Liquid flow sample loading pressure control method of flow type cell sorter

By building a fluid flow loading system in a flow cytometer and using an incremental digital PID control algorithm to accurately adjust the air pressure of the sample and sheath fluid, the problem of insufficient loading flow control accuracy in the prior art is solved, and high-precision flow control and cost reduction are achieved.

CN119717919AActive Publication Date: 2025-03-28SUZHOU INST OF BIOMEDICAL ENG & TECH CHINESE ACADEMY OF SCI

Patent Information

Application Number
CN202411683126.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-22
Publication Date
2025-03-28
Estimated Expiration
2044-11-22

AI Technical Summary

Technical Problem

The existing flow cytometers have problems with precision pressure differential control in low flow control of sample flow, resulting in insufficient control accuracy of loading flow, and the commonly used flow sensors have high cost and low reaction sensitivity, making it difficult to respond quickly to pressure differential changes.

Method used

By building a flow cell sorter fluid loading system, it connects the air supply air path, sample flow path and sheath liquid flow path, and sets the first and second electrical proportional valves in the sample flow path and sheath liquid flow path respectively. The incremental digital PID control algorithm is used to control the output pressure of the electrical proportional valve, and accurately adjust the air pressure of the sample and sheath liquid, thereby achieving high-precision loading flow control.

Benefits of technology

It improves the control accuracy of loading flow, reduces hardware costs, improves the ability to respond quickly to pressure differential changes, and enhances the efficiency of flow cytometry sorting instruments.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN119717919A_ABST
    Figure CN119717919A_ABST
Patent Text Reader

Abstract

The invention discloses a liquid flow sample loading pressure control method of a flow cytometry sorter, which belongs to the field of cell sorting, and is characterized in that a liquid flow sample loading system of the flow cytometry sorter is built, a gas supply gas path is connected with a sample flow path and a sheath liquid flow path, and the sample flow path and the sheath liquid flow path are communicated with a dropping liquid generation flow path; the sample flow path is provided with a first electric proportional valve, the first electric proportional valve is used for adjusting the air pressure in the sample tube, the sheath fluid flow path is provided with a second electric proportional valve, and the second electric proportional valve is used for adjusting the air pressure in the sheath fluid barrel; according to the Bernoulli's theorem in fluid mechanics, as # imgabs0 reflects a pressure difference corresponding to a sample loading flow, an input and output pressure difference is adopted to replace the pressure difference corresponding to the sample loading flow to obtain a theoretical value of a first electric proportional valve, and an incremental digital PID control algorithm is adopted to control to obtain kth and (k-1) th pressure output values of a PID controller; therefore, the control precision of the sample loading flow is improved.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] The invention relates to the field of cell sorting, and in particular to a method for controlling liquid flow sample loading pressure of a flow cell sorter. Background Art

[0002] A flow cytometer is a device for high-throughput analysis and sorting and enrichment of cells. It performs optical detection based on the physical, chemical, immune and other characteristic parameter information of cells, and sorts and enriches specific cell subpopulations through a preselected parameter range. Compared with a flow cytometer, the sorter also contains two important unique devices in hardware: a droplet generator and a nozzle. Among them, the droplet generator is installed at the front end of the flow chamber, and the piezoelectric transducer acts on the sheath liquid and sample flow at ultra-high frequency to generate droplets of uniform size and equal intervals; the nozzle is installed at the outlet of the flow chamber, and the tiny throttle holes on it limit the size of the generated droplets, usually with an aperture of 70 to 130 μm. Due to the large flow resistance of the tiny throttle holes of the nozzle, the liquid flow system of the sorter is very different from that of the analyzer, especially the sheath liquid pressure used to achieve three-dimensional fluid dynamic focusing will be increased by ten times or even dozens of times. Fluid pumps commonly used in flow cytometers to drive sheath fluids at constant pressure or constant current, such as diaphragm pumps, peristaltic pumps, and syringe pumps, are generally difficult to use in sorters. Therefore, flow cytometers usually use pneumatic control systems to drive sheath fluids and sample flows at constant pressure or constant current.

