic chip 10 and a detection mechanism 20. The microfluidic chip 10 includes two parallel microchannels 11. The two microchannels 11 are respectively adapted to sample a target sample and a reference sample. The microchannel 11 includes a buffer zone 111 and a detection zone 112. The microchannel of the buffer zone 111 is arranged in an S-shaped bend, which is adapted to make the microfluidic sample tend to be stable before reaching the detection zone 112. The middle section of the microchannel of the detection zone 112 has a constriction structure 113. In the flow direction of the microfluidic sample, a common signal application electrode 12 is provided on the two microchannels before the constriction structure 113, which is adapted to apply an electrical signal to the two microchannels. A first signal receiving electrode 13 and a second signal receiving electrode 14 are respectively provided on the two microchannels after the constriction structure 113; wherein, the length of the cross-section of the microchannel 11 is 20 μm, and the width is 20 μm; the length of the cross-section of the channel at the constriction structure 113 is 10 μm, and the width is 10 μm; two liquid inlets 114 are also provided in the buffer zone of the two microchannels 11.

[0075] The detection mechanism 20 includes an I / V amplifier 21, a differential arithmetic unit 22, a lock-in amplifier 23, a filter processor 24 and a computer 25 connected in sequence. The input end of the I / V amplifier 21 is connected to the first signal receiving electrode 13 and the second signal receiving electrode 14; it also includes a voltage amplifier 26, and the voltage amplifier 26 is respectively connected to the lock-in amplifier 23 and the signal application electrode 12.

[0076] Detection method:

[0077] S1. Inject the target sample and the reference sample (target sample: bacteria to be detected; reference sample: microspheres of standard size) into the two microchannels 11 from the liquid inlets 114 respectively. After the sample tends to be stable in the buffer zone 111 arranged in an S-shaped bend, it reaches the detection zone 112.

[0078] S2. After the sample passes through the constriction structure 113 of the detection zone 112, a current signal is applied to the two microchannels 11 by the signal application electrode 12, and the current signals of the target sample and the reference sample are respectively received by the first signal receiving electrode 13 and the second signal receiving electrode 14;

[0079] S3. The received current signal is converted into a voltage signal by the I / V amplifier 21, and then the differential voltage signal between the first signal receiving electrode 13 and the second signal receiving electrode 14 is calculated by the differential amplifier 22, and the fluctuation of the differential voltage is detected. After being processed by the lock-in amplifier 23 and the filter processor 24 in sequence, it is recorded in the computer 25; wherein the lock-in amplifier 23 also outputs an excitation signal according to the set frequency, amplitude and phase. This excitation signal is voltage-amplified by the voltage amplifier 26 and applied to the signal application electrode 12. The two impedance pulses are displayed on the same time series and can be located on opposite sides after subsequent processing, such asFigure 4 As shown, the dielectric properties of cells can be estimated by comparing the magnitudes of impedance pulses on opposite sides.

[0080] In summary, based on the parallel dual-microchannel impedance flow sensing system, the present invention takes a small amount of sample and sends it into the microfluidic chip. Depending on impedance detection, rapid and highly sensitive detection of pathogenic bacteria in water can be achieved without any labeling. Moreover, the calibration process is simplified, the sensitivity is enhanced, and the characteristics of rapidity and high throughput are maintained. It is expected to be widely applied to the detection of pathogenic bacteria in water in the fields of water quality detection, circulating tumor cell detection, cell counting, and other fields that require rapid and simple single-cell impedance detection.

[0081] Therefore, the present invention effectively overcomes various disadvantages in the prior art and has high industrial utilization value.

[0082] The above embodiments are only illustrative of the principles and effects of the present invention and are not intended to limit the present invention. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical ideas disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. A parallel dual microchannel impedance flow sensing system, characterized in that: The invention comprises a microfluidic chip and a detection mechanism, wherein the microfluidic chip comprises two parallel microchannels (11), wherein the two microchannels (11) are respectively suitable for injecting a target sample and a reference sample, wherein the microchannel (11) comprises a buffer zone (111) and a detection zone (112), wherein the microchannel of the buffer zone (111) is arranged in an S-shaped bend, and is suitable for stabilizing the microfluid sample before reaching the detection zone, wherein the middle section of the microchannel of the detection zone (112) is arranged as a contraction structure (113), and in terms of the flow direction of the microfluid sample, a common signal applying electrode (12) is arranged on the two microchannels before the contraction structure (113), and is suitable for applying an electrical signal to the two microchannels, and a first signal receiving electrode (13) and a second signal receiving electrode (14) are respectively arranged on the two microchannels after the contraction structure (113); The detection mechanism comprises an I / V amplifier (21), a differential operator (22), a phase-locked amplifier (23), a filter processor (24) and a computer (25) which are connected in sequence, and the input end of the I / V amplifier (21) is connected to a first signal receiving electrode (13) and a second signal receiving electrode (14).

2. The impedance flow sensing system based on parallel dual microchannels according to claim 1 is characterized in that: The detection mechanism further comprises a voltage amplifier (26), wherein the voltage amplifier (26) is respectively connected to the phase-locked amplifier (23) and the signal applying electrode (12); And / or, the two microchannels (11) are both provided with a liquid inlet (114) in the buffer zone.

3. The impedance flow sensing system based on parallel dual microchannels according to claim 1 is characterized in that: The cross-section of the microchannel (11) has a length of 18 to 25 μm and a width of 18 to 25 μm; And / or, the length of the channel cross section at the contraction structure (113) is 8 to 12 μm, and the width is 8 to 12 μm.

4. An application of the electrical impedance flow sensing system based on parallel dual microchannels as claimed in any one of claims 1 to 3 in the field of water quality detection and single cell electrical impedance detection.

5. A detection method based on the impedance flow sensing system based on parallel dual microchannels according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1, injecting the target sample and the reference sample into two microchannels (11) respectively, the samples tend to be stable in the buffer zone (111) arranged with an S-shaped bend, and then inertial focusing on a straight line in turn and then reaching the detection zone (112); S2, after the sample passes through the contraction structure (113) of the detection area (112), the signal applying electrode (12) applies a current signal to the two microchannels (11), and the first signal receiving electrode (13) and the second signal receiving electrode (14) receive the current signals of the target sample and the reference sample respectively; S3, the received current signal is converted into a voltage signal through the I / V amplifier (21), and then the differential voltage signal between the first signal receiving electrode (13) and the second signal receiving electrode (14) is calculated through the differential amplifier (22), and the fluctuation of the differential voltage is detected. Then, the signal is processed by the phase-locked amplifier (23) and the filter processor (24) in sequence and recorded in the computer (25).

6. The detection method according to claim 5, characterized in that: Step S3 also includes: the phase-locked amplifier (23) outputs an excitation signal according to a set value, the excitation signal is amplified by a voltage amplifier (26) and applied to the signal application electrode (12).

7. The detection method according to claim 6, characterized in that: The set values ​​include parameters: frequency, amplitude and phase.

8. A computer-readable storage medium, characterized in that: A computer program is stored, and when the computer program is run, the data analysis, processing and control steps in the detection method according to any one of claims 5 to 7 are implemented.

9. A terminal comprising a memory and a processor, wherein the memory comprises a computer program, characterized in that: When the computer program is executed by a processor, the data analysis, processing and control steps in the detection method according to any one of claims 5 to 7 are executed.

10. A computer program product, comprising a computer program, characterized in that When the computer program is executed by a processor, the data analysis, processing and control steps in the detection method according to any one of claims 5 to 7 are implemented.

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