Electronic microarray chip detector liquid path system and control method

Abstract

The application discloses an electronic microarray chip detector liquid path system and a control method, and belongs to the technical field of biological detection, and comprises: a four-channel structure liquid distribution needle group, the inner surface of which is Ra≤0.1 μm; a ten-channel structure rotary valve, four channels of which are connected with reagent needles, and after the reagent needles absorb reagents, ≥2 mm air columns need to be absorbed again to absorb another kind of reagent, so that physical isolation is realized; a laser bonding bus board assembly, the micro flow channel of which is a rectangular section (0.5*0.5 mm, the surface roughness Ra≤1.6 μm), and the dead volume is ≤12 μL; a temperature control unit integrated in the bus board assembly, containing an FPC heating sheet and a temperature sensor; and an injection pump linked with a flow sensor. Through three-stage cooperative control of the rotary valve, the bus board assembly and the injection pump, combined with flow channel design and process optimization, accurate control of microliter-level liquid is realized.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological detection, and relates to a liquid path system and a control method of an electronic microarray chip detector. BACKGROUND

[0002] The electronic microarray chip detector is a key equipment in the field of biological detection and plays an important role in disease diagnosis, gene research and the like. The liquid path system is a core part for guaranteeing accurate and efficient operation of detection, but there are many problems to be solved in the current system.

[0003] In terms of detection accuracy, the common use of multiple reagents in a pipeline causes serious cross contamination, such as SSC residual ions interfering with NaCl electrical signal detection and affecting the accuracy of results. The flow channel of a traditional manifold is rough, and the dead volume is as high as 120 muL, which makes the utilization rate of trace reagents low and causes resource waste. At the same time, the pulsation of a syringe pump causes flow fluctuation exceeding ±10%, and temperature fluctuation ±2℃ causes electrical signal drift ±15mV, which reduces the reliability of detection; the complex pipeline connection causes high risk of bubble retention, and bubbles can affect reagent flow and detection signal, thereby interfering with the detection result. In terms of operation convenience, chip replacement needs to reseal the pipeline, and each time takes more than 5 minutes, which is low in detection efficiency. SUMMARY

[0004] The purpose of the present application is to provide a liquid path system and a control method of an electronic microarray chip detector, which realizes accurate control of microliter liquid through three-level collaborative control of a rotary valve-manifold assembly-syringe pump, combined with flow channel design and process optimization.

[0005] The purpose of the present application is achieved by the following technical solutions:

[0006] A liquid path system of an electronic microarray chip detector, comprising:

[0007] A four-channel structure of a liquid distribution needle group, the inner surface of which is Ra≤0.1 mu m;

[0008] A rotary valve having at least four channels (actually a ten-channel structure), wherein the four channels are connected to reagent needles, and the reagent needles need to suck an air column of ≥2mm after sucking reagents to suck another kind of reagent, so as to realize physical isolation;

[0009] A manifold assembly adopting laser bonding, wherein the micro flow channel is a rectangular section (0.5*0.5mm, and the surface roughness Ra≤1.6 mu m), and the dead volume is ≤12 muL;

[0010] A temperature control unit integrated in the manifold assembly, comprising an FPC heating sheet and a temperature sensor;

[0011] A syringe pump is linked with a flow sensor.

[0012] As a further improvement of an embodiment of the application, the needle group comprises a spring buffer structure and a needle adjusting plate, and the needle body is made of passivated 316L stainless steel.

[0013] As a further improvement of an embodiment of the application, the needle group comprises four independent reagent needles, the outer surface of the reagent needle is provided with a hydrophobic coating and the inner surface is polished, and the internal roughness Ra of the reagent needle is less than 0.1 um.

[0014] As a further improvement of an embodiment of the application, the busbar assembly is a double-layer PC plate laser bonded and formed, the upper plate is provided with a liquid path interface and a micro flow channel, and the lower plate is a laser welded cover plate; the total volume of the flow channel of the busbar assembly is ≤12 μL.

[0015] As a further improvement of an embodiment of the application, the temperature control unit stabilizes the reagent temperature at 37±0.5℃, and the temperature fluctuation rate is ≤0.3℃ / s.

[0016] As a further improvement of an embodiment of the application, it further comprises a motor-driven chip crimping mechanism to realize automatic crimping and separation of the chip and the sealing ring of the busbar assembly, and the replacement time is <10 seconds.