[0003] In the sorting instrument, the sample flow is injected through the pressure difference between the injection tube and the droplet generator, and the injection flow rate is usually controlled at 10-100 μL / min. The low flow rate of the sample flow puts higher requirements on the precise control of the pressure difference. Generally, the control accuracy of the electric proportional valve used for air pressure regulation is 1%-5% of the full scale, and the price of the electric proportional valve with higher accuracy will be very expensive. In order to realize the flow of the sample flow in the test tube into the droplet generator, the air pressure in the test tube must be higher than the latter. Therefore, the range of the electric proportional valve used to control the sample flow is generally from several to more than ten atmospheres. The pressure control accuracy of the proportional valve is at the same order of magnitude as the driving pressure difference of the sample flow, making it difficult for the flow control accuracy of the sample flow to meet the use requirements of the instrument. In addition, the change in the liquid level height in the sheath liquid barrel will also change the pressure of the sheath liquid in the droplet generator, thereby changing the driving pressure difference of the sample flow, causing the sample flow rate to change. At the same time, the change in the liquid level of the sample in the test tube will also affect the driving pressure difference of the sample flow, thereby affecting the control accuracy of the sample flow.

[0004] In order to achieve low-flow loading of sample flow, currently disclosed instruments usually add a flow sensor for micro-flow detection in the flow path of sample injection for feedback control. This method can improve the flow control of sample flow to a certain extent, but there are still some problems: first, the flow sensor is relatively expensive, which increases the hardware cost of the instrument; second, compared with the pressure sensor, the response sensitivity of the flow sensor is lower, and its stable output takes a long time, and it cannot quickly respond to changes in pressure difference; third, the detection accuracy of the flow sensor is usually 5% to 10% of the full scale, and the measurement accuracy is not high. Summary of the invention

[0005] In order to overcome the deficiencies of the prior art, one of the objectives of the present invention is to provide a method for controlling the sample loading pressure of a flow cell sorter to improve the control accuracy of the sample loading flow rate.

[0006] One of the purposes of the present invention is achieved by the following technical solution:

[0007] A method for controlling liquid flow sample loading pressure of a flow cell sorter comprises the following steps:

[0008] Build a flow cell sorter liquid sample loading system, connect the gas supply path with the sample path and the sheath liquid path, the sample path and the sheath liquid path are connected with the droplet generation path, the sample path is provided with a first electrical proportional valve, the first electrical proportional valve is used to adjust the air pressure in the sample tube, the sheath liquid path is provided with a second electrical proportional valve, the second electrical proportional valve is used to adjust the air pressure in the sheath liquid barrel;

[0009] When the flow cell sorter liquid flow loading system works, there are:

[0010]

[0011] Wherein, P1 is the theoretical value of the output of the first electrical proportional valve; P2 is the theoretical value of the output of the second electrical proportional valve; P3 is the pressure value in the flow chamber; z1 is the height difference between the bottom end of the sampling needle and the output end face of the sampling needle tube in the flow chamber under the injection state; z2 is the height difference between the bottom end face of the sheath liquid barrel and the center of the flow chamber; h1 is the sample liquid level height; h2 is the sheath liquid level height; v ST is the average flow rate of the sheath fluid in the flow chamber, v SP is the average flow rate of the sample flow in the flow chamber;

[0012] Subtracting formula (1) from formula (2) yields

[0013]

[0014] because It reflects the pressure difference corresponding to the sample loading flow rate, using the input and output pressure difference ΔPSP Substituting formula (3) Too small and can be ignored, P2 uses the actual value of the second electrical proportional valve, so we get

[0015] P1=ΔP SP +P2-ρg(z2-z1+h1-h2) (4)

[0016] Using incremental digital PID control algorithm, we can get When o (k) = u o (k-1)+K P (e(k)-e(k-1))+K I e(k)+K D (e(k)-2e(k-1)+e(k-2))(5)

[0017] when When o (k) = u o (k-1)(6)

[0018] Where ε is the expected error limit percentage; u o (k) and u o (k-1) are the k-th and k-1-th pressure output values ​​of the PID controller respectively; e(k) is the output pressure error of the first electrical proportional valve at the k-th time, that is, P1(k)-P1actual(k); K P , K I , K D They are the proportional, integral and differential adjustment parameters of the PID controller respectively.

