Patent Grant
11604134
The present application relates to the technical field of particle analysis equipment, and in particular to a sheath flow impedance particle analyzer and a measurement method for a sheath flow impedance particle analyzer. The sheath flow impedance particle analyzer can use sheath flow impedance to measure and analyze the quantity, volume, and the like of particles.
An existing sheath flow impedance particle analyzer generally comprises a pre-mixing cell, a sample needle, a sheath flow impedance counting cell, a front sheath cell, a rear sheath cell, a rear sheath waste fluid cell, a waste fluid cell and other components. A measurement process of the sheath flow impedance particle analyzer is mainly as follows: cleaning the pre-mixing cell and discharging waste to the waste fluid cell, loading a sample into the pre-mixing cell and evenly mixing the sample, cleaning the sheath flow impedance counting cell and discharging waste to the waste fluid cell, preparing a sample with the sample needle, forming front and rear sheath fluids, sampling and measuring the sample, discharging a waste fluid from the rear sheath waste fluid cell, etc. The entire measurement process is finished in a sequential order. As a result, the particle analyzer using sheath flow impedance has a relatively long measurement cycle and a relatively slow measurement speed.
The objective of the present application is to provide a sheath flow impedance particle analyzer and a measurement method therefor that can shorten a measurement cycle and increase a measurement speed.
To resolve the foregoing technical problem, the present application provides a sheath flow impedance particle analyzer, comprising a pre-mixing cell, a sample needle, a sheath flow impedance counting cell, a front sheath fluid cell, a rear sheath fluid cell, a rear sheath waste fluid cell, and a waste fluid cell, wherein the pre-mixing cell is connected to the sample needle, and a valve is disposed between the pre-mixing cell and the sample needle; the sheath flow impedance counting cell comprises a front cell and a rear cell, and the sample needle is connected to the front cell; the front sheath fluid cell comprises a front sheath fluid inlet port in communication with the front cell, and the front sheath fluid cell supplies a front sheath fluid into the front cell through the front sheath fluid inlet port; the rear sheath fluid cell comprises a rear sheath fluid inlet port connected to the rear cell, and the rear sheath fluid cell supplies a rear sheath fluid into the rear cell through the rear sheath fluid inlet port; the rear sheath waste fluid cell comprises a sheath waste fluid inlet port in communication with the rear cell, and the rear sheath waste fluid cell is configured to collect a rear sheath waste fluid generated after the sheath flow impedance counting cell measures a sample fluid; the pre-mixing cell, the sample needle, the sheath flow impedance counting cell, and the rear sheath waste fluid cell are all connected to the waste fluid cell; the waste fluid cell is a main negative pressure source and is configured to receive waste fluids discharged from the pre-mixing cell, the sample needle, the sheath flow impedance counting cell, and the rear sheath waste fluid cell; and the sheath flow impedance particle analyzer further comprises a first auxiliary negative pressure source, the first auxiliary negative pressure source comprises at least one low pressure port and a first connecting port, the low pressure port is connected to the sample needle or the rear sheath waste fluid cell, and the first auxiliary negative pressure source is connected to the waste fluid cell by the first connecting port.
The present application further provides a measurement method for a sheath flow impedance particle analyzer, comprising the following steps:
providing a sheath flow impedance particle analyzer;
obtaining a sample fluid by reacting a blood sample and a reagent;
cleaning a sheath flow impedance counting cell;
transferring the sample fluid to a predetermined position;
pushing the sample fluid into a front cell of the sheath flow impedance counting cell with a syringe so that the sample fluid is surrounded by a sheath flow to enable the sheath flow impedance counting cell to measure the sample fluid; and
discharging a waste fluid in a rear sheath waste fluid cell, wherein
the step of transferring a sample fluid to a predetermined position or discharging a waste fluid in a rear sheath waste fluid cell is performed during measurement of the sample fluid by the sheath flow impedance counting cell. In the sheath flow impedance particle analyzer provided in the present application, during measurement of the sample fluid by the sheath flow impedance counting cell, at least one action of fluid discharge and cleaning of a pre-mixing cell, sample loading and even mixing in the pre-mixing cell, waste discharge of the rear sheath waste fluid cell, negative pressure pre-supplied in a buffering cell, and sample fluid sampling and transferring by a sample needle can be performed, so that the measurement cycle of the sheath flow impedance particle analyzer can be shortened, and the measurement speed is increased.
In order to illustrate the technical solutions in the embodiments of the present application more clearly, a brief introduction to the drawings required for the implementations will be provided below. Obviously, the drawings in the following description are some of the implementations of the present application, and those of ordinary skill in the art can also obtain other drawings according to these drawings without involving any inventive effort.
The technical solutions of the embodiments of the present application will be described below clearly and comprehensively in conjunction with the drawings of the embodiments of the present application. Clearly, the embodiments described are merely some embodiments of the present application and are not all the possible embodiments. Based on the embodiments given in the present application, all other embodiments that would be obtained by those of ordinary skill in the art without expending inventive effort shall all fall within the scope of protection of the present application.
The “connection” discussed herein comprises direct connection and indirect connection by another member such as a valve.
Referring to
In the sheath flow impedance particle analyzer provided in the present application, one first auxiliary negative pressure source 60 is added and is connected to the sample needle 23 or is connected to the rear sheath waste fluid cell 50. As the sheath flow impedance counting cell 20 measures the sample fluid, the first auxiliary negative pressure source 60 supplies negative pressure to the sample needle 23 or the rear sheath waste fluid cell 50 to enable the sample needle 23 to prepare the sample fluid or the rear sheath waste fluid cell 50 to discharge the waste fluid, so that the measurement cycle of the sheath flow impedance particle analyzer is shortened and the measurement speed is increased.
The sheath flow impedance particle analyzer in the present application further comprises a plurality of valves, that is, further comprises a valve V2 to a valve V10. These valves are all solenoid valves that are closed when being powered on and are opened when being powered off.
