CN121384351A - Device and method for detecting adhesion of pipettor - Google Patents
Device and method for detecting adhesion of pipettorInfo
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- CN121384351A CN121384351A CN202410991874.1A CN202410991874A CN121384351A CN 121384351 A CN121384351 A CN 121384351A CN 202410991874 A CN202410991874 A CN 202410991874A CN 121384351 A CN121384351 A CN 121384351A
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- pipette
- detection
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- pressure
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Abstract
A device for detecting the adhesion of a pipette includes an adapter, a position sensor, a pressure sensor, and a microcontroller. The adapter has an opening configured to receive a pipette tip of a pipette. A position sensor is electrically connected to the adapter and configured to detect a position of a pipette tip of the pipette in an opening of the adapter. The pressure sensor is in communication with the adapter and is configured to detect air pressure and to obtain a plurality of air pressure-time data that are used to evaluate the tightness of the pipette. A microcontroller is electrically connected to the pressure sensor and configured to receive a plurality of the air pressure-time data. A method for detecting the adhesion of a pipette is also provided.
Description
Technical Field
The present disclosure relates to a device and a method for detecting adhesion of a pipette.
Background
Air displacement pipettes (AIR DISPLACEMENT pipettor, ADP), also known as pressure pipettes, are commonly used in the field of biochemical engineering for the aspiration and dispensing of liquids. The operating principle of the pipette is that the air negative pressure in the pipette (Probe) is established by the driving of a plunger to suck the liquid into a pipette tip (tip) sleeved at the end of the pipette. Since the tightness between the plunger and the pipette of the pipette affects the tightness and thus the accuracy of the volume of the sucked liquid, the plunger in the pipette is usually designed with a gasket or sealing ring (O-ring) and lubricating grease (e.g. silicone oil) to ensure the tightness between the plunger and the pipette. However, the seal ring and silicone oil deteriorate with age, number of times, cumulative movement distance, and the like.
Often, during a fixed maintenance cycle of the pipette, the user is unaware of pipetting inaccuracies due to the problem of plunger aging and air tightness unless the user is willing to manually and routinely verify pipetting volume accuracy by laboratory common liquid volume verification methods. However, known methods of liquid volume verification, such as optical (Photometric) or gravitational (gravity), are quite cumbersome and inconvenient to handle.
Disclosure of Invention
In view of the above, the present disclosure provides a device and a method for detecting tightness of a pipette, which detect pressure data of the pipette when sucking liquid in a sealed space by a pressure sensor, and evaluate whether the tightness of a plunger of the pipette meets the requirement.
Some embodiments of the present disclosure provide a device for detecting the tightness of a pipette, which includes an adapter, a position sensor, a pressure sensor, and a microcontroller. The adapter has an opening configured to receive the tip of a pipette of the pipette. A position sensor is electrically connected to the adapter and configured to detect a position of a tip of a pipette of the pipette in an opening of the adapter. The pressure sensor is in communication with the adapter and is configured to detect air pressure and to obtain a plurality of air pressure-time data for detecting the tightness of the pipette. The microcontroller is electrically connected to the pressure sensor and configured to receive the air pressure-time data.
In some embodiments, the device for detecting the tightness of the pipette further comprises a display device. The display device is electrically connected with the microcontroller and is configured to display a detection result of the tightness of the pipette.
In some embodiments, the pipette forms an airtight space with the opening of the adapter when the tip of the pipette is in an airtight position in the opening of the adapter.
In some embodiments, the pressure sensor detects air pressure at intervals of no more than 50 milliseconds.
In some embodiments, the pressure sensor has a resolution of at least 5x10 -4 pounds force Per Square Inch (PSI).
In some embodiments, the adhesion detecting device of the pipette does not include a vacuum pump.
In some embodiments, the microcontroller is further configured to store a plurality of parameter settings for classifying the fit into one of a normal state, a sub-normal state, and an abnormal state.
Still other embodiments of the present disclosure provide a method of detecting tightness of a pipette, including forming an airtight space, wherein the airtight space includes a lower space of a pipette of the pipette, monitoring an air pressure in the airtight space during detection, wherein the detection period is from a detection start time point to a detection end time point, starting to move a plunger of the pipette upward at the plunger movement start time point to make a volume of the airtight space become an atmosphere and the air pressure decrease during the detection, moving the plunger to a predetermined position at the plunger movement stop time point, and then the plunger stays for a stop period to the detection end time point, obtaining a plurality of air pressure-time data during the detection, and judging tightness of the pipette via the air pressure-time data, wherein the tightness is classified into one of a normal state, a sub-normal state, and an abnormal state.
In some embodiments, the forming the airtight space is via inserting the tip of a pipette of the pipette into an opening of an adapter of a detection device, and the monitoring of the air pressure in the airtight space during detection is via a pressure sensor provided in the detection device.
In some embodiments, after inserting the tip of the pipette's pipette into the opening of the adapter, no air in the airtight space is pumped by the vacuum pump to depressurize.
