WO2013064033A1 - 粒子分析仪及其粒子测试控制方法、装置 - Google Patents

粒子分析仪及其粒子测试控制方法、装置 Download PDF

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Publication number
WO2013064033A1
WO2013064033A1 PCT/CN2012/083512 CN2012083512W WO2013064033A1 WO 2013064033 A1 WO2013064033 A1 WO 2013064033A1 CN 2012083512 W CN2012083512 W CN 2012083512W WO 2013064033 A1 WO2013064033 A1 WO 2013064033A1
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Prior art keywords
sample
counting
test
control
plugging
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Ceased
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PCT/CN2012/083512
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English (en)
French (fr)
Inventor
申涛
石汇林
滕锦
郭文恒
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen Mindray Bio Medical Electronics Co Ltd
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Shenzhen Mindray Bio Medical Electronics Co Ltd
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Filing date
Publication date
Application filed by Shenzhen Mindray Bio Medical Electronics Co Ltd filed Critical Shenzhen Mindray Bio Medical Electronics Co Ltd
Priority to US14/355,547 priority Critical patent/US9714916B2/en
Publication of WO2013064033A1 publication Critical patent/WO2013064033A1/zh
Anticipated expiration legal-status Critical
Priority to US15/603,384 priority patent/US10613051B2/en
Priority to US16/831,619 priority patent/US11644436B2/en
Priority to US18/138,230 priority patent/US20240125734A1/en
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/4163—Systems checking the operation of, or calibrating, the measuring apparatus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects
    • G01N15/12—Investigating individual particles by measuring electrical or magnetic effects by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects
    • G01N15/12—Investigating individual particles by measuring electrical or magnetic effects by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
    • G01N2015/137—Cleaning
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects
    • G01N15/12—Investigating individual particles by measuring electrical or magnetic effects by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
    • G01N2015/138—Detecting blocking debris

Definitions

  • the invention relates to the field of biochemical analysis, in particular to a particle analyzer and a test control method thereof.
  • Particle analyzers are used in the field of biochemical analysis involved in medical or biochemical research. They are used to classify and count the tiny particles of each component in the mixture, and more common particle analyzers such as blood cell analyzers.
  • a blood cell analyzer is an instrument for counting and classifying human blood cells by adding a quantitative blood sample to a certain amount of a diluent having a cell morphology and a conductive property, and then the mixed liquid is The micro-pores are driven by the power driving source. Because the cells have weak conductive properties, the equivalent impedance in the micro-holes will become larger when passing through the micro-holes.
  • the voltage changes and the impedance
  • the change is proportional, that is, the waveform of the voltage reflects the impedance change process of the particles passing through the micropore.
  • a voltage pulse is generated.
  • the height of the voltage pulse reflects the volume of the particle, so according to the voltage pulse.
  • the amplitude classifies the particles. This measurement method is referred to as the impedance method.
  • the microporous element used in the detection process is a valuable element with a pore diameter of 50-120 um. Due to its small pore size, the micropores are easily infected by various proteins, cell debris and blood in the blood during the detection process. Clots, oily lipids, and debris formed during the puncture of the test tube are clogged. This condition is called plugging, which can affect the reliability of the instrument's detection function.
  • the current blood cell analyzer test procedure and timing are shown in Figure 1. First, the first sample and the specified dilution are added to the reaction cell for dilution and incubation, and then the diluted quantitative sample is injected from the reaction cell.
  • the current treatment method is to re-position the first sample that has been blocked by the manual or sample rack retraction mechanism to the position to be tested.
  • the invention provides a particle analyzer and a test control method and device thereof for reducing the probability of plugging.
  • a particle analyzer test control method comprising:
  • the dosing system is controlled to suck the sample from the reaction tank again and inject into the counting pool, and then restart the impedance counting test on the sample in the counting pool.
  • a particle test control apparatus for a particle analyzer comprising:
  • a first control unit configured to control the dosing system to draw the diluted sample from the reaction pool and inject into the counting pool;
  • a second control unit coupled to the first control unit for controlling the liquid discharge control valve of the reaction tank to remain in a closed state after the first control unit controls the liquid addition system to draw the diluted sample from the reaction chamber, so that the remaining dilution The subsequent sample remains in the reaction cell;
  • a third control unit coupled to the first control unit, for controlling the sample in the counting pool to start an impedance method counting test after the sample is injected into the counting pool;
  • the plugging monitoring unit is configured to receive the sample to perform the micropore voltage output during the impedance method of the impedance test, determine whether a plugging occurs, and output a plugging event when the plugging occurs;
  • the fourth control unit is coupled to the plugging hole monitoring unit, configured to control the pause test according to the plugging event, and perform the plugging operation, and output a control signal to the first control unit after the plugging operation is completed, so that the first control unit controls the adding
  • the liquid system again draws the sample from the reaction cell and injects it into the counting cell.
  • a particle analyzer is also provided, including:
  • reaction tank for diluting a sample injected therein, the reaction tank comprising a pipette, an outlet pipe and a drain pipe, the drain pipe being provided with a switchable state between the closed state and the open state according to the control signal Switched drain control valve;
  • An impedance method counting test system comprising a counting pool, wherein the impedance method counting test system performs an impedance method counting test on a sample injected into the counting pool, and outputs a micropore voltage;
  • a dosing system for drawing a diluted sample from the reaction cell and injecting it into the counting cell
  • a signal processing and control device for receiving a micropore voltage and performing shaping processing and signal recognition, the signal processing and control device being configured to control after the dosing system draws the diluted sample from the reaction cell and injects into the counting pool
  • the drain control valve of the reaction tank is maintained in a closed state, so that the remaining diluted sample remains in the reaction tank, and whether the plugging occurs according to the micropore voltage during the counting test is controlled, and when the plugging occurs, the control is performed. Suspend the test of the next sample and perform the plugging operation. After the plugging operation is completed, the dosing system is controlled to take the sample from the reaction tank again and inject it into the counting pool, and then restart the impedance counting of the sample in the counting pool. test.
  • a particle test control method for a particle analyzer comprising:
  • the sucked sample is subjected to multi-stage dilution by injecting into a plurality of reaction cells until a diluted sample conforming to the dilution ratio is formed in the last stage reaction cell;
  • a diluted sample that meets the dilution ratio is obtained in a reaction cell in which the remaining diluted sample is left;
  • the diluted sample that meets the dilution ratio is injected into the counting cell, and then the sample in the counting cell is restarted for the impedance counting test.
  • a particle test control method for a particle analyzer comprising:
  • the dosing system is controlled to inject the diluted sample retained therein into the counting pool, and then restart the impedance counting test on the samples in the counting pool.
  • FIG. 1 is a test sequence diagram of a blood cell analyzer in an embodiment
  • FIG. 2 is a schematic structural view of a blood cell analyzer according to an embodiment of the present invention.
  • Figure 3 is a schematic diagram of particle identification and statistical results
  • 4a is a schematic diagram of a stable electric field formed by a constant current source
  • Figure 4b is a schematic diagram of a pulse signal formed when blood cells pass through the micropore
  • Figure 4c is a schematic diagram showing the increase of the micropore voltage when the hole is blocked
  • Figure 4d is a schematic diagram of abnormal fluctuation of micropore voltage when plugging holes
  • FIG. 5a is a schematic structural diagram of a particle test control apparatus according to an embodiment of the present invention.
  • FIG. 5b is a schematic structural diagram of a particle test control apparatus according to another embodiment of the present invention.
  • FIG. 6 is a flow chart of particle testing in an embodiment of the present invention.
  • FIG. 7 is a flow chart of monitoring a plugging hole according to an embodiment of the present invention.
