CN115876530A

CN115876530A - Pipetting amount detection method for pipettor and sample analyzer

Info

Publication number: CN115876530A
Application number: CN202110974897.8A
Authority: CN
Inventors: 苗壮; 肖擎国; 吴栋杨; 练子富; 李临
Original assignee: Kemei Boyang Diagnostic Technology Shanghai Co ltd
Current assignee: Kemei Boyang Diagnostic Technology Shanghai Co ltd
Priority date: 2021-08-24
Filing date: 2021-08-24
Publication date: 2023-03-31

Abstract

The invention provides a liquid transfer amount detection method for a liquid transfer device and a sample analyzer. The method comprises the following steps: in the pipetting process, detecting the pressure in the pipetting channel of the pipettor at a plurality of time points to obtain corresponding measured pressure values; and comparing each measured pressure value with preset pressure values at a plurality of preset corresponding time points, and determining whether the pipetting quantity in the pipetting process is in accordance with expectation through the difference between each measured pressure value and the preset pressure value.

Description

Pipetting amount detection method for pipettor and sample analyzer

Technical Field

The invention relates to the technical field of biochemical detection experiments, in particular to a liquid transfer amount detection method for a liquid transfer device. The invention also relates to a sample analyzer, in particular a chemiluminescence analyzer.

Background

Pipettes are an important component of sample analyzers for performing biochemical tests, which are used to move samples and reagents between different positions (e.g., from a sample tube to a reaction vessel). In many assay items, the amount of sample and reagent used (i.e., pipette volume) is closely related to the read curve after reaction and the final assay result. If there is a problem with the amount of sample and reagent used, there is a possibility that the result of the analysis will be erroneous. This may cause serious medical accidents. Therefore, ensuring the accuracy of the liquid transfer amount is an important research topic in the field.

In the prior art in the field, methods exist for detecting the pipetting volume of a pipette. However, this method mainly performs pressure detection only at one or two time points during suction or discharge and detects them with a predetermined pressure threshold. If the detected pressure is higher than the threshold value, the air leakage phenomenon of the pipettor does not occur, and the pipetting volume of the pipettor is considered to be accurate. However, in the actual use process, the detection method is not ideal, and misjudgment is easy to occur.

In addition, the prior art also provides a scheme for pressure detection of the pipettor in the whole pipetting process. However, this solution is to perform pressure detection from the time when the pipette is moved until the pipette is completely moved and returns to the original position, mainly to determine whether the nozzle at the lower end of the pipette is submerged below the liquid surface by determining whether the pressure is changed. This solution also does not allow to know accurately and effectively whether the pipetting volume of the pipettor is accurate.

Disclosure of Invention

Based on the above, the invention provides a liquid transfer amount detection method for a liquid transfer device and a sample analyzer. By the method and the sample analyzer, the liquid displacement amount of the liquid transfer device can be accurately known.

According to a first aspect of the present invention, there is provided a pipette amount detection method for a pipette, comprising the steps of: in the pipetting process, detecting the pressure in the pipetting channel of the pipettor at a plurality of time points to obtain corresponding measured pressure values; and comparing each measured pressure value with preset pressure values at a plurality of preset corresponding time points, and determining whether the pipetting quantity in the pipetting process is in accordance with expectation through the difference between each measured pressure value and the preset pressure value.

By the method, the suction pressure of the pipettor can be continuously and effectively detected and tracked in the process of pipetting by the pipettor. If an unexpected change in pressure occurs, which results in a large difference between the measured pressure value and the preset pressure value, this indicates that there is an occasional situation during pipetting, which may cause the pipetting volume to deviate from the expected volume. Compared with the method of measuring the pressure only at a certain point and judging whether the pressure is higher than the threshold value in the prior art, the method can detect more accidental situations in the pipetting process, so that whether the pipetting quantity is in accordance with the expectation can be more accurately determined. This is of great importance for determining the validity of the analysis results.

In one embodiment, during pipetting, the pipettor starts to aspirate or discharge after moving to the right position, and pressure detection is started when the pipettor starts to aspirate or discharge, so that the measured pressure value corresponds to the preset pressure value at the corresponding time point.

In one embodiment, the measured pressure value corresponding to the preset pressure value at the first point in time is fitted to a plurality of pressure values measured over a time range corresponding to said first point in time.

In one embodiment, the fitting may be achieved by arithmetic mean processing.

In one embodiment, when each of the measured pressure values is compared with a preset pressure value set in advance at a corresponding time point, a measured pressure curve is formed by a plurality of the measured pressure values and is compared with a preset pressure curve formed by the preset pressure values.