In some embodiments, the method of detecting tightness of a pipette further comprises confirming, via a position sensor, that an airtight space is formed when the tip of the pipette is inserted into the opening of the adapter.
In some embodiments, the forming of the airtight space is via sealing the tip of the pipette with a sealing cap, and the monitoring of the air pressure in the airtight space during the detection is via a pressure sensor built into the pipette.
In some embodiments, the method of pipettor tightness detection further comprises deriving a barometric-time plot from the barometric-time data, and determining the pipettor tightness via the barometric-time plot.
In some embodiments, the method of pipettor tightness detection further comprises deriving from the barometric pressure-time plot a detection initiation point corresponding to a detection start time point, a movement start point corresponding to a plunger movement start time point, a movement stop point corresponding to a plunger movement stop time point, and a detection end point corresponding to a detection end time point. Wherein it is determined whether the adhesion of the pipette is in a normal state or not through a pressure change between the movement stop point and the end point.
In some embodiments, the adhesion of the pipette is determined to be a sub-normal state or an abnormal state via the pressure value at the detection initiation point and the pressure value at the detection end point.
In some embodiments, when the slope between the movement stop point and the detection end point is smaller than the first threshold, the adhesion of the pipette is judged to be in a normal state. And when the slope between the moving stopping point and the detection ending point is larger than a first threshold value and the air pressure value of the initial point minus the air pressure value of the detection ending point is larger than a second threshold value, judging that the sealing degree of the pipette is in a sub-normal state. And when the slope between the moving stopping point and the detection ending point is larger than a first threshold value and when the air pressure value of the detection starting point minus the air pressure value of the detection ending point is smaller than a second threshold value, judging that the sealing degree of the pipette is in an abnormal state.
In some embodiments, wherein the pressure detection is performed at least about 30 times over a range from the detection initiation time point to the movement start time point.
In some embodiments, the range during the stop is greater than about 500 milliseconds.
In some embodiments, the predetermined position is a position of the plunger at least about 5% of the maximum liquid suction of the pipette.
In some embodiments, the seal is abnormal to indicate that the pipette's gasket must be replaced immediately, and the seal is sub-normal to indicate that the pipette's gasket may be replaced prophylactically.
Drawings
Various aspects of the disclosure may be best understood from the following detailed description when read with the accompanying drawings. Note that the various features are not drawn to scale according to industry standard practices. In fact, the dimensions of the various features may be arbitrarily increased or reduced for clarity of discussion.
Fig. 1 shows a schematic cross-sectional view of a tightness detection device of a pipette according to some embodiments.
Fig. 2 is a schematic view showing the adhesion detecting device of the pipette of fig. 1 when operated.
Fig. 3 illustrates a flow chart of a method of detecting tightness of a pipette according to some embodiments.
Fig. 4 illustrates a pipette with a pressure sensor according to some embodiments.
Fig. 5 illustrates a flow chart of a method of detecting tightness of a pipette according to some embodiments.
Fig. 6 illustrates a flow chart of a method of determining the tightness of a pipette according to some embodiments.
Fig. 7 shows a graph of air pressure versus time during detection of a pipette, wherein the detected tightness of the pipette is in a normal state, according to an embodiment.
Fig. 8 shows a graph of air pressure versus time during detection of a pipette, wherein the detected tightness of the pipette is in a normal state, according to an embodiment.
Fig. 9 shows a graph of air pressure versus time during detection of a pipette, wherein the detected tightness of the pipette is in a normal state, according to an embodiment.
Fig. 10 shows a graph of air pressure versus time during detection of a pipette, wherein the detected tightness of the pipette is abnormal, according to an embodiment.
Fig. 11 shows a graph of air pressure versus time during detection of a pipette, wherein the detected tightness of the pipette is a sub-normal state, according to an embodiment.
Fig. 12 shows the variation of the liquid suction amount at different times of suction of different pipette according to an embodiment.
Description of the reference numerals
100 Is a detection device,
102, A body,
110 An adapter,
112 An opening,
114, Bottom part,
120 A position sensor,
130 A pressure sensor,
132 Pipe line,
140 A microcontroller,
150 A display device,
160 An airtight space,
200 A liquid transfer device,
210 A straw,
212 End portion,
220 A plunger,
222 Plunger rod,
224 A seal assembly,
226, Lower surface,
230 An inner space,
232, Upper space,
234 A lower space,
300 Steps of,
310 Operation,
320, Operating,
330 Operation,
400 Is a liquid transfer device,
410 A straw,
412 End portion,
420 Plunger piston,
422 Plunger rod,
424 Sealing assembly,
426, Lower surface,
430 Internal space,
432, Upper space,
434 A lower space,
440, Sealing cover,
442 An opening,
444, Bottom portion,
450 A pressure sensor,
460 An airtight space,
500 Steps of,
510 Operation,
520, Operation,
530 Operations of,
600:Method,
610 Step(s),
620 Step(s),
630 Step (a),
640 Step(s),
650 In normal state,
652 Sub-normal state,
654 Abnormal state,
D1 is distance,
D2 is the height dimension,
D3 height dimension,
X is the direction,
Z is the direction.
