TWI914889B - Device for detecting tightness of pipetteor and method therefor - Google Patents

Abstract

A device for detecting the tightness of a pipettor includes an adapter, a position sensor, a pressure sensor, and a microcontroller. The adapter has an opening configured to receive the probe end of a pipettor. The position sensor is electrically connected to the adapter and configured to sense the position of the probe end of the pipettor in the opening of the adapter. The pressure sensor is in communication with the adapter and configured to sense the air pressure and obtain a plurality of air pressure-time data, which are used to evaluate the tightness of the pipettor. The microcontroller is electrically connected to the pressure sensor and configured to receive the pressure-time data. The disclosure also provides a method for detecting the tightness of a pipettor.

Description

Device and method for testing the fit of pipettes

This disclosure relates to a device and method for testing the fit of pipettes.

Air displacement pipettes (ADPs), also known as pressure pipettes, are widely used in biochemistry for the aspiration and dispensing of liquids. The operating principle of a pipette involves using a plunger to create negative air pressure within the probe, drawing liquid into the tip of the pipette. Since the seal between the plunger and the pipette affects the airtightness and consequently the accuracy of liquid volume aspiration, the plunger is typically designed with a gasket or sealing ring (O-ring) and lubricant (such as silicone oil) to ensure this airtightness. However, the sealing ring and silicone oil deteriorate over time due to factors such as usage, frequency of use, and cumulative travel distance.

During the standard maintenance cycle of a pipette, users often fail to notice pipetting inaccuracies caused by plunger aging and airtightness issues, unless they are willing to manually and routinely verify the accuracy of pipetting volumes using commonly used laboratory liquid volume verification methods. However, conventional liquid volume verification methods, such as photometric or gravimetric methods, are quite cumbersome and inconvenient to operate.

In view of the above problems, this disclosure provides a pipette fit testing device and a pipette fit testing method, which evaluates whether the pipette plunger's airtightness meets the requirements by using a pressure sensor to sense the pressure data when the pipette simulates liquid aspiration in an airtight space.

Some embodiments of this disclosure provide a pipette fit detection device, comprising: an adapter, a position sensor, a pressure sensor, and a microcontroller. The adapter has an opening configured to receive the tip of a pipette. The position sensor is electrically connected to the adapter and configured to sense the position of the pipette tip within the opening of the adapter. The pressure sensor is connected to the adapter and configured to sense air pressure and obtain multiple pressure-time data points used to detect the pipette fit. The microcontroller is electrically connected to the pressure sensor and configured to receive the pressure-time data points.

In some embodiments, the pipette fit detection device also includes a display device. The display device is electrically connected to the microcontroller and configured to display the pipette fit detection result.

In some embodiments, when the tip of the pipette is in an airtight position within the opening of the adapter, the pipette and the opening of the adapter form an airtight space.

In some implementations, the pressure sensor detects air pressure at intervals of no more than 50 milliseconds.

In some implementations, the pressure sensor has a resolution of at least 5 x ^10⁻⁴ pounds per square inch (PSI).

In some implementations, the pipette fit detection device does not include a vacuum pump.

In some implementations, the microcontroller is also configured to store multiple parameter settings to classify the fit into one of three states: normal, subnormal, and abnormal.

Other embodiments of this disclosure provide a method for detecting the seal of a pipette, comprising: forming an airtight space, wherein the airtight space includes the lower space of the pipette tube; monitoring the air pressure in the airtight space during the detection period, wherein the detection period is from the start time of the detection to the end time of the detection; and during the detection period, moving the pipette plunger upwards at the plunger movement start time. The plunger is moved to increase the volume of the airtight space and decrease the air pressure. At the point when the plunger stops moving, the plunger moves to a predetermined position and then remains stationary until the end of the test. Multiple pressure-time data points are obtained during the test. Based on these pressure-time data points, the pipette's sealing degree is determined, which is divided into one of the following: normal state, subnormal state, and abnormal state.

In some embodiments, the airtight space is formed by inserting the end of a pipette tip into the opening of an adapter of a detection device, and the monitoring of the air pressure in the airtight space during the detection period is performed by a pressure sensor disposed in the detection device.

In some implementations, after inserting the end of the pipette into the opening of the adapter, no vacuum pump is used to remove air from the airtight space to reduce the pressure.

In some implementations, the pipette fit detection method also includes using a position sensor to confirm that an airtight space is formed when the tip of the pipette is inserted into the opening of the adapter.

In some embodiments, the airtight space is formed by sealing the end of the pipette with a sealing cap, and the monitoring of the air pressure in the airtight space during the detection period is performed by a pressure sensor built into the pipette.

In some implementations, the method for detecting the pipette seal also includes obtaining a pressure-time curve from these pressure-time data and determining the pipette seal from the pressure-time curve.

In some implementations, the method for detecting the pipette's seal also includes obtaining the following from a pressure-time curve: a detection start point corresponding to the start time of detection; a movement start point corresponding to the start time of plunger movement; a movement stop point corresponding to the stop time of plunger movement; and a detection end point corresponding to the end time of detection. The pipette's seal is then determined by the pressure change between the movement stop point and the detection end point.

