A pipetting method, a pipetting system
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SICHUAN LAI BOYI AUTOMATION TECH CO LTD
- Filing Date
- 2023-06-30
- Publication Date
- 2026-06-19
Smart Images
Figure CN116832889B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pipetting mechanism technology, and more specifically, to a pipetting method and a pipetting system. Background Technology
[0002] In the process of research experiments or in the process of product reagent extraction, dispensing or pre-dispensing, pipetting mechanisms are used to perform complex tasks such as reagent extraction, transfer and sample addition.
[0003] A pipetting mechanism typically includes a pipette and disposable tips. The pipette is usually connected to a multi-axis robotic arm. The multi-axis robotic arm uses a squeezing motion in the Z-axis direction (up and down) to pick up the disposable tips and also uses the multi-axis robotic arm for positioning.
[0004] In existing technologies, a miniature high-definition camera is usually installed at a fixed position. After each liquid collection is completed, a multi-axis robotic arm will move to the shooting position to take a picture of the disposable tip. The image is then analyzed to determine whether the sample collection was successful.
[0005] However, this method of determining whether liquid collection was successful by taking a picture is lagging in response to a decrease in pipette accuracy. It lacks real-time judgment on whether there is an error in the actual liquid level, which affects subsequent production and is inefficient. Summary of the Invention
[0006] The purpose of this invention is to provide a pipetting method and system that, when using a pipette to aspirate sample liquid, collects the encoder code value on the pipette when it begins to aspirate the sample liquid and the encoder code value on the pipette during the aspiration process. It also calculates a first change value between the encoder code value during the aspiration process and the encoder code value at the beginning of aspiration, and matches this first change value with a pre-defined code value. This allows for real-time judgment of whether there is an error in the actual liquid level height, thereby improving efficiency and reducing the impact on subsequent production.
[0007] This invention is achieved through the following technical solution:
[0008] A pipetting method includes the following operations: presetting a coded value corresponding to the required pipetting volume; acquiring the coded value of the encoder on the pipette when the pipette starts to aspirate the sample, which is a first coded value; acquiring the coded value of the encoder on the pipette during the process of the pipette aspirating the sample, which is a second coded value; calculating a first change value between the first coded value and the second coded value; matching the first change value with the coded value presetting; if the matching is successful, the pipetting of the sample is completed.
[0009] Optionally, before the pipette begins to aspirate the sample, a liquid detection operation is also included: the liquid detection operation includes moving the pipette above the target reagent tube; bringing the lower end of the tip of the pipette closer to the surface of the sample liquid in the target reagent tube; monitoring the air pressure inside the pipette in real time; if the change value of the air pressure inside the pipette and the rate of change of the air pressure inside the pipette both reach the threshold, then the liquid detection is successful.
[0010] Optionally, after successful liquid detection, the following operations are also included: determining whether the volume of sample liquid in the target reagent tube is less than the required pipetting volume; if so, after the pipette is finished drawing the sample liquid, the pipette is moved to the next reagent tube to draw the sample liquid.
[0011] Optionally, the method for determining the volume of sample solution in the target reagent tube includes: selecting a reference position above the target reagent tube; acquiring the change value of the encoder code on the moving device when the moving device moves the pipette from the reference position to the bottom of the target reagent tube when the tip of the pipette contacts the bottom of the tube, and setting the change value as the pipette code value preset value; acquiring the change value of the encoder code on the moving device when the moving device moves the pipette from the reference position to the change of the gas pressure value inside the pipette, and setting the change value as the second change value; and obtaining the volume of sample solution in the target reagent tube based on the second change value and the pipette code value preset value.
[0012] Optionally, before performing the liquid probe operation, the method further includes taking the tip: the method of taking the tip includes moving the pipette above the tip holder; moving the pipette to pick up the tip.
[0013] Optionally, during the process of the pipette picking up the tip, the pipette's coding value and the torque of the load motor connected to the pipette can be used to determine whether the pipette has successfully picked up the tip.
[0014] Optionally, after the pipette has drawn the sample solution, the following operations are also included: dispensing the sample solution from the pipette into the deep well plate according to the preset dispensing volume; and retrieving the tip of the pipette into the recycling bin.
[0015] Optionally, the pipette can be controlled to dispense liquid according to a preset dispensing volume based on the changes in air pressure inside the pipette and the changes in the encoder value on the pipette.
[0016] Optionally, during the process of retrieving the tip from the pipette into the recycling bin, the successful removal of the tip can be determined by the pipette's coded value and the torque of the load motor connected to the pipette.