As shown in
The rear sheath waste fluid cell 50 is located below the sheath flow impedance counting cell 20. That is, when the sheath flow impedance particle analyzer is placed on the horizontal plane to work, the rear sheath waste fluid cell 50 is closer to the horizontal plane than the sheath flow impedance counting cell 20. The height of the highest fluid surface inside the rear sheath waste fluid cell 50 is lower than the height of the rear sheath waste fluid outlet port 222, so that a waste fluid flowing out of the rear sheath waste fluid outlet port 222 can be enabled to smoothly flow into the rear sheath waste fluid cell 50 to keep a stable sheath flow in the sheath flow impedance counting cell 20. The rear sheath waste fluid cell 50 further comprises a rear sheath waste fluid discharge port 53. The rear sheath waste fluid discharge port 53 is connected to the first auxiliary negative pressure source 60. In this embodiment, the rear sheath waste fluid cell 50 further comprises a sealing cover 54. The rear sheath waste fluid inlet port 51 is provided on the sealing cover 54. An atmosphere connecting port 55 is further provided on the sealing cover 54. The atmosphere connecting port 55 is connected to the atmosphere 300 by the valve V7. The valve V7 is set to a normally open state. That is, the rear sheath waste fluid cell 50 is in communication with the atmosphere 300. Because the sheath waste fluid cell 50 is in communication with the atmosphere 300 through the atmosphere connecting port 55, the negative pressure in the rear sheath waste fluid cell 50 can be prevented from interfering with the measurement by the sheath flow impedance counting cell 20 after the waste fluid in the rear sheath waste fluid cell 50 is emptied. The sealing cover 54 can further prevent the waste fluid in the rear sheath waste fluid cell 50 from overflowing into the sheath flow impedance particle analyzer, so that the measurement precision of the sheath flow impedance particle analyzer is prevented from being affected.
In this embodiment, the first auxiliary negative pressure source 60 is a sealed buffering cell. The buffering cell comprises two low pressure ports 61 and 63 and the valve V8 configured to control one low pressure port 63 to open or close. The other low pressure port 61 is connected to the sample needle 23 by the valve V3. The buffering cell further comprises a first connecting port 64, the valve V9 configured to control the first connecting port 64 to open or close, a second connecting port 65, and the valve V10 configured to control the second connecting port 65 to open or close. The low pressure port 61 is connected to the second discharge port 235 of the sample needle 23 by the valve V3. The low pressure port 63 is connected to the rear sheath waste fluid cell 50 by the valve V8. That is, the low pressure port 63 is connected to the rear sheath waste fluid discharge port 53 of the rear sheath waste fluid cell 50 by the valve V8. The first connecting port 64 is connected to the waste fluid cell 70 by the valve V9. The second connecting port 65 is connected to the atmosphere 300 by the valve V10. When the low pressure port 61 is closed by the valve V3, the low pressure port 63 is closed by the valve V8, the second connecting port 65 is closed by the valve V10, and the first connecting port 64 is opened by the valve V9, the waste fluid cell 70 is in communication with the buffering cell. When the negative pressure in the buffering cell is the same as the negative pressure of the waste fluid cell 70, the first connecting port 64 is closed by the valve V9 to enable the buffering cell to form an auxiliary negative pressure source.
In another embodiment, the low pressure port 61 can be connected to the rear sheath waste fluid discharge port 53 of the rear sheath waste fluid cell 50 by the valve V3. The low pressure port 63 can be connected to the second discharge port 235 of the sample needle 23 by the valve V8. The low pressure port 61 supplies a negative pressure for the rear sheath waste fluid cell 50 to discharge a waste fluid. The low pressure port 63 supplies a negative pressure for the sample needle 23 to draw in a sample fluid.
The buffering cell is located below the rear sheath waste fluid cell 50. That is, when the sheath flow impedance particle analyzer is placed on the horizontal plane to work, the buffering cell is closer to the horizontal plane than the rear sheath waste fluid cell 50. The height of the low pressure port 63 is lower than the height of lowest fluid surface inside the rear sheath waste fluid cell 50. After the buffering cell finishes preparing the sample fluid, the valve V3 is closed and the valve V8 is open, and residual negative pressure in the buffering cell is used to enable a small amount of waste fluid in the rear sheath waste fluid cell 50 to flow into the buffering cell, so that the waste fluid in the rear sheath waste fluid cell smoothly flows into the buffering cell by gravity. In addition, the valve V10 is opened to enable the buffering cell to be in communication with the atmosphere 300. The waste fluid in the rear sheath waste fluid cell 50 continues to flow into the buffering cell by gravity. Air above the waste fluid surface in the buffering cell is discharged into the atmosphere 300 through the valve V10 to enable the buffering cell to receive more waste fluid.
In other implementations that have no high test speed requirement, as a waste fluid is discharged into the buffering cell by the rear sheath waste fluid cell 50, the valve V10 may be in a closed state. That is, after the buffering cell finishes preparing a sample fluid, the valve V3 is closed and the valve V8 is open, so that remaining negative pressure in the buffering cell enables a part of waste fluid in the rear sheath waste fluid cell 50 to flow into the buffering cell. When there is balanced pressure in the buffering cell, that is, after the remaining negative pressure in the buffering cell is used up, the valve V8 is closed and the valve V9 and the valve V10 are opened to enable the waste fluid in the buffering cell to be completely discharged into the waste fluid cell 70. After auxiliary negative pressure source is formed in the buffering cell again, the valve V9 is then closed and the valve V8 is opened to enable the waste fluid in the rear sheath waste fluid cell 50 to flow into the buffering cell again. The negative pressure in the buffering cell may be adjusted to a relatively low state or the valve V8 controls the fluid flow entering the buffering cell to have a relatively slow speed. Therefore, as the waste fluid is discharged into the buffering cell by the rear sheath waste fluid cell 50, the measurement by the sheath flow impedance counting cell 20 is basically not affected.