[0019] Furthermore, the sample sampling needle and the sampling pipeline are simplified into a slender hole model to obtain ΔP SP .

[0020] Furthermore, the sample flow rate Q SP The pressure difference ΔP between the input and output of the elongated hole model SP It is a linear relationship, that is:

[0021] ΔP SP =K SP Q SP (7)

[0022] K SP is the linear coefficient. According to formula (7), different Q SP ΔP SP .

[0023] Furthermore, to ensure high-precision control of the sample loading flow rate, ε is 0.01% to 0.2%.

[0024] Furthermore, the data sampling rate in the flow cell sorter liquid flow sample loading pressure control method is 10 to 120 times / minute.

[0025] Furthermore, a first liquid level meter is provided in the sample tube in the sample flow path, and the first liquid level meter obtains the sample liquid level height h1.

[0026] Furthermore, a second liquid level meter is provided in the sheath liquid barrel in the sheath liquid flow path, and the second liquid level meter obtains the sheath liquid level height h2.

[0027] Furthermore, the cell sorter liquid flow loading system includes an air pressure feedback controller, which takes the expected air pressure output value and the actual pressure measurement value as input, and outputs a digital signal for controlling the first electrical proportional valve or the second electrical proportional valve through an air pressure feedback control algorithm.

[0028] Furthermore, the air pressure feedback controller is an incremental PID controller.

[0029] Furthermore, the sample flow path is provided with a first pressure gauge, which is used to monitor the output pressure P of the first electrical proportional valve in real time. 1实际 The sheath fluid flow path is provided with a second pressure gauge, and the second pressure gauge is used to monitor the output air pressure of the second electrical proportional valve in real time.

[0030] Compared with the prior art, the flow cell sorter liquid flow sample pressure control method of the present invention builds a flow cell sorter liquid flow sample system, connects the air supply path with the sample path and the sheath liquid path, the sample path and the sheath liquid path are connected with the droplet generation path, the sample path is provided with a first electrical proportional valve, the first electrical proportional valve is used to adjust the air pressure in the sample tube, the sheath liquid path is provided with a second electrical proportional valve, the second electrical proportional valve is used to adjust the air pressure in the sheath liquid barrel; according to Bernoulli's theorem in fluid mechanics, since It reflects the pressure difference corresponding to the sample loading flow rate. The pressure difference of input and output is used to replace the pressure difference corresponding to the sample loading flow rate to obtain the theoretical value of the first electrical proportional valve. The incremental digital PID control algorithm is used to control and obtain the kth and k-1th pressure output values ​​of the PID controller, thereby improving the control accuracy of the loading flow rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is a flow chart of the method for controlling the sample loading pressure of a flow cell sorter according to the present invention;

[0032] Figure 2 It is a schematic diagram of the structure of the liquid flow loading system of the flow cell sorter of the present invention;

[0033] Figure 3This is a control block diagram of the liquid flow loading system of the flow cell sorter of the present invention.

[0034] In the figure: 10, air supply circuit; 11, compressor; 12, filter; 13, water mist separator; 14, pressure reducing valve; 15, gas storage tank; 16, safety valve; 20, sample flow path; 21, first electrical proportional valve; 22, first pressure gauge; 23, sample tank; 24, sample tube; 25, sampling needle; 26, first liquid level gauge; 30, sheath liquid flow path; 31, second electrical proportional valve; 32, second pressure gauge; 33, sheath liquid barrel; 34, second liquid level gauge; 35, flow meter; 40, droplet generation flow path; 41, third pressure gauge; 42, flow cavity; 43, flow chamber; 44, nozzle. DETAILED DESCRIPTION