In some implementations, the pipette's seal is determined to be subnormal or abnormal by detecting the pressure values at the initial and final points.

In some implementations, when the slope between the stopping point and the end point of detection is less than a first threshold, the pipette's seal is considered normal. When the slope between the stopping point and the end point of detection is greater than the first threshold, and the difference between the initial pressure and the end pressure is greater than a second threshold, the pipette's seal is considered subnormal. When the slope between the stopping point and the end point of detection is greater than the first threshold, and the difference between the initial pressure and the end pressure is less than a second threshold, the pipette's seal is considered abnormal.

In some implementations, at least about 30 stress tests are performed over the period from the initial detection time to the start of movement.

In some implementations, the pause period is greater than approximately 500 milliseconds.

In some implementations, the predetermined position is when the plunger is positioned at least about 5% of the maximum volume of liquid aspirated by the pipette.

In some implementations, an abnormal fit indicates that the pipette gasket must be replaced immediately, while a subnormal fit indicates that the pipette gasket can be replaced preventively.

The spirit of this disclosure will be clearly illustrated below with diagrams and detailed descriptions. It should be understood that this disclosure may have various variations in different forms, but none of them shall depart from the scope of this disclosure, and the descriptions and accompanying diagrams are for illustrative purposes only and not for limiting the content of this disclosure.

In some implementations, the pipette being tested is used to manipulate liquids manually, semi-automatically, or fully automatically, such as a handheld pipette or a pipetting module in a semi-automated or fully automated device.

Referring to Figure 1, a pipette fit detection device according to some embodiments is shown. The detection device 100 includes a body 102 and an adapter 110, a position sensor 120, a pressure sensor 130, and a microcontroller 140 disposed in the body 102.

As shown in Figure 1, adapter 110 has an opening 112 for receiving the tip of a pipette. A position sensor 120 is electrically connected to adapter 110 and configured to sense the position of the pipette tip within the opening 112 of adapter 110. A pressure sensor 130 is connected to adapter 110 via conduit 132. The pressure sensor 130 is configured to sense air pressure and continuously senses at multiple time points, thus providing multiple pressure-time data points. A microcontroller 140 is electrically connected to pressure sensor 130 and includes control circuitry configured to receive and store the pressure-time data measured by pressure sensor 130.

In some embodiments, the microcontroller 140 is also configured to perform calculations on the pressure-time data received from the pressure sensor 130 and to store multiple parameter settings to classify the pipette's fit as one of a normal, subnormal, or abnormal state. In other embodiments, the pressure-time data may be transmitted to a processor outside the detection device 100 for calculations.

In some embodiments, the detection device 100 further includes a display device 150. The display device 150 is electrically connected to the microcontroller 140 and configured to display the detection result of the pipette's fit. In some embodiments, the display device may be a liquid crystal display (LCD) or a light-emitting diode (LED) display. In some embodiments, the user performs the detection after inserting the pipette into the opening 112 of the adapter 110 of the detection device 100, and the fit detection result, such as whether the pipette is in a "normal state," "subnormal state," or "abnormal state," can be quickly obtained from the display device 150 of the detection device 100. In other embodiments, the detection device 100 may be electrically or communicatively connected to another device including a display panel, automatically transmitting the detection results to this other device and displaying the fit detection results.

Figure 2 shows a schematic diagram of the detection device 100 in Figure 1 during operation. The pipette 200 is an air-replacement pipette, comprising a pipette 210 and a plunger 220. The pipette 210 has an internal space 230, and the plunger 220 is disposed within the internal space 230 of the pipette 210. The plunger 220 includes a plunger rod 222 and a sealing assembly 224. The plunger rod 222 is configured to move up and down within the internal space of the pipette 210 during aspiration and dissipation of liquid. The sealing assembly 224 is connected to the plunger rod 222 and configured to divide the internal space 230 of the pipette 210 into an upper space 232 and a lower space 234. The pipette also includes gaskets (e.g., O-rings) and lubricants (e.g., silicone oil) disposed between the inside of the pipette 210 and the sealing assembly 224, surrounding the sealing assembly 224 to ensure airtightness between the plunger 220 and the pipette 210.

As shown in Figure 2, when testing the seal of pipette 200, the end 212 of pipette 210 is inserted into the opening 112 of adapter 110. The opening 112 of adapter 110 is designed to create an airtight space 160 after engagement with the pipette 210 of pipette 200. The height dimension D2 of the airtight space 160 shown in Figure 2 extends from the bottom 114 of the opening 112 of adapter 110 to the lower surface 226 of plunger 220. That is, the airtight space 160 includes the space of the opening 112 of adapter 110 after pipette 200 is inserted and the lower space 234 of pipette 200. As shown in Figure 2, the pressure sensor 130 is connected to the airtight space 160 via the conduit 132, and can therefore sense the pressure of the airtight space 160.

The position sensor 120 ensures that the position of the pipette 210 in the Z direction (i.e., the airtight position) achieves the formation of an airtight space 160 during each test. In other words, when the end 212 of the pipette 210 is in this airtight position in the Z direction, the opening 112 of the adapter 110 is sufficiently sealed to form an airtight space 160 after engaging with the pipette of the pipette 200. In some embodiments, the position sensor 120 may be used to obtain the distance D1 by which the pipette moves downward in the Z direction within the opening, at which position the pipette 210 and the opening 112 of the adapter 110 form an airtight space 160.

