Liquid level detection method, pipetting method, pipetting system and storage medium

Abstract

The invention provides a liquid level detection method based on air pressure detection, which is applied to a pipetting system, and the pipetting system comprises a suction head; the liquid level detection method comprises the steps that the whole pipetting system is driven to move towards a target container in the first direction, the suction head is driven to suck air in the second direction at the preset speed, and the preset speed is smaller than or equal to 0.6-3 uL / s; detecting real-time air pressure; whether a suction head makes contact with liquid in the target container or not is judged according to the real-time air pressure, and when the suction head makes contact with the liquid, the liquid level position of the liquid is recorded, and the suction head is controlled to stop sucking air. The liquid level detection method based on air pressure detection is beneficial to shortening the pipetting time and improving the pipetting accuracy. The invention further provides a pipetting method and system based on air pressure detection and a computer readable storage medium.

Description

Technical Field

[0001] The present application relates to the field of liquid transfer technology, and in particular to a liquid level detection method based on air pressure detection, a liquid transfer method, a liquid transfer system, and a computer-readable storage medium. Background Art

[0002] A pipette is an experimental pipetting tool used to automatically and accurately transfer liquid from a specific container to another container to complete various experiments and reduce manual operations.

[0003] A pipette uses air pressure detection to detect the liquid level in a specific container. During the detection process, air is continuously drawn in until a sharp jump in air pressure is detected. This sudden jump in air pressure indicates that the pipette tip has touched the liquid surface, completing the liquid level detection and allowing subsequent aspiration.

[0004] However, at the moment the pipette tip touches the liquid surface, the pipette is still in the suction state and may accidentally suck up liquid. In order not to affect the subsequent suction operation, the sucked liquid needs to be discharged first, which prolongs the overall pipetting time; and the pipette tip is wetted by touching the liquid surface, which affects the accuracy of the pipette. Summary of the Invention

[0005] A first aspect of the present application provides a liquid transfer system, the liquid transfer system comprising a pipette tip;

[0006] The liquid level detection method comprises:

[0007] Driving the entire pipetting system to move in a first direction toward a target container, and driving the pipette tip to aspirate air in a second direction at a preset speed, wherein the preset speed is less than or equal to 0.6 to 3 uL / s;

[0008] Detect real-time air pressure;

[0009] The suction head is judged to be in contact with the liquid in the target container according to the real-time air pressure. When the suction head is in contact with the liquid, the liquid level position of the liquid is recorded and the suction head is controlled to stop suctioning air and to suck the liquid.

[0010] A second aspect of the present application provides a pipetting method based on air pressure detection, which is applied to a pipetting system, wherein the pipetting system includes a pipette tip;

[0011] The pipetting method comprises:

[0012] Driving the entire pipetting system to move in a first direction toward a target container, and driving the pipette tip to aspirate air in a second direction at a preset speed, wherein the preset speed is less than or equal to 0.6 to 3 uL / s;

[0013] Detect real-time air pressure;

[0014] The suction head is judged to be in contact with the liquid in the target container according to the real-time air pressure. When the suction head is in contact with the liquid, the liquid level position of the liquid is recorded, and the suction head is controlled to stop suctioning air and to suck the liquid.

[0015] A third aspect of the present application provides a pipetting system, comprising a pipette, an air pressure detection circuit, and a controller, wherein the controller is electrically connected to the pipette and the air pressure detection circuit, respectively;

[0016] The air pressure detection circuit is used to detect the air pressure of the pipette, the pipetting system stores a computer program, and the controller is used to implement the steps of the liquid level detection method based on air pressure detection and the pipetting method based on air pressure detection when executing the computer program.

[0017] A fourth aspect of the present application provides a computer-readable storage medium storing a computer program, which, when executed, can implement the steps of the above-mentioned liquid level detection method based on air pressure detection and the above-mentioned pipetting method based on air pressure detection.