[0035] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0036] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0037] See also Figure 1 The present invention provides a method for controlling the sample loading pressure of a flow cell sorter, comprising the following steps:

[0038] Build a flow cell sorter liquid sample loading system, connect the gas supply path with the sample path and the sheath liquid path, the sample path and the sheath liquid path are connected with the droplet generation path, the sample path is provided with a first electrical proportional valve, the first electrical proportional valve is used to adjust the air pressure in the sample tube, the sheath liquid path is provided with a second electrical proportional valve, the second electrical proportional valve is used to adjust the air pressure in the sheath liquid barrel;

[0039] When the flow cell sorter liquid flow loading system works, there are:

[0040]

[0041] Wherein, P1 is the theoretical value of the output of the first electrical proportional valve; P2 is the theoretical value of the output of the second electrical proportional valve; P3 is the pressure value in the flow chamber; z1 is the height difference between the bottom end of the sampling needle and the output end face of the sampling needle tube in the flow chamber under the injection state; z2 is the height difference between the bottom end face of the sheath liquid barrel and the center of the flow chamber; h1 is the sample liquid level height; h2 is the sheath liquid level height; v ST is the average flow rate of the sheath fluid in the flow chamber, v SP is the average flow rate of the sample flow in the flow chamber;

[0042] Subtracting formula (1) from formula (2) yields

[0043]

[0044] because It reflects the pressure difference corresponding to the sample loading flow rate, using the input and output pressure difference ΔP SP Substituting formula (3) Too small and can be ignored, P2 uses the actual value of the second electrical proportional valve, so we get

[0045] P1=ΔP SP +P2-ρg(z2-z1+h1-h2) (4)

[0046] Using incremental digital PID control algorithm, we can get When o (k) = u o (k-1)+K P (e(k)-e(k-1))+K I e(k)+K D (e(k)-2e(k-1)+e(k-2))(5)

[0047] when When o (k) = u o (k-1)(6)

[0048] Where ε is the expected error limit percentage; u o (k) and u o (k-1) are the k-th and k-1-th pressure output values ​​of the PID controller respectively; e(k) is the output pressure error of the first electrical proportional valve at the k-th time, that is, P1(k)-P1actual(k); K P , K I , K D They are the proportional, integral and differential adjustment parameters of the PID controller respectively.

[0049] For details, please continue to refer to Figure 2The flow sample loading system of the flow cytometer includes an air supply circuit 10, a sample circuit 20, a sheath liquid circuit 30, and a droplet generation circuit 40. The sample circuit 20 and the sheath liquid circuit 30 are respectively connected to the air supply circuit 10, the air supply circuit 10 drives the sample in the sample circuit 20 and the sheath liquid in the sheath liquid circuit 30, the sample circuit 20 and the sheath liquid circuit 30 are connected to the droplet generation circuit 40, and the sample in the sample circuit 20 and the sheath liquid in the sheath liquid circuit 30 enter the droplet generation circuit 40 to generate droplets.

[0050] The gas supply circuit 10 includes a compressor 11, a filter 12, a water mist separator 13, a pressure reducing valve 14 and a gas storage tank 15 connected in sequence, and a safety valve 16 is installed on the gas storage tank 15. The pressure reducing valve 14 is used to preliminarily adjust the output air pressure of the compressor 11, which can be adjusted manually or electrically. The output air pressure is generally set to 1.2 to 2 times the maximum air supply pressure in the sheath liquid flow path 30, but does not exceed the maximum allowable input air pressure value of the first electrical proportional valve 21 and the second electrical proportional valve 31. The gas storage tank 15 is used to store the compressed gas after the pressure reduction of the pressure reducing valve 14, and the safety valve 16 is used to ensure the safety of the air supply pressure at its rear end. The safety valve 16 can use a pressure switch with a contact tongue spring, that is, when the air pressure in the gas storage tank 15 is higher than 80% to 100% of the maximum allowable input air pressure value of the first electrical proportional valve 21 or the second electrical proportional valve 31, the safety valve 16 automatically opens and releases air to reduce the pressure of the gas storage tank 15 to the set pressure value; otherwise, the safety valve 16 is always in a closed state.