In some embodiments, the detection device 100 is applicable to pipettes of different brands and sizes. The opening 112 of the adapter 110 is designed to form an airtight space after mating with pipettes of different brands and sizes. In some embodiments, the adapter 110 is designed according to different pipettes, so an airtight seal is ensured when the tip of the pipette is inserted into the correct position in the opening 112. The position sensor 120 is used to ensure that the pipette is in the correct position. In some embodiments, different brands of pipettes 200 correspond to different opening designs of the adapter 110, and the seal between the pipette 200 and the adapter 110 is ensured only after the position sensor 120 confirms that the pipette 200 is correctly inserted into the adapter 110.

In some embodiments, when testing the seal of pipette 200, a pressure sensor 130 monitors the air pressure in the airtight space 160 during the testing period. After the airtight space 160 is formed, a liquid aspiration operation of pipette 200 is simulated by moving the plunger 220 of pipette 200 upwards. Therefore, the lower space 234 of pipette 200 gradually increases, the volume of the airtight space 160 gradually increases, and the air pressure gradually decreases, falling below 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 no longer changes. If the pipette 200 is sufficiently airtight, the airtight space 160 can maintain negative pressure. If the pipette 200 is not sufficiently airtight, outside air will enter the airtight space 160 through the rife, causing the pressure to rise. In other words, since there is a tight seal between the pipette tip of the pipette 200 and the adapter 110, the pressure rise in the airtight space 160 is due to insufficient sealing between the plunger 220 of the pipette 200 and the inner wall of the pipette 210.

When the airtightness is severely compromised, outside air can quickly enter the airtight space 160, causing the pressure inside the airtight space 160 to rise rapidly to match the ambient air pressure. When the airtightness is less compromised, for example, when the leaking groove is small, outside air enters the airtight space 160 more slowly, and therefore the pressure inside the airtight space 160 rises more slowly.

In some embodiments, the upward movement of the plunger 220 of the pipette 200 can be done manually or by using a host computer in an automated or semi-automated device to control the upward movement of the plunger 220.

After the plunger 220 of pipette 200 stops moving upward, the pressure within the hermetically sealed space 160 should no longer decrease. That is, when multiple pressure-time data points are fitted into a pressure-time curve, it should be visible that the pressure no longer decreases at the point when the plunger stops moving. Furthermore, if the pipette 200 is properly sealed, the pressure within the hermetically sealed space 160 should be maintained, and therefore the pressure value in the pressure-time curve should remain unchanged after the point when the plunger stops moving. If the pipette 200 is not properly sealed, it will take some time for outside air to pass through the plunger 220, silicone oil, or gasket into the hermetically sealed space 160, causing a pressure rise. Therefore, it should be observed that the pressure value reverses and rises again after the point when the plunger stops moving in the pressure-time curve. However, the time required for outside air to enter the hermetically sealed space 160 is short; therefore, if the pressure of the hermetically sealed space 160 is measured at longer time intervals, the pressure value will be measured after outside air has entered the hermetically sealed space 160.

In various embodiments of this disclosure, by sensing the pressure of the airtight space at shorter time intervals, it is possible to monitor pressure changes during the detection period, especially whether the pressure value rises during a short period after movement stops.

In several embodiments, by detecting the pressure in the airtight space 160, the pressure change during the brief period after the plunger 220 stops moving can be obtained, and the degree of tightness of the pipette 200 can be distinguished by the state of the pressure change during this brief period.

By continuously measuring the pressure of the airtight space 160 at short time intervals, the pressure of the airtight space 160 before and after the point in time when the plunger 220 of the pipette 200 stops its upward movement can be observed. It was also found that if the airtightness of the plunger 220 of the pipette 200 is insufficient, the pressure in the airtight space 160 begins to rise within a short period after the plunger 220 stops, for example, within approximately 500 milliseconds, approximately 1 second, approximately 2 seconds, approximately 3 seconds, or similar. If the airtightness of the plunger 220 of the pipette 200 is sufficient, the pressure in the airtight space 160 remains essentially unchanged during this short period after the plunger stops.

Furthermore, the degree of insufficient airtightness can also be distinguished by the pattern of air pressure changes during the brief period after the plunger 220 stops moving. In cases of slight airtightness, during the brief period after the plunger 220 stops moving, the air pressure value within the airtight space 160 can be observed to rise slightly, but the air pressure value does not rise to the air pressure before the plunger moved. Moreover, the volume of liquid transferred by the pipette is measured and found to meet the accuracy requirements. Therefore, such an airtightness condition is judged as subnormal. In cases of severe airtightness, shortly after the plunger 220 stops, the air pressure in the airtight space 160 noticeably rises to essentially equal the air pressure before the plunger moves. Furthermore, when the pipette volume is measured, it is found to be significantly inconsistent with the accuracy requirements. Therefore, such an airtightness condition is judged to be abnormal.

