Integrated nucleic acid extraction system
By designing an integrated nucleic acid extraction system and using the coordinated work of the rotating table and the robotic arm, the problem that existing equipment cannot dynamically add new samples is solved, and efficient and automated nucleic acid extraction is achieved, meeting the "as-as-you-can-eat" needs in large-scale screening.
Patent Information
- Application Number
- CN202210369220.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-04-08
- Publication Date
- 2025-04-25
- Estimated Expiration
- 2042-04-08
AI Technical Summary
Existing nucleic acid extraction equipment cannot add new samples when the current sample extraction process is not completed, resulting in low nucleic acid extraction efficiency and long waiting time for samples to be processed, especially in large-scale nucleic acid screening work, which is difficult to achieve "as-as-you-can-eat test".
An integrated nucleic acid extraction system is designed, including pillars, rotary tables, robotic arms and control devices, allowing the robotic arms to be dynamically distributed during the sample extraction process to process newly added samples, enabling automated, real-time allocation and parallel extraction of samples.
It improves the efficiency and resource utilization of nucleic acid extraction, shortens the waiting time of samples to be tested, realizes "inspection as you go", and reduces the mistakes and costs caused by manual operations.
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Figure CN114736766B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biotechnology, and more specifically, to an integrated nucleic acid extraction system. Background Art
[0002] Nucleic acids are divided into deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acid extraction is the first and most important step in gene cloning, gene diagnosis and gene modification. Efficient and rapid extraction of nucleic acids is the basis for subsequent analysis. Compared with manual nucleic acid extraction methods, automated nucleic acid extraction instruments have the advantages of high efficiency, high product purity and good repeatability, and can greatly save labor costs and public health resources.
[0003] Existing nucleic acid extraction equipment cannot modify the extraction process after starting work, and cannot add new samples when the nucleic acid extraction process of the current sample is not completed. That is, the new round of samples can only be added to the nucleic acid extraction equipment after the nucleic acid extraction of the previous round of samples is completed. Different sample batches need to be extracted serially, the nucleic acid extraction efficiency is low, and the waiting time for samples to be processed is long. Especially in large-scale nucleic acid screening work, it is difficult to achieve "once-in-time testing" of samples.
[0004] Therefore, it is expected to propose a highly automated nucleic acid extraction system that can improve the efficiency of nucleic acid extraction and shorten the waiting time for samples to be tested. Summary of the invention
[0005] In view of this, an object of the present invention is to provide a nucleic acid extraction system that can improve the efficiency of nucleic acid extraction, shorten the waiting time of samples to be detected, and allow newly added samples to be processed during the working process.
[0006] According to an embodiment of the present disclosure, a nucleic acid extraction system may include: a pillar; a plurality of rotating tables distributed around the pillar, the loading surface of each rotating table being used to place one or more sample containers; a plurality of first robotic arms, each of the first robotic arms having a first end connected to the pillar and a second end facing the loading surface, and the second end being provided with an operating component for performing an extraction task; and a control device, for assigning the corresponding first robotic arm in an idle state as a target robotic arm for the sample to be tested in each sample container, and controlling the target robotic arm to match the position of the sample to be tested, so that the target robotic arm performs at least one extraction step of the extraction task on the sample to be tested.
[0007] In some optional embodiments, the control device drives the target robot arm to rotate around the pillar as the axis to an operating position corresponding to the sample to be tested; and / or each of the rotating tables rotates around its own axis under the control of the control device, so that the sample container located on the carrier surface can be rotated to the corresponding operating position.
[0008] In some optional embodiments, the first ends of the plurality of first robotic arms are rotatably connected to the pillar at different heights of the pillar.