  • Figure 8 is a timing chart of testing of a blood cell analyzer in an embodiment of the present invention.
  • Figure 10 is a flow chart of particle testing in accordance with yet another embodiment of the present invention.
  • the relevant test information is monitored in real time during the counting process of the particles, and the test of the sample is suspended after the hole is found, and the plugging process is immediately performed, and then the diluted sample remaining after the sample is diluted is used for the second time.
  • the secondary test avoids the sample from being able to output the test result due to the plugging that occurs during the first measurement, and does not need to reposition the sample to the position to be tested for re-absorption and heavy dilution, thereby reducing the probability of plugging.
  • the method of fully utilizing the diluted sample remaining after dilution of the sample may be that the sample remaining in the reaction pool is not immediately discharged after the sample is taken from the reaction pool, but is waited for the sample test result to be discharged. If there is a plugging during the test, the remaining diluted sample is taken from the reaction tank after the plugging for the second test.
  • the method of making full use of the diluted sample remaining after dilution of the sample may also be to utilize the remaining diluted sample stored in the dosing system conduit from the reaction cell to the counting cell.
  • the particle analyzer is described below as an example of a blood cell analyzer.
  • the blood cell analyzer includes a reaction cell 2, a dosing system 3, an impedance method counting test system 4, and a signal processing and control device 5.
  • the sample loading system 1 performs aspirating operation on the sample placed at the position to be tested, draws a quantitative sample, and injects the aspirated sample into the reaction cell 2, and the reaction cell 2 dilutes the sample and the diluent injected therein, Multi-stage dilution is performed until the desired dilution ratio is reached.
  • the impedance method counting test system 4 includes a counting cell 41.
  • the reaction cell 2 adds the diluted sample to the counting cell 41 through the dosing system 3, and the impedance method counting test system 4 performs an impedance method counting test on the sample in the injection counting cell 41, and outputs Micropore voltage.
  • the reaction cell 2 includes an inlet pipe 21, an outlet pipe 22, and a drain pipe 23, and an inlet pipe 21 and a coupling system 1 coupled to the dosing system 3 for draining
  • the pipe 23 is provided with a drain control valve 231 that is switchable between a closed state and an open state in accordance with a control signal.
  • the impedance method counting test system 4 includes a counting cell 41, a power source driver 42 and an anode electrode 43, and a cathode electrode 44.
  • the counting cell 41 includes a front cell 411, a back cell 412, and a micropore element 413 between the front cell 411 and the back cell 412. .
  • the counting cell front cell 411 and the counting cell back cell 412 contain an electrolytic solution 45, one end of which is located in the pre-particle counting cell 411, and one end of the cathode electrode 44 is located in the particle counting back cell 412, and the anode electrode 43
  • the other end and the other end of the cathode electrode 44 are connected to the output of the power source drive 42, which is typically a constant current source.
  • the counting pool rear tank 412 is further provided with a liquid outlet 414 that communicates with the negative pressure chamber.
  • the signal processing and control device 5 receives the micropore voltage and performs processing such as shaping processing and signal recognition, and finally forms identification and statistical results. For example, as shown in FIG. 3, the result can be directly printed out or output to the display for the operator to view. Identification and statistical results can also be stored for later review.
  • the instrument takes a quantitative blood sample from the blood collection tube and mixes it with the quantitative dilution solution in the reaction tank to form a diluted blood sample with a fixed dilution ratio; then, a certain amount of the diluted blood sample is injected from the reaction tank into the counting pool for impedance counting, and then the count is obtained. result.
  • a certain amount of reagent is mixed to form a second diluted sample, and then flows from the front cell 411 through the micropores in the micropore element 413 to the back pool 412 under the action of the negative pressure.
  • the diluted blood sample flows from the front pool 411 into the back pool 412 to form a stable flow field.
  • FIG. a Since a constant current source is applied between the anode electrode 43 and the cathode electrode 44, a stable electric field is formed, as shown in FIG. a is shown.
  • a pulse signal is formed when blood cells pass through the microwell, as shown in Figure 4b.
  • the micropore voltage rises or fluctuates abnormally when foreign matter is blocked in front of the microporous element, as shown in Figures 4c and 4d.
  • the signal processing and control device 5 is further configured to control the drain control valve 231 of the reaction cell 2 to be maintained after the dosing system 3 draws the diluted sample from the reaction cell 2 and injects into the counter cell 41. In the off state, the remaining diluted sample remains in the reaction cell 2, and whether the plugging occurs according to the micropore voltage during the counting test, and the control of the next sample is suspended when the plugging occurs. And performing the plugging operation, after the draining operation is completed, the dosing system 3 is controlled to take the sample from the reaction cell 2 again and inject it into the counting cell 41, and then restart the impedance counting test on the sample in the counting cell 41.
  • the signal processing and control device includes a particle test control device 50.
  • the particle test control device 50 includes a first control unit 51, a second control unit 52, a third control unit 53, and a block. Hole monitoring unit 54 and fourth control unit 55.
  • the first control unit 51 is configured to control the dosing system 3 to draw the diluted sample from the reaction cell and inject into the counting cell;
  • the second control unit 52 is coupled to the first control unit 51 for controlling the dosing system at the first control unit 51.
  • the drain control valve 231 controlling the reaction cell continues to be in a closed state so that the remaining diluted sample remains in the reaction cell;
  • the third control unit 53 is coupled to the first control unit 51.
  • the sample in the counting pool starts the impedance method counting test, which may also be referred to as a data acquisition control unit;
  • the blocking hole monitoring unit 54 is configured to receive the sample for the impedance method. Counting the micropore voltage output during the test to determine whether a plugging occurs, and outputting a plugging event when the plugging occurs;
  • the fourth control unit 55 is coupled to the plugging monitoring unit 54 for controlling the pause of the sample according to the plugging event Testing, and performing the plugging operation, outputting a control signal to the first control unit 51 after the draining operation is completed, so that the first control unit 51 controls the liquid adding system to reverse again Sample injection and suction cell counting cell.
  • the first control unit 51 controls the liquid adding system to take the sampling from the reaction pool again, and then controls the second control unit 52 to output the emptying control signal, and controls the liquid discharging control valve of the reaction pool to switch to the open state to evacuate the remaining in the reaction pool.
  • the diluted sample is controlled.
  • the first control unit 51 may be a motor control unit that controls the motor operation of the liquid addition system 3 to draw the diluted sample from the reaction chamber and inject it into the counting pool as a motor control.
  • the unit which can also control other parts of the motor according to control commands, such as the impedance method to count the motor in the test system.
  • the second control unit 52 may be a valve control unit for controlling the closing and opening of the drain control valve 231 of the reaction cell.
  • the valve control unit may also control other parts of the control valve according to the control command, such as controlling impedance counting. Test the valve in the system or the valve in the dosing system 3.
  • the particle test control device further includes a timer 56 coupled to the third control unit 53 and the fourth control unit 55, respectively, the third control unit 53 being in the counter pool
  • the control timer 56 starts counting.
  • the timer 56 outputs a timing signal to the fourth control unit 55 after the timing reaches the set time, and the fourth control unit 55 receives the set time.
  • the plugging event is reached, the test of the suspended sample is controlled, and the draining operation is performed, and after the draining operation is completed, the control signal is output to the first control unit 51, so that the first control unit 51 controls the liquid adding system 3 to again from the reaction pool. Sampling the sample and injecting it into the counting cell.
  • the second control unit 52 is controlled to output the emptying control signal, and the drain control valve 231 of the control reaction tank is switched to the open state to evacuate the reaction pool. The remaining diluted sample.
