Pipetting control method, multichannel pipetting device, and storage medium

CN116328866BActive Publication Date: 2026-09-08GUANGZHOU GOLDMAN SACHS INTELLIGENT MFG TECH CO LTD
View PDF 2 Cites 0 Cited by

Patent Information

Application Number
CN202310485427.4
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-04-28
Publication Date
2026-09-08
Estimated Expiration
2043-04-28

AI Technical Summary

Technical Problem

[0004]本发明提供了一种移液控制方法、多通道移液设备和存储介质,以解决现有的多通道移液控制方法存在同步性低的问题

Benefits of technology

[0018]本发明实施例提供的移液控制方法的技术方案,基于移液速度控制吸头组合移液,实现多通道移液,提高移液精度和同步性。

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN116328866B_ABST
    Figure CN116328866B_ABST
Patent Text Reader

Abstract

The application discloses a pipetting control method, a multi-channel pipetting device and a storage medium. The method comprises the following steps: in the case that a pipetting instruction is detected, a pipetting parameter corresponding to a tip assembly loaded by a pipetting device arranged at the end of a mechanical arm is acquired, the pipetting parameter comprises a target pipetting volume and the capacity of each tip in the tip assembly, the target pipetting volume corresponds to a preset minimum instruction unit equivalent, and the tip assembly comprises at least two tips; a pipetting curve corresponding to the capacity is determined according to a pre-created corresponding relationship between the capacity and the pipetting curve, the pipetting curve is a curve of pipetting speed changing with time; a pipetting time corresponding to the target pipetting volume is determined according to the target pipetting volume and the pipetting curve; and the at least two tips are controlled to perform pipetting simultaneously according to the pipetting curve until the pipetting time. The application solves the problem that the existing multi-channel pipetting control method has low synchronism, realizes multi-channel pipetting, and improves pipetting precision and synchronism.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] This invention relates to the field of pipettes, and more particularly to pipetting control methods, multichannel pipetting devices, and storage media. Background Technology

[0002] Nucleic acid extraction and detection technology is widely used in the field of forensic medicine. A plunger pipette pump is a crucial component of nucleic acid extraction and detection equipment, used for operations such as mixing and pipetting multiple samples.

[0003] Existing multichannel pipetting methods for nucleic acid extraction primarily rely on the simultaneous control of multiple single-channel pipetting devices. This results in complex control commands and poor synchronization between the individual pipetting devices. In summary, existing pipetting control methods suffer from low synchronization. Summary of the Invention

[0004] This invention provides a pipetting control method, a multi-channel pipetting device, and a storage medium to solve the problem of low synchronization in existing multi-channel pipetting control methods.

[0005] According to one aspect of the present invention, a pipetting control method is provided, the method comprising:

[0006] When a pipetting command is detected, the pipetting parameters corresponding to the pipetting device loaded at the end of the robotic arm are obtained. The pipetting parameters include the target pipetting volume and the capacity of each pipette in the pipetting device assembly, the preset minimum command unit equivalent corresponding to the target pipetting volume, and the pipetting device assembly includes at least two pipettes.

[0007] Based on the pre-created correspondence between volume and pipetting curve, determine the pipetting curve corresponding to the volume. The pipetting curve is the curve of pipetting speed changing with time.

[0008] Determine the pipetting time corresponding to completing the target pipetting volume based on the target pipetting volume and the pipetting curve;

[0009] Control at least two pipette tips to pipette simultaneously until the pipetting time is reached, based on the pipetting profile.

[0010] According to another aspect of the present invention, a multichannel pipetting device is provided, the multichannel pipetting device comprising:

[0011] A pipette tip is used for suctioning liquids.

[0012] A pipette, wherein the end of the pipette is provided with at least two pipette tips;

[0013] A robotic arm, with a pipetting device fixed to its end;

[0014] At least one processor; and

[0015] A memory that is communicatively connected to at least one processor; wherein,

[0016] The memory stores a computer program that can be executed by at least one processor, such that the at least one processor is able to perform the pipetting control method of any embodiment of the present invention.

[0017] According to another aspect of the present invention, a computer-readable storage medium is provided that stores computer instructions for causing a processor to execute and implement the pipetting control method of any embodiment of the present invention.

[0018] The technical solution of the pipetting control method provided in this embodiment of the invention is based on pipetting speed control of pipetting tip combination pipetting, realizing multi-channel pipetting and improving pipetting accuracy and synchronization.

