The present disclosure relates to the field of biochemical analysis, and more particularly to particle analyzers and particle test control methods and devices thereof.
The present disclosure relates to particle analyzers and particle test control methods and devices thereof that may reduce probability of pore blocking.
In one aspect of the present disclosure, a particle test control method is provided that can include: controlling a sample acquisition system to acquire a sample in a test location; injecting the acquired sample into a reaction cell to obtain a diluted sample; controlling a liquid addition system to acquire the diluted sample from the reaction cell and inject the acquired diluted sample into a counting cell, and keeping a liquid discharge valve of the reaction cell in a close status to maintain a residual diluted sample in the reaction cell; counting the sample in the counting cell by impedance method, and monitoring whether a pore blocking event occurs during the counting; suspending a next sample test and performing an unblocking operation when a pore blocking event occurs; and controlling the liquid addition system to acquire the diluted sample again from the reaction cell and inject the acquired diluted sample into the counting cell after the unblocking operation, and re-counting the sample in the counting cell by impedance method.
In another aspect of the present disclosure, a particle test control device used in a particle analyzer is provided that can include: a first control unit, which controls a liquid addition system to acquire a diluted sample from a reaction cell and inject the acquired diluted sample into a counting cell; a second control unit, which couples to the first control unit and controls a liquid discharge valve of the reaction cell to be in a close status so as to maintain a residual diluted sample in the reaction cell after the first control unit controls the liquid addition system to acquire the diluted sample from the reaction cell; a third control unit, which couples to the first control unit and controls counting of the sample of the counting cell by impedance method after the sample is injected into the counting cell; a pore blocking monitoring unit, which receives outputted pore voltage during the counting process by impedance method, determines whether pore blocking occurs, and outputs a pore blocking event when pore blocking occurs; and a fourth control unit, which couples to the pore blocking monitoring unit, and suspends a test and performs an unblocking operation, outputs a control signal to the first control unit after the unblocking operation so that the first control unit controls the liquid addition system to acquire the diluted sample again from the reaction cell and inject the acquired diluted sample into the counting cell.
In still another aspect of the present disclosure, a particle analyzer is provided that can include: a reaction cell, where a sample is diluted, the reaction cell including a liquid inlet tube, a liquid outlet tube and a liquid discharge tube, the liquid discharge tube having a liquid discharge valve which can switch between a close status and an open status based on a control signal; a counting system, which including a counting cell, the counting system counts the sample injected into the counting cell by impedance method and output a pore voltage; a liquid addition system, which can acquire the diluted sample from the reaction cell and inject the acquired diluted sample into the counting cell; and a signal processing and control apparatus, which receives the pore voltage, and shapes and recognizes signals; is configured to control the liquid discharge valve of the reaction cell to be close status so as to maintain a residual diluted sample in the reaction cell after the liquid addition system acquires the diluted sample from the reaction cell and inject the acquired diluted sample into the counting cell; monitors pore blocking based on the pore voltage during the counting, suspends a next sample test and performs an unblocking operation when the pore blocking occurs, and controls the liquid addition system to acquire and inject the diluted sample to the counting cell again after the unblocking operation, and re-counting the sample of the counting cell by impedance method.
In yet another aspect of the present disclosure, a particle test control method of a particle analyzer is provided that can include: controlling a sample acquisition system to acquire a sample in a test location; injecting the sample into a plurality of reaction cells to perform multistage dilution, until a diluted sample having a satisfactory dilution ratio is obtained in the last reaction cell; controlling a liquid addition system to acquire the diluted sample from the last reaction cell and inject the acquired diluted sample into a counting cell, and keeping a liquid discharge valve of at least one of the reaction cells in a close status to maintain a residual diluted sample in the reaction cell; counting the sample of the counting cell by impedance method, and monitoring whether a pore blocking event occurs during the counting; suspending a sample test and performing an unblocking operation when a pore blocking event occurs; obtaining a diluted sample having the satisfactory dilution ratio from a reaction cell having the residual diluted sample; and injecting the diluted sample having the satisfactory dilution ratio into the counting cell again, and re-counting the sample in the counting cell by impedance method.