In one embodiment, when comparing each measured pressure value with a preset pressure value at a respective predetermined point in time, it is determined that the pipetting volume during pipetting is not as expected if the difference between the measured pressure value and the corresponding preset pressure value exceeds a preset threshold value.

In one embodiment, at the corresponding point in time, if the measured pressure value is above a preset pressure value and the difference exceeds a preset threshold, it is determined that the pipetting channel of the pipette is blocked.

In one embodiment, at the corresponding point in time, if the measured pressure value is below a preset pressure value and the difference exceeds a preset threshold, a pipette channel leak is determined for the pipette.

In one embodiment, an alarm is issued in case it is determined that the pipetting volume during pipetting is not as expected.

In one embodiment, in case it is determined that the pipetting quantity during pipetting is not as expected, the analysis process is completed with the alarm being raised, resulting in an analysis result, wherein it is determined whether pipetting and analysis need to be repeated on the basis of said analysis result.

According to a second aspect of the present invention, there is provided a sample analyzer for performing the above-described pipette amount detection method for a pipette. The sample analyzer includes: the pressure sensor is communicated to a pipetting channel of the pipettor through a pipeline and is used for detecting the pressure in the pipetting channel to obtain the measured pressure value; and a data comparator configured to compare the measured pressure value with the preset pressure value.

In one embodiment, the data comparator is configured for forming a measured pressure curve from a plurality of measured pressure values and forming a preset pressure curve from the measured pressure curve and preset pressure values in the same coordinate system.

In one embodiment, the pressure sensor is connected by a line to a pipetting channel in a pipetting pump of the pipette.

In one embodiment, the sample analyzer further comprises: the liquid transfer device comprises an adapting component and a liquid transfer pump, wherein the adapting component is used for being connected with a suction nozzle, the liquid transfer pump is connected with the adapting component, a liquid transfer channel communicated with the suction nozzle is formed in the adapting component, and the liquid transfer pump is constructed to be capable of carrying out positive pressure or negative pressure in the liquid transfer channel so as to realize liquid suction or liquid discharge through the suction nozzle; and an actuator configured to issue an alarm if it is determined that the pipetting volume during pipetting is not as expected.

In one embodiment, the actuator is configured to cause the sample analyzer to complete an analysis process while the alarm is issued, resulting in an analysis result.

In one embodiment, the actuator is configured to determine whether to repeat pipetting and analyzing based on the analysis result.

In one embodiment, the actuator is configured to initiate pipetting or draining after the pipettor is moved into position, and the pressure sensor begins to detect pressure within the pipetting channel from the same time as the pipettor begins to aspirate or drain.

Drawings

The present invention will be described below with reference to the accompanying drawings.

Fig. 1 is a preset pressure curve during pipetting in a pipetting volume detection method for a pipette according to an embodiment of the present invention;

fig. 2 is a preset pressure curve during liquid discharge in a pipette amount detection method for a pipette according to an embodiment of the present invention;

fig. 3 is a schematic block diagram of a sample analyzer according to one embodiment of the present invention.

Fig. 4 is a schematic diagram of a detailed structure of a portion of the sample analyzer of fig. 3.

In the drawings, like parts are provided with like reference numerals. In the present application, the drawings are all schematic and are used only for illustrating the principles of the invention and are not drawn to scale.

Detailed Description

The invention is described below with reference to the accompanying drawings.

The invention provides a pipetting quantity detection method for a pipettor, which is mainly used for determining whether the pipetting quantity of the pipettor is in accordance with expectation in the pipetting process.

First, during pipetting, the pressure in the pipetting channel of the pipette is detected at a plurality of points in time to obtain corresponding measured pressure values. In this pipetting process, the pipettor is first moved into position, for example by a translational and descending movement, to a predetermined position for pipetting or draining. Thereafter, the pipette resumes suction or discharge action to effect a pipetting or draining process, respectively. The pressure detection may be started when the pipette starts pipetting or discharging, and stopped when pipetting or discharging ends. This facilitates convenient correspondence between time points and measured pressure values.