[0051] The sample flow path 20 includes a first electrical proportional valve 21, a first pressure gauge 22, a sample tank 23, a sample tube 24 and a sampling needle 25 which are connected in sequence, and a first liquid level gauge 26 is installed on the sample tube 24. The first electrical proportional valve 21 is used to adjust the air pressure in the sample tube 24; the first pressure gauge 22 is used to monitor the output air pressure of the first electrical proportional valve 21 in real time; the compressed gas output by the first electrical proportional valve 21 is input into the sample tank 23 to drive the sample under positive pressure; the sample tube 24 is fixed in the sample tank 23, and the sample in the sample tube 24 flows out through the sampling needle 25 under air pressure; the sampling needle 25 is matched with a first liquid level gauge 26, which is a capacitive liquid level gauge, used for sample transmission and monitoring the liquid level height of the sample in the sample tube 24.

[0052] The sheath liquid flow path 30 includes a second electrical proportional valve 31, a second pressure gauge 32, a sheath liquid barrel 33 and a flow meter 35 which are connected in sequence, and a second liquid level meter 34 is installed in the sheath liquid barrel 33. The second electrical proportional valve 31 is used to adjust the air pressure in the sheath liquid barrel 33; the second pressure gauge 32 is used to monitor the output air pressure of the second electrical proportional valve 31 in real time; the compressed gas output by the second electrical proportional valve 31 is input into the sheath liquid barrel 33 to drive the sheath liquid with positive pressure; the second liquid level meter 34 is installed in the sheath liquid barrel 33 to monitor the liquid level of the sheath liquid; the flow meter 35 is connected to the sheath liquid pipeline to measure the flow rate of the sheath liquid; the second liquid level meter 34 is preferably a continuous liquid level sensor of float type or ultrasonic principle.

[0053] The droplet generation flow path 40 includes a flow chamber 42, a flow chamber 43 and a nozzle 44 connected in sequence, and a third pressure gauge 41 is installed in the flow chamber 42. The flow chamber 42 in the droplet generation flow path 40 is used for three-dimensional fluid dynamic focusing of the sample. After the sheath liquid and the sample flow into the flow chamber 42, the sheath liquid wraps the sample to achieve single-cell arrangement of cells in the sample; the third pressure gauge 41 is connected to the pipeline in the flow chamber 42 to monitor the hydraulic pressure of the fluid in the flow chamber 42; the inlet of the flow chamber 43 is connected to the outlet of the flow chamber 42 for flow detection and analysis of cells; the inlet of the nozzle 44 is connected to the outlet of the flow chamber 43; the inner diameter of the nozzle 44 is 70 to 130 μm, and is used to generate droplets of stable size.

[0054] Please continue reading Figure 3 The control module of the liquid flow loading system of the flow cell sorter includes a microprocessor and a central controller to monitor or control the liquid flow system. Among them, the analog / digital converter (A / D) in the microprocessor is used to receive in real time the output electrical signals (current signals or voltage signals) of the first pressure gauge 22, the second pressure gauge 32, and the third pressure gauge 41 for monitoring the pressure size, as well as the output electrical signals of the first liquid level gauge 26 and the second liquid level gauge 34 for monitoring the liquid level height, and convert the received electrical signals into corresponding digital signals; the microprocessor receives the expected air pressure output value (theoretical value) of the first electrical proportional valve 21 and the second electrical proportional valve 31 output by the central controller; the microprocessor includes a pressure feedback controller, which takes the expected pressure output value and the actual pressure measurement value as input, and outputs the digital signal for controlling the first electrical proportional valve 21 and the second electrical proportional valve 31 through the pressure feedback control algorithm; the digital / analog converter (D / A) in the microprocessor converts the digital signal output by the pressure feedback controller into an analog electrical signal, and outputs the analog electrical signal to the actuator, namely the first electrical proportional valve 21 or the second electrical proportional valve 31; the resolution of the A / D or D / A chip is preferably 16bit or 24bit; the pressure feedback controller is preferably an incremental PID controller.