[0017] Optionally, during the process of pipetting sample liquid aspirating, the amount of sample liquid aspirated by the pipette can be compensated by the air pressure inside the pipette.
[0018] A pipetting system for the aforementioned pipetting method includes: a control module, wherein the control module has a preset coded value corresponding to the required pipetting volume; a first acquisition module, wherein the first acquisition module acquires the encoder coded value on the pipette when the pipette begins to aspirate the sample, the value being a first coded value; a second acquisition module, wherein the second acquisition module acquires the encoder coded value on the pipette during the sample aspiration process, the value being a second coded value; a calculation module, wherein the calculation module calculates a first change value between the first coded value and the second coded value; and a matching module, wherein the matching module matches the first coded value change value with the preset coded value; if the matching is successful, the pipetting of the sample is completed.
[0019] Optionally, the pipetting system further includes: a tip holder containing a tip and a reagent tube containing sample solution; a moving device and a pipette mounted on the moving device, wherein the moving device and the pipette are electrically connected to a control module, and the control module is used to control the movement of the moving device so that the pipette can pick up the tip and draw sample solution from the reagent tube.
[0020] Optionally, the pipette is equipped with a pressure sensor and an encoder.
[0021] Optionally, the mobile device is equipped with an encoder; the encoder on the mobile device is used to acquire the encoded value of the pipette.
[0022] Compared with the prior art, the present invention has the following advantages and beneficial effects:
[0023] By collecting the encoder value on the pipette when it begins to draw sample liquid, and using this value as the first encoded value, and simultaneously collecting the encoder value on the pipette during sample drawing, and using this value as the second encoded value, the first change value between the first and second encoded values is calculated and matched with a preset encoded value. This allows for control of the sample volume drawn by the pipette, thereby enabling real-time judgment of whether there is an error in the actual liquid level height, improving efficiency and reducing the impact on subsequent production. Attached Figure Description
[0024] To more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly described below. It should be understood that the following drawings only show some embodiments of the present invention and should not be considered as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort. In the drawings:
[0025] Figure 1 This is a schematic diagram of a pipetting method in Example 1;
[0026] Figure 2 This is a schematic diagram of a pipetting system structure in Example 2.
[0027] The attached diagram shows the markings and corresponding component names:
[0028] 1-Control module; 2-First acquisition module; 3-Matching module; 4-Tip placement box; 5-Reagent tube; 6-Moving device; 7-Pipette; 8-Pressure sensor; 9-Encoder; 10-Second acquisition module; 11-Calculation module. Detailed Implementation
[0029] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the embodiments and accompanying drawings. The illustrative embodiments and descriptions of the present invention are only used to explain the present invention and are not intended to limit the present invention.
[0030] Example 1
[0031] This embodiment provides a pipetting method, such as Figure 1 As shown, the following operations are included:
[0032] S1. Preset the coded value corresponding to the required pipetting volume;
[0033] S2. Obtain the encoder value on the pipette when the pipette starts to aspirate the sample liquid. This value is the first encoder value.
[0034] In this embodiment, a liquid probing operation is also included before the pipette begins to aspirate the sample liquid:
[0035] S21. The liquid detection operation includes:
[0036] S211. Move the pipette above the target reagent tube;
[0037] S212. Bring the lower end of the tip on the pipette closer to the surface of the sample solution in the target reagent tube;
[0038] S213. Real-time monitoring of air pressure inside the pipette;
[0039] S214. If both the change in gas pressure inside the pipette and the rate of change in gas pressure inside the pipette reach the threshold, then the liquid detection is successful. Specifically:
[0040] When probing with a pipette, the sample tends to flow into the tip when the lower end of the pipette tip contacts the sample surface. This increases the gas pressure inside the pipette. Probing is considered successful when both the change in gas pressure and the rate of change (the rate of change of gas pressure per unit time) reach a threshold. This confirms the liquid level in the reagent tube, ensuring accurate sample aspiration.
[0041] In this embodiment, after successful liquid detection, the following operations are also included:
[0042] S22. Determine if the volume of sample solution in the target reagent tube is less than the required pipetting volume; if so, after the pipette has finished drawing the sample solution, move the pipette to the next reagent tube to draw the sample solution. Specifically:
[0043] When the volume of sample solution in a target reagent tube is less than the required volume, the pipette will draw up the sample solution in the target reagent tube and then enter another target reagent tube to draw up the sample solution. This process is repeated until the volume of sample solution in the pipette reaches the required volume.