[0018] The above-mentioned liquid level detection method, pipetting method, pipetting system and computer-readable storage medium based on air pressure detection, by controlling the preset speed of the suction of the pipette tip to be less than or equal to 0.6~3uL / s, can ensure that the time from the moment the pipette tip touches the liquid surface to the moment the pipette tip stops suctioning and the pipetting system stops moving does not exceed 10ms, and the volume of liquid sucked by the pipette tip does not exceed 0.006~0.03uL. Therefore, the amount of liquid sucked by the pipette tip during the detection period is small and has almost no effect on the amount of subsequent liquid suction. Therefore, in the pipetting system of the above embodiment of the present application, the pipette tip does not need to discharge the liquid before suctioning, which is beneficial to saving the overall time of pipetting and improving the efficiency of pipetting. In addition, compared with the pipetting system that sucks in air and exhausts air at the same time, it also avoids the accuracy impact caused by the return stroke difference of the motor and the suction pump. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Schematic diagram of the module structure of the pipetting system according to an embodiment of the present application.

[0020] Figure 2 for Figure 1 Schematic diagram of the structure of each pipette.

[0021] Figure 3 This is a flow chart of the steps of the pipetting method based on air pressure detection according to an embodiment of the present application.

[0022] Figure 4 The line graph shows the change in air pressure over time when the pipetting system is in standby mode.

[0023] Figure 5The line graph shows the change in air pressure detected over time when the pipetting system is in the startup period and the detection period.

[0024] Figure 6 This is a line graph showing the change in air pressure over time when the tip contacts the liquid surface.

[0025] Description of main component symbols

[0026] Pipetting system 1

[0027] Controller 10

[0028] Air pressure detection circuit 20

[0029] Pipette 30

[0030] Tip adapter 31

[0031] Pipeline 32

[0032] Air pressure sensor 33

[0033] Steps S1, S2, S3, S4, S5, S6, S7

[0034] Target container 2

[0035] Liquid 3

[0036] The following specific implementation methods will further illustrate the present application in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION

[0037] This application provides a pipetting system, primarily used in biochemistry, medicine, and pharmacy experiments, for accurately transferring liquid from one container to another to complete an experiment. The pipetting system offers high precision and efficiency, making it suitable for a variety of liquid handling and dispensing operations.

[0038] See also Figure 1 The pipetting system 1 of the present embodiment includes a controller 10, an air pressure detection circuit 20, and at least one pipette 30. The controller 10 is electrically connected to the air pressure detection circuit 20 and each pipette 30, and is configured to control the workflow of each pipette 30 based on the air pressure detected by the air pressure detection circuit 20. In this embodiment, the controller 10 is a control chip, and the chip model can be, for example, STM32F103C8T6, which has multiple communication interfaces such as CANBU S, SPI, and IIC for communication.

[0039] See also Figure 2Each pipette 30 includes a tip adapter 31, a pipette line 32, and an air pressure sensor 33. The tip adapter 31 is used to removably mount a pipette tip (not shown). The tip adapter 31 has a cavity within it, and the pipe 32 connects the cavity to the air pressure sensor 33, allowing the air pressure sensor 33 to sense the air pressure within the cavity. The air pressure detection circuit 20 is electrically connected to the air pressure sensor 33 to receive the electrical signal output by the air pressure sensor 33 and obtain air pressure data.

[0040] The present application also provides a liquid level detection method based on air pressure detection and a pipetting method including the liquid level detection method. The liquid level detection method and the pipetting method are applied to the above-mentioned pipetting system 1. The target container 2 contains a liquid 3, and the pipetting system 1 is used to aspirate the liquid 3 to transfer the liquid 3 to another container. Before aspirating the liquid 3, the pipetting system 1 needs to first detect the liquid level of the liquid 3 so that the aspiration operation can be started at the appropriate time to accurately calculate the aspirated amount (the amount of each type needs to be strictly controlled during the experiment).

[0041] The liquid level detection method described in the embodiment of the present application continuously monitors the air pressure of the pipetting system 1 as it approaches the liquid surface, determines whether the pipette tip of the pipetting system 1 has contacted the liquid surface, and stops movement at the moment of contact to detect the liquid level. The pipetting method described in the embodiment of the present application utilizes the liquid level detection method to detect the liquid level, thereby initiating aspiration at the correct location.