Then, each detected pressure value is compared with a preset pressure value set in advance corresponding to the same time point. Determining whether the amount of liquid removed is as expected by comparing the difference between the obtained measured pressure value and the predicted pressure value. The measured pressure value at the same point in time may be compared to a preset pressure value. If the difference obtained by comparison exceeds a predetermined threshold value, the difference between the measured pressure value and the preset pressure value is over-large. At this time, it is considered that the pipetting process of the pipette is in an unexpected state, and the pressure fluctuates abnormally. Deviations in pressure can lead to a joint check of the flow rate, so that it can be determined that the pipetting volume of the pipette is not as expected. If all the measured pressure values are consistent with the expected pressure values, namely the difference is within a preset threshold value, the pipetting process is normally carried out, and finally the pipetting amount which is consistent with the expectation can be obtained.

Here, the preset pressure value may be a corresponding average value or a reasonable fitting value through a plurality of calibration operation processes. The predetermined threshold may be determined as desired and in use, and may be, for example, between-100 p and +100 p.

In the whole liquid suction or liquid discharge process, pressure detection can be frequently and uniformly carried out at a plurality of time points, so that the measured pressure value can be effectively distributed in the whole liquid suction or liquid discharge process, and the pressure value and the pressure change condition in the whole liquid suction or liquid discharge process can be expressed representatively.

For example, fig. 1 shows a preset pressure curve formed by preset pressure values of the pipetting process. As can be seen from FIG. 1, the whole pipetting process starts from 0.1s and ends at 1.9 s. During the whole imbibing process, 19 pressure measurements were performed, every 0.1s, thus obtaining 19 preset pressure values evenly distributed along the time line. Accordingly, it is possible to perform the detection every 0.1s also during the actual pipetting process, resulting in 19 measured pressure values.

For example, fig. 2 shows a preset pressure curve formed by preset pressure values during a liquid discharge. As can be seen from fig. 2, the whole draining process starts from 0.1s and ends at 1.3 s. During the whole liquid discharge process, 13 pressure detections were performed, every 0.1s, thus obtaining 13 preset pressure values evenly distributed along the time line. Accordingly, in the actual liquid discharge process, the detection can be performed every 0.1s, and 13 measured pressure values can be obtained.

Furthermore, in a preferred embodiment, the measured pressure value may be a fitted value. That is, the measured pressure value corresponding to the preset pressure value at the first time point may be a value fitted to pressure values measured over a period of time corresponding to the time point. The fitting here is preferably achieved by arithmetic mean processing. For example, the time range corresponding to the first time point may be a time range that is expanded by a range around the time point. In addition, the time points may be measured at a higher frequency, for example every 0.05 s. For example, a plurality (e.g., 3) of pressure values measured in the range of 0.35s to 0.45s may be subjected to an arithmetic average process to obtain a corresponding measured pressure value corresponding to a preset pressure value of 0.4 s. This is advantageous for more accurate knowledge of the pressure changes during pipetting.

In one embodiment, a pair-wise comparison between values may be made between the measured pressure value and the preset pressure value.

In another embodiment, the measured pressure curve may be formed by a plurality of measured pressure values and the preset pressure curve may be formed by a plurality of preset pressure values (fig. 1 and 2). By placing the measured pressure curve and the preset pressure curve in the same coordinate system and aligned along the time axis, a comparison between the two curves can be achieved, thereby achieving a comparison between the measured pressure value and the preset pressure value from another angle.

When the measured pressure value is basically consistent with the preset pressure value, namely is within the range of the preset threshold value, the fact that the liquid transfer machine works normally can be determined, and the liquid transfer amount which is consistent with the expectation can be obtained.

When the measured pressure value is higher than the preset pressure value and the difference therebetween exceeds the preset range, it can be determined that a blockage has occurred in the pipetting channel of the pipette. In the case of a pipette equipped with a disposable tip, it is possible to judge that a clogging has occurred in a suction port of the disposable tip. This may be caused by the presence of unintended impurities such as blood clots in the liquid (sample or reagent).

When the measured pressure value is lower than the preset pressure value and the difference between the measured pressure value and the preset pressure value exceeds the preset pressure value, it can be determined that an air leakage phenomenon occurs in the liquid transfer channel of the pipettor, or a certain amount of air is sucked in the liquid transfer channel (for example, the suction nozzle of the pipettor is not effectively submerged into the liquid surface). For pipettes equipped with disposable tips, it is possible that the disposable tips are not effectively and sealingly mounted on the pipettes.

In the above method, by uniformly and dispersedly performing pressure measurement throughout the whole pipetting or discharging process, a plurality of measured pressure values are obtained, and it is possible to comprehensively and effectively know the pressure change during the pipetting or discharging process and thereby determine whether the pipetting quantity is as expected. Compared with the prior art, the method has more accurate determination of the pipetting quantity, and can generally determine the possibility of error (such as blockage or sealing failure) of the pipetting quantity by comparing the difference between the measured pressure value and the preset pressure value, and has the function of guiding and indicating the subsequent working step.