[0009] In some optional embodiments, each of the first robotic arms includes a first part, a second part, and a connecting structure for connecting the first part and the second part, a non-zero angle is formed between the extension directions of the first part and the second part, the first part is connected between the first end of the first robotic arm and the connecting structure, the second part is located between the connecting structure and the second end of the first robotic arm, and the second part is connected to the operating part at the second end of the first robotic arm, and the lengths of the first robotic arms are different, so as to allow the first robotic arms to rotate freely around the pillar as the axis without interfering with each other under the control of the control device.
[0010] In some optional embodiments, the operating component includes: a magnetic rod for attracting magnetic beads in a corresponding sample container; and a magnetic-resistance sleeve for isolating the magnetic rod from the magnetic beads. When the magnetic rod is placed in the magnetic-resistance sleeve, the magnetic beads and / or adsorbates of the magnetic beads are gathered on the bottom surface of the magnetic-resistance sleeve under the gravitational force of the magnetic rod, so that the magnetic beads and / or adsorbates of the magnetic beads move with the magnetic-resistance sleeve and the magnetic rod. When the magnetic rod is moved out of the magnetic-resistance sleeve, the magnetic beads and / or adsorbates of the magnetic beads gathered on the bottom surface of the magnetic-resistance sleeve are released to the receiving position of the corresponding sample container.
[0011] In some optional embodiments, the operating component further includes a clamp, at least for detachably connecting the anti-magnetic sleeve to the corresponding second end of the first mechanical arm, and the clamping and releasing of the anti-magnetic sleeve by the clamp is controlled by the control device.
[0012] In some optional embodiments, the nucleic acid extraction system also includes: at least one second robotic arm, rotatably connected to the support, for adding one or more reaction liquids and / or magnetic beads required for the extraction task to each sample container under the control of the control device, and / or removing or recovering the liquid and / or magnetic beads in each sample container.
[0013] In some optional embodiments, at least one of the rotating tables provides a material area for storing the one or more reaction liquids and / or magnetic beads, and each of the second robotic arms is configured under the control of the control device to: obtain one of the one or more reaction liquids from the material area, and inject it into a designated position in a designated sample container under the control of the control device; and / or move the magnetic beads from the material area to a designated position in a designated sample container under the control of the control device, or recover the magnetic beads from each sample container to the material area.
[0014] In some optional embodiments, the nucleic acid extraction system also includes a sensor for detecting the position of the sample to be detected to obtain position data; a communication module, coupled to the sensor, is used to provide the corresponding position data to the control device, so that the control device records the position information of the sample to be detected and assigns the corresponding target robot arm to it, each of the rotating tables has an independent number, and each of the sample containers on the rotating table has an independent number, and the position information includes the independent number corresponding to the rotating table where the sample to be detected is located and the independent number corresponding to the sample container where the sample to be detected is located.
[0015] In some optional embodiments, the control device includes: a memory, storing a sample queue of unfinished extraction tasks; and a processor, communicatively coupled to the memory, for independently and parallelly controlling each of the first robotic arms, and allocating the corresponding target robotic arms to the samples in the sample queue according to a first-in-first-out principle.
[0016] In some optional embodiments, the control device is suitable for: selecting an operating mode, the operating mode including a first operating mode and a second operating mode. In the first operating mode, the control device selects the corresponding target robot arm for the sample to be tested, so that the target robot arm serially performs each extraction step in the extraction task on the sample to be tested. In the second operating mode, the control device selects the corresponding target robot arm for each extraction step of the sample to be tested, so as to allow different first robots to perform different extraction steps on the sample to be tested.
[0017] In some optional embodiments, the control device is also suitable for: in the second working mode, establishing and managing multiple sub-sample queues corresponding to the multiple extraction steps, each sub-sample queue is used to record and sort the samples to be subjected to the extraction steps corresponding to the sub-sample queue; and based on each sub-sample queue, executing an allocation algorithm respectively, the allocation algorithm is used to select the corresponding target robot arm for the sample in the sub-sample queue, so that the target robot arm executes the extraction step corresponding to the sample queue on the sample.