[0042] See also Figure 3 The pipetting method based on air pressure detection of this embodiment includes:

[0043] Step S1, detecting the standby air pressure of the pipetting system;

[0044] Step S2, driving the pipetting system to move along a first direction toward the target container, and driving the pipette tip to aspirate along a second direction at a preset speed, wherein the preset speed is less than or equal to 0.6 to 3 uL / s;

[0045] Step S3, detecting the working air pressure of the pipetting system;

[0046] Step S4, determining whether the difference between the standby air pressure and the working air pressure is greater than a preset first threshold;

[0047] If the answer in step S4 is yes, then step S5 is executed to detect the real-time air pressure of the pipetting system;

[0048] Step S6, determining whether the absolute value of the difference between the real-time air pressure and the working air pressure is greater than a preset second threshold;

[0049] If the answer in step S6 is yes, step S7 is executed to record the liquid level, stop suctioning, and control the suction head to suck the liquid in the target container.

[0050] Before the liquid aspiration operation, the pipetting system 1 is first moved to the top of the target container 2. At this time, the pipetting system 1 does not start to aspirate or move, and remains in a suspended state. It is defined that the pipetting system 1 is in a standby state at this time.

[0051] When the pipetting system 1 is in the standby state, the air pressure detected by the air pressure detection circuit 20 is as follows: Figure 4 As shown, Figure 4 The horizontal axis represents time, and the vertical axis represents air pressure. When the pipetting system 1 is in the standby state, due to interference from the external environment, even if the pipetting system 1 does not perform an air suction operation, the air pressure detected by the air pressure detection circuit 20 is not constant, but fluctuates within a certain range. The air pressure detection circuit 20 detects the air pressure once every preset time period. In this embodiment, the preset time period is 2ms. That is, the air pressure detection circuit 20 detects the air pressure once every 2ms, and the air pressure detected in the standby state is the standby air pressure. That is, in step S1 of this embodiment, the air pressure detection circuit 20 detects the standby air pressure P1 once every 2ms when the pipetting system 1 is in the standby state.

[0052] In step S2, the pipetting system 1 is activated, and the controller 10 outputs a signal to control the entire pipetting system 1 to move vertically downward (i.e., in the first direction) toward the target container 2. The controller 10 also outputs a signal to drive the pipette tip to draw air vertically upward (i.e., in the second direction) under the action of the cylinder. In other words, the first direction and the second direction are parallel.

[0053] From the moment the pipetting system 1 is activated, the pipetting system 1 continuously moves toward the target container 2, and the pipette tip continuously aspirates. In this embodiment, the period from the moment the pipetting system 1 begins to move until the pipetting system 1 reaches stable operation is defined as the activation period of the pipetting system 1, and the period from the moment the pipetting system 1 reaches stable operation until the pipette tip touches the liquid surface in the target container 2 is defined as the detection period of the pipetting system 1.

[0054] In step S3 , the air pressure detection circuit 20 detects the air pressure of the pipetting system 1 every 2 ms during the startup period and the detection period.

[0055] See also Figure 5The difference between the various air pressures detected by the air pressure detection circuit 20 during the startup period is greater than the difference between the various air pressures detected by the air pressure detection circuit 20 during the detection period. In other words, the air pressure of the pipetting system 1 during the detection period is more stable than the air pressure during the startup period. In this embodiment, the average air pressure detected by the air pressure detection circuit 20 during the startup period (between 0 and 0.5) is greater than the average air pressure detected by the air pressure detection circuit 20 during the detection period (between -1.5 and -1).

[0056] Therefore, by detecting the air pressure in real time, it is possible to determine whether the pipetting system 1 is in the start-up period or the detection period. In this embodiment, the air pressure when the pipetting system 1 enters the detection period is defined as the working air pressure P2 during the stable working period.