  • the timer may be integrated in the signal processing and control device, may be integrated in the particle test control device, may not be integrated in the particle test control device, or may exist as a discrete component outside the signal processing and control device.
  • the method of testing the particles is as shown in FIG. 6, and includes the following steps:
  • step S61 the sample suction system is controlled to perform a sample suction operation on the sample placed in the position to be tested.
  • step S62 the aspirated sample is injected into the reaction cell for dilution.
  • step S63 the dosing system is controlled to draw the diluted sample from the reaction cell and inject into the counting cell, while controlling the liquid discharging control valve of the reaction cell to remain in the closed state, so that the remaining diluted sample remains in the reaction cell.
  • Step S64 performing an impedance method counting test on the samples in the counting pool, and performing step S65 in the counting test.
  • step S65 it is determined whether a hole blocking event occurs. If a hole blocking event occurs, step S66 is performed, otherwise step S68 is performed.
  • the plugging event is output.
  • the set time may be the time T of the extracted diluted sample all passing through the microwell, or may be less than the time T of the extracted diluted sample all passing through the microwell.
  • the set time can be determined according to the performance of the instrument and the subsequent algorithm for signal extraction and recognition. It is sufficient to collect accurate and reliable particle counts and classifications according to the signals collected during the set time. For example, the extracted diluted samples are all passed.
  • the time of the micropore is T, and the set time can be T/2 depending on the performance of the instrument and the algorithm used for subsequent signal extraction and recognition.
  • the process of monitoring the plugging holes within the set time is as shown in FIG. 7, and includes the following steps:
  • Step S71 starting timing after starting the test by using the impedance method
  • step S72 it is determined whether the set time is up. If the set time is up, step S74 is executed to output the emptying control signal, otherwise step S73 is performed to determine the micropore voltage detected in real time.
  • step S73 the micropore voltage detected in real time is judged during the counting test.
  • step S75 is performed to output a plugging event. Otherwise, the process proceeds to step S72.
  • step S66 when the plugging event occurs, the sample test is suspended, including the ongoing sample test and the test of the next sample, and the plugging operation is performed.
  • Step S67 after the plugging operation is completed, the dosing system is controlled to suck the sample from the reaction pool again and inject into the counting pool, and then restart the impedance counting test on the sample in the counting pool.
  • the emptying control signal can also be output, and step S68 is performed. Or continue to monitor whether a plugging event occurs during the impedance measurement test of the sample in the counting pool again, until step S68 is performed after the sample test is successful.
  • step S68 the drain control valve of the control reaction tank is switched to the open state to evacuate the remaining diluted sample in the reaction tank.
  • the micropore voltage detected in real time it is determined that there are various schemes for blocking the hole.
  • the micropore voltage can be determined according to the combination of the amplitude of the micropore voltage detected in real time, the baseline voltage, and the pulse shape. Whether it is abnormal or not, it is judged that a hole is blocked when the voltage is abnormal. E.g:
  • Determining whether a hole is blocked according to the amplitude of the micropore voltage detected in real time includes the following steps: comparing the amplitude of the micropore voltage with a first threshold; and when the amplitude of the micropore voltage exceeds the first threshold, recording the amplitude of the micropore exceeds a duration of the first threshold; comparing the duration to a second threshold; and determining that a plugging event occurs when the duration exceeds the second threshold.
  • the step of determining a baseline voltage of the micropore voltage detected in real time includes: calculating a baseline voltage of the micropore voltage; comparing the baseline voltage with a third threshold; and considering that the baseline voltage is greater than a third threshold Hole event.
  • the test sequence of the sample can be as shown in Figure 8.
  • the quantitative reagent and the quantified blood sample of the first sample are separately injected into the reaction tank for mixing and incubation to obtain a dilution that meets the prescribed dilution ratio.
  • sample. A quantitative dilution sample is taken from the reaction tank and injected into the counting cell for counting test.
  • the reaction tank is not immediately emptied, but the discharge control valve of the control tank is maintained in the closed state, so that the remaining diluted sample remains in the reaction tank.
  • the second test is used after plugging. During the test, it is monitored whether the hole is blocked within the set time.
  • the diluted sample is taken from the reaction tank for the second time to be injected into the counting pool for counting test. If the plugging is not performed within the set time, or after the second dilution of the diluted sample is taken from the reaction tank, the control tank is controlled to switch to the open state, and the reaction tank is evacuated. The evacuated reaction cell is cleaned, and then the second sample is tested, and the quantitative reagent and the quantified second sample blood sample are separately injected into the reaction cell for mixing and incubation.
  • the remaining sample can be extracted for the second time after the first dilution of the sample, so it is not necessary to find the sample that has been blocked and place it again.
  • the sample to be tested is subjected to re-absorption and re-dilution, thereby reducing the probability of plugging. And because there is no second blood sample, the sample demand is reduced, reducing the minimum blood draw requirement of the test subject.
  • the cell analyzer has a plurality of reaction cells of multiple dilutions, and the method of testing the particles is as shown in FIG. 9, and includes the following steps:
  • step S91 the sample suction system is controlled to perform a sample suction operation on the sample placed in the position to be tested.
  • step S92 the aspirated sample is subjected to multi-stage dilution by injecting into a plurality of reaction cells until a diluted sample conforming to the dilution ratio is formed in the final stage reaction cell.
  • the dilution of the sample is not completed in one reaction cell, and multi-stage dilution is required through multiple reaction cells, that is, the quantitative sample and the quantitative reagent are separately injected into the first reaction cell to perform the first-stage mixing.
  • incubating then taking a quantitative first-stage dilution sample from the first reaction cell and then injecting the quantitative reagent into the second reaction cell for the second-stage mixing and incubation, until a diluted sample conforming to the dilution ratio is formed.
  • the diluted sample in the last stage of the reaction is the diluted sample that meets the dilution ratio.
  • Step S93 controlling the liquid adding system to take the diluted sample from the last stage reaction pool and injecting into the counting pool, and controlling the liquid discharging control valve of at least one of the plurality of reaction cells to remain in the closed state, so that the remaining diluted sample is Continue to remain in the reaction cell.
  • the drain control valve of the last stage reaction tank can be kept in the closed state, and the remaining dilution sample can be kept in the last stage reaction tank, and the discharge control valve of the other stage reaction tank can be kept closed. The remaining intermediate level of diluted sample is retained in the reaction cell.
  • Step S94 performing an impedance method counting test on the samples in the counting pool.
  • step S95 it is monitored whether a plugging event occurs during the counting test.
  • the scheme for judging whether or not a plugging event occurs may be the same as the above embodiment.
  • step S96 when the plugging event occurs, the test of the suspended sample is controlled, and the plugging operation is performed.
  • step S97 a diluted sample conforming to the dilution ratio is obtained in the reaction cell in which the remaining diluted sample is left. If, in step S93, the remaining diluted sample is retained in the last stage of the reaction, the diluted sample is taken from the last stage of the reaction, which is originally a diluted sample that meets the dilution ratio, so that dilution is not required. If in step S93, the remaining intermediate level dilution sample is retained in the other stage of the reaction cell, the diluted sample is taken from the reaction cell, but since the extracted diluted sample is not yet a diluted sample that meets the dilution ratio, it is also required Dilute until a diluted sample that meets the dilution ratio is formed. The diluted sample that meets the dilution ratio is injected into the counting cell, and then the sample in the counting cell is restarted to perform the impedance counting test again.
  • step S98 all reaction cells are emptied.
  • steps S67 and S72 determine whether or not a hole is blocked.