[0055] The central controller calculates or outputs the expected air pressure output value of the first electrical proportional valve 21 or the second electrical proportional valve 31 through the input information such as the liquid flow state, nozzle model, sample injection flow rate set by the instrument user in the upper computer software. Among them, the liquid flow state includes but is not limited to the power-on state, normal operation state, bubble exhaust state, power-off state, cleaning state, etc.; the nozzle model refers to the nozzle aperture size used in the flow cell sorter, such as the commonly used specifications of 70μm, 85μm, 100μm or 130μm; the sample injection flow rate is the flow rate size set by the instrument user in the upper computer software, and the conventional flow rate setting range is 10-120μL / min; the central controller outputs the automatically calculated expected air pressure output value to the microprocessor as an input variable of the microprocessor.

[0056] This reflects the flow rate of sample loading, because v SP Very small, for v SP The measurement is very inconvenient. Therefore, in practical applications, the sample sampling needle 25 and the sampling pipeline need to be simplified into a slender hole model. Through actual experiments, it can be obtained that for the horizontally placed slender hole model, the sample flow rate Q SP The pressure difference ΔP between the input and output of the model SP It is a linear relationship, that is:

[0057] ΔP SP =K SP Q SP (7)

[0058] K SP is the linear coefficient. According to formula (7), different Q SP ΔP SP .

[0059] To ensure high-precision control of the sample loading flow rate, ε is 0.01% to 0.2%. The sampling rate of the sensor has a great influence on the three adjustment parameters of the PID controller. At the same time, considering the response time of each pressure gauge and level gauge, the data sampling rate is 10 to 120 times / minute.

[0060] The flow cell sorter liquid flow sample pressure control method of the present invention builds a flow cell sorter liquid flow sample system, connects the gas supply path 10 with the sample flow path 20 and the sheath liquid flow path 30, the sample flow path 20 and the sheath liquid flow path 30 are connected with the droplet generation flow path 40, the sample flow path 20 is provided with a first electrical proportional valve 21, the first electrical proportional valve 21 is used to adjust the air pressure in the sample tube 24, the sheath liquid flow path 30 is provided with a second electrical proportional valve 31, the second electrical proportional valve 31 is used to adjust the air pressure in the sheath liquid barrel 33; according to the Bernoulli theorem in fluid mechanics, since It reflects the pressure difference corresponding to the sample loading flow rate. The pressure difference of input and output is used to replace the pressure difference corresponding to the sample loading flow rate to obtain the theoretical value of the first electrical proportional valve 21. The incremental digital PID control algorithm is used to control and obtain the kth and k-1th pressure output values ​​of the PID controller, thereby improving the control accuracy of the loading flow rate.

[0061] The above embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the present invention, which are equivalent modifications and improvements made to the above embodiments based on the essential technology of the present invention, and all of them belong to the protection scope of the present invention.