[0017] As a further improvement of an embodiment of the application, the main channel of the rotary valve is connected to the busbar assembly through a PTFE pipe (ID 0.5 mm), and the standby channel supports calibration liquid access, waste liquid diversion and new reagent integration.

[0018] As a further improvement of an embodiment of the application, the busbar assembly is provided with a three-way electromagnetic valve to realize the bypass function of the chip flow channel.

[0019] A liquid path control method applied to the liquid path system of the electronic microarray chip detector, characterized by comprising:

[0020] Step 1, turn on the heating sheet to stabilize the temperature of the busbar assembly at 37±0.5℃;

[0021] Step 2, clean the flow channel at a flow rate of 150 μL / s, and switch the channel when the temperature fluctuation is ≤0.3℃ / s; wherein the different reagent channels are physically isolated by the rotary valve, and a graded flushing process of SSC solution→water→NaCl is performed after the reagent is switched;

[0022] Step 3, the electrical signal acquisition needs to meet the following conditions simultaneously: flow fluctuation ≤±2% for 5s, temperature fluctuation ≤±0.5℃, and pressure change rate ≤0.01 kPa / s.

[0023] As a further improvement of the embodiment of the present application, the injection pump extracts the reagent in a negative pressure mode, and the single suction volume is not more than the single stroke volume of the injection pump.

[0024] The above technical solution has the following beneficial effects: the rotary valve is used for switching, the pipeline can be cleaned after each use of reagent, and cross contamination caused by shared pipeline is effectively solved; the high-precision injection pump is used for extracting the reagent in a negative pressure mode, and the internal volume of the instrument is much lower than the suction stroke of the injection pump, so that the extraction of the reagent is within the suction stroke of the injection pump each time, and the pulsation interference caused by switching of the injection pump is completely avoided; the manifold assembly is precisely machined, and the flow channel is polished with Ra<1.6 μm, so that the residual and liquid resistance are reduced, and the electromagnetic valves of the instrument are concentrated on the manifold assembly, and the liquid is switched and delivered through the micro flow channel; the motor lifting is used for controlling the sealing of the chip and the manifold assembly, and the motor control is used for the in-and-out storage of the chip, so that the time for replacing the chip is greatly reduced, and the replacement time of the chip is less than 10 seconds each time. BRIEF DESCRIPTION OF DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the following embodiment or prior art description will be briefly introduced. Obviously, the drawings in the following description are only exemplary, and for those skilled in the art, other embodiments can be derived from the provided drawings without creative labor.

[0026] The structures, proportions, sizes, etc. shown in the specification are only used to cooperate with the content disclosed in the specification, to be understood and read by those skilled in the art, and do not define the limiting conditions for the implementation of the present application, so they do not have technical significance. Any modification of the structure, change of the proportion relationship or adjustment of the size, without affecting the effects and purposes that can be achieved by the present application, should still fall within the scope of the technical content disclosed by the present application.

[0027] Figure 1 The liquid path principle schematic diagram provided by the present application.

[0028] Figure 2 The combination schematic diagram of the liquid distribution needle group and the driving mechanism in the present application.

[0029] Figure 3 The structure schematic diagram of the liquid distribution needle group provided by the present application.

[0030] Figure 4 The Figure 3 The cross-sectional schematic diagram along A-A.

[0031] Figure 5 The first state schematic diagram of the manifold assembly provided by the present application.

[0032] Figure 6 The second state diagram of the busbar assembly provided by the present application.

[0033] Figure 7 The distribution diagram of the micro flow channel on the busbar provided by the present application.