In the case that a deviation exists between the measured pressure value and the preset pressure value and the difference is large, the subsequent work (for example, the analysis process of the sample analyzer on the sample) can be continuously completed while the alarm or prompt is issued, and then the analysis result and the alarm are output together. Thus, it can be determined from the analysis result and the alarm whether pipetting and analysis need to be repeated or whether further processing of the liquid is required.

The present invention also provides a sample analyzer 100 that can be used to implement the above-described method. As shown in fig. 3, the sample analyzer 100 may include a pipette 110, a pressure sensor 130, and a data comparator 140. Pipette 110 may be a pipette 110 equipped with a disposable nozzle 113. Such a pipette 110 may comprise a pipette pump 111, an adaptation member 112, and a disposable suction nozzle 113. The adapter member 112 is connected between the pipetting pump 111 and the disposable suction nozzle 113 and forms a pipetting channel for pipetting or discharging liquid between them.

The pressure sensor 130 may be in communication with the pipetting channel via line 120 for measuring the pressure in the pipetting channel resulting in the measured pressure value described above. In one embodiment, the pressure sensor may be connected by a line to a pipetting channel within the pipetting pump. In the preferred embodiment shown in fig. 3, the pressure sensor 130 is connected to the pipetting channel in the adapter member 112 via line 120. As shown in fig. 4, the adapter member 112 may include a pressure measurement interface 112A disposed at the side of the tubular connection in the adapter member 112. The pressure measurement interface communicates to the pipetting channel within the adapter member 112. Thus, when the line 120 is connected to the pressure measurement interface 112A, communication between the line 120 and the pipetting channel can be achieved. The arrangement is compact and simple, and can realize accurate measurement of pressure.

The data comparator 140 may be configured to receive the measured pressure value from the pressure sensor 130 and compare it to a pre-stored pre-set pressure value.

In one embodiment, the data comparator 140 may directly compare the measured pressure value with a preset pressure value at the corresponding time point.

In an alternative or additional embodiment, the data comparator 140 may fit a plurality of measured pressure values to a measured pressure curve. In addition, the data comparator 140 may also fit a pre-stored preset pressure value to a preset pressure curve. The data comparator 140 may place the measured pressure curve and the preset pressure curve into the same coordinate system with the time delay axes aligned. Thus, a form of comparison between the curves can be provided.

For example, the data comparator 140 may directly compare the measured pressure value with a preset pressure value one by one, and output a comparison difference value or a result indicating whether the comparison difference exceeds a preset threshold. In particular, an alarm may be issued when the comparison difference exceeds a preset threshold. The alarm may include, for example, a reason or the like that may cause the pressure differential. In addition, the data comparator 140 may also output a coordinate system having a measured pressure curve and a preset pressure curve to the operator. Thus, the operator can visually check and analyze the measured pressure curve and the preset pressure curve by comparing the comparison difference value output from the data comparator 140 or the result of whether the comparison difference exceeds the preset threshold value.

In addition, the sample analyzer 100 is also provided with an actuator (not shown). The actuator may be independent of the data comparator 140 or may be integrally formed with the data comparator 140. The actuator controls movement of the pipettor (including lateral movement, raising and lowering) and pipetting and draining actions. Particularly, the actuator can control the liquid transfer device to move firstly and then control the liquid transfer device to suck or discharge liquid.

In addition, the actuator can control the pressure sensor to start detecting the pressure in the liquid transfer channel to obtain the measured pressure value at the same time of controlling the liquid transfer device to start liquid suction or liquid discharge.

Further, the actuator can receive the difference between the measured pressure value and the predicted pressure value from the data comparator 140 and determine whether to re-pipette and analyze based on the difference and the analysis results. Alternatively or additionally, the operator determines whether or not pipetting and analysis need to be performed anew based on the difference and the analysis result, and the actuator controls the sample analyzer 100 and the pipetter therein based on the determination result of the operator.

By the method and the sample analyzer, whether the liquid transfer amount of the liquid transfer device is in accordance with the expectation can be effectively and accurately detected. If not, possible problems or situations can be output according to the measurement result. The method and the sample analyzer can effectively help operators to obtain the analysis result of the sample, indicate the validity of the analysis result and further help the operators to analyze the sample more efficiently.