[0018] In some optional embodiments, based on each of the sub-sample queues, the processor executes the allocation algorithm to be suitable for: selecting a corresponding number of the target robotic arms to perform corresponding extraction steps on the samples to be tested in the sample queue according to the quantity interval of the samples in the sub-sample queue.
[0019] In some optional embodiments, if the number of the first robotic arms in the idle state is less than the number of target robotic arms required in the number interval, the processor executes a time optimization algorithm, which is used to estimate the waiting time required for each of the first robotic arms, and selects the first robotic arm that is about to be released to the idle state as the target robotic arm based on the estimated waiting time.
[0020] In some optional embodiments, the control device is further suitable for: dividing the multiple first robotic arms into multiple groups, each group of first robotic arms being configured to perform one of the multiple extraction steps required for the extraction task; and for each extraction step of the current sample to be processed, selecting the first robotic arm in an idle state from a group of first robotic arms corresponding to the extraction step as the target robotic arm.
[0021] In some optional embodiments, the multiple extraction steps include at least a first extraction step and a second extraction step, the time required to execute the first extraction step is longer than the time required to execute the second extraction step, the multiple first robotic arms include a first group of robotic arms corresponding to the first extraction step and a second group of robotic arms corresponding to the second extraction step, and the number of the first robotic arms included in the first group of robotic arms is greater than the number of the first robotic arms included in the second group of robotic arms.
[0022] In summary, the nucleic acid extraction scheme of the embodiment of the present disclosure can assign corresponding target robotic arms to samples according to whether each robotic arm is in an idle state, and the control device can control the rotating table and / or the robotic arm to automatically match the samples to be tested to the corresponding target robotic arms in sequence. Therefore, compared with the traditional scheme that does not allow new samples to be added during the working process, the nucleic acid extraction scheme of the embodiment of the present disclosure allows the addition of new samples at any time, and can automatically and in real time use the robotic arm that is currently in an idle state to extract nucleic acids from new samples, which is conducive to realizing "on-demand testing" in the scenario of batch nucleic acid testing, and is conducive to the automatic parallel execution of nucleic acid extraction steps / tasks, reducing waiting time, and improving the efficiency of nucleic acid extraction and resource utilization.
[0023] Compared with the traditional technology that relies on manual labor to add and distribute samples, add and recover magnetic beads, the solution adopted by the present invention can automatically realize functions such as adding, inputting and distributing samples, adding and recovering magnetic beads based on a highly integrated and intelligent nucleic acid extraction system, without the need for human intervention throughout the process, thereby improving the efficiency of nucleic acid extraction and reducing labor costs. Automated control is conducive to the realization of automated data management, and can greatly reduce errors caused by manual operations.
[0024] In some preferred embodiments, in the second working mode, based on a preset control mechanism, each robotic arm as a sub-node works in coordination and in parallel, and each sample can complete the lysis, cleaning and purification steps respectively under the operation of one or more robotic arms, without being limited to completing all the steps for nucleic acid extraction based on the same robotic arm. Based on this pipeline-style second working mode, the efficiency of nucleic acid extraction can be improved by executing each step in parallel.
[0025] In some preferred embodiments, when selecting a target robot for the sample to be assigned, the waiting time required for each sub-node and each working mode can be traversed and estimated and trial-and-error can be performed, and the sub-node with the shortest estimated waiting time can be selected as the target robot for the sample to be assigned based on the time optimization algorithm, thereby further improving the intelligence and automation performance of the nucleic acid extraction system and further improving the efficiency of nucleic acid extraction. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] The above and other objects, features and advantages of the present invention will become more apparent through the following description of the embodiments of the present invention with reference to the accompanying drawings.