The height of the first connecting port 64 is lower than that of lowest fluid surface inside the buffering cell. Therefore, after the valve V9 and the valve V10 are opened and the valve V8 is closed, the waste fluid in the buffering cell can be completely emptied into the waste fluid cell 70. The low pressure port 61, the low pressure port 63, and the second connecting port 65 are located at an upper portion of the buffering cell. The first connecting port 64 is located at a lower portion of the buffering cell. In this embodiment, the low pressure port 61 is provided in the top wall of the buffering cell, the low pressure port 63 and the second connecting port 65 are provided at an upper portion of a side wall of the buffering cell. The first connecting port 64 is provided at a lower portion of a side wall of the buffering cell.
In another embodiment, the low pressure port 63 may be provided in the top wall of the buffering cell. The second connecting port 65 may be provided in the top wall of the buffering cell. The first connecting port 64 may be provided in the bottom wall of the buffering cell.
A counting circuit 80 comprises a high potential electrode 81 electrically connected to the sheath fluid in the rear cell 22, a zero potential electrode 83 electrically connected to the sheath fluid in the front cell 21, and a signal processing unit 85 disposed between the high potential electrode 81 and the zero potential electrode 83. The front cell 21, the rear cell 22, the barrier 24, the sample needle 23, and the gem hole 242 are all made of an insulating material. In addition, connecting ports connected to the sheath flow impedance counting cell 20 are all made of an insulating material. In this way, the gem hole 242 is the only flow body path from a high potential electrode to a zero potential electrode.
In the sheath flow impedance particle analyzer of the present application, the valve V1 to the valve V10 are all solenoid valves that are in an open state when being powered off and in a closed state when being powered on. The valve V6 and the valve V7 are functional valves. That is, the valve V6 is always in a powered-on and closed state, and the valve V7 is always in a powered-off and open state.
Refer to both
cleaning the pre-mixing cell 10, in which the valve V1 is powered on and closed, that is, the sample outlet port 16 is closed, a diluent is added to the pre-mixing cell 10 for cleaning, and a waste fluid generated after cleaning is discharged into the waste fluid cell 70; and
cleaning the sheath flow impedance counting cell 20, in which the front cell 21 is cleaned by a sheath fluid in the front sheath fluid cell 25 through the front sheath fluid inlet port 251, the rear cell 22 is cleaned by a sheath fluid in the rear sheath fluid cell 27 through the rear sheath fluid inlet port 271, a waste fluid generated after the front cell 21 is cleaned is discharged into the waste fluid cell 70 through the waste fluid discharge port 213, and a waste fluid generated after the rear cell 22 is cleaned is discharged into the rear sheath waste fluid cell 50 through the rear sheath waste fluid outlet port 222 and the rear sheath waste fluid inlet port 51. During cleaning of the sheath flow impedance counting cell 20, a part of sheath fluid in the front cell 21 flows into the buffering cell through the first discharge port 232 and the second discharge port 235 of the sample needle 23, the valve V3, and the low pressure port 61 of the buffering cell to clean the sample needle 23. Alternatively, the sheath fluid in the syringe 236 flows into the buffering cell through the feeding port 231 and the second discharge port 235 of the sample needle 23, the valve V3, and the low pressure port 61 of the buffering cell, so that the sample needle 23 can be cleaned. Alternatively, the sheath fluid in the front cell 21 flows into the buffering cell through the first discharge port 232 and the second discharge port 235 of the sample needle 23, the valve V3, and the low pressure port 61 of the buffering cell, at the same time, the sheath fluid in the syringe 236 also flows into the buffering cell through the feeding port 231 and the second discharge port 235 of the sample needle 23, the valve V3, and the low pressure port 61 of the buffering cell, to jointly clean the sample needle 23, and the waste fluid in the buffering cell is discharged into the waste fluid cell 70. In addition, during cleaning of the sheath flow impedance counting cell 20, a blood sample is added to the pre-mixing cell 10 and a reagent is added, so that the blood sample and the reagent react to obtain a sample fluid with a predetermined dilution ratio. In addition, the valve V3, the valve V8, and the valve V10 are powered on and closed, to close the low pressure port 61, the low pressure port 63, and the second connecting port 65 of the buffering cell. In this case, the waste fluid cell 70 is in communication with the buffering cell through the valve V9, and the negative pressure in the waste fluid cell 70 enables the buffering cell to form a pre-supplied negative pressure source. Therefore, the cleaning of the sheath flow impedance counting cell 20, the addition and even mixing of a sample fluid in the pre-mixing cell 10, the cleaning of the sample needle 23, and negative pressure pre-supply in the buffering cell can be performed within the same period. When the cleaning of the sheath flow impedance counting cell 20 is completed, the sample has been evenly mixed in the pre-mixing cell 10.