[0034] In the figure:

[0035] 1, the distribution needle group;

[0036] 11, the needle adjusting plate;

[0037] 12, the reagent needle;

[0038] 13, the reagent needle welding screw;

[0039] 14, the spring;

[0040] 15, the spring joint;

[0041] 16, the liquid suction needle seat;

[0042] 2, the rotary valve;

[0043] 3, the busbar assembly;

[0044] 31, the busbar;

[0045] 32, the back cover plate;

[0046] 33, the busbar bonding cover plate;

[0047] 34, the copper plate for even heating;

[0048] 35, the FPC heating sheet;

[0049] 36, the rubber sheet;

[0050] 37, the large three-way electromagnetic valve;

[0051] 38, the small three-way electromagnetic valve;

[0052] 39, the chip cover plate sealing gasket;

[0053] 310, the electrode sealing glue column;

[0054] 311, the electrode;

[0055] 312, the 1 / 4-28 threaded joint;

[0056] 313, the 6-40 threaded joint;

[0057] 4, the injection pump;

[0058] 5, the valve;

[0059] 6, the liquid pump. Detailed Implementation

[0060] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0061] It should be noted that, unless otherwise specified, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0062] In this invention, unless otherwise stated, directional terms such as "upper," "lower," "top," and "bottom" are generally used in relation to the direction shown in the accompanying drawings, or in relation to the vertical, perpendicular, or gravitational direction of the component itself; similarly, for ease of understanding and description, "inner" and "outer" refer to the inner and outer contours of each component itself, but the above directional terms are not intended to limit this invention.

[0063] Terminology Explanation:

[0064]

[0065] See Figure 1 As shown, a liquid circuit system for an electronic microarray chip detector includes:

[0066] The four-channel dispensing needle assembly 1 has an inner surface Ra ≤ 0.1 μm;

[0067] The rotary valve 2 has a ten-channel structure, with four channels connected to reagent needles. After the reagent needle draws in reagent 1, it needs to draw in an air column of ≥2mm before it can draw in reagent 2, which effectively prevents cross-contamination and achieves physical isolation.

[0068] The laser-bonded manifold assembly 3 has a rectangular cross-section for its microchannels (0.5×0.5mm, surface roughness Ra≤1.6μm) and a dead volume ≤12μL, which greatly improves the utilization rate of trace reagents.

[0069] The temperature control unit integrated into the manifold assembly 3 includes an FPC heating element (hereinafter referred to as the heating element) and a temperature sensor (PT1000), which can accurately control the temperature of the liquid circuit system;

[0070] Injection pump 4 is linked to the flow sensor.

[0071] Specifically, the liquid distribution needle group 1 includes four independent reagent needles, which are respectively inserted into four reagent bottles containing NaCl solution, 0.1xSSC solution, 2xSSC solution and water. The reagent needles are connected to four channels of the rotary valve 2 through pipelines, and then led out from the main channel of the rotary valve 2 to the manifold assembly 3 through pipelines. The manifold assembly 3 has micro flow channels for delivering liquid to the biochip. The inlet and outlet of the manifold assembly 3 are connected and sealed with the inlet and outlet of the chip, and then the liquid is sucked from the manifold assembly 3 to the syringe pump 4. Finally, the waste liquid is discharged through the outlet of the syringe pump 4 (when the syringe pump 4 needs to be maintained, open the valve 5, and rely on the liquid pump 6 to discharge the waste liquid into the waste liquid bottle).

[0072] Instrument liquid circuit process:

[0073] 1. Fill the whole machine pipeline with NaCl and then monitor the initial electrical signal;

[0074] 2. Use 2xSSC solution and 0.1xSSC solution to clean the manifold assembly and the chip in turn;

[0075] 3. Flush with NaCl to fill the chip and measure the electrical signal;

[0076] 4. The algorithm gives the result.

[0077] In this embodiment, the rotary valve 2 has four channels enabled, and the reserved channels can be used for: calibration liquid access, waste liquid diversion and new reagent integration.

[0078] Specifically, as shown in Figures 2-4 , the liquid distribution needle group 1 includes a needle adjusting plate 11, and the reagent needles 12 are vertically arranged on the needle adjusting plate 11 and fixed through a spring buffer structure. In this embodiment, two needle adjusting plates 11 are sequentially placed on the liquid suction needle seat 16.

[0079] In actual operation, when the reagent needle 12 touches the bottom of the container, the spring buffer structure can play a buffering effect, effectively preventing the reagent needle 12 from breaking or bending. In addition, by moving the needle adjusting plate 11, the position of the reagent needle 12 can be flexibly adjusted to meet the needs of different detection scenarios.