In some implementation methods, subsequent testing of pipettes in a subnormal state reveals that after a period of aspiration operations, the pipette's seal deteriorates, and the pipetting volume significantly fails to meet accuracy requirements. Therefore, the subnormal state represents a transitional period from a normal to an abnormal state. Although the pipette's aspiration volume may still meet accuracy requirements during this time, users may consider preventative replacement.

In some embodiments of this disclosure, the pressure of the airtight space 160 is continuously measured by pressure sensor 130 at time intervals not exceeding 50 milliseconds, thus accurately capturing pressure changes in the airtight space 160 during the detection period of simulated aspiration. In some embodiments, the time interval for pressure detection may be, for example, 5 milliseconds, 10 milliseconds, 15 milliseconds, 20 milliseconds, 25 milliseconds, 30 milliseconds, 40 milliseconds, 50 milliseconds, or similar.

In some embodiments of this disclosure, the pipette's seal is determined by the pressure change of the gas pressure in the airtight space during a stop period after the plunger stops moving. In some embodiments, this stop period is at least about 500 milliseconds. In some embodiments, the pressure change during the stop period of about 500 milliseconds to about 3 seconds is sufficient to determine the pipette's seal. In some embodiments, the monitored stop 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 similar. In some embodiments, other suitable time ranges are also within the scope of this disclosure.

In some embodiments, the pressure sensor 130 of the detection device 100 detects the air pressure value over a period of 500 milliseconds to 3 seconds (e.g., within 1 second or 2 seconds) after the plunger 220 of the pipette 200 stops moving, to obtain continuous pressure-time data for determining pressure changes during the stop period. In some embodiments, the number of pressure measurements is approximately 30 to approximately 70, for example, 50.

In some implementations, pressure measurements are taken approximately 100 to 300 times using a pressure sensor throughout the entire testing period—from the initial testing point, through the start and stop of plunger movement, to the end of the testing period. For example, a measurement is taken every 20 milliseconds, for a total of 150 measurements. This yields pressure values evenly distributed along the time axis over a period of 3 seconds. In other implementations, a measurement is taken every 20 milliseconds, for a total of approximately 250 measurements. This yields pressure values evenly distributed along the time axis over a period of approximately 5 seconds. Obtaining more pressure readings of the confined space with shorter pressure sensing intervals allows for a more accurate understanding of pressure changes during the testing period.

In some implementations of this disclosure, pipette fit is categorized into three types: normal, abnormal, and subnormal. An abnormal fit indicates that the pipette gasket must be replaced immediately. A subnormal fit indicates that the pipette gasket can be replaced preventively.

Conventional devices for testing pipette seals require depressurizing the space containing the pipette tip within the device, at least below atmospheric pressure, or creating a vacuum, before pressure sensing to check the pipette's seal. However, such conventional devices require a vacuum pump either internally or connected to an external vacuum pump via a connecting tube, necessitating a large device size or connection to a vacuum pump during use. Furthermore, depressurization in these conventional devices is time-consuming. In several embodiments of this disclosure, controlling the upward movement of the pipette plunger increases the volume of the sealed space, reducing pressure and achieving a pressure reduction effect similar to vacuuming.

In various embodiments of this disclosure, the pressure sensor has a detection resolution of at least 5 x ^10⁻⁴ PSI (pounds per square inch), and preferably, a pressure sensor with a finer resolution may be used. In some embodiments, the detection resolution of the pressure sensor may be, for example, about 5 x ^10⁻⁴ PSI, about 1 x ^10⁻⁴ , about 5 x ^10⁻⁵ , 1 x ^10⁻⁵ , or similar. In some embodiments, other suitable detection resolutions of the pressure sensor are also within the scope of this disclosure.

In several embodiments, the size of the detection device can be reduced, and a vacuum pump does not need to be connected during use; the detection can be started simply by inserting a pipette into the opening of the adapter. In some embodiments, the entire detection process can be completed in about 10 seconds, for example, in about 5 seconds.

In some embodiments, the fit testing period extends from a test initiation point to a test end point, and covers the time from when the pipette plunger begins to move upwards to when it stops moving. In some embodiments, at least about 30 (e.g., about 50) pressure test data points are obtained within the range from the test initiation point to the start of movement (e.g., about 1 second) to obtain the pressure value data of the airtight space when the plunger is not moving. In some embodiments, about 100 pressure test data points are obtained during the period from the start of plunger movement to the stop of plunger movement (about 2 seconds). In some implementations, the plunger stops moving from the point where the test ends in the range of about 0.5 to 3 seconds, resulting in about 30 to 100 pressure test data (e.g., 50, 70, 80, or 90).

Figure 3 shows a flowchart of a pipette fit testing method according to some embodiments. In operation 310 of method 300, the pipette tip is first inserted into the adapter opening of the testing device to form an airtight space.

In operation 320 of method 300, the pressure value of the airtight space is monitored, and the plunger of the pipette is moved upward to a predetermined position to obtain multiple pressure-time data points during the detection period. In some embodiments, this predetermined position is where the plunger is positioned at least about 5% (e.g., about 10%) of the maximum volume aspirated by the pipette. For example, with a 1000 μL pipette, the plunger is moved to a position where at least 50 μL (e.g., 100 μL) of liquid is aspirated. In other embodiments, the plunger is moved to a position where other volumes are aspirated, such as about 20%, about 50%, about 75%, about 90%, or similar positions of the maximum volume aspirated.