[0044] In this embodiment, the method for determining the amount of sample solution in the target reagent tube includes:
[0045] S221. Select a reference position above the target reagent tube;
[0046] S222. Obtain the change value of the encoder value on the moving device when the moving device moves the pipette from the reference position to the tip of the pipette and the tip of the pipette contacts the bottom of the target reagent tube, and set the change value as the pre-value of the pipette encoding value.
[0047] S223. Obtain the change value of the encoder value on the mobile device when the mobile device moves the pipette from the reference position to the change value of the gas pressure inside the pipette, and the change value is the second change value;
[0048] S224. Based on the second change value and the pre-defined value of the pipette code, the volume of sample solution in the target reagent tube is obtained. Specifically:
[0049] First, calculate the difference between the second change value and the pre-defined value of the pipette code. Then, based on this difference and the size of the target reagent tube, the amount of sample solution in the target reagent tube can be calculated.
[0050] In this embodiment, before performing the S21 liquid detection operation, the tip is also taken:
[0051] S20. The method for retrieving the tip header includes:
[0052] S201. Move the pipette above the tip holder;
[0053] S202. Using a mobile pipette to attach the tip. Specifically:
[0054] During the process of using a pipette to pick up a tip, the success of the pipette tip pickup is determined by the coded value on the pipette and the torque of the load motor connected to the pipette. Specifically:
[0055] When retrieving a tip, the success of the tip retrieval is determined by the pipette's encoding value and the torque of the load motor. When the encoding value reaches the preset position where the tip can be retrieved, and the motor torque reaches the threshold for retrieving the tip, it indicates that the tip retrieval was successful.
[0056] S3. Obtain the encoder value on the pipette during the sample aspiration process; this value is the second encoder value. Specifically, the sample aspiration process involves aspirating the sample according to its position and volume after the liquid probe is completed. For example, when aspirating the sample, it is necessary to determine whether there is a sufficient volume of sample in the reagent tube; and when aspirating the sample, it is necessary to determine the position of the reagent tube.
[0057] In this embodiment, the amount of sample liquid drawn by the pipette is compensated by the air pressure inside the pipette during the process of the pipette drawing the sample liquid.
[0058] In the specific implementation process, the correspondence between the actual sample volume drawn by the pipette and the coded value is shown in formula (1):
[0059] V = a * (N / n * 360) 2 +b*(N / n*360)+c*ΔP (1)
[0060] Where V is the actual volume of sample liquid aspirated by the pipette; N is the encoder value on the pipette during sample aspiration; n is the encoder resolution; a, b, and c are coefficients; and ΔP is the difference between the air pressure inside the pipette when it is empty and the air pressure inside the pipette when it aspirates a sample.
[0061] In this embodiment, S3, after the pipette has drawn the sample solution, also includes the following operation:
[0062] S31. Dispense the sample solution from the pipette into the deep well plate according to the preset dispensing volume, specifically:
[0063] Based on the changes in air pressure inside the pipette and the changes in encoder values on the pipette, the pipette is controlled to dispense liquid at a preset volume.
[0064] In the specific implementation process, the correspondence between the preset liquid output volume and the values detected by the pressure sensor and the encoder encoding is shown in formula (2):
[0065] V1 = a1 * (N1 / n * 360)2 +b1*(N1 / n*360)+c1*ΔP1 (2)
[0066] Where V1 is the actual volume of liquid dispensed by the pipette; n is the encoder resolution; a1, b1, and c1 are coefficients; N1 is the encoder value on the pipette during the dispensing process; and ΔP1 is the difference between the air pressure inside the pipette before dispensing the sample and the air pressure inside the pipette during dispensing.
[0067] S32. Return the pipette tip to the recycling bin, specifically:
[0068] In S5, the success of tip removal is determined by the pipette's coded value and the torque of the load motor connected to the pipette. Specifically:
[0069] When removing the tip, the success of the removal is determined by the pipette's code value and the torque of the load motor. The tip is successfully removed when the code value reaches the preset position where the tip can be removed, and the motor torque reaches the threshold for removing the tip.
[0070] S4. Calculate the first change value between the first encoded value and the second encoded value;
[0071] S5. Match the first change value with the pre-defined coded value; if the match is successful, the pipette is used to aspirate the sample.