In yet another aspect of the present disclosure, a particle test control method of a particle analyzer is provided that can include: controlling a sample acquisition system to acquire a sample in a test location; injecting the sample into a reaction cell to obtain a diluted sample; controlling a liquid addition system to acquire the diluted sample from the reaction cell, inject part of the diluted sample to a counting cell and keep a residual diluted sample in the liquid addition system; counting the sample of the counting cell by impedance method, and monitoring whether a pore blocking event occurs during the counting; suspending a sample test and performing an unblocking operation when a pore blocking event occurs; and controlling the liquid addition system to inject the residual diluted sample into the counting cell after the unblocking operation, and re-counting the sample of the counting cell by impedance method.
A particle analyzer may be used in medical or biochemical study such as biochemical analysis, which can classify and count particles of a mixture. A blood cell analyzer is a common particle analyzer. A blood cell analyzer can count and classify human blood cells, whose measurement method may include: adding a certain amount of blood sample to a certain amount of diluent that can keep cell morphology and have conductive property; the mixture is pushed through a pore by a driving source. The equivalent impedance of the pore may increase when a cell passes the pore because the cell can be less conductive. Under constant current condition, voltage may change with the impedance proportionally, i.e. voltage waveform may reflect the impedance change while the cell passes through the pore. A voltage pulse can be obtained when a cell passes through a pore, where the pulse height indicates volume size of the cell. So cells can be classified depending on their height of voltage pulse, this method is called impedance method.
The pore used in the measurement is a precision element, where the pore size is between 50-120 μm. Due to the small size of the pore, the pore can be easily blocked by proteins, cell debris, blood clot, lipids, or debris formed during puncturing a tube cap in the measurement. This situation is called a pore blocking event, which may reduce reliability of the analyzer measurement. Conventional measurement time sequence of a blood cell analyzer is shown in
The present disclosure provides particle analyzers and particle test control methods and devices thereof, which are used to reduce probability of pore blocking.
The present disclosure is further illustrated by below embodiments and drawings thereof.
In one embodiment of the present disclosure, the test information of particles counting process is monitored in real time. When a pore blocking event occurs, a handling process may include suspending the sample test, performing an unblocking operation immediately, and then carrying out a second test using the remaining sample dilution. The handling process may avoid failure to output test result because a pore blocking event occurs in the first test, and the sample does not need to be placed again at the test location to do acquisition and dilution again, so as to reduce probability of pore blocking.
Full utilization of the residual diluted sample of the sample dilution can be achieved by not discharging the residual sample dilution after some of the diluted sample is extracted from a reaction cell. The residual sample dilution can be discharged after the test result is obtained. If a pore blocking event occurs during a first test, the residual diluted sample can be extracted from the reaction cell for a second test after unblocking operation. Fully utilization of the residual diluted sample of the sample dilution also can be achieved by using residual diluted sample kept in a tube between the reaction cell and a counting cell.
In following embodiments, a blood cell analyzer is an example of a particle analyzer for detailed description.
Referring to
In the embodiment, the reaction 2 may include a liquid inlet tube 21, a liquid outlet tube 22 and a liquid discharge tube 23. The liquid inlet tube 21 may connect to the sample acquisition system 1, the liquid outlet tube 22 may connect to the liquid addition system 3, and the liquid discharge tube 23 has a liquid discharge valve 231 which can switch between open and close status based on a control signal.
The counting system 4 may include a counting cell 41, a power supply 42, an anode electrode 43, and a cathode electrode 44. The counting cell 41 may include a front cell 411, a back cell 412 and a pore 413 which may locate between the front cell 411 and the back cell 412. When a sample is counted, there is electrolytic solution in the front cell 411 and back cell 412. One end of the anode electrode 43 is in the front cell 411 and one end of the cathode electrode 44 is in the back cell 412. The other ends of the anode electrode 43 and the cathode electrode 44 are connected to an output end of the power supply 42. The power supply 42 is usually a source having constant current. The back cell 412 further has a liquid outlet 414 which may be connected to a negative pressure chamber.
As shown in
In the embodiment, the working process of the blood analyzer may include following steps.