In operation 330 of method 300, the sealing condition of the pipette is determined by the pressure-time data.

In some implementations, a pressure-time curve is obtained from these pressure-time data, and the pipette seal is determined by the pressure-time curve.

In some embodiments, the microcontroller 140 of the detection device 100 can receive pressure-time data, fit the pressure-time data into a pressure-time curve, and determine the pipette's sealing degree by storing and setting parameters.

In some implementation methods, alternatively, machine learning can be used to collect pressure-time data or pressure-time curves of different airtightness conditions as training data for airtightness classification, and establish an airtightness classification model.

In an alternative implementation, a pipette with a built-in pressure sensor can be used to detect pressure changes in the airtight space formed when the end of the pipette is sealed, obtaining pressure-time data. This data can then be transmitted to a computing device to determine the pipette's sealing condition.

Figure 4 illustrates a pipette with a built-in pressure sensor according to some embodiments. Pipette 400 is similar to pipette 200 in Figure 2, therefore descriptions of some identical or similar parts are omitted. Pipette 400 includes a pipette 410 and a plunger 420. The pipette 410 has an internal space 430, and the plunger 420 is disposed within the internal space 430 of the pipette 410. The plunger 420 includes a plunger rod 422 and a sealing assembly 424. The plunger rod 422 is configured to move up and down within the internal space 430 of the pipette 410 during aspiration and dispensing of liquid. The sealing assembly 424 is connected to the plunger rod 422 and configured to divide the internal space 430 of the pipette 410 into an upper space 432 and a lower space 434. The pressure sensor 450 can sense the pressure in the space below the straw of the straw 410.

In some embodiments, when testing the seal of pipette 400, the end 412 of pipette 410 is sealed with a sealing cap 440, thus forming an airtight space 460 between the lower space 434 of pipette 410 and the opening 442 of the sealing cap 440. The height dimension D3 of the airtight space 460 shown in Figure 4 extends from the bottom 444 of the opening 442 of the sealing cap 440 to the lower surface 426 of the plunger 420. Subsequently, a pressure sensor 450 can be used to detect pressure changes within the airtight space 460 before and after the plunger 420 moves upward and stops moving.

In some embodiments, to sensitively detect pressure changes during a brief period after the plunger stops moving, pressure sensor 450 senses the air pressure within the airtight space 460 at intervals not exceeding 50 milliseconds (e.g., approximately 20 milliseconds). In some embodiments, the pressure sensor 450 may have a pressure resolution of at least 5 x ^10⁻⁴ PSI (pounds per square inch), for example, a resolution of 5 x ^10⁻⁵ PSI to 5 x ^10⁻⁴ PSI.

Figure 5 shows a flowchart of a method for detecting the tightness of a pipette using a built-in pressure sensor, according to some embodiments. Method 500 is similar to method 300, except that the pressure-time data of the airtight space during the detection period are obtained using a built-in pressure sensor.

In operation 510 of method 500, the pipette tip is first sealed (e.g., by sealing the opening at the tip of the pipette with a sealing cap) to form an airtight space.

In operation 520 of method 500, the pressure value of the airtight space is monitored by the built-in pressure sensor, and the plunger of the pipette is moved upward to a predetermined position to obtain multiple pressure-time data during the detection period.

In operation 530 of method 500, the sealing condition of the pipette is determined by the pressure-time data.

Figure 6 illustrates a flowchart of a method for determining the fit of a pipette according to some implementation methods. Method 600 is used to distinguish the fit of the tested pipette based on the graphical characteristics of the pressure-time curve.

In step 610 of method 600, pressure-time data is received. In some embodiments, a microcontroller in a fit detection device collects the pressure-time data. In other embodiments, the pressure-time data sensed by the pressure sensor is transmitted to an external computing device.

In step 620 of method 600, the detection start point, movement start point, movement stop point, and detection end point are identified from the pressure-time curve. The detection start point corresponds to the detection start time. The movement start point corresponds to the plunger movement start time. The movement stop point corresponds to the plunger movement stop time. The detection end point corresponds to the detection end time. Significant pressure changes occur at the movement start point and movement stop point.

The pressure values corresponding to these time points in the pressure-time curve can be used to assess the pipette's seal condition. In some implementations, the pipette seal condition can be determined by the pressure change between the stop and end points of the movement. In other implementations, the pipette seal condition can be determined by detecting the pressure values at the initial and end points, indicating a subnormal or abnormal seal.

In step 630 of method 600, it is confirmed whether the slope between the movement stop point and the detection end point is less than a first threshold. If yes, in step 630, the pipette's fit is determined to be normal 650. If no, in step 630, it indicates a fit problem with the pipette, and the process continues to step 640 to determine the degree of pipette leakage.

In some embodiments, an increase in the slope indicates an increase in pressure within the airtight space between the point of movement stop and the detection end point, and also indicates leakage. In some embodiments, a suitable value can be defined for the first threshold, depending on the volume of the airtight space, the applicable pipette, the pressure sensor reading settings, etc.