Detailed Description
The following drawings and detailed description are provided to clearly illustrate the spirit of the present disclosure. It will be understood that the present disclosure is capable of various modifications in various aspects, all without departing from the scope of the present disclosure, and that the description and drawings are intended to be illustrative, rather than limiting.
In some embodiments, the detected pipettes are used to manipulate liquids in a manual, semi-automatic, or fully automatic manner, e.g., a handheld pipettor, a pipetting module in a semi-automated device or a fully automated device.
Referring to fig. 1, a device for detecting the tightness of a pipette according to some embodiments is shown. The detection device 100 includes a body 102, an adapter 110 disposed in the body 102, a position sensor 120, a pressure sensor 130, and a microcontroller 140.
As shown in FIG. 1, the adapter 110 has an opening 112 for receiving the pipette tip of the pipette. The position sensor 120 is electrically connected to the adapter 110 and is configured to detect the position of the tip of the pipette's pipette in the opening 112 of the adapter 110. The pressure sensor 130 communicates with the adapter 110 via a conduit 132. The pressure sensor 130 is configured to detect air pressure and to detect it continuously at a plurality of time points, so that a plurality of air pressure-time data can be obtained. The microcontroller 140 is electrically connected to the pressure sensor 130, and the microcontroller 140 contains control circuitry and is configured to receive and store the measured barometric pressure-time data from the pressure sensor 130.
In some embodiments, the microcontroller 140 is further configured to perform an operation process after receiving the air pressure-time data from the pressure sensor 130, and store a plurality of parameter settings for classifying the tightness of the pipette into one of a normal state, a sub-normal state and an abnormal state. In other embodiments, the barometric pressure-time data may be transmitted to a processor external to the detection device 100 for processing.
In some embodiments, the detection apparatus 100 further comprises a display device 150. The display device 150 is electrically connected to the microcontroller 140 and configured to display the detection result of the tightness of the pipette. In some implementations, the display device may be a liquid crystal screen or a Light Emitting Diode (LED) screen. In some embodiments, the user performs the test after inserting the pipette into the opening 112 of the adapter 110 of the test device 100, and the tightness test result may be quickly obtained from the display apparatus 150 of the test device 100, for example, to show that the pipette is in a "normal state", "sub-normal state", or "abnormal state". In other embodiments, the detection device 100 may be electrically or communicatively connected to another device including a display panel, and automatically transmit the detection result to the other device and display the adhesion detection result.
Fig. 2 shows a schematic view of the detection device 100 of fig. 1 in operation. The pipette 200 is an air displacement pipette, comprising a pipette 210 and a plunger 220. The pipette 210 has an interior space 230, and the plunger 220 is disposed in the interior space 230 of the pipette 210. Plunger 220 includes a plunger rod 222 and a seal assembly 224. The plunger rod 222 is configured to move up and down in the interior space of the pipette 210 as the pipette is pipetting and draining. The seal assembly 224 is coupled to the plunger rod 222 and is configured to divide the interior space 230 of the straw 210 into an upper space 232 and a lower space 234. The pipette further comprises a gasket (e.g., an O-ring) and a lubricating oil (e.g., silicone oil) disposed between the interior of the pipette 210 and the seal assembly 224, surrounding the seal assembly 224 to ensure air tightness between the plunger 220 and the pipette 210.
As shown in fig. 2, when detecting the tightness of the pipette 200, the tip 212 of the pipette 210 is inserted into the opening 112 of the adapter 110, through the tight design of the opening 112 of the adapter 110, so that the opening 112 of the adapter 110 creates an airtight space 160 after engagement with the pipette 210 of the pipette 200. The height dimension D2 of the airtight space 160 shown in fig. 2 is from the bottom 114 of the opening 112 of the adapter 110 to the lower surface 226 of the plunger 220. That is, the airtight space 160 includes a space of the opening 112 of the adapter 110 after the pipette 200 is inserted and a lower space 234 of the pipette 200. As shown in fig. 2, the pressure sensor 130 communicates with the airtight space 160 via the pipe 132, and thus the pressure of the airtight space 160 can be detected.
The position sensor 120 is used to ensure that the position of the pipette 210 in the Z-direction (i.e., the airtight position) reaches the airtight space 160 formed at each test. In other words, with the tip 212 of the pipette 210 in this airtight position in the Z-direction, the opening 112 of the adapter 110 is sufficiently sealed to form the airtight space 160 after engagement with the pipette of the pipette 200. In some embodiments, the position sensor 120 may be used to take the distance D1 that the pipette moves downward in the opening in the Z-direction, where the pipette 210 forms an airtight space 160 with the opening 112 of the adapter 110.