The step of using the sheath flow impedance counting cell 20 to measure the sample fluid is as follows: feeding the sheath fluid in the front sheath fluid cell 25 into the front cell 21 through the front sheath fluid inlet port 251, and feeding the sheath fluid in the rear sheath fluid cell 27 into the rear cell 22 through the rear sheath fluid inlet port 271, to form a sheath fluid flow of the sheath fluid in the front cell 21 flowing toward the rear cell 22 through the gem hole 242 in the sheath flow impedance counting cell 20. That is, sheath fluid preparation in the front cell 21 and the rear cell 22 are made in the sheath flow impedance counting cell 20, to finish forming the sheath fluid in the sheath flow impedance counting cell 20. During the sheath fluid preparation in the front cell 21 and the rear cell 22 in the sheath flow impedance counting cell 20, the valve V1 and the valve V3 are powered off. That is, the valve V1 and the valve V3 are opened. The negative pressure pre-supplied in the buffering cell draws the sample fluid in the pre-mixing cell 10 into the sample needle 23 to prepare the sample fluid. That is, under the negative pressure, the sample fluid in the pre-mixing cell 10 flows into the sample needle 23 through the sample outlet port 16, the valve V1, and the feeding port 231, so that a conduit between the valve V1 and the second discharge port 235 is filled with the sample fluid. When the sheath fluid preparation in the front cell 21 and the rear cell 22 is finished, the sample needle 23 also finishes preparing a sample fluid. The valve V1 and the valve V3 are powered on and closed, that is, the sample outlet port 16 is closed, and the low pressure port 61 is closed. The syringe 236 pushes the sample fluid in the sample needle 23 into the front cell 21 through the first discharge port 232. The sample fluid starts to converge, gradually turns thinner, accelerates, and flows in an axial direction of the gem hole 242 at the first discharge port 232 of the sample needle 23 under a sheath fluid flow, and is surrounded by the sheath fluid flow to pass through the center of the gem hole 242 to form a particle flow beam. The diameter of the particle flow beam is equal to the diameter of a single particle passing through the gem hole 242, so that a plurality of particles can be prevented from passing through the gem hole 242 at the same time. Because particles (for example, blood cells) to be tested are poor conductors, when a sample fluid that contains the particles to be tested passes through the gem hole 242, the particles to be tested take place of a conductive fluid body to cause a change in the impedance characteristic of the gem hole 242. Because the gem hole 242 is the only path from a high potential electrode to a zero potential electrode, a change correspondingly occurs in the impedance characteristic between the high potential electrode 81 and the zero potential electrode 83. The magnitude of the change is directly proportional to the volume of a particle. The signal processing unit 85 converts such changes into a pulse waveform. The volume and quantity of particles can be obtained by analyzing the magnitude and quantity of the pulse waveform. The sample fluid is surrounded by a front sheath fluid to pass through the gem hole 242 to enter the rear cell 22, and turns into a rear sheath waste fluid. The rear sheath waste fluid flows into the rear sheath waste fluid cell 50 through the rear sheath waste fluid outlet port 222 and the rear sheath waste fluid inlet port 51. The sampling and measurement by the sheath flow impedance particle analyzer are completed, so that the first time of measurement of a sample fluid since the sheath flow impedance particle analyzer is turned on is completed.
During measurement of the sample fluid by the sheath flow impedance counting cell 20, a plurality of parallel actions are designed. For example, in parallel, the pre-mixing cell 10 performs cleaning in a next measurement cycle (second time of measurement of a sample fluid), a waste fluid is discharged into the buffering cell by the rear sheath waste fluid cell 50, the waste fluid in the buffering cell is emptied into a waste fluid cell 700, and the buffering cell completes a next time of negative pressure pre-supply. Details are as follows: The valve 1 is in a powered-on and closed state, that is, the sample outlet port 16 is in a closed state. Therefore, during measurement of the sample fluid by the sheath flow impedance counting cell 20, a remaining useless sample fluid in a previous time of measurement in the pre-mixing cell 10 is eliminated and a fluid is added for cleaning. The valve V8 is powered off to be opened. The rear sheath waste fluid discharge port 53 of the rear sheath waste fluid cell 50 is in communication with the low pressure port 63 of the buffering cell. The waste fluid in the rear sheath waste fluid cell 50 flows into the buffering cell under the remaining pre-supplied negative pressure in the buffering cell. After a waste fluid is discharged into the buffering cell by the rear sheath waste fluid cell 50 for a period of time, that is, there is already no pre-supplied negative pressure in the buffering cell, the valve V10 is powered off to be opened so that the buffering cell is in communication with the atmosphere 300. The waste fluid in the rear sheath waste fluid cell 50 flows into the buffering cell by gravity. The valve V8 is then powered on and closed. At this time, the low pressure port 63 is closed by the valve V8. The buffering cell is in communication with the atmosphere 300. The waste fluid in the buffering cell is completely discharged into the waste fluid cell 700 through the first connecting port 64 and the valve V9. That is, the waste fluid in the buffering cell is emptied. The valve 10 is then powered on and closed. At this time, only the first connecting port 64 of the buffering cell is in communication with the waste fluid cell 700. The waste fluid cell 700 enables the buffering cell to complete negative pressure pre-supply in a next measurement cycle. During measurement of the sample fluid by the sheath flow impedance counting cell 20, the rear sheath waste fluid in the rear cell 22 keeps being discharged into the rear sheath waste fluid cell 50. Negative pressure can be pre-supplied repeatedly in the buffering cell, a waste fluid can be repeatedly discharged into the buffering cell by the rear sheath waste fluid cell 50, and the waste fluid in the buffering cell can be repeatedly emptied into the waste fluid cell 700. When the measurement is completed, the waste fluids in the rear sheath waste fluid cell 50 and the buffering cell also have been basically discharged, and a next time of measurement can be performed without a need to wait. During measurement of the sample fluid by the sheath flow impedance counting cell 20, it may be set to evenly mix the sample fluid in the pre-mixing cell 10.
Referring to both
cleaning the sheath flow impedance counting cell 20, powering on and closing the valve V1, adding a sheath fluid to the sheath flow impedance counting cell 20 for cleaning, and cleaning the sample needle 23. During the cleaning of the sheath flow impedance counting cell 20, a current sample fluid is added to the pre-mixing cell 10 to perform even mixing. The two steps can be completed at the same time point. That is, when the cleaning of the sheath flow impedance counting cell 20 is completed, the sample fluid in the pre-mixing cell 10 has been evenly mixed. Alternatively, the sample loading and even mixing of the current sample fluid in the pre-mixing cell 10 may start from a last measurement cycle and last until a current cleaning stage of the sheath flow impedance counting cell, provided that sample loading and even mixing of the current sample fluid are completed when the current cleaning of the sheath flow impedance counting cell is completed.