  • the cell analyzer has a long pipe dosing system, and the method of testing the particles is as shown in FIG. 10, and includes the following steps:
  • Step S101 the sample suction system is controlled to perform a sample suction operation on the sample placed in the position to be tested.
  • step S102 the sucked sample is injected into the reaction cell for dilution.
  • step S103 the dosing system is controlled to draw the diluted sample from the reaction cell and inject into the counting cell, while allowing the dosing system to retain the partially diluted sample.
  • a control valve can be provided in the pipe of the dosing system. When the diluted sample is added to the counting cell for the first time, the control valve disposed at both ends of the pipe can be closed, so that the remaining diluted sample in the pipe is closed in the pipe.
  • the control valves at both ends of the control line are opened and the remaining diluted sample in the line is injected into the counting cell. It is also possible to set the control valve only at the end of the dosing system close to the counting cell. After the diluted sample is added to the counting cell for the first time, the valve is closed, so that the remaining diluted sample in the pipe is enclosed in the pipe, when the second is needed. When the diluted sample is added to the counting cell, the valve is controlled to open and the remaining diluted sample in the pipe is injected into the counting cell.
  • a syringe or pneumatic device can be used to connect the dosing system to control the discharge of the diluted sample to the counting cell or to remain in the tubing of the dosing system by controlling the movement of the syringe or pneumatic device.
  • Step S104 performing an impedance method counting test on the samples in the counting pool, and monitoring whether a plugging event occurs during the counting test.
  • the scheme for judging whether or not a plugging event occurs may be the same as the above embodiment.
  • step S105 when a plugging event occurs, the test is suspended and the draining operation is performed.
  • Step S106 after the draining operation is completed, the dosing system is controlled to inject the diluted sample retained therein into the counting pool, and then restart the impedance method counting test on the samples in the counting pool.
  • reaction cell it is not necessary to consider when the reaction cell is emptied, and the reaction cell may be emptied after the sample is taken therefrom for the first time, or may be emptied for some time.
  • steps S67 and S72 determine whether or not a hole is blocked.
  • the particle test control device 50 controls the changeover switch 45 to switch from the power source drive 42 to the ignition circuit 46, thereby forming a local high temperature at the micropores of the microporous member, even making the liquid Boiling, thereby destroying the foreign body structure near the micropores.
  • the voltage on both sides of the micropore element in the measurement process is monitored in real time during the counting process; when the voltage on both sides of the microporous element is abnormally increased or abnormally fluctuated, it is considered that the micropore has been blocked at the time.
  • the sample test is suspended (in continuous injection mode), and after the necessary action is completed, the plugging process is performed immediately, and then the retained sample is re-extracted to dilute the remaining diluted sample for the first time and retested. .