In some embodiments, the detection device 100 may be adapted for use with pipettes of different brands, sizes, etc. The opening 112 of the adapter 110 may be designed to form an airtight space with a different brand, size, pipette after engagement. In some embodiments, the adapter 110 may be designed for different pipettes, so that the tip of the pipette may be inserted in the correct position in the opening 112 to ensure an airtight seal. The position sensor 120 is used to ensure that the pipette is in this correct position. In some embodiments, different brands of pipettes 200 may be designed to correspond to different openings of the adapter 110, and the position sensor 120 may be used to ensure proper placement of the pipettes 200 into the adapter 110, thereby ensuring a tight fit between the pipettes 200 and the adapter 110.
In some embodiments, in performing the detection of the tightness of the pipette 200, the pressure sensor 130 is utilized to monitor the air pressure of the airtight space 160 during the detection. After the airtight space 160 is formed, the pipetting operation of the pipette 200 is simulated, and the plunger 220 of the pipette 200 is moved upward, so that the lower space 234 of the pipette 200 is gradually enlarged, the volume of the airtight space 160 is gradually enlarged, and the air pressure is gradually reduced, which is lower than the external pressure, that is, the pressure in the airtight space 160 is negative. After the plunger 220 stops moving, the volume of the airtight space 160 is no longer changed. The airtight space 160 may maintain a negative pressure if the airtightness of the pipette 200 is sufficient. If the air tightness of the pipette 200 is insufficient, the outside air may enter the airtight space 160 from the fine groove (Riefe) to cause an increase in air pressure. In other words, since the sealing between the pipette tip of the pipette 200 and the adapter 110 is performed, the air pressure in the airtight space 160 increases due to insufficient sealing between the plunger 220 of the pipette 200 and the inner wall of the pipette 210.
When the air tightness is insufficient, the outside air can rapidly enter the airtight space 160, so that the pressure value in the airtight space 160 rapidly rises to be consistent with the air pressure of the outside environment. When the insufficient air tightness is slight, for example, a fine groove causing leakage is small, external air slowly enters the airtight space 160, and thus, the pressure rise in the airtight space 160 is slow.
In some embodiments, the upward movement of the plunger 220 of the pipette 200 may be controlled manually, or by an upper computer in an automated or semi-automated device.
After the plunger 220 of the pipette 200 stops moving upward, the pressure in the airtight space 160 should not drop any more. That is, when fitting the plurality of barometric pressure-time data to the barometric pressure-time plot, it should be seen that at the point in time when the plunger stops moving, the pressure is no longer downward. Also, if the sealability of the pipette 200 is normal, the pressure within the airtight space 160 should be maintained, and thus the air pressure value may be maintained unchanged after the point of time when the plunger stops moving in the air pressure-time graph. If the sealability of the pipette 200 is insufficient, the pressure rise caused by the external air passing through the plunger 220, silicone oil, or gasket into the airtight space 160 needs a certain period of time, and thus it should be seen that the air pressure value is inversely raised after the point of time when the plunger stops moving in the air pressure-time graph. However, the time required for the outside air to enter the airtight space 160 is short, and thus, if the pressure of the airtight space 160 is detected at a long time interval, the air pressure value after the outside air has entered the airtight space 160 is detected.
In various embodiments of the present disclosure, by detecting the pressure of the airtight space at shorter time intervals, it is possible to grasp whether the air pressure changes during the detection, particularly, a short period after stopping the movement, has a phenomenon that the air pressure value rises during the short period.
In various embodiments, by detecting the pressure of the airtight space 160, a change in air pressure during a short period after the plunger 220 stops moving can be obtained, and the degree of tightness of the pipette 200 can be distinguished from the pattern of the change in air pressure during the short period.
By continuously measuring the air pressure value of the airtight space 160 at short time intervals, it can be seen that the air pressure value of the airtight space 160 before and after the point of time at which the plunger 220 of the pipette 200 stops moving upward. And it was found that if the air tightness of the plunger 220 of the pipette 200 is insufficient, the air pressure value in the airtight space 160 starts to rise within, for example, about 500 milliseconds, about 1 second, about 2 seconds, about 3 seconds, or the like, a short period after the point of time after the plunger 220 is stopped. If the tightness of the plunger 220 of the pipette 200 is sufficient, the air pressure value of the air-tight space 160 remains substantially unchanged during this short period after the point in time after the plunger has stopped.
The degree of insufficient adhesion may be determined by the pressure change pattern of the plunger 220 during a short period after stopping the movement. In the case of a slight lack of air tightness, the air pressure value in the airtight space 160 is slightly increased in a short period after the time point at which the plunger 220 stops moving, but the air pressure value is not increased to the air pressure before the plunger moves, and the amount of the transferred liquid of the pipette is detected, and it is found that the accuracy is required, so that such a state of tightness is judged as a sub-normal state. In a serious insufficient air tightness condition, it is seen that the air pressure value of the airtight space 160 is significantly increased to be substantially equal to the air pressure before the plunger is moved, and the pipetting volume of the pipette is detected, and it is found that the accuracy requirement is significantly not met, in a short period after the time point after the plunger 220 is stopped, so that such a tightness condition is judged as an abnormal state.