The analyzer may take a certain amount of blood sample from a coagulation vacuum tube. The sample maybe mixed with a certain amount of diluents in a reaction cell to get the diluted sample with a fixed dilution ratio. Then, a certain amount of the diluted sample maybe acquired from the reaction cell and injected into a counting cell for counting by impedance method and obtaining counting results. The diluted sample maybe further mixed with a certain amount of reagent to get a second diluted sample when it is injected into the front cell 411. Driven by negative pressure, the second diluted sample may flow from the front cell 411 to the back cell 412 through the pore 413. During counting process, the sample may flow from the front cell 411 to the back cell 412. At the same time a stable electric current may be form. As shown in
Therefore, in the embodiment, the signal processing and control apparatus 5 maybe further control the liquid discharge valve 231 of the reaction cell 2 to be close status so as to maintain a residual diluted sample in the reaction cell 2 after the liquid addition system 3 acquires the diluted sample from the reaction cell 2 and injects the acquired diluted sample into the counting cell 41. And the apparatus 5 also may monitor a pore blocking event during counting process based on a pore voltage. If a pore blocking event occurs, a next test will be suspended and an unblocking operation will be performed. When unblocking operation is finished, the liquid addition system 3 acquires diluted sample again from the reaction cell 2 and inject the acquired diluted sample into the counting cell 41, then the sample in the counting cell will be re-counted by the impedance method.
In another embodiment, the signal processing and control apparatus 5 may include particles measurement control apparatus 50. As shown in
As shown in
In yet another embodiment, the particles measurement control apparatus 50 may include a timer 56, which may couple to the third control 53 and the fourth control 55. The third control unit 53 may control the timer 56 to start timing once the sample in the counting cell is to be counted. The timer 56 may output a time signal to the fourth control unit 55 when a predetermined period is reached. If the fourth control unit 55 receives a pore blocking event in the predetermined period, a test may be suspended and an unblocking operation may be performed. When the unblocking operation finishes, the fourth control unit 55 may output a control signal to the first control unit 51, the latter may control the liquid addition system 3 to acquire again the sample from the reaction cell and inject the acquired diluted sample into the counting cell. If the fourth control unit 55 does not receive a pore blocking event in the predetermined period, it may control the second control unit 52 to output a discharging signal. The liquid discharge valve 231 of the reaction cell may be switched to an open status, so that the residual diluted sample in the reaction cell may be discharged.
The timer may be integrated in the signal processing and control apparatus, or integrated the particles measurement control apparatus. Alternatively, the timer may be put apart from the signal processing and control apparatus as an independent element.
As shown in
Step S61, controlling a sample acquisition system to acquire a sample in a test location.
Step S62, injecting the sample into a reaction cell to obtain a diluted sample.
Step S63, controlling a liquid addition system to acquire the diluted sample from the reaction cell, inject the acquired diluted sample into a counting cell, and keeping a liquid discharge valve of the reaction cell in a close status to maintain a residual diluted sample in the reaction cell.
Step S64, counting the sample in the counting cell by impedance method, and performing step S65 during the counting.
Step S65, monitoring and determining whether a pore blocking event occurs. If a pore blocking event occurs, performing step S66 otherwise performing Step S68. In one embodiment, when pore blocking is monitored and decided during a predetermined period beginning at counting by impedance method, a pore blocking event will be outputted. The predetermined period may be a period T, in which all of the acquired sample passes through the pore, or may be a period which is less than the period T. The predetermined period may be determined according to an analyzer's performance or computational algorithm for signal extraction and recognition. The predetermined period is not specially limited as long as collected signals during the period could obtain accurate counting and classification result. For example, if the time period of all of dilution sample through a pore is T, the predetermined period may be T/2.
As shown in
Step S71, starting timing once starting measurement by impedance method.
Step S72, determining whether a predetermined period is reached, if the predetermined period is reached, performing step S74 where a discharging signal is outputted, otherwise performing step S73 where a received pore voltage is determined instantly.
Step S73, instantly determining a received pore voltage in real time during the counting, if the pore voltage is abnormal, performing step S75 which includes outputting a pore blocking event, otherwise performing step S72.
Step S66, suspending a sample test which includes current and next test and performing an unblocking operation when pore blocking occurs.