[0057] When the pipetting system 1 is in the detection period, it is also determined whether the pipetting system 1 is working properly. Specifically, in step S4, it is determined whether the difference between the standby air pressure P1 and the working air pressure P2 (i.e., P1-P2) is greater than a preset first threshold value X1. If it is determined to be yes, that is, the difference between the standby air pressure P1 and the working air pressure P2 is greater than the first threshold value X1, then it indicates that the pipetting system 1 is working properly and the next operation is performed. If it is determined to be no, that is, the difference between the standby air pressure P1 and the working air pressure P2 is less than or equal to the first threshold value X1, then it indicates that the pipetting system 1 is working abnormally, the pipetting system 1 reports an abnormality, stops subsequent operations, and executes step S1 again after the abnormality is eliminated. In this embodiment, the first threshold value is 1-1.5Pa. In other embodiments of the present application, step S4 may also be: determine whether the difference between the standby air pressure and the working air pressure is greater than or equal to the preset first threshold value.

[0058] If the answer is yes in step S4, step S5 is executed to detect the air pressure of the pipetting system 1 during the detection period as the real-time air pressure P3.

[0059] At the moment the suction head touches the liquid surface, the air pressure detected by the air pressure detection circuit 20 changes suddenly. Figure 6As shown at points M and N, the air pressure at point M fluctuates slightly compared to the pressure at the previous point, while the air pressure at point N drops sharply compared to the air pressure at point M. Based on the real-time air pressure P3 fed back by the air pressure detection circuit 20, the controller 10 calculates whether the absolute value of the difference between the real-time air pressure P3 and the working air pressure P2 (i.e., |P3-P2|) is greater than a preset second threshold value X2. If the judgment is yes, i.e., |P3-P2|>X2, it is determined that the pipette tip has now contacted the liquid surface. Step S7 is then executed to record the liquid surface position of liquid 3, control the pipetting system 1 to stop moving, control the pipette tip to stop aspirating, end the liquid surface detection period, and control the pipette tip to begin aspirating. If the judgment is no, i.e., |P3-P2|≤X2, it is determined that the pipette tip has not yet contacted the liquid surface. The pipetting system 1 is controlled to continue moving toward the target container 2 and control the pipette tip to continue aspirating. In this embodiment, the second threshold value is 3-10 Pa. In other embodiments of the present application, step S6 may also be: determining whether the absolute value of the difference between the real-time air pressure and the working air pressure is greater than or equal to a preset second threshold.

[0060] Due to the delay in the electrical signal, it's difficult for the pipette system 1 to stop moving and aspirate simultaneously when the pipette tip touches the liquid surface. Consequently, the pipette tip may have already aspirated a small amount of liquid 3 before the pipette system 1 stops moving and the tip stops aspirating. As mentioned above, the amount of liquid 3 that the tip is programmed to aspirate is strictly defined. Liquid aspirated by the tip during the detection period may result in errors in the final amount of liquid 3 aspirated by the tip.

[0061] In some pipetting systems, to avoid the above-mentioned errors, after the detection period ends, that is, after determining that the pipette tip has touched the liquid surface, the pipetting system 1 is first controlled to stop moving toward the target container 2 and the pipette tip is controlled to stop aspirating. The pipette tip is then controlled to lift to a certain height to perform a liquid discharge operation to remove the erroneously aspirated liquid 3. After the liquid discharge operation is completed, the pipette tip is controlled to descend to the liquid surface position recorded in step S7 to perform the liquid aspiration operation. However, this method adds additional operations such as lifting the pipette tip, draining the liquid, and lowering the pipette tip back to the liquid surface position, which increases the total pipetting time and is not conducive to improving pipetting efficiency.

[0062] In other pipetting systems, to avoid the above errors, the pipette tip is controlled to simultaneously inhale and exhaust during the detection period, so that any erroneous liquid can be expelled in time. However, this method can also easily affect the pipetting accuracy due to the return stroke difference of the motor and liquid pump in the pipetting system.

[0063] In this embodiment, each pipette 30 includes a built-in pump (not shown), which is connected to the cavity in the tip adapter 31, thereby connecting to the tip installed on the tip adapter 31. The above descriptions of "controlling the tip to inhale", "controlling the tip to stop inhaling", "controlling the tip to exhaust", "controlling the tip to aspirate liquid", etc. are actually achieved by controlling the working process of the pump. For example, "controlling the tip to inhale" is actually controlling the pump to generate negative pressure so that gas is sucked into the tip, rather than directly controlling the force generated by the tip to inhale gas. For another example, "controlling the tip to stop inhaling" is actually controlling the pump to stop working, and "controlling the tip to exhaust" is actually controlling the pump to generate a positive differential pressure so that the gas in the tip connected to the pump is squeezed out, rather than directly controlling the tip itself to generate a force to expel gas.