In some embodiments, in subsequent detection of a sub-normal pipette, the sub-normal pipette is found, and after a period of pipetting operation, the adhesion may be changed to an abnormal state and the pipetting volume of the pipette may not significantly meet the accuracy requirement. Thus, the sub-normal state is a transition period from the normal state to the abnormal state. The liquid suction amount of the liquid shifter still meets the precision requirement, but a user can consider to perform preventive replacement.
In some embodiments of the present disclosure, the air pressure value of the airtight space 160 is continuously measured at time intervals of not more than 50 ms via the pressure sensor 130, and thus the air pressure change of the airtight space 160 during the detection of the simulated pipetting action by the pipette 200 can be accurately captured. In some embodiments, the time interval for air pressure detection may be, for example, 5 milliseconds, 10 milliseconds, 15 milliseconds, 20 milliseconds, 25 milliseconds, 30 milliseconds, 40 milliseconds, 50 milliseconds, or the like.
In some embodiments of the present disclosure, the tightness state of the pipette is determined via a pressure change of the air pressure value of the airtight space during a stop after the point in time when the plunger stops moving. In some embodiments, this stopping period is at least about 500 milliseconds. In some embodiments, a change in air pressure value during a stop within about 500 milliseconds to about 3 seconds is sufficient to determine the tightness state of the pipette. In some embodiments, the monitored stopping period may be, for example, about 600 milliseconds, 800 seconds, 1 second, 1.2 seconds, 1.5 seconds, 2 seconds, 2.5 seconds, 3 seconds, or the like. In some embodiments, other suitable time ranges are also within the scope of the present disclosure.
In some embodiments, the pressure sensor 130 of the detection device 100 detects the air pressure value of the air pressure value within 500 ms to 3 seconds (e.g., within 1 second or within 2 seconds) after the plunger 220 of the pipette 200 stops moving, to obtain continuous air pressure-time data for judging the air pressure change during the stop. In some embodiments, the number of air pressure detections is from about 30 to about 70, such as 50.
In some embodiments, the pressure sensor is used to perform pressure detection from about 100 to about 300 times, for example, every 20 milliseconds, 150 times during the entire detection period, i.e., from the detection initial time point, the plunger movement start time point and the plunger movement stop time point, to the detection end time point, so that the air pressure values uniformly distributed along the time axis within 3 seconds can be obtained. In other embodiments, the detection is performed every 20 milliseconds, about 250 detections are performed, and thus air pressure values within about 5 seconds are obtained that are evenly distributed along the time axis. The pressure change during the detection can be grasped more accurately by obtaining the air pressure value of the closed space more times with a shorter air pressure detection interval.
In some embodiments of the present disclosure, the tightness of the pipettes is classified into three types, normal state, abnormal state, and sub-normal state. The abnormal state represents that the gasket of the liquid shifter should be replaced immediately. The sub-normal state represents that the pipette's gasket can be replaced prophylactically.
The known device for detecting the tightness of a pipette requires that the space in the device containing the tip of the pipette is first evacuated for pressure reduction, at least below atmospheric pressure or for vacuum, and then pressure detection is performed to detect the tightness of the pipette. However, such a known device requires a vacuum pump to be provided therein or to be connected to an external vacuum pump via a communication pipe, and requires a large volume or to be connected to the vacuum pump in use. Moreover, such known devices also take a while to perform the evacuation and depressurization. In various embodiments of the present disclosure, the volume of the enclosed space is increased and the pressure is reduced by controlling the plunger of the pipette to move upward, thereby achieving the effect of reduced pressure similar to that of vacuum pumping.
In various embodiments of the present disclosure, the detection resolution of the pressure sensor is a resolution of at least 5x10 -4 PSI (pounds force per square inch), and preferably, a pressure sensor with finer resolution may be utilized. In some implementations, the detection resolution of the pressure sensor may be, for example, a resolution of about 5x10 -4 PSI, a resolution of about 1x10 -4, a resolution of about 5x10 -5, a resolution of 1x10 -5, or the like. In some embodiments, other suitable pressure sensor detection resolutions are also within the scope of the present disclosure.
In various embodiments, the volume of the testing device can be saved and the testing can be started without connecting a vacuum pump and inserting the pipette into the opening of the adapter. In some embodiments, the entire detection period may be completed within about 10 seconds, such as within about 5 seconds.
In some embodiments, the duration of the tightness test is from a test initiation time point to a test end time point, and covers a time point when the plunger of the pipette starts moving upward to a time point when the movement is stopped. In some embodiments, pressure detection data is obtained at least about 30 times (e.g., about 50 times) over the range from the initial time point to the movement start time point (e.g., about 1 second) to obtain pressure value data for the airtight space when the plunger is not moved. In some embodiments, about 100 times of pressure detection data are obtained during the period from the start of plunger movement to the stop of plunger movement of the pipette (about 2 seconds). In some embodiments, the range of plunger stop movement to the end of test time point is about 0.5 seconds to 3 seconds, resulting in about 30 to 100 (e.g., 50, 70, 80, or 90) times of pressure test data.