In this context, atmospheric pressure is defined as 0 Pa, positive pressure is greater than 0 Pa and negative pressure is less than 0 Pa.

Finally, it should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and do not limit the present invention in any way. Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described in the foregoing examples, or that equivalents may be substituted for elements thereof. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A pipetting volume detection method for a pipette, comprising the steps of:

in the pipetting process, detecting the pressure in the pipetting channel of the pipettor at a plurality of time points to obtain corresponding measured pressure values;

and comparing each measured pressure value with preset pressure values at a plurality of preset corresponding time points, and determining whether the pipetting quantity in the pipetting process is in accordance with expectation through the difference between each measured pressure value and the preset pressure value.

2. The pipette amount detection method for a pipette according to claim 1, wherein, during pipetting, the pipette starts pipetting or discharging after moving to a position, and pressure detection is started from when the pipette starts pipetting or discharging, so that the measured pressure value corresponds to a preset pressure value at a corresponding time point.

3. A pipette detection method for a pipette according to claim 1, characterized in that the measured pressure value corresponding to a preset pressure value at a first point in time is obtained by fitting a plurality of pressure values measured over a time range corresponding to the first point in time.

4. A pipette detection method for a pipette according to claim 1, characterized in that the fitting is achievable by arithmetic mean processing.

5. The pipette amount detection method according to claim 1, wherein in comparing each of the measured pressure values with a preset pressure value at a corresponding time point set in advance, a measured pressure curve is formed by a plurality of the measured pressure values and is compared with a preset pressure curve formed by the preset pressure values.

6. The pipette amount detection method according to claim 1, wherein in comparing each measured pressure value with a preset pressure value at a corresponding time point set in advance, if a difference between the measured pressure value and the corresponding preset pressure value exceeds a preset threshold value, it is determined that the pipette amount during pipetting does not meet an expectation.

7. The pipette volume detection method for a pipette according to claim 6, wherein it is determined that a pipette channel of the pipette is clogged if the measured pressure value is higher than a preset pressure value and the difference exceeds a preset threshold value at the corresponding time point.

8. The pipette detection method according to claim 6, wherein at the corresponding time point, if the measured pressure value is lower than a preset pressure value and the difference exceeds a preset threshold value, it is determined that the pipette channel of the pipette is air-leaking.

9. A pipette volume detection method for a pipette according to any one of claims 1 to 8, characterized in that an alarm is issued in the event that it is determined that the pipette volume during pipetting is not as expected.

10. The pipette detection method according to any one of claims 1 to 8, wherein in the case where it is determined that the pipette amount during pipetting does not meet the expectation, the analysis process is completed while an alarm is issued, resulting in an analysis result,

wherein it is determined whether pipetting and analyzing need to be performed anew based on the analysis result.

11. A sample analyzer for performing the pipette amount detection method for a pipette according to any one of claims 1 to 10, the sample analyzer comprising:

the pressure sensor is communicated to a pipetting channel of the pipettor through a pipeline and is used for detecting the pressure in the pipetting channel to obtain the measured pressure value; and

a data comparator configured to compare the measured pressure value to the preset pressure value.

12. The sample analyzer of claim 11, wherein the data comparator is configured to form a measured pressure curve from a plurality of measured pressure values and to form a preset pressure curve from the measured pressure curve and preset pressure values in the same coordinate system.

13. The sample analyzer of claim 11, wherein the pressure sensor communicates through a line to a pipetting channel in an adapter member of the pipette.

14. The sample analyzer of claim 11, further comprising:

the liquid transfer device comprises an adapting component and a liquid transfer pump, wherein the adapting component is used for being connected with a suction nozzle, the liquid transfer pump is connected with the adapting component, a liquid transfer channel communicated with the suction nozzle is formed in the adapting component, and the liquid transfer pump is constructed to be capable of carrying out positive pressure or negative pressure in the liquid transfer channel so as to realize liquid suction or liquid discharge through the suction nozzle; and

an actuator configured to issue an alarm if it is determined that the amount of pipetting during pipetting is not as expected.

15. The sample analyzer of claim 14, wherein the actuator is configured to cause the sample analyzer to complete an analysis process while an alarm is issued, resulting in an analysis result.

16. The sample analyzer of claim 14, wherein the actuator is configured to determine whether to re-pipette and analyze based on the analysis results.

17. The sample analyzer of claim 14 wherein the actuator is configured to initiate pipetting or draining after the pipettor is moved into position, and the pressure sensor begins to detect pressure within the pipetting channel at the same time that the pipettor begins to aspirate or drain.