[0064] It should be understood that in step S7, during the process of "stopping suction and controlling the pipette tip to aspirate the liquid in the target container," the pump in the pipette system 1 continuously generates negative pressure. Specifically, when the pipette tip switches between aspirating and aspirating, the pump maintains its negative pressure-generating state. However, the action of the pipette tip changes depending on its position. Specifically, when the pipette tip is suspended, the pump generates negative pressure to cause the pipette tip to aspirate; when the pipette tip touches the liquid surface, the pump generates negative pressure to cause the pipette tip to aspirate.

[0065] The pipetting system 1 of the above-mentioned embodiment of the present application controls the preset suction speed of the pipette tip to be less than or equal to 0.6 to 3 uL / s, and then controls the overall movement speed of the pipetting system 1 toward the target container 2 to be less than 70 mm / s. This ensures that the volume of liquid 3 aspirated by the pipette tip does not exceed 0.006 to 0.03 uL in the time from the moment the pipette tip touches the liquid surface to the moment the pipette tip stops aspirating and the pipetting system 1 stops moving, which is less than 10 ms. Therefore, the suction speed of the pipette tip is low during the detection period, and the continuous aspiration time of the pipette tip is short, resulting in a small amount of liquid 3 aspirated, which has almost no impact on the subsequent aspiration volume. Therefore, the pipetting system 1 of the above-mentioned embodiment of the present application does not need to be raised to a certain height before actual aspiration and then drained, and then lowered back to the previously recorded liquid level position after draining is completed. This helps to ensure the accuracy of the aspirated volume, improve pipetting efficiency and stability, while saving overall pipetting time. Moreover, compared to pipetting systems that simultaneously aspirate and exhaust, it also avoids the accuracy impact caused by the return stroke difference of the motor and pipetting pump.

[0066] The controller 10 of the embodiment of the present application includes an electrically connected memory, a processor, and a computer program stored in the memory and executable on the processor. When the processor executes the program, any step of the above-mentioned liquid level detection method and pipetting method based on air pressure detection is implemented.

[0067] An embodiment of the present application also provides a non-volatile computer-readable storage medium having a computer program stored thereon. When the computer program is executed by a processor, the steps of any of the above-mentioned liquid level detection methods and pipetting methods based on air pressure detection are implemented.

[0068] When the above-mentioned liquid level detection method and pipetting method based on air pressure detection are implemented and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on such understanding, the present application implements all or part of the processes in the above-mentioned embodiment method, and can also be completed by instructing related hardware through a computer program. The computer program can be stored in a computer-readable storage medium, and the computer program can implement the steps of the above-mentioned various method embodiments when executed by a processor. Wherein, the computer program includes computer program code, and the computer program code can be in source code form, object code form, executable file or some intermediate form, etc. The computer-readable storage medium may include: any entity or device that can carry the computer program code, recording medium, U disk, mobile hard disk, magnetic disk, optical disk, computer memory, read-only memory (ROM, Read-Only Memory), random access memory (RAM, Random Access Memory), electric carrier signal, telecommunication signal and software distribution medium, etc.

[0069] The processor may be a central processing unit (CPU), other general-purpose processors, digital signal processors (DSP), application-specific integrated circuits (ASIC), field-programmable gate arrays (FPGA), other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor may be a microprocessor or any conventional processor, etc. The processor serves as the control center of the sample processing system / sample processing device, connecting various parts of the entire sample processing system / sample processing device using various interfaces and lines.

[0070] The memory is used to store the computer programs and / or modules, and the processor implements the various functions of the sample processing system / sample processing device by running or executing the computer programs and / or modules stored in the memory, and calling the data stored in the memory. The memory may mainly include a program storage area and a data storage area, wherein the program storage area may store an operating system, at least one application required for a function (such as a sound playback function, an image playback function, etc.). In addition, the memory may include a high-speed random access memory, and may also include a non-volatile memory, such as a hard disk, a memory, a plug-in hard disk, a smart memory card (Smart Media Card, SMC), a secure digital (Secure Digital, SD) card, a flash card (Flash Card), at least one disk storage device, a flash memory device, or other volatile solid-state storage device.