Fig. 3 illustrates a flow chart of a method of detecting tightness of a pipette according to some embodiments. In operation 310 of method 300, a pipette tip of a pipette is first inserted into an adapter opening of a detection device to form an airtight space.
In operation 320 of the method 300, the air pressure value of the air-tight space is monitored and the plunger of the pipette is moved upward to a predetermined position, resulting in a plurality of air pressure-time data during the detection. In some embodiments, this predetermined position is a position of the plunger at least about 5% (e.g., about 10%) of the maximum liquid suction of the pipette. For example, taking a 1000 microliter pipette as an example, the plunger of the pipette is moved to a position that aspirates at least 50 microliters (e.g., 100 microliters) of liquid. In other embodiments, the plunger of the pipette is moved to a position that aspirates other volumes, such as a position of about 20% of the maximum aspiration, a position of about 50%, a position of about 75%, a position of about 90%, or the like.
In operation 330 of the method 300, the tightness state of the pipette is determined via the air pressure-time data.
In some embodiments, a barometric-time plot is derived from these barometric-time data, and the tightness of the pipette is determined via the barometric-time plot.
In some embodiments, the microcontroller 140 of the detection device 100 may be configured to receive the air pressure-time data, fit the air pressure-time data to an air pressure-time curve, and determine the tightness of the pipette via the stored and set parameters.
In some embodiments, alternatively, the air pressure-time data or air pressure-time curve of different tightness conditions can be collected as training data of tightness classification by a machine learning method, and a classification model of tightness is built.
In an alternative embodiment, a pipette with a built-in pressure sensor may be used to detect pressure changes in the airtight space formed when the tip of the pipette is sealed, and pressure-time data may be obtained, and then these data may be transmitted to a computing device to determine the tightness of the pipette.
Fig. 4 illustrates a pipette with a built-in pressure sensor according to some embodiments. The pipette 400 is similar to the pipette 200 in fig. 2, and thus a description of some of the same or similar parts is omitted. Pipette 400 includes a pipette 410 and a plunger 420. Straw 410 has an interior space 430 and plunger 420 is disposed within interior space 430 of straw 410. The plunger 420 includes a plunger rod 422 and a seal assembly 424. Plunger rod 422 is configured to move up and down within interior space 430 of straw 410 as the straw aspirates and discharges liquid. Seal assembly 424 is coupled to plunger rod 422 and is configured to divide interior space 430 of straw 410 into an upper space 432 and a lower space 434. The pressure sensor 450 may detect the pressure in the lower space of the straw 410.
In some embodiments, when detecting the tightness of pipette 400, tip 412 of pipette 410 is sealed with sealing cap 440, so that lower space 434 of pipette 410 forms airtight space 460 with opening 442 of sealing cap 440. The height dimension D3 of the airtight space 460 shown in fig. 4 is from the bottom 444 of the opening 442 of the sealing cap 440 to the lower surface 426 of the plunger 420. Thereafter, the pressure sensor 450 may be used to detect a pressure change in the airtight space 460 before and after the point in time at which the plunger 420 moves upward and stops moving.
In some embodiments, to sensitively detect a pressure change for a short period of time after the plunger stops moving, the pressure sensor 450 detects the air pressure within the airtight space 460 at intervals of not more than 50 milliseconds (e.g., at intervals of about 20 milliseconds). In some embodiments, the pressure of the pressure sensor 450 may have a resolution of at least 5x10 -4 PSI (pounds force per square inch), for example, a resolution of 5x10 -5 PSI to 5x10 -4 PSI.
Fig. 5 illustrates a flow chart of a method of detecting tightness with a built-in pressure sensor pipette according to some embodiments. Method 500 may be similar to method 300, except that pressure-time data for the airtight space during detection is obtained with a built-in pressure sensor.
In operation 510 of method 500, the pipette tip of the pipette is first sealed (e.g., the opening of the pipette tip is sealed with a sealing cap) to form an airtight space.
In operation 520 of method 500, the air pressure value of the air-tight space is monitored with a built-in pressure sensor and the plunger of the pipette is moved up to a predetermined position, resulting in a plurality of air pressure-time data during the detection.
In operation 530 of the method 500, the tightness state of the pipette is determined via the air pressure-time data.
Fig. 6 illustrates a flow of a method of determining the tightness of a pipette according to some embodiments. The method 600 is used to distinguish between detected pipettes based on the graphical characteristics of the barometric pressure versus time plot.
In step 610 of method 600, barometric pressure-time data is received. In some embodiments, the air pressure-time data is collected using a microcontroller in the tightness detection device. In other embodiments, the barometric pressure-time data detected by the pressure sensor is transmitted to an external computing device.