[0080] The spring buffering structure comprises a spring joint 15, a reagent needle welding threaded part 13 and a spring 14. The specific installation mode is as follows: first, the reagent needle 12 is vertically arranged on the reagent needle welding threaded part 13, then the spring 14 is sleeved outside the reagent needle welding threaded part 13, then the two are placed in the installation hole of the needle adjusting plate 11 from bottom to top, and finally the spring joint 15 is fixedly connected with the reagent needle welding threaded part 13 from above the needle adjusting plate 11. At this time, one end of the spring 14 abuts against the needle adjusting plate 11 on the outer periphery of the installation hole, and the other end abuts against the reagent needle welding threaded part 13. In the unforced state, the combination of the spring joint 15 and the reagent needle welding threaded part 13 sinks under the action of the spring 14; when the reagent needle 12 is forced to the bottom, the combination body moves upward as a whole, thereby playing a good buffering effect on the reagent needle 12. The upper end of the reagent needle 12 is connected with the rotary valve 2 through a PTFE tube.

[0081] In the embodiment, the reagent needle 12 is made of passivated 316L stainless steel, which has good corrosion resistance and chemical stability and can meet the requirements of contact with various reagents during detection. The inner diameter is set to 0.5 mm, which can ensure smooth flow of the reagent and facilitate accurate control of the reagent flow. The outer surface is coated with a hydrophobic coating, which can effectively reduce reagent residue and avoid cross contamination. The inner surface is polished to reduce the needle internal roughness Ra to less than 0.1, thereby reducing the liquid flow resistance.

[0082] The rotary valve 2 with ten channels plays a key role in the embodiment. Four channels are respectively connected with reagent needles for accurately introducing different reagents, and the other six channels are reserved for expansion, thereby reserving sufficient space for subsequent addition of detection reagents or functions. The main channel outlet is connected with the busbar assembly 3 through a PTFE tube with an ID of 0.5 mm, and the PTFE tube can be replaced with other chemical corrosion-resistant and good sealing same-specification tubes. The architecture design of “one main channel + multiple standby channels” makes it possible to flexibly expand the types of reagents when facing different detection requirements, without the need to make large-scale changes to the overall liquid system, thereby improving the versatility and adaptability of the system.

[0083] In combination with Figure 5 , Figure 6As shown, the laser-bonded manifold assembly 3 is integrally formed from a double-layer PC board using a laser bonding process. The upper layer, the manifold 31, is equipped with a fluid interface and microchannels. The microchannels have a rectangular cross-section of 0.5mm × 0.5mm, but can be adjusted to other regular or irregular shapes according to actual needs. The lower layer is the rear cover plate 32, which serves as a sealing cover for the laser welding process. Between the manifold 31 and the rear cover plate 32, from top to bottom, are arranged a manifold bonding cover plate 33, a heat-spreading copper plate 34, an FPC heating element 35, and a rubber sheet 36. The locking method between the manifold 31 and the rear cover plate 32 can be replaced with other compatible threaded connectors, in addition to using 1 / 4-28 threaded connectors 312 and 6-40 threaded connectors 313. The manifold 31 is equipped with a large three-way solenoid valve 37 and a small three-way solenoid valve 38 on its outer side. Four small three-way solenoid valves 38 are reserved on the manifold for future reagent additions. The large three-way solenoid valve 37 enables bypassing of the chip flow channels. Furthermore, the FPC heating element 35 has a built-in temperature sensor that can monitor the temperature within the microchannels in real time, ensuring stable system operation.

[0084] A chip cover sealing gasket 39 is specially provided on one side of the busbar 31. This sealing gasket can also be made of materials with good sealing properties and elasticity, such as rubber or silicone, to prevent liquid leakage. Meanwhile, an electrode 311 is also inserted into the busbar 31. The electrode 311 can be cylindrical to adapt to different electrical connection requirements. To fix the electrode 311, an electrode sealing post 310 is provided on the busbar 31, firmly fixing the electrode 311 to the busbar 31 and ensuring the reliability of the electrical connection.

[0085] The manifold assembly 3 and the chip's inlet / outlet are equipped with silicone sealing rings. These rings can also be replaced with seals made of other corrosion-resistant and well-sealing materials such as fluororubber to ensure a good sealing effect. Simultaneously, a motor-driven chip pressing mechanism is employed. This mechanism can be flexibly designed in different forms, such as screw drive or rack and pinion drive, to achieve automatic and precise pressing and rapid separation of the chip and the manifold assembly's sealing ring. Chip replacement time is strictly controlled within <10 seconds, significantly improving operational efficiency.