[0019] It should be understood that the description in this section is not intended to identify key or essential features of the embodiments of the present invention, nor is it intended to limit the scope of the invention. Other features of the invention will become readily apparent from the following description. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1A This is a structural block diagram of a multichannel pipetting device provided according to an embodiment of the present invention;

[0022] Figure 1B This is a structural block diagram of another multichannel pipetting device provided according to an embodiment of the present invention;

[0023] Figure 1C This is a schematic diagram of a pipetting device according to an embodiment of the present invention;

[0024] Figure 1D This is a schematic diagram of another pipetting device provided according to an embodiment of the present invention;

[0025] Figure 1E This is a left view of a pipetting device structure provided according to an embodiment of the present invention;

[0026] Figure 1F This is a top view of a pipetting device structure provided according to an embodiment of the present invention;

[0027] Figure 1GThis is a front view of a pipetting device structure provided according to an embodiment of the present invention;

[0028] Figure 1H This is a schematic diagram of the structure of another pipetting device provided according to an embodiment of the present invention;

[0029] Figure 1I This is a schematic diagram of another pipetting device provided according to an embodiment of the present invention;

[0030] Figure 2A This is a flowchart of a pipetting control method provided according to an embodiment of the present invention;

[0031] Figure 2B This is a schematic diagram of a pipetting profile provided according to an embodiment of the present invention;

[0032] Figure 3A This is a flowchart of another pipetting control method provided according to an embodiment of the present invention;

[0033] Figure 3B This is a quadratic polynomial function regression curve provided by an embodiment of the present invention;

[0034] Figure 3C This is a power function regression curve provided according to an embodiment of the present invention. Detailed Implementation

[0035] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0036] It should be noted that the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion, for example, a process, method, system, product, or device that includes a series of steps or units is not necessarily limited to those steps or units that are explicitly listed, but may include other steps or units that are not explicitly listed or that are inherent to such process, method, product, or device.

[0037] Figure 1A This is a structural block diagram of a multichannel pipetting device according to an embodiment of the present invention. The components, their connections and relationships, and their functions shown herein are merely examples and are not intended to limit the implementation of the invention described and / or claimed herein.

[0038] like Figure 1AAs shown, the multichannel pipetting device 10 includes a pipette tip 4 for aspirating liquid; a pipetting device 5 with at least two pipette tips at its end; a robotic arm 6 with the pipetting device 5 fixed at its end; at least one processor 11; and a memory, such as a read-only memory (ROM) 12 or a random access memory (RAM) 13, which is communicatively connected to the at least one processor 11.

[0039] The processor 11 controls the pipetting device 5 and the robotic arm 6 to pipette liquid samples through the pipette tip 4.

[0040] Optional, such as Figure 1B As shown, the multichannel pipetting device 10 also includes a nucleic acid extraction and detection device 7 for extracting nucleic acid from the target sample; the processor 11 is also used to control the nucleic acid extraction and detection device 7 to perform nucleic acid extraction on the target sample. The pipetting device 5 is compatible with 24-well and 96-well plates used by the nucleic acid extraction and detection device 7, and can simultaneously perform multichannel liquid addition, pipetting, and mixing operations. Then, the processor 11 controls the nucleic acid extraction and detection device 7 to extract nucleic acid from the target sample to achieve nucleic acid detection of the target sample.

[0041] In one embodiment, Figure 1C This is a schematic diagram of a pipetting device structure provided according to an embodiment of the present invention, as shown below. Figure 1C As shown, the pipetting device is a plunger pipetting pump equipped with four pipette tips. It can be mounted at the end of a robotic arm and can be moved to any position within its range of motion by controlling the movement of the robotic arm. It is suitable for 24-well plates used in the nucleic acid extraction and detection device 7. In one embodiment, Figure 1D This is a schematic diagram of another pipetting device structure provided according to an embodiment of the present invention, as shown below. Figure 1D As shown, the plunger pipette pump is equipped with 8 pipette tips and is suitable for the 96-well plate used in the nucleic acid extraction and detection device 7. Figure 1E , Figure 1F and Figure 1G The images show a left view, a top view, and a front view of a plunger pipette pump equipped with eight pipette tips. For example, a robotic arm is controlled to move the pipette device above a 24-well plate, where liquid is aspirated / dispensed using the pipette tips. The robotic arm can also be controlled to move to a target position to load / unload pipette tips.