In step 620 of method 600, a detection initiation point, a movement start point, a movement stop point, and a detection end point are found from the barometric pressure-time curve. The detection initial point corresponds to a detection start time point. The movement start point corresponds to a plunger movement start time point. The movement stop point corresponds to a plunger movement stop time point. The detection end point corresponds to a detection end time point. Wherein the pressure value varies significantly between a start point of movement and a stop point of movement.
The corresponding pressure values at these time points in the barometric pressure-time diagram can be used to evaluate the tightness of the pipette. In some embodiments, it may be determined whether the adhesion of the pipette is in a normal state via a pressure change between the movement stop point and the end point. In some embodiments, the adhesion of the pipette may be determined to be a sub-normal state or an abnormal state via the pressure value at the initial point of detection and the pressure value at the end point of detection.
In step 630 of method 600, it is determined whether the slope between the movement stopping point and the detection ending point is less than a first threshold. In step 630, if yes, it may be determined that the detected adhesion condition of the pipette is a normal state 650. If no, the step 630 indicates that the pipette has a problem of tightness, and the step 640 is followed to determine the leakage degree of the pipette.
In some embodiments, the rise in slope represents a condition where there is a rise in pressure in the airtight space between the movement stopping point and the detection ending point, and further, there is a leak. In some embodiments, the first threshold may define a suitable value depending on the volume of the airtight space, the applicable pipettes, the reading settings of the pressure sensor, etc.
In step 640 of method 600, it is determined whether the barometric pressure value at the initial detection point minus the barometric pressure value at the end detection point is less than a second threshold. In step 640, if yes, it may be determined that the detected adhesion condition of the pipette is a sub-normal condition 652. In step 640, if no, this pipette is indicated as being in an abnormal state 654.
If the tightness of the pipette is normal, the air pressure value to the detection end point should be maintained substantially unchanged after the plunger stops moving upward. The slope of the curve is upward during the stop and a small difference of the air pressure value at the detection initiation point minus the detection end point represents an increase in the corresponding air pressure value at the detection end point, and a larger amplitude of the air pressure increase represents a higher degree of leakage.
In some embodiments, the second threshold may define a suitable value depending on the volume of the airtight space, the applicable pipettes, the reading settings of the pressure sensor, etc.
Figures 7-11 below illustrate air pressure versus time graphs of pipettes during testing according to various embodiments. Wherein the squat target value is a pressure reading from a digital-to-Analog converter (ADC) in the pressure sensor, ranging from a 32767 reading corresponding to a 3.6PSI. The abscissa is the time axis and the units of the values are 20 milliseconds. In the various embodiments of fig. 7-11, the entire test period is about 5 seconds, with no more than 250 pressure readings taken.
The pipettes a (adp_a), F (adp_f) and B (adp_b) of fig. 7, 8 and 9 are pipettes with normal pipetting conditions. The pipettes B2 (adp_b2) of fig. 10 and B3 (adp_b3) of fig. 11 are tested after the pipettes B are replaced with old gaskets. Table 1 below shows the average value (mean) and Coefficient of Variation (CV) of the actual liquid suction amounts, which were collected in 100. Mu.L of liquid suction by the gravity method (GRAVIMETRIC METHOD), respectively, and measured by a balance.
TABLE 1
Wherein NA represents inapplicability.
Referring first to fig. 7 to 9, it can be seen that in the detection curves of the pipettes A, F and B in which the liquid suction amount is normal, the pressure in the closed space does not rise significantly from the time point when the plunger stops moving to the time point when the detection is completed.
Referring to fig. 10, it can be seen that in the detection curve of the pipette B2, the pressure of the closed space significantly rises to a pressure value approximately equal to the detection initial time point from the time point when the plunger stops moving to the time point when the detection ends. And referring to table 1, it can be seen that the average value of the actual liquid suction amount of the pipette B2 deviates significantly from the preset liquid suction amount, and the actual liquid suction amount variation coefficient is as high as 2.7. It can be seen from the detection curve of fig. 10 that the adhesion of the pipettes is abnormal.
Referring to fig. 11, it can be seen that in the detection curve of the pipette B3, the pressure in the closed space slightly increases from the time point when the plunger stops moving to the time point when the detection ends. Referring to table 1, it can be seen that the average value and the variation coefficient of the actual liquid suction amount of the liquid dispenser B3 are similar to the test result of the liquid dispenser A, F, B in the normal state, which means that the liquid dispenser B3 has leakage, but the actual liquid suction amount meets the requirement of liquid suction accuracy. It can be seen that the detection curve of fig. 11 reflects the state that the adhesion of the pipette is sub-normal.
The barometric pressure-time data detected by the embodiment pipettes of fig. 7-11 are shown below as corresponding barometric pressure values at various points in time obtained in the steps of method 600 in fig. 6, and parameters associated with these barometric pressure values.