[0027] Figure 1 A schematic diagram showing the structure of a nucleic acid extraction system according to an embodiment of the present disclosure;
[0028] Figure 2a A schematic diagram showing the structure of an example of a nucleic acid extraction system according to an embodiment of the present disclosure;
[0029] Figure 2b A schematic diagram showing the structure of an example of a nucleic acid extraction system according to an embodiment of the present disclosure;
[0030] Figure 3 An exemplary structural schematic diagram showing a robotic arm and a support of a nucleic acid extraction system according to an embodiment of the present disclosure;
[0031] Figure 4 A schematic diagram showing the structure of the operating components of an embodiment of the present disclosure;
[0032] Figure 5 A schematic diagram showing the structure of a clamp according to an embodiment of the present disclosure;
[0033] Figure 6A schematic diagram showing the principle of nucleic acid extraction by a robotic arm according to an embodiment of the present disclosure;
[0034] Figure 7 A schematic structural diagram showing an example of a sample container according to an embodiment of the present disclosure;
[0035] Figure 8 A schematic diagram showing a control method flow chart of an embodiment of the present disclosure is shown;
[0036] Fig. 9 A flowchart showing an example of a control method according to an embodiment of the present disclosure;
[0037] Fig.10 A schematic diagram showing a flow chart of a subnode allocation algorithm according to an embodiment of the present disclosure;
[0038] Fig.11 A schematic diagram showing an example of a flow chart of a subnode allocation algorithm according to an embodiment of the present disclosure;
[0039] Fig.12 A schematic diagram showing an exemplary flow chart of a time optimization algorithm according to an embodiment of the present disclosure;
[0040] Fig.13 A flow chart showing an example of a control method according to an embodiment of the present disclosure implementing a stack operation based on a sample queue and a sub-node queue;
[0041] Fig.14 A flowchart showing an example of implementing a stack operation based on a sample queue and a sub-node queue according to an embodiment of the present disclosure is shown. DETAILED DESCRIPTION
[0042] Various embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. In each of the accompanying drawings, the same elements are represented by the same or similar reference numerals. For the sake of clarity, the various parts in the accompanying drawings are not drawn to scale.
[0043] The present invention may be embodied in various forms, some examples of which will be described below.
[0044] Figure 1 A schematic block diagram of a nucleic acid extraction system according to an embodiment of the present disclosure is shown. Figure 2a An exemplary structural schematic diagram of a nucleic acid extraction system according to an embodiment of the present disclosure is shown. Figure 2b Another exemplary structural schematic diagram of the nucleic acid extraction system according to an embodiment of the present disclosure is shown.
[0045] The nucleic acid extraction system of the disclosed embodiment is used to perform extraction tasks on samples on a “on-demand” basis.
[0046] like Figure 1 , 2aAs shown in FIG. 2b , the nucleic acid extraction system 1000 of the embodiment of the present disclosure may include: a control device 100, a plurality of mechanical arms 200, a plurality of rotating tables 300, and a support column 400. Figure 2a and 2b The difference between the embodiments shown is the number of turntables. It should be noted that the embodiments of the present disclosure do not limit the number of turntables, the number of robotic arms, and the quantitative relationship between the turntables and the robotic arms. For example, the number of turntables can be any value greater than / equal to 2, the number of robotic arms can be any value greater than / equal to 3, and the number of robotic arms can be less than, greater than, or equal to the number of turntables.
[0047] The plurality of rotating tables 300 are distributed around the support column 400, and the loading surface 3 of each rotating table 300 is used to place one or more sample containers 210 (eg Figure 7 each robot arm 200 has a first end 1 connected to the support 400 and a second end 2 facing the object surface, and the second end 2 is provided with an operating component 20 for performing an extraction task.
[0048] The control device 100 is a parent node, which is coupled to multiple robot arms 200 in communication, and each robot arm 200 is controlled by the control device 100 as a child node. The control device 100 can detect whether each robot arm 200 is in an idle state, and select one of the multiple robot arms 200 in an idle state as a target robot arm corresponding to the sample to be tested, that is, the control device 100 is used to assign a corresponding robot arm in an idle state as a target robot arm for the sample to be tested in each sample container, and control the target robot arm to match the position of the sample to be tested, so that the target robot arm performs the entire extraction task or one or more extraction steps in the extraction task on the sample to be tested.