  • the instrument automatically resumes testing for the next sample.
  • the particle analyzer may be another body fluid analyzer such as an analysis station or a urine analyzer.

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Abstract

一种离子分析仪及其测试控制方法、装置。该方法包括：在抽取稀释后的样本后保留部分样本，在技术测试过程中监测是否发生堵孔事件；当发生堵孔事件时则控制暂停样本的测试，并执行排堵操作；在排堵操作完成后控制加液系统再次从反应池或加液系统的管道中吸取保留的部分样本并注入计数池，然后重新开始对计数池中的样本再次进行阻抗法计数测试。该方法充分利用样本稀释后剩余的稀释样本进行第二次测试，消除该样本第一次测量时发生的堵孔对测试结果的影响，并且不需要将该样本重新放置到待测试位进行重吸样和重稀释，从而降低了堵孔概率。以及使用该方法的装置。

Description

粒子分析仪及其粒子测试控制方法、装置
【技术领域】
本发明涉及生化分析领域，尤其涉及一种粒子分析仪及其测试控制方法。
【背景技术】
粒子分析仪应用于医疗或生化研究中所涉及的生化分析领域，其用于对混合液中的各组成微小粒子进行分类统计，比较常见的粒子分析仪如血液细胞分析仪。血液细胞分析仪是一种对人体血液细胞进行计数和分类的仪器，其测量方法为：将定量的血液样本加入一定量的具保持细胞形态作用和导电特性的稀释液中，然后此混合液体在动力驱动源的作用下通过微孔，因细胞具有较弱的导电特性，故其通过微孔时微孔内的等效阻抗将变大，在恒流源的作用下，电压的变化与阻抗的变化成正比例，即电压的波形反映了粒子通过微孔过程中的阻抗变化过程，粒子通过微孔时会产生一个电压脉冲，此电压脉冲的高度即反映了粒子的体积大小，因此根据电压脉冲的幅度可对粒子进行分类。此测量方法简称阻抗法。
在检测过程中用到的微孔元件是一种孔径在50—120um之间的贵重元件，由于其孔径很小，在检测过程中，微孔容易被血液中的各类蛋白、细胞碎片、血凝块、油性脂类以及试管帽穿刺过程中形成的碎屑等堵塞，这种情况称为堵孔，堵孔会影响仪器的检测功能的可靠性。目前血液细胞分析仪的测试流程和时序如图1所示，首先将第一个样本和规定的稀释液加入到反应池中进行稀释和孵育，然后从反应池中抽取稀释后的定量的样本注入计数池，一边对抽取的样本进行阻抗法测试，另一边同时控制排空反应池，等待第二个样本的加入，在第二个样本吸样后，将第二个样本和规定的稀释液加入到反应池中，开始第二个样本的稀释和孵育。而当第一个样本在进行阻抗法测试过程中发生堵孔时，目前的处理方式为：将发生堵孔的第一个样本通过人工或样本架回退机制重新放置到待测试位重新进行吸样操作，并将吸取的第一个样本和规定的稀释液加入到反应池中进行稀释和孵育，然后再从反应池中抽取稀释后的定量的样本，对抽取的样本注入计数池，重新进行阻抗法计数。样本因发生堵孔而导致无法输出测试结果的概率称为堵孔概率。目前对堵孔后的处理方式不但操作复杂，而且对样本的采集量要求也高，对于连续进样的系统，也提高了其控制的复杂程度。因此如何降低堵孔概率，是血液细胞分析仪设计时需要考虑的一个问题。
【发明内容】
本发明提供一种粒子分析仪及其测试控制方法、装置，用于降低堵孔概率。
根据本发明的一方面，提供一种粒子分析仪测试控制方法，包括：
控制吸样系统对放置在待测试位的样本进行吸样操作；
将吸取的样本注入反应池进行稀释；
控制加液系统从反应池吸取稀释后的样本并注入计数池，同时控制反应池的排液控制阀继续处于关闭状态，以使剩余的稀释后的样本继续保留在反应池中；
对计数池中的样本进行阻抗法计数测试，并在计数测试过程中监测是否发生堵孔事件；
当发生堵孔事件时则控制暂停下一样本的测试，并执行排堵操作；
在排堵操作完成后控制加液系统再次从反应池中吸取样本并注入计数池，然后重新开始对计数池中的样本进行阻抗法计数测试。
根据本发明的另一方面，还提供一种用于粒子分析仪的粒子测试控制装置,包括：
第一控制单元，用于控制加液系统从反应池吸取稀释后的样本并注入计数池；
第二控制单元，耦合到第一控制单元，用于在第一控制单元控制加液系统从反应池吸取稀释后的样本后控制反应池的排液控制阀继续处于关闭状态，以使剩余的稀释后的样本继续保留在反应池中；
第三控制单元，耦合到第一控制单元，用于在样本注入计数池后控制计数池中的样本开始阻抗法计数测试；
堵孔监测单元，用于接收样本进行阻抗法计数测试过程中输出的微孔电压，判断是否发生堵孔，当发生堵孔时则输出堵孔事件；
第四控制单元，耦合到堵孔监测单元，用于根据堵孔事件控制暂停测试，并执行排堵操作，在排堵操作完成后输出控制信号至第一控制单元，使第一控制单元控制加液系统再次从反应池中吸取样本并注入计数池。
还提供一种粒子分析仪，包括：
反应池，用于对注入其中的样本进行稀释，所述反应池包括吸液管、出液管和排液管，所述排液管上设置有可根据控制信号在关闭状态和打开状态之间切换的排液控制阀；
阻抗法计数测试系统，其包括计数池，所述阻抗法计数测试系统对注入计数池的样本进行阻抗法计数测试，输出微孔电压；
加液系统，其用于从反应池吸取稀释后的样本并注入计数池；
信号处理及控制装置，其用于接收微孔电压并进行整形处理和信号识别，所述信号处理及控制装置被配置为在加液系统从反应池吸取稀释后的样本并注入计数池后仍控制反应池的排液控制阀维持在关闭状态，以使剩余的稀释后的样本继续保留在反应池中，并在计数测试过程中根据微孔电压监测是否发生堵孔，当发生堵孔时则控制暂停下一样本的测试，并执行排堵操作，在排堵操作完成后控制加液系统再次从反应池中吸取该样本并注入计数池，然后重新开始对计数池中的该样本进行阻抗法计数测试。
在另一种实施例中，还提供一种用于粒子分析仪的粒子测试控制方法,包括：
控制吸样系统对放置在待测试位的样本进行吸样操作；
将吸取的样本通过注入多个反应池进行多级稀释，直到在最末级反应池中形成符合稀释比的稀释样本；
控制加液系统从最末级反应池吸取稀释后的样本并注入计数池，控制多个反应池中的至少一个的排液控制阀继续处于关闭状态，以使剩余的稀释后的样本继续保留在该反应池中；
对计数池中的样本进行阻抗法计数测试，并在计数测试过程中监测是否发生堵孔事件；
当发生堵孔事件时则控制暂停样本的测试，并执行排堵操作；
基于留有剩余的稀释后的样本的反应池中得到符合稀释比的稀释样本；
将符合稀释比的稀释样本注入计数池，然后重新开始对计数池中的样本进行阻抗法计数测试。
在又一种实施例中，还提供一种用于粒子分析仪的粒子测试控制方法,包括：
控制吸样系统对放置在待测试位的样本进行吸样操作；
将吸取的样本注入反应池进行稀释；
控制加液系统从反应池吸取稀释后的样本，然后将稀释后的样本的一部分注入计数池，并使加液系统保留剩余的稀释后的样本；
对计数池中的样本进行阻抗法计数测试，并在计数测试过程中监测是否发生堵孔事件；
当发生堵孔事件时则控制暂停样本的测试，并执行排堵操作；
在排堵操作完成后控制加液系统将其中保留的稀释后样本注入计数池，然后重新开始对计数池中的样本进行阻抗法计数测试。
【附图说明】
图1为一种实施例中血液细胞分析仪的测试时序图；
图2为本发明一种实施例中血液细胞分析仪的结构示意图；
图3为粒子识别和统计结果示意图；
图4a为恒流源形成的稳定电场示意图；
图4b为血细胞通过微孔时形成的脉冲信号示意图；
图4c为堵孔时微孔电压升高示意图；
图4d为堵孔时微孔电压异常波动示意图；
图5a为本发明一种实施例中粒子测试控制装置的结构示意图；
图5b为本发明另一种实施例中粒子测试控制装置的结构示意图；
图6为本发明一种实施例中粒子测试流程图；
图7为本发明一种实施例中监测堵孔的流程图；