[0042] In one embodiment, Figure 1H This is a schematic diagram of another pipetting device provided according to an embodiment of the present invention, as shown below. Figure 1H As shown, the pipetting device includes: a throttle valve 30, a housing 31, a motor 32, a pump head 33, a drive plate 34, a cylinder 35, and a lead screw 36. Figure 1I This is a schematic diagram of another pipetting device provided according to an embodiment of the present invention, as shown below. Figure 1IAs shown, the pipetting device also includes: a guide rail 37, a push plate 38, a piston 39, and a moving plate 40. When the pipetting device 5 is pipetting, the processor 11 controls the pipetting device 5 to descend, so that the pump head 33 can be inserted into the pipette tip for loading. The drive plate 34 drives the motor 32 to rotate, and the rotation of the motor 32 drives the lead screw 36 to rotate, which further pushes the guide rail 37 to move the moving plate 40 and the piston 39. The cylinder 35 drives the push plate 38 to descend the pump head 33. The throttle valve 30 is used to control the pipetting speed to realize the liquid aspiration / discharge action. Furthermore, the simultaneous descent of 4 channels or 8 channels can be controlled according to actual needs.

[0043] Optionally, the multichannel pipetting device 10 is also equipped with a sensor status feedback module. This module is specifically used to perform self-tests on the pipetting device 5, for example, detecting whether a pipette tip is mounted at the end of the pipetting device 5 and whether the reference point has returned to zero. The advantage of this is that it allows for timely detection of any malfunctions in the multichannel pipetting device 10, enabling users to address the issues promptly.

[0044] The memory stores computer programs executable by at least one processor. The processor 11 can perform various appropriate actions and processes based on the computer programs stored in the read-only memory (ROM) 12 or loaded from the storage unit 18 into the random access memory (RAM) 13. The RAM 13 can also store various programs and data required for the operation of the surgical navigation system. The processor 11, ROM 12, and RAM 13 are interconnected via a bus 14. An input / output (I / O) interface 15 is also connected to the bus 14. Multiple components of the surgical navigation system 10 are connected to the I / O interface 15, including: an input unit 16, such as a keyboard or mouse; an output unit 17, such as various types of displays or speakers; a storage unit 18, such as a disk or optical disk; and a communication unit 19, such as a network card, modem, or wireless transceiver. The communication unit 19 allows the electronic device 10 to exchange information / data with other devices through computer networks such as the Internet and / or various telecommunications networks.

[0045] Processor 11 can be a variety of general-purpose and / or special-purpose processing components with processing and computing capabilities. Some examples of processor 11 include, but are not limited to, central processing unit (CPU), graphics processing unit (GPU), various special-purpose artificial intelligence (AI) computing chips, various processors running machine learning model algorithms, digital signal processors (DSPs), and any suitable processor, controller, microcontroller, etc. Processor 11 is capable of controlling the nucleic acid extraction and detection device 7 to perform nucleic acid extraction operations on the target sample and to execute the pipetting control method described below.

[0046] Figure 2AThis is a flowchart of a pipetting control method provided by an embodiment of the present invention. This embodiment is applicable to scenarios where multiple liquids are simultaneously pipetted and is configured in the processor of a multi-channel pipetting device.

[0047] like Figure 2A As shown, the pipetting control method includes the following steps:

[0048] S210. When a pipetting command is detected, the pipetting parameters corresponding to the pipetting device loaded at the end of the robotic arm are obtained. The pipetting parameters include the target pipetting volume and the capacity of each pipette in the pipetting device assembly, and the preset minimum command unit equivalent corresponding to the target pipetting volume. The pipetting device assembly includes at least two pipettes.

[0049] The target pipetting volume is the volume of liquid pipetted in this pipetting operation corresponding to the pipetting command.

[0050] Understandably, when performing pipetting operations using pipette tips, it is necessary to determine the tip capacity and the volume of liquid to be pipetted. The advantage of doing so is that an appropriate tip capacity can be selected for pipetting operations, avoiding situations where the tip capacity and the target volume differ too much, affecting pipetting accuracy.

[0051] The minimum instruction unit equivalent is the number of minimum instruction units corresponding to 1 μL of liquid transferred by the pipette. The minimum instruction unit is the minimum volume of liquid aspirated by the pipette in a single operation. The minimum instruction unit equivalent can be preset according to a range of liquid transfer volumes; the larger the liquid transfer volume, the larger the minimum instruction unit equivalent. Specifically, when a pipetting command is detected, the range of the target liquid transfer volume is determined based on the pipetting parameters, and the minimum instruction unit equivalent corresponding to that range is obtained.

[0052] For example, when the pipette tip capacity is 1000 μL, the correspondence between the target pipetting volume (x) and the minimum instruction unit equivalent (y) is: y = 1E-05x 2 -0.0282x + 227.7, when the pipette tip capacity is 50 μL, the correspondence between the target pipetting volume (x) and the minimum command unit equivalent (y) is: y = 302.79x -0.097 When using a 1000μL pipette tip to aspirate 300μL of liquid, the minimum instruction unit equivalent is 220, which means the minimum instruction unit equivalent is 220 minimum instruction units.