Step S67, controlling the liquid addition system acquire sample again from the reaction cell and inject the acquired diluted sample into the counting cell, and re-counting the sample in the counting cell by impedance method. After acquiring the sample again from the reaction cell, performing step S68 which includes outputting a discharging control signal. Alternatively, keeping monitoring pore blocking during re-counting process, performing step S68 when the test finishes successfully.
Step S68, controlling the liquid discharge valve to an open status for discharging the residual diluted sample in the reaction cell.
There are several methods for determining whether pore blocking occurs according to real-time pore voltage. For example, base on at least one of the intensity of the real-time pore voltage, baseline voltage and pulse form, it may be determined whether pore voltage is abnormal or not. The abnormal pore voltage occurs may mean that pore blocking occurs.
In one embodiment, judging whether pore blocking occurs according to the intensity of the real-time pore voltage may include: comparing the intensity of the pore voltage with a first threshold value; recording a time duration when the intensity exceeds the first threshold value; comparing the time duration with a second threshold value; and identifying a pore blocking event when the time duration exceeds the second threshold value.
In one embodiment, determining whether pore blocking occurs according to the baseline voltage of the real-time pore voltage may include: calculating the baseline voltage of the pore voltage; comparing the baseline voltage with a third threshold value; and identifying a pore blocking event when the baseline voltage exceeds the third threshold value.
In the above embodiments, there is no need to find out the sample tube whose sample has a pore blocking event, place it again in the test location, acquire and dilute the sample again, because the residual diluted sample in the reaction cell could be acquired again for a second counting process when the pore blocking occurs. So the probability of pore blocking may be reduced. Moreover, the amount blood sample could be reduced, and requirement for minimum blood drawing amount to a tested person also could be reduce, because there is no need to acquire the blood sample twice.
Based on the above analyzer, in another embodiment, the blood cell analyzer may have a plurality of reaction cells for multiage dilution.
As shown in
Step S91, controlling a sample acquisition system to acquire a sample in a test location.
Step S92, injecting the sample into a plurality of reaction cells to perform multistage dilution, until a diluted sample having the satisfactory dilution ratio is obtained in the last reaction cell. In this embodiment, the sample dilution may not be finished in one reaction cell but in a plurality of reaction cells for multiage dilution. A certain amount of reagent and sample are respectively injected into a first reaction cell for a first level mixing and incubation, and then a certain amount of first level diluted sample is acquired from the first reaction cell and mixed with a certain amount of reagent in a second reaction cell for a second level mixing and incubation. These processes may be repeated several times until a diluted sample having the satisfactory dilution ratio is formed in the last reaction cell.
Step S93, controlling the liquid addition system to acquire the diluted sample from the last reaction cell and inject the acquired diluted sample into a counting cell, and keeping a liquid discharge valve of at least one of the reaction cells in a close status to maintain remainder diluted sample in at least one of the reaction cells. The liquid discharge valve of the last reaction cell may be kept in a close status for storing a remainder the last level diluted sample in the last reaction. Alternatively, the liquid discharge valve of the intermediate reaction cell may be kept in a close status for storing a remainder the intermediate level diluted sample in the reaction.
Step S94, counting the sample in the counting cell by impedance method.
Step S95, monitoring whether a pore blocking event occurs during the counting. The methods for determining a pore blocking event are as the same as that of above embodiments.
Step S96, suspending a sample test and performing an unblocking operation when a pore blocking event occurs.
Step S97, obtaining the diluted sample having the satisfactory dilution ratio from a reaction cell having residual diluted sample. If it is the last reaction cell that keeps the remainder in step S93, the diluted sample may be acquired from the last reaction cell, which may have the satisfactory dilution ratio and may not need to be diluted. If it is other reaction cell that keeps the remainder of intermediate level diluted sample in step S93, the diluted sample may be acquired from the reaction cell, which may not have the satisfactory dilution ratio and may need to be diluted until a diluted sample having the satisfactory dilution ratio is obtained. The diluted sample having the satisfactory dilution ratio may be injected into a counting cell, and counting again by impedance method.
Step S98, discharging all reaction cells.