The sheath flow impedance counting cell 20 is used to perform measurement. After the cleaning of the sheath flow impedance counting cell 20 is completed, the sheath fluid in the front sheath fluid cell 25 is fed into the front cell 21 through the front sheath fluid inlet port 251, and the sheath fluid in the rear sheath fluid cell 27 is fed into the rear cell 22 through the rear sheath fluid inlet port 271. That is, the sheath fluid preparation in the front tank 21 and the rear tank 22 is performed in the sheath flow impedance counting tank 20. During the sheath fluid preparation in the front cell 21 and the rear cell 22 in the sheath flow impedance counting cell 20, the valve 1 is powered off, the negative pressure in the buffering cell draws the sample fluid in the pre-mixing cell 10 into the sample needle 23, the valve 1 and the valve 3 are then powered on and closed, and the sample outlet port 16 is closed. Therefore, when the sheath fluid preparation in the front cell 21 and the rear cell 22 is completed, the sample needle 23 also finishes preparing the sample fluid. The syringe 236 pushes the sample fluid in the sample needle 23 into the front cell 21 through the first discharge port 232 to enable the particle flow beam in the front cell 21 of the sheath flow impedance counting cell 20 to pass through the gem hole 242 for measurement. During measurement of the sample fluid by the sheath flow impedance counting cell 20, the pre-mixing cell 10 can complete cleaning in a further next (third time of measurement of a sample fluid) measurement cycle, a waste fluid is discharged into the buffering cell again by the rear sheath waste fluid cell 50, the waste fluid in the buffering cell is emptied into the waste fluid cell 700 again. The buffering cell completes another time of negative pressure pre-supply.
Therefore, in this embodiment, in every measurement cycle after the first time of measurement of the sample fluid since the sheath flow impedance particle analyzer is turned on, only the time required for the step of cleaning the sheath flow impedance counting cell 20 and the step of measurement by the sheath flow impedance counting cell 20 is needed. The fluid discharge and cleaning of the pre-mixing cell 10, the sample loading and even mixing of the pre-mixing cell 10, the discharge of the waste fluid in the rear sheath waste fluid cell 50, the emptying of the waste fluid in the buffering cell, the negative pressure pre-supply of the buffering cell, and the sampling and preparation of the sample fluid in the sample needle 23 can all be completed during the cleaning of the sheath flow impedance counting cell 20 and the measurement of the sample fluid by the sheath flow impedance counting cell 20. Details are as follows: During cleaning of the sheath flow impedance counting cell 20, the pre-mixing cell 10 performs sample loading and even mixing. When the cleaning of the sheath flow impedance counting cell 20 is completed, the sample loading and even mixing of the pre-mixing cell 10 have been completed. During measurement of the sample fluid by the sheath flow impedance counting cell 20, the fluid discharge and cleaning of the pre-mixing cell 10, the discharge of the waste fluid in the rear sheath waste fluid cell 50, the emptying of the waste fluid in the buffering cell, the negative pressure pre-supplied in the buffering cell, and the sample preparation of the sample needle 23 are all completed in this period. In addition, during measurement of the sample fluid by the sheath flow impedance counting cell 20, the buffering cell may establish negative pressure pre-supply repeatedly, and the pre-supplied negative pressure is used to enable the rear sheath waste fluid cell 50 to discharge the waste fluid. A person skilled in the art can understand that the discharge of the waste fluid in the rear sheath waste fluid cell 50 may be performed during the cleaning of the sheath flow impedance counting cell 20. Compared with the serial measurement actions by an existing sheath flow impedance particle analyzer, one buffering cell is added to the sheath flow impedance particle analyzer in this embodiment to enable the waste fluid in the rear sheath waste fluid cell 50 to first enter the buffering cell. In addition, in this process, the pressure in the rear sheath waste fluid cell 50 can be approximately equal to the atmospheric pressure, and a stable sample flow in the sheath flow impedance counting cell 20 is not affected. The buffering cell and the rear sheath waste fluid cell 50 are then isolated. The waste fluid cell 70 and the buffering cell are then connected, and the waste fluid in the buffering cell is rapidly emptied. In this way, the discharge of the waste fluid in the rear sheath waste fluid cell 50 can be completed in parallel during the measurement by the sheath flow impedance counting cell 20, so that the measurement cycle of the sheath flow impedance particle analyzer is greatly shortened, and the measurement speed is increased. In addition, the negative pressure in the buffering cell may supply a power source for sample preparation. Therefore, sample preparation does not need an additional power source, so that the structure can be simplified.
Referring to
A measurement procedure of the second embodiment of the sheath flow impedance particle analyzer in the present application is similar to that of the first embodiment. The first time of measurement of a sample fluid since the sheath flow impedance particle analyzer in the second embodiment is turned on comprises the following steps:
cleaning the pre-mixing cell 10, powering on and closing the valve V1, adding a sheath fluid to the pre-mixing cell 10 for cleaning, and discharging a waste fluid generated from cleaning into the waste fluid cell 70; and
cleaning the sheath flow impedance counting cell 20, in which the front cell 21 is cleaned by a sheath fluid in the front sheath fluid cell 25 through the front sheath fluid inlet port 251, the rear cell 22 is cleaned by a sheath fluid in the rear sheath fluid cell 27 through the rear sheath fluid inlet port 271, a waste fluid generated after the front cell 21 is cleaned is discharged into the waste fluid cell 70 through the waste fluid discharge port 213, and a waste fluid generated after the rear cell 22 is cleaned is discharged into the rear sheath waste fluid cell 50 through the rear sheath waste fluid outlet port 222 and the rear sheath waste fluid inlet port 51, so that the cleaning of the sheath flow impedance counting cell 20 is completed. During cleaning of the sheath flow impedance counting cell 20, the sample needle 23 is also cleaned. In addition, during the cleaning of the sheath flow impedance counting cell 20, a blood sample is added to the pre-mixing cell 10 and a reagent is added, so that the blood sample and the reagent react to obtain a sample fluid with a predetermined dilution ratio. In addition, the valve V3 and the valve V10 are powered on and closed, to close the low pressure port 61 of the buffering cell and the second connecting port 65. At this time, the waste fluid cell 70 is in communication with the buffering cell through the valve V9. The negative pressure in the waste fluid cell 70 enables the buffering cell to form one auxiliary negative pressure source. Therefore, the cleaning of the sheath flow impedance counting cell 20, the addition and even mixing of a sample fluid in the pre-mixing cell 10, and negative pressure pre-supplied in the buffering cell are completed within the same period.