[0053] Furthermore, before acquiring the pipetting parameters corresponding to the loaded pipette tip assembly of the pipetting device located at the end of the robotic arm, the process also includes:

[0054] Step a1: Determine the spatial location information of the target orifice plate.

[0055] Step a2: Based on the spatial position information, control the movement of the robotic arm to move the suction head assembly above the target perforated plate.

[0056] Specifically, the target well plate is located in a designated space. A pre-established correspondence between the designated space and the target well plate can be created, and the position information of the target well plate can be stored. For example, a pipette tip assembly is installed at the end of the robotic arm. By determining the coordinates of the designated space corresponding to the target well plate in the coordinate system of the robotic arm's end effector, the robotic arm is controlled to move to the designated space, causing the pipette tip assembly to move above the target well plate, performing liquid addition / absorption operations on the target well plate to achieve sample transfer.

[0057] S220. Based on the pre-created correspondence between volume and pipetting curve, determine the pipetting curve corresponding to the volume. The pipetting curve is the curve of pipetting speed changing with time.

[0058] It is understandable that in order for the pipette to complete the pipetting, a motor is required to complete the movement. Therefore, the pipetting process of the target sample with the target volume corresponds to the motor movement process. The pipetting speed is the motor speed. Therefore, the pipetting curve is the curve of the motor speed changing with time. The pipetting process includes an acceleration section, a constant speed section and a deceleration section. The pipetting curve of the pipetting process is shown in formula (1):

[0059]

[0060] Specifically, the pipetting process includes an acceleration phase [T0, T1], a constant speed phase (T1, T2) and a deceleration phase (T2, T3). Here, v(t) represents the pipetting speed of the device at time t. A default value can be set empirically, or it can be adjusted according to actual needs. S V is the initial velocity of the pipetting process. M To set the pipetting speed, V E A is the final velocity of the pipetting process. mp To set the acceleration, A mm To set the deceleration, T1 is the pipetting speed with acceleration A. mp Accelerating from 0 to V m At the moment T3, the pipetting speed decreases by velocity A. mm From V m The time from T0 to T3 when the flow rate drops to 0 is the total pipetting time.

[0061] S230. Determine the pipetting time corresponding to completing the target pipetting volume based on the target pipetting volume and the pipetting curve.

[0062] In one specific embodiment, A mp For 2000, A mm For 2000, V S V is 0M V is the pipetting speed input by the user. E V is 0 m To set the pipetting speed, A mp To set the acceleration, A mm To set the deceleration, substitute t = T1 into formula (1) to get:

[0063]

[0064] Therefore, from V S Accelerate to V M The required time T1 is:

[0065]

[0066] Substituting t = T3 into formula (1), we obtain the duration of the deceleration phase (T3 - T2):

[0067]

[0068] Therefore, by combining the initial time T0, the duration of the acceleration phase (T1-T0), the duration of the constant speed phase (T2-T1), and the duration of the deceleration phase (T3-T2) can be calculated. The total duration of the three phases (T3-T0) is the pipetting time corresponding to the target pipetting volume.

[0069] Furthermore, the pipetting time corresponding to achieving the target pipetting volume is determined based on the target pipetting volume and the pipetting curve, including:

[0070] Step b1: Integrate the curve of pipetting speed versus time to obtain the curve of pipetting displacement versus time.

[0071] In a specific embodiment, the target sample pipetting process of the target volume corresponds to the motor movement process. The pipetting displacement is the motor movement displacement. Therefore, the pipetting displacement change curve with time is the motor movement displacement change curve with time. The pipetting process is divided into acceleration segment, uniform speed segment and deceleration segment. The pipetting speed change curve with time in formula (1) is integrated to obtain the motor movement displacement change curve with time shown in formula (5). Formula (5) is specifically used to represent the motor movement displacement corresponding to time t as s(t). Figure 2B This is a schematic diagram of a pipetting profile provided according to an embodiment of the present invention, such as... Figure 2B As shown, s(t) is the motor displacement at time t, and v(t) is the motor speed at time t. The total displacement of each liquid transfer process is divided into the displacement of the acceleration segment, the constant speed segment and the deceleration segment. S1 is the motor displacement from time T0 to time T1, and (S2-S1) is the motor displacement from time T1 to time T2.

[0072]

[0073] Step b2: Determine the pipetting time corresponding to the target pipetting volume based on the pipetting displacement corresponding to the target pipetting volume and the pipetting displacement change curve over time.