[0072] Example 2
[0073] This embodiment provides a pipetting system, such as Figure 2 As shown, the pipetting method described in Example 1 includes:
[0074] The system includes a control module 1, which has a preset encoding value corresponding to the required pipetting volume; a first acquisition module 2, which acquires the encoding value of the encoder 9 on the pipette 7 when the pipette 7 starts to aspirate the sample, which is a first encoding value; a second acquisition module 10, which acquires the encoding value of the encoder 9 on the pipette 7 during the sample aspiration process, which is a second encoding value; a calculation module 11, which calculates a first change value between the first encoding value and the second encoding value; and a matching module 3, which matches the first encoding value change value with the preset encoding value. If the matching is successful, the pipette 7 completes the sample aspiration.
[0075] In this embodiment, the pipetting system further includes: a tip holder 4 with a tip and a reagent tube 5 containing sample solution; a moving device 6 and a pipette 7 disposed on the moving device 6. The moving device 6 and the pipette 7 are electrically connected to the control module 1. The control module 1 is used to control the moving device 6 to move so that the pipette 7 can pick up the tip and draw sample solution from the reagent tube 5.
[0076] In this embodiment, the pipette 7 is equipped with a pressure sensor 8 and an encoder 9.
[0077] In this embodiment, the mobile device 6 is equipped with an encoder 9.
[0078] In specific implementation, the aforementioned mobile device 6 includes a first robotic arm and a second robotic arm.
[0079] The first robotic arm is equipped with an absolute encoder 9 and a slotted sensor. The control module 1 is electrically connected to the first robotic arm, the absolute encoder 9 on the first robotic arm, and the slotted sensor.
[0080] With this scheme, when pipetting is required, control module 1 first controls the movement of the first robotic arm. When the first robotic arm moves, it moves the reagent tube 5 held by the electric gripper on the first robotic arm to the pipetting position. At this time, the absolute encoder 9 on the first robotic arm detects the position of the first robotic arm's movement. At the same time, the slotted sensor in the first robotic arm, i.e., the origin switch, accurately positions the first robotic arm, thereby controlling the first robotic arm to move precisely to the designated position.
[0081] The second robotic arm is equipped with a pipette 7, an absolute encoder 9, and a slotted sensor. The control module 1 is electrically connected to the second robotic arm, the pipette 7, the absolute encoder 9 on the second robotic arm, and the slotted sensor.
[0082] With this scheme, while the control module 1 controls the movement of the first robotic arm, the control module 1 will also control the second robotic arm to move to the tip head placement box 4 first, and then control the second robotic arm to descend to pick up the tip head. During this process, the absolute encoder 9 on the second robotic arm will detect the position of the second robotic arm. At the same time, the slotted sensor on the second robotic arm, i.e. the origin switch, will position the second robotic arm to ensure that the second robotic arm can move accurately to the designated position.
[0083] When the second robotic arm descends to retrieve the tip, the pipette 7 uses its internal pressure sensor 8 and encoder 9 to determine whether the tip has been successfully retrieved. When the tip has been successfully retrieved, the control module 1 controls the second robotic arm to rise to the designated position.
[0084] When the first robotic arm transports the clamped reagent tube 5 to the sample aspiration position, the control module 1 will move the second robotic arm above the sample aspiration position. When the second robotic arm reaches the designated position, it will first perform liquid detection. During liquid detection, the encoder 9 in the pipette 7 will work with the second robotic arm to descend and detect the liquid, and the air pressure sensor 8 will determine whether it has come into contact with the sample liquid.
[0085] After successful liquid detection, the pipette 7 will aspirate the sample liquid according to the liquid volume input by the control module 1. During the aspiration of the sample liquid, the encoder 9 in the pipette 7 will precisely control the liquid volume. After the sample liquid is aspirated, the second robotic arm will rise to a safe position.
[0086] Once the second robotic arm is raised to a safe position, the control module 1 will control the second robotic arm to move to the position of reagent tube 5. At this time, the infrared slow reflection at the position of reagent tube 5 will perform infrared sensing of the object. If the object is detected, the control module 1 will control the second robotic arm to descend to the position of the dispensing hole on the reagent tube 5, so that the pipette 7 can dispense liquid according to the required settings. During the dispensing process, the air pressure sensor 8 and absolute encoder 9 in the pipette 7 will process the dispensing according to the dispensing requirements.
[0087] After the liquid is dispensed, the control module 1 will control the second robotic arm to move to the guide slot for retrieving the tip and push off the tip on the pipette 7. During the process of pushing off the tip, the air pressure sensor 8 and encoder 9 inside the pipette 7 will detect the pressure and position to determine whether the tip has been successfully pushed off. If successful, the control module 1 will raise the second robotic arm to a safe position.