The sheath flow impedance counting cell 20 is used to measure a sample fluid. The sheath fluid in the front sheath fluid cell 25 is fed into the front cell 21 through the front sheath fluid inlet port 251, and the sheath fluid in the rear sheath fluid cell 27 is fed into the rear cell 22 through the rear sheath fluid inlet port 271, to form front and rear sheath fluids in the sheath flow impedance counting cell 20. During the formation of the front and rear sheath fluids in the sheath flow impedance counting cell 20, the valve V1 and the valve V3 are powered off. The negative pressure in the buffering cell draws the sample fluid in the pre-mixing cell 10 into the sample needle 23. That is, the sample fluid flows into the sample needle 23 through the valve V1 and the feeding port 231, so that a conduit between the valve V1 and the second discharge port 235 is filled with the sample fluid. The valve V1 and the valve V3 are powered on and closed. The syringe 236 pushes the sample fluid in the sample needle 23 into the front cell 21 through the first discharge port 232 to enable a particle flow beam in the front cell 21 to pass through the gem hole 242 for measurement. During measurement of the sample fluid by the sheath flow impedance counting cell 20, a rear sheath waste fluid in the rear cell 22 keeps being discharged into the rear sheath waste fluid cell 50. Because there is no sealing cover, the rear sheath waste fluid cell 50 is connected to the waste fluid cell 70 by the valve V8. During measurement, the valve V8 is opened, and the waste fluid in the rear sheath waste fluid cell 50 is discharged into the waste fluid cell 70. Because there is no sealing cover 54, as a waste fluid is discharged by the rear sheath waste fluid cell 50, the pressure is kept approximately equal to the atmospheric pressure, so that the measurement by the sheath flow impedance counting cell 20 is not affected. When the measurement is completed, the waste fluids in the rear sheath waste fluid cell 50 and the buffering cell also have been basically discharged, and a next time of measurement can be performed without a need to wait. During measurement of the sample fluid by the sheath flow impedance counting cell 20, it may also be set to complete even mixing of the sample fluid in the pre-mixing cell 10.
The measurement of a next measurement cycle in the second embodiment of the sheath flow impedance particle analyzer in the present application comprises the following step:
cleaning the sheath flow impedance counting cell 20, powering on and closing the valve V1, adding a sheath fluid to the sheath flow impedance counting cell 20 for cleaning, and cleaning the sample needle 23. During the cleaning of the sheath flow impedance counting cell 20, a current sample fluid is added to the pre-mixing cell 10 to perform even mixing. The two steps can be completed at the same time point. That is, when the cleaning of the sheath flow impedance counting cell 20 is completed, the sample fluid in the pre-mixing cell 10 has been evenly mixed. Alternatively, the sample loading and even mixing of the current sample fluid in the pre-mixing cell 10 may start from a last measurement cycle and last until a current cleaning stage of the sheath flow impedance counting cell 20, provided that sample loading and even mixing of the current sample fluid are completed when the current cleaning of the sheath flow impedance counting cell 20 is completed.
The sheath flow impedance counting cell 20 is used to perform measurement. After the cleaning of the sheath flow impedance counting cell 20 is completed, the sheath fluid in the front sheath fluid cell 25 is fed into the front cell 21 through the front sheath fluid inlet port 251, and the sheath fluid in the rear sheath fluid cell 27 is fed into the rear cell 22 through the rear sheath fluid inlet port 271, to form front and rear sheath fluids required by the sheath flow impedance counting cell 20. During the formation of the front and rear sheath fluids in the sheath flow impedance counting cell 20, the valve V1 is powered off. The negative pressure in the buffering cell draws the sample fluid in the pre-mixing cell 10 into the sample needle 23. The valve V1 and the valve V3 are then powered on and closed. When the sheath fluid preparation in the front cell 21 and the rear cell 22 is completed, the sample needle 23 also finishes preparing a sample fluid. The syringe 236 pushes the sample fluid in the sample needle 23 into the front cell 21 through the first discharge port 232 to enable the particle flow beam in the front cell 21 of the sheath flow impedance counting cell 20 to pass through the gem hole 242 for measurement. During measurement of the sample fluid by the sheath flow impedance counting cell 20, the pre-mixing cell 10 can complete cleaning in a further next measurement cycle. A waste fluid is discharged into the waste fluid cell 70 by the rear sheath waste fluid cell 50. The buffering cell completes another time of negative pressure pre-supply.
Therefore, in a measurement cycle after the first time of measurement of a sample fluid since the sheath flow impedance particle analyzer in the second embodiment is turned on, only the time required for the step of cleaning the sheath flow impedance counting cell 20 and the step of measurement by the sheath flow impedance counting cell 20 is needed in each measurement cycle. The fluid discharge and cleaning of the pre-mixing cell 10, the sample loading and even mixing of the pre-mixing cell 10, the negative pressure pre-supply of the buffering cell, and the sampling and preparation of the sample fluid in the sample needle 23 can all be completed during the cleaning of the sheath flow impedance counting cell 20 and the measurement of the sample fluid by the sheath flow impedance counting cell 20. Compared with the serial measurement actions by an existing sheath flow impedance particle analyzer, the sheath flow impedance particle analyzer in this embodiment is connected to the buffering cell of the waste fluid cell 70. The negative pressure of the waste fluid cell 70 is used to establish stable negative pressure in the buffering cell to provide a stable power source for sample preparation, so that the costs are low and parallel measurement and sample preparation can be implemented. In addition, the sealing cover of the rear sheath waste fluid cell 50 is omitted, so that parallel measurement and the discharge of the waste fluid in the rear sheath waste fluid cell 50 are implemented, so that the measurement cycle of the sheath flow impedance particle analyzer is shortened and the measurement speed is increased.