In step 640 of method 600, it is confirmed whether the difference between the pressure value at the initial detection point and the pressure value at the end detection point is less than a second threshold. If yes, in step 640, the pipette's seal condition is determined to be subnormal 652. If no, in step 640, the pipette is considered abnormal 654.

If the pipette seal is normal, the pressure should remain essentially unchanged from the moment the plunger stops moving upwards until the end of the test. During the pause, an upward slope of the curve and a small difference between the initial and final pressure readings indicate a pressure increase at the end of the test; a greater increase in pressure indicates a higher degree of leakage.

In some implementations, the second threshold can define a suitable value depending on the volume of the airtight space, the available pipettes, the pressure sensor reading settings, etc.

Figures 7 through 11 below show the pressure-time curves of the pipette during the detection period according to different embodiments. The vertical axis values represent the pressure readings from the digital-to-digital converter (ADC) in the pressure sensor, ranging from ±32767 readings to ±3.6 PSI. The horizontal axis is the time axis, with values in 20 milliseconds. In each embodiment of Figures 7 through 11, the entire detection period is approximately 5 seconds, with no more than 250 pressure readings obtained.

Pipettes A (ADP_A) in Figure 7, F (ADP_F) in Figure 8, and B (ADP_B) in Figure 9 are pipettes with normal aspiration function. Pipettes B2 (ADP_B2) in Figure 10 and B3 (ADP_B3) in Figure 11 were tested after replacing the old gaskets on pipette B. Table 1 below shows the mean and coefficient of variation (CV) of the actual aspirated volume, collected using the gravimetric method and measured using a balance after aspirating 100 μL.

Table 1 pipette number Number of inhalations and exhalations Straw tip type Liquid absorption volume (μL) Average actual volume of liquid absorbed (μL) Coefficient of variation of actual aspirated volume A 43,000 Boyu P1000 100 91.906 0.386 F 260,000 Boyu P1000 100 90.580 0.279 B 160,000 Boyu P1000 100 90.248 0.172 B2 NA Boyu P1000 100 38.825 2.710 B3 NA Boyu P1000 100 91.276 0.076 NA indicates that it is not applicable.

First, referring to Figures 7 to 9, it can be seen that in the test curves of pipettes A, F, and B with normal aspiration volume, the pressure in the sealed space did not increase significantly from the time when the plunger stopped moving to the time when the test ended.

Referring to Figure 10, it can be seen that in the test curve for pipette B2, from the point when the plunger stops moving to the point when the test ends, the pressure in the sealed space rises significantly to approximately the same pressure value as at the initial test point. Furthermore, referring to Table 1, it can be seen that the average actual aspirated volume of pipette B2 deviates significantly from the preset aspirated volume, and the coefficient of variation for the actual aspirated volume is as high as 2.7. Therefore, the test curve in Figure 10 reflects an abnormal state of pipette seal.

Referring to Figure 11, it can be seen that in the test curve of pipette B3, the pressure in the sealed space slightly increases from the point when the plunger stops moving to the point when the test ends. Furthermore, referring to Table 1, it can be seen that the average actual aspirated volume and coefficient of variation of pipette B3 are close to the test results of pipettes A, F, and B under normal conditions. This indicates that although pipette B3 has leakage, the actual aspirated volume meets the requirements for aspirated accuracy. Therefore, the test curve in Figure 11 reflects a sub-normal sealing condition of the pipette.

The following shows the pressure-time data detected by the pipettes of the embodiments in Figures 7 through 11, with corresponding pressure values at each time point obtained in the steps of method 600 in Figure 6, and parameters associated with these pressure values.

Referring to Figure 7, in the pressure-time curve for pipette A's fit detection, the pressure value at the initial detection point is 21371.0, the pressure value at the start of movement is 21295.0, the pressure value at the stop of movement is -1273.0, and the pressure value at the end of detection is -1200. Therefore, the slope between the stop of movement and the end of detection can be calculated to be 1.089.

Referring to Figure 8, in the pressure-time curve for the fit test of pipette F, the pressure value at the initial detection point is 23450.0, the pressure value at the start of movement is 23384.0, the pressure value at the stop of movement is 50.0, and the pressure value at the end of detection is 127.0. Therefore, the slope between the stop of movement and the end of detection can be calculated to be 0.6.

Referring to Figure 9, in the pressure-time curve for the fit test of pipette B, the pressure value at the initial detection point is 21310.0, the pressure value at the start of movement is 21216.0, the pressure value at the stop of movement is -3334.0, and the pressure value at the end of the test is -3299.0. Therefore, the slope between the stop of movement and the end of the test can be calculated to be 0.507.

Referring to Figure 10, in the pressure-time curve for the fit test of pipette B2, the pressure values at the initial and final points are 238.0, -673.0, and 240.0 respectively. Therefore, the slope between the final and final points is 16.6. Furthermore, the difference between the initial and final pressure values is -2.

Referring to Figure 11, in the pressure-time curve of the pipette B3's fit test, the pressure value at the initial detection point is 12751.0, the pressure value at the start of movement is 11362.0, the pressure value at the stop of movement is -11096.0, and the pressure value at the end of the test is -10248.0. Therefore, the slope between the stop of movement and the end of the test can be calculated as 12.11. Furthermore, the difference between the initial pressure value and the end pressure value is 22999.