[0071] Those skilled in the art should recognize that the above embodiments are merely intended to illustrate the present application and are not intended to limit the present application. As long as they are within the spirit of the present application, appropriate changes and modifications to the above embodiments are within the scope of protection claimed in the present application.

Claims

1. A liquid level detection method based on air pressure detection, characterized in that: Applicable to a pipetting system, the pipetting system comprising a pipette tip; The liquid level detection method comprises: Driving the entire pipetting system to move in a first direction toward a target container, and driving the pipette tip to aspirate air in a second direction at a preset speed, wherein the preset speed is less than or equal to 0.6 to 3 uL / s; Detect real-time air pressure; It is determined whether the suction head contacts the liquid in the target container according to the real-time air pressure. When the suction head contacts the liquid, the liquid level position of the liquid is recorded and the suction head is controlled to stop suctioning.

2. The liquid level detection method based on air pressure detection according to claim 1, characterized in that: The first direction is parallel to the second direction.

3. The liquid level detection method based on air pressure detection according to claim 1, characterized in that: Before the step of driving the pipetting system to move toward the target container along the first direction, the method further includes: detecting the standby air pressure of the pipetting system; Before the step of detecting the real-time air pressure, the method further includes: The working air pressure of the pipetting system is detected, and when the difference between the standby air pressure and the working air pressure is greater than a preset first threshold, it is determined that the pipetting system is in a normal working state during the detection period.

4. The liquid level detection method based on air pressure detection according to claim 3, characterized in that: The step of determining whether the suction head contacts the liquid in the target container according to the real-time air pressure, and controlling the suction head to stop suctioning when the suction head contacts the liquid comprises: When the absolute value of the difference between the real-time air pressure and the working air pressure is greater than a preset second threshold, when the absolute value of the difference between the real-time air pressure and the working air pressure is greater than the second threshold, the suction head is controlled to stop suctioning and the pipetting system is controlled to stop moving.

5. The liquid level detection method based on air pressure detection according to claim 4, characterized in that: The first threshold is smaller than the second threshold.

6. The liquid level detection method based on air pressure detection according to claim 4, characterized in that: The first threshold value is 1-1.5Pa, and the second threshold value is 3-10Pa.

7. The liquid level detection method based on air pressure detection according to claim 1, characterized in that: The step of driving the pipetting system to move along a first direction toward the target container comprises: The pipetting system is driven to move along a first direction toward a target container at a speed of less than 70 mm / s, and a time duration between a moment when the suction head contacts the liquid and a moment when the suction head stops aspirating is controlled to be less than or equal to 10 ms.

8. A pipetting method based on air pressure detection, characterized in that: Applicable to a pipetting system, the pipetting system comprising a pipette tip; The pipetting method comprises: Driving the entire pipetting system to move in a first direction toward a target container, and driving the pipette tip to aspirate air in a second direction at a preset speed, wherein the preset speed is less than or equal to 0.6 to 3 uL / s; Detect real-time air pressure; The suction head is judged to be in contact with the liquid in the target container according to the real-time air pressure. When the suction head is in contact with the liquid, the liquid level position of the liquid is recorded, and the suction head is controlled to stop suctioning air and to suck the liquid.

9. A pipetting system, characterized in that: It includes a pipette, an air pressure detection circuit and a controller, wherein the controller is electrically connected to the pipette and the air pressure detection circuit respectively; The air pressure detection circuit is used to detect the air pressure of the pipette, the pipetting system stores a computer program, and the controller is used to implement the steps of the liquid level detection method based on air pressure detection as described in any one of claims 1 to 7 and the pipetting method based on air pressure detection as described in claim 8 when executing the computer program.

10. A computer-readable storage medium, characterized in that A computer program is stored, which, when executed, can implement the steps of the liquid level detection method based on air pressure detection as described in any one of claims 1 to 7 and the pipetting method based on air pressure detection as described in claim 8.

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