Referring to
In the third embodiment, the first auxiliary negative pressure source 60 is a buffering cell. The low pressure port 61 is omitted in the buffering cell based on the first embodiment. The second auxiliary negative pressure source 90 is a syringe (as shown in
Referring to
Measurement procedures in the third and fourth embodiments of the sheath flow impedance particle analyzer in the present application are similar to the measurement procedure in the first embodiment. A first time of measurement of a sample fluid after the sheath flow impedance particle analyzer in the third and fourth embodiments is turned on comprises the following steps:
cleaning the pre-mixing cell 10, powering on and closing the valve V1, adding a sheath fluid to the pre-mixing cell 10 for cleaning, and discharging a waste fluid generated from cleaning into the waste fluid cell 70; and
cleaning the sheath flow impedance counting cell 20, in which the front cell 21 is cleaned by a sheath fluid in the front sheath fluid cell 25 through the front sheath fluid inlet port 251, the rear cell 22 is cleaned by a sheath fluid in the rear sheath fluid cell 27 through the rear sheath fluid inlet port 271, a waste fluid generated after the front cell 21 is cleaned is discharged into the waste fluid cell 70 through the waste fluid discharge port 213, a waste fluid generated after the rear cell 22 is cleaned is discharged into the rear sheath waste fluid cell 50 through the rear sheath waste fluid outlet port 222 and the rear sheath waste fluid inlet port 51, and during cleaning of the sheath flow impedance counting cell 20, a blood sample is added to the pre-mixing cell 10 and a reagent is added, so that the blood sample and the reagent react to obtain a sample fluid with a predetermined dilution ratio. Therefore, the cleaning of the sheath flow impedance counting cell 20 and the addition and even mixing of a sample fluid in the pre-mixing cell 10 are performed within the same period. When the cleaning of the sheath flow impedance counting cell 20 is completed, the sample has been evenly mixed in the pre-mixing cell 10.
The sheath flow impedance counting cell 20 is used to measure a sample fluid. The sheath fluid in the front sheath fluid cell 25 is fed into the front cell 21 through the front sheath fluid inlet port 251, and the sheath fluid in the rear sheath fluid cell 27 is fed into the rear cell 22 through the rear sheath fluid inlet port 271, to form front and rear sheath fluids in the sheath flow impedance counting cell 20. During the formation of the front and rear sheath fluids in the sheath flow impedance counting cell 20, the valve V1 and the valve V3 are powered off. That is, the valve V1 and the valve V3 are opened. The negative pressure in the second auxiliary negative pressure source 90 draws the sample fluid in the pre-mixing cell 10 into the sample needle 23. That is, the second auxiliary negative pressure source 90 draws the sample fluid to flow into the sample needle 23 through the valve V1 and the feeding port 231, so that a conduit between the valve V1 and the second discharge port 235 is filled with the sample fluid. When the sheath fluid preparation in the front cell 21 and the rear cell 22 is completed, the sample needle 23 also finishes preparing a sample fluid. The valve V1 and the valve V3 are powered on and closed, the syringe 236 pushes the sample fluid in the sample needle 23 into the front cell 21 through the first discharge port 232 to enable the particle flow beam in the front cell 21 of the sheath flow impedance counting cell 20 to pass through the gem hole 242 for measurement.
During measurement of the sample fluid by the sheath flow impedance counting cell 20, a plurality of parallel actions are designed. For example, in parallel, the pre-mixing cell 10 can perform cleaning in a next measurement cycle (a second time of measurement of a sample fluid), a waste fluid is discharged into the buffering cell by the rear sheath waste fluid cell 50, the waste fluid in the buffering cell is emptied into the waste fluid cell 700, and the buffering cell completes a next time of negative pressure pre-supply. Details are as follows: The valve V8 is powered off to be opened. The rear sheath waste fluid discharge port 53 of the rear sheath waste fluid cell 50 is in communication with the low pressure port 63 of the buffering cell. The remaining pre-supplied negative pressure in the buffering cell enables the waste fluid in the rear sheath waste fluid cell 50 to flow into the buffering cell. After the negative pressure pre-supplied in the buffering cell is used up, the valve V8 is powered on and closed, and the valve V10 is powered on to be opened. The buffering cell is in communication with the atmosphere 300. The waste fluid in the rear sheath waste fluid cell 50 flows into the buffering cell by gravity. The valve V8 is then powered on and closed, and the valve V9 is then opened so that the waste fluid in the buffering cell is completely discharged into the waste fluid cell 700, that is, the waste fluid in the buffering cell is emptied. The valve V10 is then powered on and closed. At this time, only the first connecting port 64 of the buffering cell is in communication with the waste fluid cell 700. The waste fluid cell 700 enables the buffering cell to complete negative pressure pre-supply in a next measurement cycle. During measurement of the sample fluid by the sheath flow impedance counting cell 20, a rear sheath waste fluid in the rear cell 22 keeps being discharged into the rear sheath waste fluid cell 50. When the measurement is completed, the waste fluids in the rear sheath waste fluid cell 50 and the buffering cell also have been basically discharged, and a next time of measurement can be performed without a need to wait. During measurement of the sample fluid by the sheath flow impedance counting cell 20, it may also be set to complete even mixing of a sample in the pre-mixing cell 10.