图8为本发明一种实施例中血液细胞分析仪的测试时序图；
图9为本发明另一种实施例中粒子测试流程图；
图10为本发明又一种实施例中粒子测试流程图。
【具体实施方式】
下面通过具体实施方式结合附图对本发明作进一步详细说明。
在本发明实施例中，在对粒子计数过程中对相关测试信息实时监控，在发现堵孔后暂停样本的测试，立刻进行排堵处理，之后充分利用该样本稀释后剩余的稀释样本进行第二次测试，避免该样本因第一次测量时发生的堵孔而无法输出测试结果，并且不需要将该样本重新放置到待测试位进行重吸样和重稀释，从而降低了堵孔概率。
对该样本稀释后剩余的稀释样本进行充分利用的方法可以是在从反应池中抽取样本后并不立即将反应池中剩余的样本排放掉，而是等待可得出该样本测试结果后再排放掉，在测试期间如果发生堵孔，则在排堵后从反应池中抽取剩余的稀释样本进行第二次测试。对该样本稀释后剩余的稀释样本进行充分利用的方法还可以是利用存放在从反应池到计数池之间的加液系统管道中的剩余的稀释样本。
下面以粒子分析仪为血液细胞分析仪为例进行详细说明。
请参考图2，血液细胞分析仪包括反应池2、加液系统3、阻抗法计数测试系统4和信号处理及控制装置5。加样系统1对放置在待测试位置上的样本进行吸样操作，吸取定量的样本，并将吸取的样本注入到反应池2中，反应池2对注入其中的样本和稀释液进行稀释，可进行多级稀释，直到达到要求的稀释比。阻抗法计数测试系统4包括计数池41，反应池2通过加液系统3将稀释样本加入到计数池41中，阻抗法计数测试系统4对注入计数池41中的样本进行阻抗法计数测试，输出微孔电压。
在本实施例中，反应池2包括进液管21、出液管22和排液管23，进液管21和耦合到加样系统1，出液管22耦合到加液系统3，排液管23上设置有可根据控制信号在关闭状态和打开状态之间切换的排液控制阀231。
阻抗法计数测试系统4包括计数池41、电源驱动42和阳极电极43、阴极电极44，计数池41包括前池411、后池412和位于前池411、后池412之间的微孔元件413。在工作，计数池前池411和计数池后池412中容纳有电解溶液45，阳极电极43的一端位于粒子计数前池411中，阴极电极44的一端位于粒子计数后池412中，阳极电极43的另一端和阴极电极44的另一端连接到电源驱动42的输出端，电源驱动42通常为恒流源。计数池后池412上还设有连通负压室的出液口414。
信号处理及控制装置5接收微孔电压并进行整形处理和信号识别等处理，最后形成识别和统计结果，例如图3所示，该结果可直接打印输出或输出到显示器，以便操作者查看。还可将识别和统计结果进行存储，以便后续查看。
其工作过程是：
仪器从采血管中摄入定量的血样，与定量的稀释液在反应池内混匀，形成固定稀释比的稀释血样；之后从反应池内抽取一定量的稀释血样注入计数池进行阻抗计数，进而得到计数结果。样本注入前池411中时再混合一定量的试剂形成二次稀释样本，然后在负压的作用下，由前池411经微孔元件413中的微孔流到后池412中。计数过程中，稀释后的血样样本从前池411流入到后池412中，形成稳定的流场。由于在阳极电极43和阴极电极44之间加上恒流源，故形成稳定的电场，如图4 a所示。当血细胞通过微孔时会形成脉冲信号，如图4 b所示。当有异物挡在微孔元件前方时微孔电压会升高或异常波动，如图4c和4d所示。
因此本实施例中，所述信号处理及控制装置5还被配置为在加液系统3从反应池2吸取稀释后的样本并注入计数池41后仍控制反应池2的排液控制阀231维持在关闭状态，以使剩余的稀释后的样本继续保留在反应池2中，并在计数测试过程中根据微孔电压监测是否发生堵孔，当发生堵孔时则控制暂停下一样本的测试，并执行排堵操作，在排堵操作完成后控制加液系统3再次从反应池2中吸取该样本并注入计数池41，然后重新开始对计数池41中的该样本进行阻抗法计数测试。
在一种实施例中，信号处理及控制装置包括粒子测试控制装置50，如图5a所示，粒子测试控制装置50包括第一控制单元51、第二控制单元52、第三控制单元53、堵孔监测单元54和第四控制单元55。第一控制单元51用于控制加液系统3从反应池吸取稀释后的样本并注入计数池；第二控制单元52耦合到第一控制单元51，用于在第一控制单元51控制加液系统从反应池吸取稀释后的样本后控制反应池的排液控制阀231继续处于关闭状态，以使剩余的稀释后的样本继续保留在反应池中；第三控制单元53耦合到第一控制单元51，用于在样本注入计数池后控制阻抗法计数测试系统4对计数池中的样本开始阻抗法计数测试，也可称为是数据采集控制单元；堵孔监测单元54用于接收样本进行阻抗法计数测试过程中输出的微孔电压，判断是否发生堵孔，当发生堵孔时则输出堵孔事件；第四控制单元55耦合到堵孔监测单元54，用于根据堵孔事件控制暂停样本的测试，并执行排堵操作，在排堵操作完成后输出控制信号至第一控制单元51，使第一控制单元51控制加液系统再次从反应池中吸取样本并注入计数池。第一控制单元51控制加液系统再次从反应池中吸取样本后控制第二控制单元52输出排空控制信号，控制反应池的排液控制阀切换到打开状态，以排空反应池中剩余的稀释后的样本。
在一种具体实施例中，如图5b所示，第一控制单元51可以是电机控制单元，其控制加液系统3的电机工作从反应池吸取稀释后的样本并注入计数池，作为电机控制单元，其也可以根据控制命令控制其它部分的电机，例如阻抗法计数测试系统中的电机。第二控制单元52可以是阀控制单元，其用于控制反应池的排液控制阀231的关闭与打开，同样，阀控制单元也可以根据控制命令控制其它部分的控制阀，例如控制阻抗法计数测试系统中的阀或加液系统3中的阀。
在一种具体实例中，粒子测试控制装置还包括定时器56，所述定时器56分别耦合到第三控制单元53和第四控制单元55，所述第三控制单元53在对计数池中的样本采用阻抗法开始测试后即控制定时器56开始计时，所述定时器56在计时到达设定时间后输出定时信号至第四控制单元55，所述第四控制单元55在设定时间内接收到堵孔事件时，则控制暂停样本的测试，并执行排堵操作，在排堵操作完成后输出控制信号至第一控制单元51，使第一控制单元51控制加液系统3再次从反应池中吸取样本并注入计数池。如果第四控制单元55在设定时间内没有接收到堵孔事件时则控制第二控制单元52输出排空控制信号，控制反应池的排液控制阀231切换到打开状态，以排空反应池中剩余的稀释后的样本。
上述定时器可以集成在信号处理及控制装置中，可以集成在粒子测试控制装置内，也可以不集成在粒子测试控制装置内，还可以作为分立的元件存在于信号处理及控制装置之外。
基于上述细胞分析仪，在一种实施例中，对粒子进行测试的方法如图6所示，包括以下步骤：
步骤S61，控制吸样系统对放置在待测试位的样本进行吸样操作。
步骤S62，将吸取的样本注入反应池进行稀释。
步骤S63，控制加液系统从反应池吸取稀释后的样本并注入计数池，同时控制反应池的排液控制阀继续处于关闭状态，以使剩余的稀释后的样本继续保留在反应池中。
步骤S64，对计数池中的样本进行阻抗法计数测试，并在计数测试过程中执行步骤S65。
步骤S65，判断是否发生堵孔事件，如果发生堵孔事件，则执行步骤S66，否则执行步骤S68。在一种具体实例中，在对计数池中的样本采用阻抗法开始测试后设定时间内监测到堵孔时，则输出堵孔事件。设定时间可以是抽取的稀释样本全部通过微孔的时间T，也可以是小于抽取的稀释样本全部通过微孔的时间T的一个时间。设定时间可根据仪器的性能和后续采用的信号提取和识别的算法确定，只要根据这段设定时间内收集的信号足以形成准确可靠的粒子计数和分类即可，例如抽取的稀释样本全部通过微孔的时间是T，根据仪器的性能和后续采用的信号提取和识别的算法，设定时间可以是T/2。
在一种具体实例中，在设定时间内监测堵孔的流程如图7所示，包括以下步骤：
步骤S71，在采用阻抗法开始测试后即开始计时；
步骤S72，判断设定时间是否到，若设定时间到，则执行步骤S74，输出排空控制信号，否则执行步骤S73，对实时检测到的微孔电压进行判断。
步骤S73，在计数测试过程中对实时检测到的微孔电压进行判断，当判断微孔电压异常时则执行步骤S75，输出堵孔事件。否则转向执行步骤S72。