Claims

1. A method for controlling the sample loading pressure of a flow cell sorter, characterized in that: The following steps are involved: Build a flow cell sorter liquid sample loading system, connect the gas supply path with the sample path and the sheath liquid path, the sample path and the sheath liquid path are connected with the droplet generation path, the sample path is provided with a first electrical proportional valve, the first electrical proportional valve is used to adjust the air pressure in the sample tube, the sheath liquid path is provided with a second electrical proportional valve, the second electrical proportional valve is used to adjust the air pressure in the sheath liquid barrel; When the flow cell sorter liquid flow loading system works, there are: Wherein, P1 is the theoretical value of the output of the first electrical proportional valve; P2 is the theoretical value of the output of the second electrical proportional valve; P3 is the pressure value in the flow chamber; z1 is the height difference between the bottom end of the sampling needle and the output end face of the sampling needle tube in the flow chamber under the injection state; z2 is the height difference between the bottom end face of the sheath liquid barrel and the center of the flow chamber; h1 is the sample liquid level height; h2 is the sheath liquid level height; v ST is the average flow rate of the sheath fluid in the flow chamber, v SP is the average flow rate of the sample flow in the flow chamber; Subtracting formula (1) from formula (2) yields because It reflects the pressure difference corresponding to the sample loading flow rate, using the input and output pressure difference ΔP SP Substituting formula (3) Too small and can be ignored, P2 uses the actual value of the second electrical proportional valve, so we get P1=ΔP SP +P2-ρg(z2-z1+h1-h2) (4) Using incremental digital PID control algorithm, we can get When u o (k) = u o (k - 1)+K P (e(k)-e(k - 1))+K I e(k)+K D (e(k)-2e(k - 1)+e(k - 2))(5) when When o (k) = u o (k-1)(6) Where ε is the expected error limit percentage; u o (k),u o (k-1) are the k-th and k-1-th pressure output values ​​of the PID controller respectively; e(k) is the output pressure error of the first electrical proportional valve at the k-th time, that is, P1(k)-P1actual(k); K P , K I , K D They are the proportional, integral and differential adjustment parameters of the PID controller respectively.

2. The method for controlling liquid flow sample loading pressure of a flow cell sorter according to claim 1, characterized in that: The sample sampling needle and sampling pipeline are simplified into a slender hole model to obtain ΔP SP .

3. The method for controlling the sample loading pressure of a flow cell sorter according to claim 2, characterized in that: Sample flow rate Q SP The pressure difference ΔP between the input and output of the elongated hole model SP It is a linear relationship, that is: ΔP SP =K SP ·Q SP (7) K SP is the linear coefficient. According to formula (7), different Q SP ΔP SP .

4. The method for controlling liquid flow sample loading pressure of a flow cell sorter according to claim 1, characterized in that: To ensure high-precision control of the sample loading flow rate, ε is 0.01% to 0.2%.

5. The method for controlling liquid flow sample loading pressure of a flow cell sorter according to claim 1, characterized in that: The data sampling rate in the flow cell sorter liquid flow sample loading pressure control method is 10 to 120 times / minute.

6. The method for controlling liquid flow sample loading pressure of a flow cell sorter according to claim 1, characterized in that: A first liquid level meter is disposed in the sample tube in the sample flow path, and the first liquid level meter obtains the sample liquid level height h1.

7. The method for controlling liquid flow sample loading pressure of a flow cell sorter according to claim 1, characterized in that: A second liquid level meter is arranged in the sheath liquid barrel in the sheath liquid flow path, and the second liquid level meter obtains the sheath liquid level height h2.

8. The method for controlling liquid flow sample loading pressure of a flow cell sorter according to claim 1, characterized in that: The cell sorter liquid flow loading system includes an air pressure feedback controller, which takes the expected air pressure output value and the actual pressure measurement value as input, and outputs a digital signal for controlling the first electrical proportional valve or the second electrical proportional valve through an air pressure feedback control algorithm.

9. The method for controlling liquid flow sample loading pressure of a flow cell sorter according to claim 8, characterized in that: The air pressure feedback controller is an incremental PID controller.

10. The method for controlling liquid flow sample loading pressure of a flow cell sorter according to claim 8, characterized in that: The sample flow path is provided with a first pressure gauge, which is used to monitor the output air pressure P of the first electrical proportional valve in real time. 1实际 The sheath fluid flow path is provided with a second pressure gauge, and the second pressure gauge is used to monitor the output air pressure of the second electrical proportional valve in real time.

Citation Information

Patent Citations

  • Liquid flow focusing control system of flow cytometer

    CN103900944A

  • Flow cytometry analysis device and method

    CN104280328A

  • Liquid flow system, test method, control method of negative pressure device and flow cytometry

    CN110118718A

  • Stable liquid path system of flow cytometer

    CN112730204A

  • Flow cytometric apparatus and method

    US20080250876A1

Cited By

  • Method for monitoring and cleaning blockage of nozzle of flow cytometer

    CN119738137A

  • A flow cell sorter nozzle blockage monitoring and cleaning method

    CN119738137B