[0074] In one embodiment, the rotation of the motor drives the lead screw to move, which in turn pushes the piston to aspirate liquid. When using a 1000μL pipette tip to aspirate 300μL of liquid, the rotation of the motor drives the lead screw to move, which in turn pushes the piston to aspirate liquid. The minimum instruction unit equivalent is 220 minimum instruction units / μL. The product of the target pipetting volume of 300μL and the minimum instruction unit equivalent is the number of minimum instruction units the motor rotates. Therefore, the motor rotates 300 * 220 = 66000 minimum instruction units. For example, the movement displacement of the motor to complete the target pipetting volume is determined according to the angle of motor rotation. The minimum instruction unit of the motor is 0.001°. Therefore, during this pipetting process, the motor rotates a total of 66000 * 0.001° = 66°, which is the pipetting displacement from time T0 to time T3. Substitute the pipetting displacement corresponding to the target pipetting volume into formula (5) to calculate the time T1 of the acceleration phase, the time T2 of the constant speed phase, and the time T3 of the deceleration phase. The duration of the three phases (T3-T0) is the pipetting time corresponding to the pipetting displacement of the target pipetting volume.

[0075] Specifically, when t = T1, substituting into formula (5) yields:

[0076]

[0077] Similarly, the displacement during the deceleration phase can be obtained:

[0078]

[0079] Based on the minimum instruction unit equivalent and the target liquid transfer volume, the total displacement S0 is determined. S0 is the motor displacement corresponding to completing the target liquid transfer volume. Therefore, the motor displacement during the constant speed segment is:

[0080]

[0081] The duration of the uniform speed segment is (T2-T1):

[0082]

[0083] In summary, we arrive at T2:

[0084]

[0085] Furthermore, based on the duration of the deceleration phase (T3-T2), T3 is calculated as follows:

[0086]

[0087] Therefore, the acceleration phase time T1, the constant speed phase duration (T2-T1), and the deceleration phase duration (T3-T2) can be calculated from T1, T2, and T3. The total duration of the three phases (T3-T0) is the total pipetting time corresponding to the target pipetting volume, and T3 is the pipetting time for this pipetting operation.

[0088] S240. Control at least two pipette tips to pipette simultaneously until the pipetting time is reached, based on the pipetting profile.

[0089] Specifically, the motor is controlled according to the pipetting curve to move in the time intervals of acceleration, constant speed and deceleration until the pipetting time is reached, so as to control at least two pipette tips to pipette simultaneously until the pipetting time is reached, so as to complete the pipetting of the target sample.

[0090] The technical solution of this embodiment controls the movement time and displacement of the motor to control the pipetting of the pipette tip assembly, thereby further improving the pipetting accuracy and synchronization.

[0091] Figure 3A This is a flowchart of another pipetting control method provided by an embodiment of the present invention. This embodiment is applicable to scenarios where multiple liquids are simultaneously pipetted, especially to scenarios where multi-channel nucleic acid extraction is achieved through a plunger pump, and is configured in the processor of a multi-channel pipetting device. This embodiment belongs to the same inventive concept as the pipetting control method in the above embodiments. Based on the above embodiments, the following steps are added: when a pipetting accuracy detection command is detected, the target pipetting volume corresponding to the pipetting accuracy is determined, and the pipetting operation is performed by controlling the pipetting tip through the pipetting device; the pipetting accuracy of the pipetting device is determined according to the target pipetting volume and the actual pipetting volume corresponding to the pipetting operation; if the pipetting accuracy does not meet the set accuracy range, the pipetting device is calibrated to make the pipetting accuracy meet the set accuracy range.

[0092] like Figure 3A As shown, the pipetting control method includes the following steps:

[0093] S310. When a pipetting command is detected, the pipetting parameters corresponding to the pipetting device loaded at the end of the robotic arm are obtained. The pipetting parameters include the target pipetting volume and the capacity of each pipette in the pipetting device assembly, and the preset minimum command unit equivalent corresponding to the target pipetting volume. The pipetting device assembly includes at least two pipettes.

[0094] S320. Based on the pre-created correspondence between volume and pipetting curve, determine the pipetting curve corresponding to the volume. The pipetting curve is the curve of pipetting speed changing with time.

[0095] S330. Determine the pipetting time corresponding to completing the target pipetting volume based on the target pipetting volume and the pipetting curve.

[0096] S340. Control at least two pipette tips to pipette simultaneously until the pipetting time is reached, based on the pipetting curve.