[0088] Compared with the prior art, the technical solution in this embodiment uses an absolute encoder 9 to detect the absolute position of the shaft, avoiding the problem of origin loss. At the same time, by using a slotted sensor, it achieves precise control and positioning of the pipette 7 coordinates, thereby improving the accuracy and efficiency of pipetting operations.
[0089] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. A pipetting method, characterized in that, Includes the following operations: Preset the coded value corresponding to the required pipetting volume; Obtain the encoder value on the pipette when the pipette starts to aspirate the sample liquid; this value is the first encoded value. Obtain the encoder value on the pipette during the process of pipetting sample liquid aspiration; this value is the second encoded value. Calculate the first change value between the first encoded value and the second encoded value; The first change value is matched with the pre-defined coded value; if the match is successful, the pipette is used to aspirate the sample. Before the pipette begins to aspirate the sample solution, a liquid detection operation is also included: the liquid detection operation includes moving the pipette above the target reagent tube; and bringing the lower end of the tip of the pipette closer to the surface of the sample solution in the target reagent tube. Real-time monitoring of the gas pressure inside the pipette; if the monitored change value and the rate of change of the gas pressure inside the pipette both reach the threshold, the liquid detection is successful; After successful liquid detection, the following operations are also included: determine whether the volume of sample liquid in the target reagent tube is less than the required volume; if so, after the pipette is finished drawing the sample liquid, move the pipette to the next reagent tube to draw the sample liquid. Before performing the liquid detection operation, the procedure also includes taking the tip: the method for taking the tip includes moving the pipette above the tip holder; moving the pipette to pick up the tip; During the process of using a pipette to pick up a tip, the pipette's coding value and the torque of the load motor connected to the pipette are used to determine whether the pipette has successfully picked up the tip. During the process of pipetting sample liquid aspirating, the amount of sample liquid aspirated by the pipette is compensated by the air pressure inside the pipette.
2. A pipetting method according to claim 1, characterized in that The method for determining the volume of sample solution in the target reagent tube includes: Select a reference position above the target reagent tube; The change in the encoder value on the moving device is obtained when the moving device moves the pipette from the reference position to the bottom of the target reagent tube when the tip of the pipette contacts the bottom of the target reagent tube, and this change value is set as the pre-value of the pipette encoding value. The change in the encoder value on the mobile device is obtained when the mobile device moves the pipette from the reference position to the change in the gas pressure inside the pipette. This change value is the second change value. Based on the second change value and the pre-defined value of the pipette code, the volume of sample solution in the target reagent tube is obtained.
3. The pipetting method according to claim 1, characterized in that, After the sample solution is aspirated by the pipette, the following steps are also included: Dispense the sample solution from the pipette into the deep well plate according to the preset dispensing volume; Return the pipette tip to the recycling bin.
4. The pipetting method according to claim 3, characterized in that: Based on the changes in air pressure inside the pipette and the changes in encoder values on the pipette, the pipette is controlled to dispense liquid at a preset volume.
5. The pipetting method according to claim 3, characterized in that: During the process of retrieving the tip from the pipette into the recycling bin, the system uses the pipette's coded value and the torque of the load motor connected to the pipette to determine whether the tip has been successfully removed.
6. A pipetting system characterized in that, The pipetting method according to any one of claims 1-5 includes: Control module (1), wherein the control module (1) is preset with a coded value corresponding to the required pipetting volume; The first acquisition module (2) acquires the encoder (9) value on the pipette (7) when the pipette (7) starts to aspirate the sample liquid. This value is the first encoding value. The second acquisition module (10) is used to acquire the encoder (9) value on the pipette (7) during the process of the pipette (7) aspirating the sample liquid. The value is the second encoding value. The calculation module (11) is used to calculate a first change value between the first encoded value and the second encoded value; The matching module (3) is used to match the first coded value change value with the coded value pre-value; if the matching is successful, the pipette (7) completes the aspiration of the sample liquid.
7. A pipetting system according to claim 6, characterized in that Also includes: A tip holder (4) with a tip tip and a reagent tube (5) containing a sample solution; The mobile device (6) and the pipette (7) mounted on the mobile device (6) are electrically connected to the control module (1). The control module (1) is used to control the movement of the mobile device (6) so that the pipette (7) can pick up the sample liquid from the tip and the reagent tube (5).
8. A pipetting system according to claim 7, characterized in that: The pipette (7) is equipped with a pressure sensor (8) and an encoder (9).
9. A pipetting system according to claim 7, characterized in that: The mobile device (6) is equipped with an encoder (9).