[0049] The extraction task referred to in the present disclosure refers to the task of extracting nucleic acid from a sample, and the extraction task may include multiple extraction steps such as a lysis step, one or more cleaning / washing steps, and a purification step.
[0050] It should be noted that the “sample” described in the embodiments of the present disclosure may refer to one or more samples to be tested contained in the same sample container.
[0051] The control device 100 can manage samples based on the sample queue, and can assign corresponding target robotic arms to samples according to whether each robotic arm is in an idle state. Therefore, compared with the traditional scheme that does not allow new samples to be added during the working process, the nucleic acid extraction system 1000 of the embodiment of the present disclosure allows new samples to be added to the sample queue at any time, and can use the robotic arm that is currently in an idle state to extract nucleic acid from the new sample in real time, which is conducive to realizing "on-demand testing" in the scenario of batch nucleic acid testing, and is conducive to the automated parallel operation of robotic arms, reducing waiting time, and improving the efficiency of nucleic acid extraction and resource utilization.
[0052] In some embodiments, the control device 100 drives the target robot arm to rotate around the support 400 to an operating position corresponding to the sample to be tested, and / or each rotating table 300 can rotate around its own axis under the control of the control device 100, so that the sample container 210 located on the loading surface 3 can be rotated to a corresponding operating position.
[0053] In some embodiments, the plurality of robotic arms 200 include a plurality of first robotic arms 200 for performing the extraction step and at least one second robotic arm 200 for automatically maintaining the extraction environment.
[0054] In some embodiments, the structures of the first robotic arms 200 can be completely the same, so that the number of first robotic arms 200 can be added or reduced in the nucleic acid extraction system 1000 according to needs, which facilitates the expansion and reduction of the system scale. In addition, each first robotic arm 200 can independently perform the entire extraction task on the sample in series, or can work in conjunction with other robotic arms and only be used to perform one or more extraction steps in the extraction task on the sample, which is conducive to flexible allocation of resources.
[0055] In some embodiments, the second robot arm 200 is rotatably connected to the support column 400, and is used to add one or more reaction liquids and / or magnetic beads required for the extraction task to each sample container 210 under the control of the control device 100, and / or remove or recover the liquid and / or magnetic beads in each sample container 210. As an example, the second robot arm 200 can use a dropper and / or a magnetic substance to move various reaction liquids and magnetic beads.
[0056] In some embodiments, at least one rotating table 300 provides a material area (not shown) for storing one or more reaction solutions and / or magnetic beads, and each second robotic arm 200 is configured under the control of the control device 100 to obtain one of the one or more reaction solutions from the material area and inject it into a designated position (e.g., Figure 7one of the working areas shown in the figure) to provide the operating environment required for the corresponding extraction step; and / or, under the control of the control device 100, the magnetic beads are moved from the material area to a specified position in the specified sample container 210 (for example Figure 7 or recovering the magnetic beads from each sample container to the material area.
[0057] Specifically, Figure 1 , 2a As shown in Figure 2b, the control device 100 is communicatively coupled with each robotic arm 200, thereby exchanging information with each robotic arm 200. As an example, the control device 100 and each robotic arm 200 can be communicatively coupled based on a networking protocol, for example, the control device 100 serves as a parent node, each robotic arm 200 serves as a child node, and the parent node and each child node work together through a specific communication protocol networking, such as the TCP / IP protocol (Transmission Control Protocol / Internet Protocol), and the child node will send a data packet to the parent node at a specified time to facilitate reporting the working status of the robotic arm where the child node is located (for example, including the working attributes of the child node, working progress, sensor data such as temperature, estimated working time / waiting time, etc.).
[0058] However, the embodiments of the present disclosure are not limited thereto, and the control device 100 and each robotic arm 200 may also communicate with each other via other coupling methods (e.g., wired connection, local area network, etc.), so that each robotic arm 200 and the control device 100 are networked to form a workstation for nucleic acid extraction.