A skilled artisan will understand that the example illustrations of apparatus or steps in above embodiments may also be used in this embodiment, such as step S67, step S72 or methods for determining whether pore blocking occurs.
Based on the above analyzer, in still another embodiment, a liquid addition system of the blood cell analyzer may have longer tube. As shown in
Step S101, controlling a sample acquisition system to acquire a sample in a test location.
Step S102, injecting the sample into a reaction cell to obtain a diluted sample.
Step S103, controlling a liquid addition system to acquire the diluted sample from the reaction cell, inject part of the diluted sample to a counting cell and keep a residual diluted sample in the liquid addition system. For example, the tube of the liquid addition system may be long enough to keep the diluted sample. Alternatively, the liquid addition system may have extra control valves. The control valves, which are installed at two ends of the tube, may be switched to a close status so as to keep the remainder the diluted sample in the tube after a diluted sample for a first counting is injected into a counting cell. When it is necessary to perform a second counting, the valves of tube may be switched to an open status, and the remainder diluted sample kept in the tube may be injected into a counting cell again. Alternatively, the valve may be installed at one end of the liquid addition system, which is near to the counting cell. The valve may be closed for keeping the remainder the diluted sample in the tube after a diluted sample for a first counting is injected into a counting cell. When it is necessary to perform a second counting, the valves of tube may be switched to an open status, and the remainder diluted sample kept in the tube may be injected into a counting cell again. Or, a syringe or an air pressure apparatus may be connected to the liquid addition system. The syringe or the air pressure apparatus may be used to control the diluted sample keeping in the tube of the liquid addition system or to be injected into the counting cell.
Step S104, counting the sample in the counting cell by impedance method, and monitoring whether a pore blocking event occurs during the counting. The methods for determining a pore blocking event are as the same as that of above embodiments.
Step S105, suspending the counting and performing an unblocking operation when a pore blocking event occurs.
Step S106, controlling the liquid addition system to inject the residual diluted sample into the counting cell after the unblocking operation, and re-counting the sample in the counting cell by impedance method.
In this embodiment, there is no need to consider when the reaction cell should be discharged. The reaction cell may be discharged once acquiring diluted sample at the first time or sometime after the first acquisition.
A skilled artisan will understand that the example illustrations of apparatus or steps in above embodiments may also be used in this embodiment, such as step S67, step S72 or methods for determining whether pore blocking occurs.
In above embodiments, an unblocking operation may preformed by one or more of following methods.
1. Backswing. In this method, liquid in the back cell is pushed to the front cell in a relatively high speed, so as to move away the foreign matter blocking the pore.
2. Burning. In the method, a relatively high electric current is set between the anode electrode and the cathode electrode. As shown in
In above embodiments, voltage in both sides of the pore element may be instantly monitored during counting process. When voltage in both sides of the pore element (i.e. pore voltage) rises or fluctuates abnormally, it may be identified that a pore blocking event occurs. Once the pore blocking occurs, sample counting may be suspended, an unblocking operation may be performed immediately after some necessary movements. And then, some sample may be acquired again from residual first diluted sample and re-counted. After that, the analyzer may automatically start a next blood sample test when the analyzer is in continuous sample injection mode.
Besides the blood cell analyzer described above, particles analyzer may be a workstation, urine analyzer, or other body fluid analyzer.
Although the present disclosure has been illustrated by way of the above embodiments and particular examples thereof, it will be appreciated by those skilled in the art that various changes, alterations and modifications may be made to the present disclosure without departing from the spirit and scope of the present disclosure as claimed.
Number | Date | Country | Kind |
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2011 1 0338176 | Oct 2011 | CN | national |
This application is a continuation of U.S. patent application Ser. No. 14/355,547, filed Aug. 8, 2014, for “Particle Analyzers and Particle Test Control Methods and Devices Thereof,” which claims priority to Chinese Patent Application No. 201110338176.4, filed on Oct. 31, 2011, both of which are fully incorporated herein by reference.
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Number | Date | Country |
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101173887 | May 2008 | CN |
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Number | Date | Country | |
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20170276642 A1 | Sep 2017 | US |
Number | Date | Country | |
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Parent | 14355547 | US | |
Child | 15603384 | US |