Referring to fig. 7, in the pressure-time curve of the adhesion detection of the pipette a, it can be seen that the pressure value at the detection start point is 21371.0, the pressure value at the movement start point is 21295.0, the pressure value at the movement stop point is-1273.0, and the pressure value at the detection end point is-1200. Thus, the slope between the movement stop point and the detection end point can be found to be 1.089.
Referring to fig. 8, in the pressure-time curve of the adhesion detection of the pipette F, it can be seen that the pressure value at the detection start point is 23450.0, the pressure value at the movement start point is 23384.0, the pressure value at the movement stop point is 50.0, and the pressure value at the detection end point is 127.0. Thus, the slope between the movement stop point and the detection end point can be found to be 0.6.
Referring to fig. 9, in the pressure-time curve of the adhesion detection of the pipette B, it can be seen that the pressure value at the detection start point is 21310.0, the pressure value at the movement start point is 21216.0, the pressure value at the movement stop point is-3334.0, and the pressure value at the detection end point is-3299.0. Thus, the slope between the movement stop point and the detection end point can be found to be 0.507.
Referring to fig. 10, in the pressure-time curve of the adhesion detection of the pipette B2, it can be seen that the pressure value at the detection start point is 238.0, the pressure value at the movement stop point is-673.0, and the pressure value at the detection end point is 240.0. Thus, the slope between the movement stop point and the detection end point can be found to be 16.6. Further, the air pressure value of the initial point minus the air pressure value of the detection end point is-2.
Referring to fig. 11, in the pressure-time curve of the adhesion detection of the pipette B3, it can be seen that the pressure value at the detection start point is 12751.0, the pressure value at the movement start point is 11362.0, the pressure value at the movement stop point is-11096.0, and the pressure value at the detection end point is-10248.0. Thus, the slope between the movement stop point and the detection end point can be found to be 12.11. Further, the air pressure value of the initial point minus the air pressure value of the detection end point is 22999.
The embodiment of fig. 7 to 11 is used to detect the air pressure-time data and determine the detected tightness state of the pipette according to the flow of the method 600 in fig. 6, and in step 630, the first threshold may be set to 2 when it is confirmed whether the slopes of the movement stop point and the detection end point are smaller than the first threshold. Further, in step 640, when it is confirmed whether the air pressure value at the detection start point minus the air pressure value at the detection end point is smaller than the second threshold value, the second threshold value may be set to 5000 (pressure reading).
Fig. 12 shows the variation of the liquid suction amount at different times of suction of different pipette according to an embodiment. In FIG. 12, the pipettes tested are automated pipettes capable of pipetting up to 1000 microliters (μl). The test is to use the pipette tip of P50 to suck 5 microliters according to different using times (such as 1 ten thousand times, 11 ten thousand times, 21 ten thousand times, 31 ten thousand times, 41 ten thousand times, 51 ten thousand times and 61 ten thousand times), detect by a gravity method, operate 10 times and calculate a variation coefficient to judge whether the performance of the pipette is in compliance. Wherein pipettes I and J are new pipettes, the gasket of pipettes B is replaced with an old gasket, and pipettes B are judged to be in a sub-normal state after the adhesion detection method of the present disclosure (see FIGS. 2, 3, and 6). In FIG. 12, the spec line is a standard value of the Coefficient of Variation (CV) at the time of pipetting of 5. Mu.L by the P50 pipette, and is fixed at 2.
As shown in fig. 12, it can be seen that the coefficient of variation in the liquid suction amount significantly increases after a lapse of a certain period of time (51 ten thousand times of liquid suction) in the pipette B judged to be in the sub-normal state, and the liquid suction stability is not good. Therefore, it is understood that the method for detecting the adhesion of the present disclosure can predict that the adhesion of the pipette will be abnormal, that the leakage is serious, and that the pipetting error is large. Therefore, the pipette judged as being in a sub-normal state in the detection result can perform preventive maintenance such as replacement of the gasket.
The sealing degree detection device of the pipettor and the method for detecting the sealing degree of the pipettor provided by the embodiments of the disclosure can directly perform sealing test on the pipettor without pumping air by a vacuum pump, so that the detection time can be effectively reduced. The judging method is simple and convenient, so that the method can be applied to pipettes of different brands, and the interface for accommodating the pipettes is in an airtight state only when detecting.
Embodiments of the present disclosure may determine the degree of tightness of a plunger of a pipette and may give preventive maintenance advice. The user can be prompted to perform maintenance in advance before the air density is deteriorated to the level affecting the accuracy of the pipetting volume, so that the problem of pipetting volume abnormality due to air tightness abnormality of the pipetter can be avoided. In addition, the classification result of the tightness condition can enable a user to refer to the time for updating the consumable in the pipette, so that the problem of air tightness is avoided from affecting the performance of the pipette. Furthermore, the user may not have to periodically perform a more cumbersome fluid volume verification method (e.g., gravity).
While the present disclosure has been illustrated and described with respect to several embodiments and examples, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the disclosure, and it is therefore intended that the scope of the disclosure be limited only by the terms of the appended claims.
Claims (20)
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