[0059] In this embodiment, the control device 100 acts as a parent node and a host computer, and is mainly used to control, calculate, coordinate, and monitor the working status of each robot arm 200. For example, the control device 100 can check all manageable child nodes (robot arms) in the nucleic acid extraction system 1000, monitor the current working status of all child nodes that are communicatively coupled to the control device 100 in real time, calculate the expected working time, set the working attributes of the child nodes, and assign work tasks to the child nodes. In some embodiments, the control device 100 can also use a time optimization algorithm to establish a sample queue, a child node queue, and / or an idle child node queue.
[0060] In this embodiment, the working attribute of the subnode is used to indicate one of the lysis working state, cleaning working state, and purification working state, for example. Each subnode can be used as an independent nucleic acid extraction device, or can be configured as a branch device with one of the three working attributes (i.e., only one of the three lysis, cleaning, and purification steps is completed), and the other steps are completed by other subnodes. The working attributes and working methods of each subnode can be independently set by the control device according to the number of samples in the sample queue, the working mode, and the actual needs.
[0061] As an example, Figure 1 As shown, the control device 100 may include a processor 110 and a memory 120. The memory 120 is used to store the sample queue, and the processor 110 is communicatively coupled with the memory 120 to independently and parallelly control each robot 200, and assign corresponding target robots to the samples in the sample queue according to the first-in-first-out principle. The memory 120 may also store a series of control instructions, and the processor 110 executes a control toolkit based on these control instructions to facilitate at least one of the functions of time control, lysis control, cleaning / washing control, purification control, and error detection. The processor 110 is, for example, a general / special purpose processor, and the memory 120 includes, for example, various types of memories such as a read-only memory (ROM) and / or a flash memory, and the control device 100 is, for example, a general / special purpose computer.
[0062] In some embodiments, the nucleic acid extraction system 1000 may further include a sensor (not shown, such as a photoelectric sensor and / or a weight sensor, etc.) and a communication module. The sensor is used to detect the position of the sample to be detected to obtain position data; the communication module is coupled to the sensor and is used to provide the corresponding position data to the control device 100, so that the control device 100 records the position information of the sample to be detected and allocates a corresponding target robot arm to it.
[0063] As an example, the sensor can perform a detection at preset time intervals and report position data to the control device 100 through the communication module after each detection, so that the control device 100 can allocate a corresponding target robot arm to the newly added sample to be tested according to a preset mechanism.
[0064] As an example, the sensor can detect the position of a sample newly added to the nucleic acid extraction system 1000, and number the newly added sample directly or via the control device 100 to facilitate the control device 100 to manage the transfer and distribution of the sample.
[0065] As an example, each rotating stage 300 may have an independent number, each sample container 210 on each rotating stage 300 may have an independent number, and the position data reported by the sensor and / or the position information recorded by the control device 100 may include the independent number corresponding to the rotating stage 300 where the sample to be detected is located and the independent number corresponding to the sample container 210 where the sample to be detected is located. It should be noted that the position information of each sample to be detected may also be encoded based on other methods, and the present disclosure does not limit the position, type, and composition of the position data of the sensor.
[0066] Since the sensor can identify whether a new sample has been entered into the current nucleic acid extraction system, after receiving the position data from the sensor, the control device 100 can select a reasonable allocation scheme to allocate the corresponding target robot arm to the new sample according to the different working modes. For example, after learning that a new sample has been entered, the control device 100 can add the new sample to the sample queue, estimate the waiting time and / or extraction task execution time required under different working modes, and select the working mode with the best efficiency (e.g., the shortest waiting time) (e.g., one of the first working mode and the second working mode described below) according to the estimation result to allocate the new sample, so as to select the corresponding target robot arm to perform one or more extraction steps on the sample.