The pressure-time data obtained from the embodiments in Figures 7 to 11 are used to determine the contact condition of the pipette in the process of method 600 in Figure 6. In step 630, if it is confirmed that the slope between the movement stop point and the detection end point is less than a first threshold, the first threshold can be set to 2. Furthermore, in step 640, if it is confirmed that the difference between the pressure value at the detection start point and the pressure value at the detection end point is less than a second threshold, the second threshold can be set to 5000 (pressure reading).

Figure 12 illustrates the variation in volume aspirated by different pipettes at different numbers of aspirations, according to an embodiment. In Figure 12, the pipettes tested are automatic pipettes with a maximum aspiration capacity of 1000 microliters (μl). This test is based on the pipette being used at different numbers of aspirations (e.g., 10,000, 110,000, 210,000, 310,000, 410,000, 510,000, and 610,000) with a P50 pipette tip to aspirate 5 μL, and the performance of the pipette is determined by gravity method after 10 operations and the coefficient of variation is calculated. Pipettes I and J are new pipettes; the gasket of pipette B has been replaced with an old one, and pipette B is determined to be subnormal after being tested using the fit testing method disclosed herein (see Figures 2, 3, and 6). In Figure 12, the spec line represents the specification value of the coefficient of variation (CV) when the P50 pipette aspirates 5 μL of liquid, which is fixed at 2.

As shown in Figure 12, pipette B, judged to be in a subnormal state, exhibits a significant increase in its coefficient of variation for aspiration volume after a period of time (510,000 aspirations), indicating poor aspiration stability. Therefore, the contact fit testing method disclosed herein can predict when a pipette's contact fit will become abnormal, resulting in severe leakage and large aspiration errors. Consequently, pipettes judged to be in a subnormal state based on test results can undergo preventative maintenance, such as replacing the gaskets.

The pipette sealing test apparatus and method disclosed herein, which allow for direct sealing tests on the pipette without the need for a vacuum pump, effectively reduce testing time. Furthermore, the sealing condition is determined by comparing the difference in the upward slope over a time interval during the test, and/or the initial and final pressure values during the test. This method is simple and applicable to pipettes from different brands, provided the pipette interface is airtight during the test.

The various implementations disclosed herein can determine the airtightness of a pipette plunger and provide preventative maintenance recommendations. Because it alerts users to perform maintenance before airtightness deteriorates to the point of affecting the accuracy of pipetting volume, it avoids pipetting volume abnormalities caused by airtightness issues. Furthermore, the classification of airtightness conditions allows users to determine when to replace consumables in the pipette, preventing airtightness problems from affecting pipette performance. Moreover, users no longer need to periodically perform cumbersome liquid volume verification methods (such as gravity methods).

Although the contents of this disclosure have been disclosed above in various embodiments and examples, they are not intended to limit the contents of this disclosure. Anyone skilled in the art may make various modifications and alterations without departing from the spirit and scope of this disclosure. Therefore, the scope of protection of this disclosure shall be determined by the scope of the appended patent application.

100: Detection Device 102: Body 110: Adapter 112: Opening 114: Bottom 120: Position Sensor 130: Pressure Sensor 132: Tubing 140: Microcontroller 150: Display Device 160: Airtight Space 200: Pipette 210: Pipette 212: End 220: Plunger 222: Plunger Rod 224: Sealing Assembly 226: Lower Surface 230: Internal Space 232: Upper Space 234: Lower Space 300: Method 310: Operation 320: Operation 330: Operation 400: Pipette 410: Pipette 412: End 420: Plunger 422: Plunger Rod 424: Sealing Assembly 426: Lower Surface 430: Internal Space 432: Upper Space 434: Lower Space 440: Sealing Cap 442: Opening 444: Bottom 450: Pressure Sensor 460: Airtight Space 500: Method 510: Operation 520: Operation 530: Operation 600: Method 610: Step 620: Step 630: Step 640: Step 650: Normal State 652: Subnormal State 654: Abnormal State D1: Distance D2: Height Dimension D3: Height Dimension X: Direction Z: Direction

The various aspects of this disclosure can be best understood by reading the following detailed description in conjunction with the accompanying figures. Note that, according to industry standard practice, the features are not drawn to scale. In fact, the dimensions of the features can be arbitrarily increased or decreased for clarity of discussion. Figure 1 shows a schematic cross-sectional view of a pipette fit detection device according to some embodiments. Figure 2 shows a schematic diagram of the pipette fit detection device of Figure 1 in operation. Figure 3 shows a flowchart of a pipette fit detection method according to some embodiments. Figure 4 shows a pipette with a pressure sensor according to some embodiments. Figure 5 shows a flowchart of a pipette fit detection method according to some embodiments. Figure 6 illustrates the flowchart of a method for determining pipette seal according to some embodiments. Figure 7 shows a pressure-time curve during pipette testing according to an embodiment, where the tested pipette seal is normal. Figure 8 shows a pressure-time curve during pipette testing according to an embodiment, where the tested pipette seal is normal. Figure 9 shows a pressure-time curve during pipette testing according to an embodiment, where the tested pipette seal is normal. Figure 10 shows a pressure-time curve during pipette testing according to an embodiment, where the tested pipette seal is abnormal. Figure 11 shows a pressure-time curve during pipette testing according to an embodiment, where the pipette's seal is subnormal. Figure 12 shows the variation in volume aspirated by different pipettes at different numbers of aspirations, according to an embodiment.