[0097] S3501. Upon detecting a pipetting accuracy detection command, determine the target pipetting volume corresponding to the pipetting accuracy, and control the pipetting tip to perform the pipetting operation through the pipetting device.

[0098] Understandably, after a period of use, pipetting accuracy may decrease due to wear or liquid aspiration into the pipette column, necessitating calibration. For example, pipetting devices should be calibrated at least once a year.

[0099] In one specific embodiment, the pipetting apparatus is calibrated by weighing the distilled water drawn up by the pipette tip at room temperature (20°C ± 5°C). The temperature difference between the distilled water and room temperature must not exceed 2°C. Specifically, distilled water is placed in a liquid tank, the pipette tip is placed in the tip box, the pipette tip is loaded, and the weighing cup is placed on a balance for weighing. After the balance display stabilizes, the balance is zeroed. The processor runs the pre-set calibration script, which is set to blow distilled water back and forth three times to wet the tip when using a new pipette tip for the first time. The script controls the robotic arm to move the pipette tip above the distilled water, immersing it 3mm below the liquid surface, and drawing a set volume of distilled water, for example, 10% of the pipette tip's capacity. The robotic arm is then controlled to lift the pipette tip off the liquid surface and move it above the weighing cup to drain all the distilled water from the tip. The weighing cup is placed on the balance for weighing, and the weighing value is recorded. The set volume of distilled water is drawn and weighed multiple times, and the average value of the multiple weighings is taken as the actual weight of the distilled water. Based on this actual weight and the density of distilled water, the actual volume of distilled water is determined.

[0100] S3502. Determine the pipetting accuracy of the pipetting device based on the target pipetting volume and the actual pipetting volume corresponding to the pipetting operation.

[0101] Specifically, determine the difference between the actual pipetting volume and the target pipetting volume, obtain the absolute value of the difference, and divide the absolute value by the target pipetting volume to obtain the pipetting accuracy of the pipetting device.

[0102] In one specific embodiment, the difference between the actual volume and the set volume of distilled water is determined, the absolute value of the difference is determined, and the absolute value is divided by the set volume to obtain the pipetting accuracy of the pipetting device.

[0103] S3503. If the pipetting accuracy does not meet the set accuracy range, calibrate the pipetting device to ensure that the pipetting accuracy meets the set accuracy range.

[0104] Specifically, a precision range is preset. When the pipetting accuracy of the pipetting device does not meet the preset precision range, the parameters of the pipetting device need to be calibrated to ensure that the pipetting accuracy meets the preset precision range. For example, the equivalent of the minimum instruction unit of the pipetting device is calibrated.

[0105] In one embodiment, calibrating a pipetting device includes: acquiring a calibration script corresponding to the pipetting speed, and calibrating the preset minimum instruction unit equivalent of the pipetting device according to the calibration script. It is understood that the faster the pipetting speed, the larger the minimum instruction unit equivalent; therefore, corresponding calibration scripts are set and stored for calibration at different pipetting speeds. First, the calibration script corresponding to the pipetting speed is read, and the pipetting device for that speed is calibrated. Then, by changing the parameter of the minimum instruction unit equivalent of the pipetting device, the actual volume of liquid aspirated / blown by the pipette tip each time is changed, further ensuring that the pipetting accuracy meets the set accuracy range.

[0106] Furthermore, the preset minimum instruction unit equivalent of the pipetting device is calibrated according to the calibration script, including:

[0107] Step c1: Obtain at least four calibrated pipette volumes and the minimum instruction unit equivalent corresponding to the at least four calibrated pipette volumes.

[0108] Step c2: Determine the calibration curve with the calibrated pipetting volume as the independent variable and the minimum instruction unit equivalent as the dependent variable, so as to obtain the correspondence between the target pipetting volume and the preset minimum instruction unit equivalent.

[0109] In one specific embodiment, the pipetting device was calibrated using a 1000 μL pipette tip. During the calibration process, four sets of data on actual pipetting volume (r) and minimum instruction unit equivalent (y) were obtained, as shown in Table 1. A quadratic polynomial function regression curve was applied to the four sets of data for the 1000 μL pipette tip: (q is the dependent variable, p is the independent variable) q = ap 2 +bp+c yields a quadratic polynomial function regression curve of the actual pipetting volume (r) and the minimum command unit equivalent (y). This curve serves as the correspondence between the target pipetting volume and the minimum command unit equivalent, y = 1E-05x. 2 -0.0282x+227.7,R 2 =0.9991, the corresponding relationship is as follows Figure 3B As shown in Table 1, when the pipette tip capacity is 50 μL, seven sets of data on actual pipetting volumes (x) and minimum instruction unit equivalents (y) were obtained during the calibration process. A power function regression curve was used for the 50 μL pipette tip: q = dp fThe power function regression curve of the actual pipetting volume (r) and the minimum instruction unit equivalent (y) was obtained, and this curve was used as the correspondence between the target pipetting volume and the minimum instruction unit equivalent: y = 302.79x -0.097 R 2 =0.8173, the correspondence is as follows Figure 3C As shown.