[0086] The FPC heating element 35 integrates a high-precision temperature sensor, forming a closed-loop temperature control system. This system maintains the reagent temperature stably within a precise range of 37±0.5℃, effectively reducing the electrical signal drift caused by temperature fluctuations from ±15mV to ±2mV. Combined with precise flow rate control, this significantly improves the signal-to-noise ratio to 45dB, compared to 32dB in traditional solutions, resulting in a marked improvement in detection accuracy and reliability.

[0087] like Figure 7 The microchannel structure on the manifold shown, when connected to rotary valve 2, was tested, and the flow rate was measured as follows:

[0088]

[0089] Therefore, the total amount of reagent in the busbar is only 11.27ul. The reagent waste is greatly reduced, and the total volume of the flow channel is 11.27ul. The actual dead volume calculation includes the liquid displacement rate.

[0090] The comparison of the microfluidic channel design of the busbar in this embodiment with the traditional method is as follows:

[0091]

[0092] The temperature-electrical signal correlation table in this embodiment is as follows:

[0093]

[0094] Therefore, the liquid path system provided by the application has small temperature fluctuation, and the electrical signal drift performance is obviously improved.

[0095] A liquid path control method applied to the liquid path system of the electronic microarray chip detector, characterized by comprising:

[0096] Step 1, start the FPC heating sheet 35, and use the self-contained temperature sensor to build a closed loop temperature control, so that the temperature of the busbar assembly is stably set in the range of 37±0.5℃;

[0097] Step 2, clean the flow channel at a flow rate of 150ul / s, and continuously monitor the temperature fluctuation during the cleaning process. When the temperature fluctuation is less than or equal to 0.3℃ / s, the different reagent channels are physically isolated by the rotary valve, and then the channels are switched. After the reagent is switched, the graded flushing process of SSC solution→water→NaCl is performed to ensure the cleanliness of the flow channel;

[0098] Step 3, when collecting the electrical signal, the following conditions need to be met simultaneously: the flow rate fluctuation is less than or equal to ±2% and lasts for 5s, the temperature fluctuation is less than or equal to ±0.5℃, and the pressure change rate is less than or equal to 0.01kPa / s, so as to ensure the accuracy and stability of the collected data.

[0099] In this embodiment, the syringe pump 4 operates in the mode of negative pressure extraction of reagents. Here, the syringe pump can also be replaced by a peristaltic pump or other pump structure capable of realizing negative pressure extraction function. At the same time, in order to ensure the stability and accuracy of the extraction process, the amount of reagent sucked at a time is strictly controlled within the range of not more than the single stroke volume of the syringe pump. The mapping relationship between the operation parameters of the syringe pump and the electrical signal acquisition is as follows:

[0100]

[0101] The advantages of the application can be summarized as follows:

[0102]

[0103] Therefore, the application achieves the following effects:

[0104] 1. Reduce the instrument dead volume;

[0105] 2. Reduce reagent consumption;

[0106] 3. Improve the signal-to-noise ratio of the electrical signal;

[0107] 4. Improve the consistency of chip analysis;

[0108] 5. Improve flow rate stability, the following data is measured using the weighing method, and the measured data is shown in the following table

[0109]

[0110]

[0111] The application adopts a rotary valve to switch, can clean the pipeline after each use of reagent, effectively solves the cross contamination caused by the shared pipeline; uses a high-precision syringe pump to extract reagent under negative pressure, and the internal volume of the instrument is much lower than the suction stroke of the syringe pump, so that it is ensured that each time of extracting reagent is within one suction stroke of the syringe pump, and the pulsation interference caused by switching of the syringe pump is completely avoided; the manifold assembly is precisely machined, the flow channel is polished, Ra<1.6 μm, the residual and liquid resistance are reduced, at the same time, the electromagnetic valves of the instrument are concentrated on the manifold assembly, and the liquid is conveyed through the micro flow channel; the chip and the manifold assembly use a motor to lift to control sealing, and the chip in and out of the warehouse are controlled by the motor, so that the time for replacing the chip is greatly reduced, and the chip replacement time is less than 10 s / time.

[0112] Obviously, the above-described embodiments are only part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor should belong to the protection scope of the application.