100: Detection Device 102: Body 110: Adapter 112: Opening 120: Position Sensor 130: Pressure Sensor 132: Pipeline 140: Microcontroller 150: Display Device

Claims (20)

A pipette fit detection device includes: an adapter having an opening configured to receive a tip of a pipette from a pipette such that a lower portion of the pipette and the opening of the adapter form an airtight space; a position sensor electrically connected to the adapter and configured to sense a position of the tip of the pipette within the opening of the adapter; a pressure sensor connected to the adapter and configured to sense air pressure and obtain multiple pressure-time data points used to evaluate a fit of the pipette; and a microcontroller electrically connected to the pressure sensor and configured to receive the pressure-time data points. The pipette fit detection device as described in claim 1 further includes: a display device electrically connected to the microcontroller and configured to display the fit detection result of the pipette. The pipette fit detection device as described in claim 1, wherein when the end of the pipette is in an airtight position in the opening of the adapter, the lower space of the pipette and the opening of the adapter form the airtight space. The pipette fit detection device as described in claim 1, wherein the pressure sensor senses air pressure at intervals not exceeding 50 milliseconds. The pipette fit detection device as described in claim 1, wherein the pressure sensor has a resolution of at least 5 x ^10⁻⁴ pounds per square inch (PSI). The pipette fit detection device as described in claim 1 does not include a vacuum pump. The pipette fit detection device as described in claim 1, wherein the microcontroller is further configured to store multiple parameter settings for classifying the fit into one of a normal state, a subnormal state, and an abnormal state. A method for detecting the seal of a pipette includes: forming an airtight space, wherein the airtight space includes a lower portion of a pipette tube of a pipette; monitoring the pressure in the airtight space during a detection period, wherein the detection period extends from a detection start time to a detection end time; during the detection period, at a plunger movement start time, moving a plunger of the pipette upward to increase the volume of the airtight space and decrease the pressure, moving the plunger to a predetermined position at a plunger movement stop time, and then holding the plunger for a stop period until the detection end time; obtaining multiple pressure-time data points during the detection period; and The pipette's seal is determined using these pressure-time data, and this seal is categorized into one of three states: normal, subnormal, or abnormal. The method for testing the airtightness of a pipette as described in claim 8, wherein the airtight space is formed by inserting one end of the pipette tube into an opening of an adapter of a detection device, and the monitoring of the air pressure in the airtight space during the detection period is performed by a pressure sensor disposed in the detection device. The pipette sealing test method as described in claim 9, wherein after inserting the end of the pipette tube into the opening of the adapter, the air in the airtight space is not depressurized by using a vacuum pump. The pipette fit detection method as described in claim 9 further includes using a position sensor to confirm that an airtight space is formed when the end of the pipette tube is inserted into the opening of the adapter. The method for testing the airtightness of a pipette as described in claim 8, wherein the airtight space is formed by sealing one end of the pipette tube with a sealing cap, and the monitoring of the air pressure in the airtight space during the testing period is performed by a pressure sensor built into the pipette. The pipette fit detection method as described in claim 8 further includes obtaining a pressure-time curve from the pressure-time data, and determining the fit of the pipette from the pressure-time curve. The pipette fit testing method as described in claim 13 further comprises: obtaining from the pressure-time curve: a test start point, corresponding to the test start time point; a movement start point, corresponding to the plunger movement start time point; a movement stop point, corresponding to the plunger movement stop time point; and a test end point, corresponding to the test end time point; wherein the pipette fit is determined to be in the normal state by a pressure change between the movement stop point and the test end point. The pipette fit testing method as described in claim 14, wherein: the pipette fit is determined to be in the subnormal or abnormal state by measuring a pressure value at the initial testing point and a pressure value at the end testing point. The pipette fit detection method as described in claim 14, wherein: when the slope between the point of stop and the point of detection is less than a first threshold, the pipette fit is determined to be in the normal state; when the slope between the point of stop and the point of detection is greater than the first threshold, and when the difference between the pressure at the initial detection point and the pressure at the end of the detection is greater than a second threshold, the pipette fit is determined to be in the subnormal state; and when the slope between the point of stop and the point of detection is greater than the first threshold, and when the difference between the pressure at the initial detection point and the pressure at the end of the detection is less than the second threshold, the pipette fit is determined to be in the abnormal state. The pipette fit testing method as described in claim 8, wherein at least about 30 pressure tests are performed within the range from the initial testing time to the start of the movement. The pipette fit testing method as described in claim 8, wherein the stop period is greater than about 500 milliseconds. The method for testing the fit of a pipette as described in claim 8, wherein the predetermined position is at least about 5% of the maximum aspirable volume of the pipette by the plunger. The pipette fit testing method as described in claim 8, wherein the abnormal state indicates that a gasket of the pipette must be replaced immediately, and the subnormal state indicates that the gasket of the pipette can be replaced preventively.