A next measurement cycle in the third and fourth embodiments of the sheath flow impedance particle analyzer in the present application comprises the following step:
cleaning the sheath flow impedance counting cell 20, powering on and closing the valve V1, and adding a sheath fluid to the sheath flow impedance counting cell 20 for cleaning. During the cleaning of the sheath flow impedance counting cell 20, a current sample fluid is added to the pre-mixing cell 10 to perform even mixing. The two steps can be completed at the same time point. That is, when the cleaning of the sheath flow impedance counting cell 20 is completed, the sample fluid in the pre-mixing cell 10 has been evenly mixed. Alternatively, the sample loading and even mixing of the current sample fluid in the pre-mixing cell 10 may start from a last measurement cycle and last until a current cleaning stage of the sheath flow impedance counting cell 20, provided that sample loading and even mixing of the current sample fluid are completed when the current cleaning of the sheath flow impedance counting cell 20 is completed.
The sheath flow impedance counting cell 20 is used to perform measurement. After the cleaning of the sheath flow impedance counting cell 20 is completed, the sheath fluid in the front sheath fluid cell 25 is fed into the front cell 21 through the front sheath fluid inlet port 251, and the sheath fluid in the rear sheath fluid cell 27 is fed into the rear cell 22 through the rear sheath fluid inlet port 271, to form front and rear sheath fluids required by the sheath flow impedance counting cell 20. During the formation of the front and rear sheath fluids in the sheath flow impedance counting cell 20, the valve V1 is powered off. The negative pressure in the second auxiliary negative pressure source 90 draws the sample fluid in the pre-mixing cell 10 into the sample needle 23. When the sheath fluid preparation in the front cell 21 and the rear cell 22 is completed, the sample needle 23 also finishes preparing a sample fluid. The valve V1 and the valve V3 are then powered on and closed. The syringe 236 pushes the sample fluid in the sample needle 23 into the front cell 21 through the first discharge port 232 to enable the particle flow beam in the front cell 21 of the sheath flow impedance counting cell 20 to pass through the gem hole 242 for measurement. During measurement of the sample fluid by the sheath flow impedance counting cell 20, the pre-mixing cell 10 can complete cleaning in a further next measurement cycle. A waste fluid is discharged into the buffering cell again by the rear sheath waste fluid cell 50. The waste fluid in the buffering cell is emptied into the waste fluid cell 700 again. The buffering cell completes another time of negative pressure pre-supply.
Therefore, in a measurement cycle after the sheath flow impedance particle analyzer in the third and fourth embodiments has measured a sample fluid for the first time, only the time required for the step of cleaning the sheath flow impedance counting cell 20 and the step of measurement by the sheath flow impedance counting cell 20 is needed in each measurement cycle. The fluid discharge and cleaning of the pre-mixing cell 10, the sample loading and even mixing of the pre-mixing cell 10, the discharge of the waste fluid in the rear sheath waste fluid cell 50 to the buffering cell, the emptying of the waste fluid in the buffering cell into the waste fluid cell 700, another time of negative pressure pre-supply in the buffering cell, and sample fluid preparation in the sample needle 23 can all be completed during the cleaning of the sheath flow impedance counting cell 20 and the measurement by the sheath flow impedance counting cell 20. A person skilled in the art can understand that the discharge of the waste fluid in the rear sheath waste fluid cell 50 may be performed during the cleaning of the sheath flow impedance counting cell 20. Compared with the serial measurement actions by an existing sheath flow impedance particle analyzer, one buffering cell and one second auxiliary negative pressure source 90 are added to the sheath flow impedance particle analyzer in this embodiment, and a plurality of measurement actions can be completed in parallel during measurement, so that the measurement cycle of the sheath flow impedance particle analyzer is greatly shortened, and the measurement speed is increased.
A person skilled in the art can understand that in another embodiment, there may be no first auxiliary negative pressure source. The second auxiliary negative pressure source 90 provides a power source for sample preparation, so that measurement of the sample fluid and sample preparation in the sheath flow impedance counting cell 20 are performed in parallel. The sealing cover is omitted, so that measurement of the sample fluid in the sheath flow impedance counting cell 20 and the discharge of the waste fluid in the rear sheath waste fluid cell 50 are performed in parallel, thereby shortening the measurement cycle of the sheath flow impedance particle analyzer. If the sealing cover 54 is omitted, a waste fluid may overflow into the instrument. In another embodiment, the rear sheath waste fluid cell 50 has the sealing cover 54, but the diameter of a hole in communication with the atmosphere is appropriately increased, to adjust the magnitude of negative pressure when the waste fluid cell 70 is in communication with the rear sheath waste fluid cell 50 to discharge the waste fluid, so that during measurement, when the waste fluid is discharged by the rear sheath waste fluid cell 50, the internal pressure can be kept approximately equal to the atmospheric pressure, so that a stable sample flow is not affected during measurement by the sheath flow impedance counting cell 20.
For the sheath flow impedance particle analyzer provided in the embodiments of the present application, during the cleaning of the sheath flow impedance counting cell 20, the sample loading and even mixing of the pre-mixing cell 10 can be performed at the same time. During measurement of the sample fluid by the sheath flow impedance counting cell 20, the discharge of the waste fluid in the rear sheath waste fluid cell 50 and the sampling and preparation in the sample needle 23 can be at least partially completed within this period, so that the measurement cycle of the sheath flow impedance particle analyzer is shortened and the measurement speed is increased.
The above describes preferred implementations of the present application. It should be noted that, for a person of ordinary skill in the art, several improvements and modifications may be made without departing from the principle of the present application. These improvements and modifications are also construed as falling within the scope of protection of the present application.
This application is a bypass continuation of Patent Cooperation Treaty Application No. PCT/CN2017/120374, filed on Dec. 30, 2017, the content thereof is hereby incorporated by reference in its entirety.
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| Number | Date | Country |
|---|---|---|
| 101965517 | Feb 2011 | CN |
| 102533536 | Jul 2012 | CN |
| 103575634 | Feb 2014 | CN |
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| Entry |
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| International Search Report issued in corresponding International Application No. PCT/CN2017/120374, dated Sep. 26, 2018, 5 pages. |
| Number | Date | Country | |
|---|---|---|---|
| 20200319078 A1 | Oct 2020 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/CN2017/120374 | Dec 2017 | US |
| Child | 16907114 | US |