[0110] Table 1

[0111]

[0112] Optionally, other forms of functions can be used as regression curves to regress the calibration data of the actual pipetting volume and the minimum instruction unit equivalent to obtain the correspondence between the target pipetting volume and the preset minimum instruction unit equivalent.

[0113] In one embodiment, the preset minimum instruction unit equivalent corresponding to the target pipetting volume is determined based on the correspondence between the target pipetting volume and the preset minimum instruction unit equivalent. Specifically, the minimum instruction unit equivalent corresponding to the target pipetting volume is obtained by substituting the target pipetting volume into the pipette tip capacity and the correspondence between the target pipetting volume and the minimum instruction unit equivalent.

[0114] The technical solution of this embodiment calibrates the preset minimum instruction unit equivalent of the pipetting device through a calibration script, and uses the calibrated pipetting device to perform pipetting, thereby further improving pipetting accuracy and synchronization.

[0115] Various embodiments of the systems and techniques described above herein can be implemented in digital electronic circuit systems, integrated circuit systems, field-programmable gate arrays (FPGAs), application-specific integrated circuits (ASICs), application-specific standard products (ASSPs), systems-on-a-chip (SoCs), payload-programmable logic devices (CPLDs), computer hardware, firmware, software, and / or combinations thereof. These various embodiments may include implementations in one or more computer programs that can be executed and / or interpreted on a programmable system including at least one programmable processor, which may be a dedicated or general-purpose programmable processor, capable of receiving data and instructions from a storage system, at least one input device, and at least one output device, and transferring data and instructions to the storage system, the at least one input device, and the at least one output device.

[0116] Computer programs used to implement the methods of the present invention may be written in any combination of one or more programming languages. These computer programs may be provided to a processor of a general-purpose computer, a special-purpose computer, or other programmable data processing device, such that when executed by the processor, the computer programs cause the functions / operations specified in the flowcharts and / or block diagrams to be implemented. The computer programs may be executed entirely or partially on a machine, or as a standalone software package, partially on a machine and partially on a remote machine, or entirely on a remote machine or server.

[0117] In the context of this invention, a computer-readable storage medium can be a tangible medium that may contain or store a computer program for use by or in conjunction with an instruction execution system, apparatus, or device. A computer-readable storage medium may include, but is not limited to, electronic, magnetic, optical, electromagnetic, infrared, or semiconductor systems, apparatus, or devices, or any suitable combination thereof. Alternatively, a computer-readable storage medium may be a machine-readable signal medium. More specific examples of machine-readable storage media include electrical connections based on one or more wires, portable computer disks, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), optical fibers, portable compact disk read-only memory (CD-ROM), optical storage devices, magnetic storage devices, or any suitable combination thereof.

[0118] To provide interaction with a user, the systems and techniques described herein can be implemented on an electronic device having: a display device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) for displaying information to the user; and a keyboard and pointing device (e.g., a mouse or trackball) through which the user provides input to the electronic device. Other types of devices can also be used to provide interaction with the user; for example, feedback provided to the user can be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user can be received in any form (including sound input, voice input, or tactile input).

[0119] The systems and technologies described herein can be implemented in computing systems that include backend components (e.g., as data servers), or computing systems that include middleware components (e.g., application servers), or computing systems that include frontend components (e.g., user computers with graphical user interfaces or web browsers through which users can interact with implementations of the systems and technologies described herein), or any combination of such backend, middleware, or frontend components. The components of the system can be interconnected via digital data communication of any form or medium (e.g., communication networks). Examples of communication networks include local area networks (LANs), wide area networks (WANs), blockchain networks, and the Internet.

[0120] A computing system can include clients and servers. Clients and servers are generally located far apart and typically interact through communication networks. The client-server relationship is created by computer programs running on the respective computers and having a client-server relationship with each other. The server can be a cloud server, also known as a cloud computing server or cloud host, which is a hosting product within the cloud computing service system to address the shortcomings of traditional physical hosts and VPS services, such as high management difficulty and weak business scalability.