步骤S66，当发生堵孔事件时则控制暂停样本测试，包括正在进行的样本测试和下一个样本的测试，并执行排堵操作。
步骤S67，在排堵操作完成后控制加液系统再次从反应池中吸取样本并注入计数池，然后重新开始对计数池中的样本再次进行阻抗法计数测试。再次从反应池中吸取样本后也可以输出排空控制信号，执行步骤S68。或者继续在对计数池中的样本再次进行阻抗法计数测试的过程中监测是否发生堵孔事件，直到样本测试成功后再执行步骤S68。
步骤S68，控制反应池的排液控制阀切换到打开状态，以排空反应池中剩余的稀释后的样本。
根据实时检测到的微孔电压判断是否发生堵孔有多种方案，例如可以根据实时检测到的微孔电压的幅度、基线电压和脉冲形态中的任一种或多种的组合判断微孔电压是否异常，当电压异常时判断为发生堵孔。例如：
根据实时检测到的微孔电压的幅度来判断是否发生堵孔，包括以下步骤：将微孔电压幅度与第一阈值进行比较；当微孔电压幅度超过第一阈值时，记录微孔电压幅度超过第一阈值的持续时间；将所述持续时间与第二阈值进行比较；当所述持续时间超过第二阈值时认为发生堵孔事件。
对实时检测到的微孔电压的基线电压进行判断的步骤包括：计算微孔电压的基线电压；将所述基线电压与第三阈值进行比较；当所述基线电压超过第三阈值时认为发生堵孔事件。
样本的测试时序可以如图8所示，首先对第一个样本进行测试，将定量试剂和定量的第一个样本的血样分别注入反应池中进行混匀和孵育，得到符合规定稀释比的稀释样本。从反应池中抽取定量的稀释样本注入计数池，进行计数测试。在从反应池中抽取定量的稀释样本后并不对反应池立即排空，而是控制反应池的排液控制阀继续维持于关闭状态，以使剩余的稀释后的样本继续保留在反应池中以备发生堵孔后第二次测试用。在测试的过程中监测是否在设定时间内发生堵孔，如果发生，则排堵后从反应池中第二次抽取定量的稀释样本注入计数池，进行计数测试。如果在设定时间内没有发生堵孔，或从反应池中第二次抽取定量的稀释样本后才控制反应池的排液控制阀切换到打开状态，对反应池进行排空。对排空后的反应池进行清洗，然后对第二个样本进行测试，将定量试剂和定量的第二个样本的血样分别注入反应池中进行混匀和孵育。
根据以上分析可知，当样本测试过程中发生堵孔时，可抽取保留的样本第一次稀释时剩余的稀释样本进行第二次测试，所以不需要再将发生堵孔的样本查找出来并再次放置到待测试位进行重吸样和重稀释，从而降低了堵孔概率。并由于不存在第二次抽取血样，所以样本需求量减少，减少了对被测试者最小抽血量的要求。
基于上述细胞分析仪，在另一种实施例中，细胞分析仪具有多级稀释的多个反应池，对粒子进行测试的方法如图9所示，包括以下步骤：
步骤S91，控制吸样系统对放置在待测试位的样本进行吸样操作。
步骤S92，将吸取的样本通过注入多个反应池进行多级稀释，直到在最末级反应池中形成符合稀释比的稀释样本。本实施例中样本的稀释不是在一个反应池内完成的，需要通过多个反应池进行多级稀释，即先将定量的样本和定量的试剂分别注入第一个反应池内进行第一级的混匀和孵育，然后从第一个反应池内抽取定量的一级稀释样本再配以定量的试剂分别注入第二个反应池内进行第二级的混匀和孵育，如此直到形成符合稀释比的稀释样本，最末级反应池中的稀释样本即为符合稀释比的稀释样本。
步骤S93，控制加液系统从最末级反应池吸取稀释后的样本并注入计数池，控制多个反应池中的至少一个的排液控制阀继续处于关闭状态，以使剩余的稀释后的样本继续保留在该反应池中。这种情况下可使最末级反应池的排液控制阀继续处于关闭状态，在最末级反应池保留剩余的稀释样本，也可使其它级的反应池的排液控制阀继续处于关闭状态，在该反应池内保留剩余的中间级别的稀释样本。
步骤S94，对计数池中的样本进行阻抗法计数测试。
步骤S95，在计数测试过程中监测是否发生堵孔事件。判断是否发生堵孔事件的方案可与上述实施例相同。
步骤S96，当发生堵孔事件时则控制暂停样本的测试，并执行排堵操作。
步骤S97，基于留有剩余的稀释后的样本的反应池中得到符合稀释比的稀释样本。如果在步骤中S93中，在最末级反应池保留剩余的稀释样本，则从最末级反应池中抽取稀释样本，该稀释样本原本就是符合稀释比的稀释样本，所以不需要在进行稀释。如果在步骤中S93中，在其它级的反应池内保留剩余的中间级别的稀释样本，则从该反应池内抽取稀释样本，但由于抽取的该稀释样本还不是符合稀释比的稀释样本，所以还需要进行稀释直到形成符合稀释比的稀释样本。将符合稀释比的稀释样本注入计数池，然后重新开始对计数池中的样本再次进行阻抗法计数测试。
步骤S98，排空所有反应池。
本领域技术人员能够理解，前述实施例中的优选的装置或步骤，也适用于本实施例。例如，步骤S67、步骤S72、判断是否发生堵孔的方案等。
基于上述细胞分析仪，在又一种实施例中，细胞分析仪具有较长管道的加液系统，对粒子进行测试的方法如图10所示，包括以下步骤：
步骤S101，控制吸样系统对放置在待测试位的样本进行吸样操作。
步骤S102，将吸取的样本注入反应池进行稀释。
步骤S103，控制加液系统从反应池吸取稀释后的样本并注入计数池，同时使加液系统保留部分稀释后的样本。例如加液系统的管道足够长时，可在管道中保留足够测试用的稀释样本。例如可在加液系统的管道设置控制阀，当第一次将稀释样本加入计数池后，可使设置在管道两端的控制阀关闭，使剩余在管道中的稀释样本被封闭在管道中，当需要第二次将稀释样本加入计数池时，控制管道两端的控制阀打开，剩余在管道中的稀释样本被注入到计数池中。也可以只在加液系统靠近计数池的一端设置控制阀，在第一次将稀释样本加入计数池后，关闭该阀，使剩余在管道中的稀释样本被封闭在管道中，当需要第二次将稀释样本加入计数池时，控制该阀打开打开，剩余在管道中的稀释样本被注入到计数池中。或者，也可以用注射器或气压装置连接加液系统，通过控制注射器或气压装置的运动来控制稀释样本的排放到计数池或保留在加液系统的管道中。
步骤S104，对计数池中的样本进行阻抗法计数测试，并在计数测试过程中监测是否发生堵孔事件。判断是否发生堵孔事件的方案可与上述实施例相同。
步骤S105，当发生堵孔事件时则控制暂停测试，并执行排堵操作。
步骤S106，在排堵操作完成后控制加液系统将其中保留的稀释后的样本注入计数池，然后重新开始对计数池中的样本再次进行阻抗法计数测试。
本实施例中，不需要考虑反应池何时排空，反应池可以在第一次从其中抽取样本后就排空，或者稍微滞后一些时间再排空。
本领域技术人员能够理解，前述实施例中的优选的装置或步骤，也适用于本实施例。例如，步骤S67、步骤S72、判断是否发生堵孔的方案等。
上述实施例中，在对微孔进行排堵时，可以采用以下方法中的一种或多种的组合：
1. 反冲。即设法使后池中的液体以较高速度回流到前池中，从而冲开微孔元件前方的异物；
2. 灼烧。即在在阳极和阴极之间加入强电流。如图2中所示，当需要排堵时，粒子测试控制装置50控制切换开关45从电源驱动42切换到灼烧电路46上，从而在微孔元件的微孔处形成局部高温，甚至使液体沸腾，从而破坏掉微孔附近的异物结构。
上述实施例是在计数过程中实时监控测量过程中的微孔元件两侧的电压；当微孔元件两侧的电压出现异常升高或者异常波动时，即认为此时微孔处发生了堵孔；一旦发现有堵孔发生，暂缓样本测试（连续进样模式时），待必要的动作完成后，立刻进行排堵处理，然后重新抽取保留的样本第一次稀释剩余的稀释样本，并重新测试。对于连续进样的系统，仪器会自动恢复下一个样本的测试。
除了以上举例的血液细胞分析仪外，粒子分析仪还可以是分析站、尿液分析仪等其他体液分析仪。
以上内容是结合具体的实施方式对本发明所作的进一步详细说明，不能认定本发明的具体实施只局限于这些说明。对于本发明所属技术领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干简单推演或替换，都应当视为属于本发明的保护范围。

Claims (20)

  1. 用于粒子分析仪的粒子测试控制方法,其特征在于包括：
    控制吸样系统对放置在待测试位的样本进行吸样操作；
    将吸取的样本注入反应池进行稀释；
    控制加液系统从反应池吸取稀释后的样本并注入计数池，同时控制反应池的排液控制阀继续处于关闭状态，以使剩余的稀释后的样本继续保留在反应池中；