[0113] It should be noted that the terms used herein are only intended to describe specific embodiments, and are not intended to limit the exemplary embodiments according to the present application. As used herein, the singular form is intended to include the plural form unless the context clearly indicates otherwise, and it should also be understood that when the terms "comprise" and / or "include" are used in the specification, there is a feature, step, work, device, component and / or combination thereof.

[0114] It should be noted that the terms "first", "second", and the like, used in the description and in the claims of the present application as well as above-mentioned figures are used to distinguish between similar objects and not necessarily for describing a specific sequential or chronological order. It is to be understood that the use of data so designated is not meant to limit a given item described by such data to the same category as other data designated by the same designations, but instead is so designated only for convenience as a means of discriminating between the two series of items that refer to a same data.

[0115] The preferred embodiments of the application described herein are examples of the present application and are not intended to limit the scope of the application. Various modifications and changes can be made thereto by those skilled in the art which freely adapt to the idea and principles of the application, without departing from the spirit and scope thereof, and it is to be understood that such modifications and changes are to be included within the scope of the application as defined by the appended claims.

Claims

1. A liquid circuit system for an electronic microarray chip detector, characterized in that, include: The four-channel dispensing needle assembly has an inner surface Ra≤0.1μm; The rotary valve has at least four channels, four of which are connected to a reagent needle. After the reagent needle draws in a reagent, it needs to draw in an air column of ≥2mm before it can draw in another reagent, thus achieving physical isolation. The manifold assembly using laser bonding has a rectangular cross-section for its microchannels, with a surface roughness Ra≤1.6μm and a dead volume≤12μL. Temperature control unit integrated into the busbar assembly, including FPC heating element and temperature sensor; The syringe pump is linked to the flow sensor; The syringe pump draws reagents using negative pressure, and the amount drawn in a single operation does not exceed the single-stroke volume of the syringe pump.

2. The liquid circuit system of the electronic microarray chip detector according to claim 1, characterized in that, The dispensing needle assembly includes a spring buffer structure and a needle adjustment plate, and the needle body is made of passivated 316L stainless steel.

3. The liquid circuit system of the electronic microarray chip detector according to claim 2, characterized in that, The dispensing needle assembly includes four independent reagent needles. The outer surface of each reagent needle is coated with a hydrophobic coating and the inner surface is polished. The internal roughness Ra of each reagent needle is less than 0.1 μm.

4. The liquid circuit system of the electronic microarray chip detector according to claim 1, characterized in that, The manifold assembly is a double-layer PC board laser bonded composite, with the upper board having a liquid channel interface and microchannels, and the lower board being a laser-welded cover plate; the total flow channel volume of the manifold assembly is ≤12μL.

5. The liquid circuit system of the electronic microarray chip detector according to claim 1, characterized in that, The temperature control unit stabilizes the reagent temperature at 37±0.5℃, with a temperature fluctuation rate ≤0.3℃ / s.

6. The liquid circuit system of the electronic microarray chip detector according to claim 1, characterized in that, It also includes a motor-driven chip pressing mechanism to automatically press and separate the chip from the busbar assembly sealing ring, with a replacement time of less than 10 seconds.

7. The liquid circuit system of the electronic microarray chip detector according to claim 1, characterized in that, The main channel of the rotary valve is connected to the manifold assembly via a PTFE tube, while the backup channel supports calibration solution input, waste liquid diversion, and integration of new reagents.

8. The liquid circuit system of the electronic microarray chip detector according to claim 1, characterized in that, The busbar assembly has a built-in three-way solenoid valve to enable bypass function of the chip flow channel.

9. A liquid circuit control method, applied to the liquid circuit system of an electronic microarray chip detector as described in any one of claims 1-8, characterized in that... include: Step 1: Turn on the heating element to stabilize the busbar assembly temperature at 37±0.5℃; Step 2: Clean the flow channel at a flow rate of 150 μL / s. When the temperature fluctuation is ≤0.3℃ / s, switch channels. Different reagent channels are physically isolated by a rotary valve, and a graded rinsing process of SSC solution → water → NaCl is performed after reagent switching. Step 3: The electrical signal acquisition must simultaneously meet the following requirements: flow rate fluctuation ≤ ±2% for 5 seconds, temperature fluctuation ≤ ±0.5℃, and pressure change rate ≤ 0.01kPa / s.

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