[0121] It should be understood that the various forms of processes shown above can be used, with steps reordered, added, or deleted. For example, the steps described in this invention can be executed in parallel, sequentially, or in different orders, as long as the desired result of the technical solution of this invention can be achieved, and this is not limited herein.

[0122] The specific embodiments described above do not constitute a limitation on the scope of protection of this invention. Those skilled in the art should understand that various modifications, combinations, sub-combinations, and substitutions can be made according to design requirements and other factors. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this invention should be included within the scope of protection of this invention.

Claims

1. A pipetting control method, configured in the processor of a multi-channel pipetting device, characterized in that, include: Upon detecting a pipetting command, the pipetting parameters corresponding to the pipetting device and tip combination mounted on the end of the robotic arm are acquired. The pipetting parameters include the target pipetting volume and the capacity of each tip in the tip combination, and the preset minimum instruction unit equivalent corresponding to the target pipetting volume. The tip combination includes at least two tips. The minimum instruction unit equivalent is the number of minimum instruction units corresponding to 1 μL of liquid pipetting by the pipetting device, and the minimum instruction unit is the minimum volume of liquid aspirated by the pipetting device in a single operation. Based on the pre-established correspondence between volume and pipetting curve, the pipetting curve corresponding to the volume is determined, and the pipetting curve is the curve of pipetting speed changing with time; The pipetting time corresponding to completing the target pipetting volume is determined based on the target pipetting volume and the pipetting curve. The at least two pipette tips are controlled to simultaneously perform pipetting until the specified pipetting time, based on the pipetting curve. Determining the preset minimum instruction unit equivalent corresponding to the target pipetting volume includes: At the given capacity, at least four calibrated pipette volumes and the minimum instruction unit equivalent corresponding to the at least four calibrated pipette volumes are obtained; A calibration curve is determined with the calibrated pipetting volume as the independent variable and the minimum instruction unit equivalent as the dependent variable, so as to obtain the correspondence between the target pipetting volume and the preset minimum instruction unit equivalent; Based on the target pipetting volume and the correspondence between the target pipetting volume and the preset minimum instruction unit equivalent, the preset minimum instruction unit equivalent corresponding to the target pipetting volume is determined.

2. The method according to claim 1, characterized in that, The method further includes: Upon detecting a pipetting accuracy detection command, the target pipetting volume corresponding to the pipetting accuracy is determined, and the pipetting device controls the pipette tip to perform a pipetting operation. The pipetting accuracy of the pipetting device is determined based on the target pipetting volume and the actual pipetting volume corresponding to the pipetting operation. If the pipetting accuracy does not meet the set accuracy range, the pipetting device is calibrated to ensure that the pipetting accuracy meets the set accuracy range.

3. The method according to claim 2, characterized in that, The calibration of the pipetting device includes: Obtain the calibration script corresponding to the pipetting speed. The preset minimum instruction unit equivalent of the pipetting device is calibrated according to the calibration script.

4. The method according to claim 1, characterized in that, The step of determining the pipetting time corresponding to completing the target pipetting volume based on the target pipetting volume and the pipetting curve includes: Integrating the curve of the pipetting speed versus time yields the curve of the pipetting displacement versus time. The pipetting time corresponding to the target pipetting volume is determined based on the pipetting displacement corresponding to the target pipetting volume and the pipetting displacement changing over time.

5. The method according to claim 1, characterized in that, Before acquiring the pipetting parameters corresponding to the loaded pipette tip assembly of the pipetting device located at the end of the robotic arm, the method further includes: Determine the spatial location information of the target orifice plate; Based on the spatial position information, the robotic arm is controlled to move, causing the suction head assembly to move above the target perforated plate.

6. A multi-channel pipetting device, characterized in that, The multichannel pipetting device includes: A pipette tip is used for suctioning liquids. A pipette, wherein at least two pipette tips are provided at the end of the pipette; A robotic arm, the end of which is fixed with the pipetting device; At least one processor; and A memory communicatively connected to the at least one processor; wherein, The memory stores a computer program that can be executed by the at least one processor to enable the at least one processor to perform the pipetting control method according to any one of claims 1-5.

7. The device according to claim 6, characterized in that, The device also includes: Nucleic acid extraction and detection device, used to extract nucleic acid from target samples; The processor is also used to control the nucleic acid extraction and detection device to perform nucleic acid extraction operations on the target sample.

8. A computer-readable storage medium, characterized in that, The computer-readable storage medium stores computer instructions that cause a processor to execute the pipetting control method according to any one of claims 1-5.

Citation Information

Patent Citations

  • Pipetting method and pipetting device

    CN109937365A

  • Control unit for pipetting machines

    US20160139166A1