    对计数池中的样本进行阻抗法计数测试，并在计数测试过程中监测是否发生堵孔事件；
    当发生堵孔事件时则控制暂停样本的测试，并执行排堵操作；
    在排堵操作完成后控制加液系统再次从反应池中吸取样本并注入计数池，然后重新开始对计数池中的样本进行阻抗法计数测试。
  2. 如权利要求1所述的方法，其特征在于，控制加液系统再次从反应池中吸取样本后输出排空控制信号，控制反应池的排液控制阀切换到打开状态，以排空反应池中剩余的稀释后的样本。
  3. 如权利要求1或2所述的方法，其特征在于，在对计数池中的样本采用阻抗法开始测试后设定时间内监测到堵孔时，则输出堵孔事件。
  4. 如权利要求1-3中任一项所述的方法，其特征在于，如果在设定时间内没有接收到堵孔事件，则输出排空控制信号，控制反应池的排液控制阀切换到打开状态，以排空反应池中剩余的稀释后的样本。
  5. 如权利要求4所述的方法，其特征在于，所述在计数测试过程中监测是否发生堵孔事件包括：
    在采用阻抗法开始测试后即开始计时；
    在计时过程中对实时检测到的微孔电压进行判断，当判断微孔电压异常时输出堵孔事件；
    判断设定时间是否到，若是则输出排空控制信号，否则继续对实时检测到的微孔电压进行判断。
  6. 如权利要求5所述的方法，其特征在于，对实时检测到的微孔电压进行判断包括：根据实时检测到的微孔电压的幅度、基线电压和脉冲形态中的任一种或多种的组合判断微孔电压是否异常。
  7. 用于粒子分析仪的粒子测试控制装置,其特征在于包括：
    第一控制单元，用于控制加液系统从反应池吸取稀释后的样本并注入计数池；
    第二控制单元，用于在第一控制单元控制加液系统从反应池吸取稀释后的样本后控制反应池的排液控制阀继续处于关闭状态，以使剩余的稀释后的样本继续保留在反应池中；
    第三控制单元，用于在样本注入计数池后控制计数池中的样本开始阻抗法计数测试；
    堵孔监测单元，用于接收样本进行阻抗法计数测试过程中输出的微孔电压，判断是否发生堵孔，当发生堵孔时则输出堵孔事件；
    第四控制单元，耦合到堵孔监测单元，用于根据堵孔事件控制暂停测试，并执行排堵操作，在排堵操作完成后输出控制信号至第一控制单元，使第一控制单元控制加液系统再次从反应池中吸取样本并注入计数池。
  8. 如权利要求7所述的装置，其特征在于，所述第一控制单元控制加液系统再次从反应池中吸取样本后控制第二控制单元输出排空控制信号，控制反应池的排液控制阀切换到打开状态，以排空反应池中剩余的稀释后的样本。
  9. 如权利要求7或8所述的装置，其特征在于，所述粒子测试控制装置还包括定时器，所述定时器分别耦合到第三控制单元和第四控制单元，所述第三控制单元在对计数池中的样本采用阻抗法开始测试后即控制定时器开始计时，所述定时器在计时到达设定时间后输出定时信号至第四控制单元，所述第四控制单元在设定时间内接收到堵孔事件时，则控制暂停样本的测试，并执行排堵操作，在排堵操作完成后输出控制信号至第一控制单元，使第一控制单元控制加液系统再次从反应池中吸取样本并注入计数池。
  10. 如权利要求9所述的装置，其特征在于，所述第四控制单元在设定时间内没有接收到堵孔事件时则控制第二控制单元输出排空控制信号，控制反应池的排液控制阀切换到打开状态，以排空反应池中剩余的稀释后的样本。
  11. 如权利要求10所述的装置，其特征在于，所述在计数测试过程中监测是否发生堵孔事件包括：
    在采用阻抗法开始测试后即开始计时；
    在计时过程中对实时检测到的微孔电压进行判断，当判断微孔电压异常时输出堵孔事件；
    判断设定时间是否到，若是则输出排空控制信号，否则继续对实时检测到的微孔电压进行判断。
  12. 如权利要求11所述的装置，其特征在于，对实时检测到的微孔电压进行判断包括：根据实时检测到的微孔电压的幅度、基线电压和脉冲形态中的任一种或多种的组合判断微孔电压是否异常。
  13. 一种粒子分析仪, 其特征在于包括：
    反应池，用于对注入其中的样本进行稀释，所述反应池包括吸液管、出液管和排液管，所述排液管上设置有可根据控制信号在关闭状态和打开状态之间切换的排液控制阀；
    阻抗法计数测试系统，其包括计数池，所述阻抗法计数测试系统对注入计数池的样本进行阻抗法计数测试，输出微孔电压；
    加液系统，其用于从反应池吸取稀释后的样本并注入计数池；
    信号处理及控制装置，其用于接收微孔电压并进行整形处理和信号识别，所述信号处理及控制装置被配置为在加液系统从反应池吸取稀释后的样本并注入计数池后仍控制反应池的排液控制阀维持在关闭状态，以使剩余的稀释后的样本继续保留在反应池中，并在计数测试过程中根据微孔电压监测是否发生堵孔，当发生堵孔时则控制暂停下一样本的测试，并执行排堵操作，在排堵操作完成后控制加液系统再次从反应池中吸取该样本并注入计数池，然后重新开始对计数池中的该样本进行阻抗法计数测试。
  14. 如权利要求13所述的粒子分析仪，其特征在于，所述信号处理及控制装置被配置为控制加液系统再次从反应池中吸取样本后输出排空控制信号至排液控制阀，控制排液控制阀切换到打开状态，以排空反应池中剩余的稀释后的样本。
  15. 如权利要求13或14所述的粒子分析仪，其特征在于，所述粒子分析仪还包括定时器，所述定时器耦合到所述信号处理及控制装置，所述信号处理及控制装置在对计数池中的样本采用阻抗法开始测试后即控制定时器开始计时，所述定时器在计时到达设定时间后输出定时信号至信号处理及控制装置，所述信号处理及控制装置被配置为在设定时间内监测到堵孔时，则控制暂停样本的测试，并执行排堵操作，在排堵操作完成后控制加液系统再次从反应池中吸取该样本并注入计数池，然后重新开始对计数池中的该样本进行阻抗法计数测试。
  16. 如权利要求15所述的粒子分析仪，其特征在于，所述信号处理及控制装置被配置为如果在设定时间内没有监测到堵孔，则输出排空控制信号，控制反应池的排液控制阀切换到打开状态，以排空反应池中剩余的稀释后的样本。
  17. 如权利要求13所述的粒子分析仪，其特征在于，所述信号处理及控制装置被配置为根据实时检测到的微孔电压的幅度、基线电压和脉冲形态中的任一种或多种的组合判断是否发生堵孔。
  18. 用于粒子分析仪的粒子测试控制方法,其特征在于包括：
    控制吸样系统对放置在待测试位的样本进行吸样操作；
    将吸取的样本通过注入多个反应池进行多级稀释，直到在最末级反应池中形成符合稀释比的稀释样本；
    控制加液系统从最末级反应池吸取稀释后的样本并注入计数池，控制多个反应池中的至少一个的排液控制阀继续处于关闭状态，以使剩余的稀释后的样本继续保留在该反应池中；
    对计数池中的样本进行阻抗法计数测试，并在计数测试过程中监测是否发生堵孔事件；
    当发生堵孔事件时则控制暂停样本的测试，并执行排堵操作；
    基于留有剩余的稀释后的样本的反应池中得到符合稀释比的稀释样本；
    将符合稀释比的稀释样本注入计数池，然后重新开始对计数池中的样本进行阻抗法计数测试。
  19. 用于粒子分析仪的粒子测试控制方法,其特征在于包括：
    控制吸样系统对放置在待测试位的样本进行吸样操作；
    将吸取的样本注入反应池进行稀释；
    控制加液系统从反应池吸取稀释后的样本，然后将稀释后的样本的一部分注入计数池，并使加液系统保留剩余的稀释后的样本；
    对计数池中的样本进行阻抗法计数测试，并在计数测试过程中监测是否发生堵孔事件；
    当发生堵孔事件时则控制暂停样本的测试，并执行排堵操作；
    在排堵操作完成后控制加液系统将其中保留的稀释后的样本注入计数池，然后重新开始对计数池中的样本进行阻抗法计数测试。
  20. 如权利要求19所述的方法,其特征在于：所述加液系统的管道两端设置控制阀，当控制加液系统从反应池吸取稀释后的样本并注入计数池后，控制管道两端的控制阀关闭，当排堵操作完成后，控制管道两端的控制阀打开，使剩余在管道中的稀释样本被注入到计数池中。
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