[0067] Figure 3 An exemplary structural schematic diagram of a robotic arm and a support of a nucleic acid extraction system according to an embodiment of the present disclosure is shown.
[0068] like Figure 3 As shown, the first ends 1 of the plurality of robot arms 200 may be rotatably connected to the support column 400 at different heights of the support column 400 , for example.
[0069] In some examples, each mechanical arm 200 may include a first portion 201, a second portion 202, and a connection structure (e.g., a connection shaft or a slide rail) for connecting the first portion and the second portion, and a non-zero angle (e.g., fixed to 90 degrees or an angle that can be flexibly changed under the control of the control device 100) is formed between the extension directions of the first portion 201 and the second portion 202. The first portion 201 is connected between the first end 1 of the mechanical arm and the connection structure (not shown), the second portion 202 is located between the connection structure and the second end 2 of the mechanical arm, and the second portion 202 is connected to the operating component 20 at the second end 2 of the mechanical arm.
[0070] In some examples, the lengths of the robotic arms 200 are different, so as to allow the robotic arms 200 to freely rotate around the support column 400 without interfering with each other under the control of the control device 100 .
[0071] Figure 4 A schematic diagram showing the structure of the operating components of an embodiment of the present disclosure. Figure 5 A schematic structural diagram of a clamp according to an embodiment of the present disclosure is shown. Figure 6 A schematic diagram showing the principle of nucleic acid extraction achieved by the robotic arm according to an embodiment of the present disclosure. Figure 7 A schematic structural diagram showing an example of a sample container according to an embodiment of the present disclosure.
[0072] The robotic arm 200 of the disclosed embodiment uses magnetic beads to extract nucleic acids (DNA and / or RNA) from a sample. After the surface of superparamagnetic nanoparticles is improved and modified using nanotechnology, superparamagnetic silica nanomagnetic beads can be prepared. The magnetic beads can specifically recognize and efficiently bind to nucleic acid molecules at a microscopic interface. Under the action of an external magnetic force, the magnetic beads can quickly separate and purify nucleic acid DNA / RNA, which is safe and easy to automate. The nanomagnetic bead nucleic acid extraction method used in the disclosed embodiment refers to a method for extracting nucleic acids using superparamagnetic silica nanomagnetic microspheres (hereinafter referred to as magnetic beads) as carriers, using magnetic beads to adsorb nucleic acids in high-salt, low-PH solutions, and separating nucleic acids from the surface of the magnetic beads in low-salt solutions.
[0073] In the embodiment of the present disclosure, at least one operating component 20 located at the second end 2 of each first mechanical arm 200 includes, for example: a magnetic rod 220 for attracting magnetic beads in the corresponding sample container; and a magnetic blocking sleeve 230 for isolating the magnetic rod 220 from the magnetic beads. The magnetic rod 220 and the magnetic blocking sleeve 230 provided on each first mechanical arm 200 are assembled in pairs, and one or more pairs of magnetic rods 220 and magnetic blocking sleeves 230 may be provided on the second end 2 of the first mechanical arm 200. The configuration of multiple pairs of magnetic rods 220 and magnetic blocking sleeves 230 is conducive to batch operation of multiple samples.
[0074] The sample container 210 for carrying samples includes a plurality of accommodating positions for accommodating samples; the magnetic rod 220 is used to attract magnetic beads; the magnetic blocking sleeve 230 is used to separate the magnetic rod 220 from the magnetic beads; and each first mechanical arm 220A is at least used to move the magnetic rod 220 and the magnetic blocking sleeve 230.
[0075] When the magnetic rod 220 is placed in the magnetic-resistance sleeve 230, the magnetic beads and / or the adsorbed substances of the magnetic beads gather on the bottom surface of the magnetic-resistance sleeve 230 under the gravitational force of the magnetic rod 220, so that the magnetic beads and / or the adsorbed substances of the magnetic beads move between different accommodation positions following the magnetic-resistance sleeve 230 and the magnetic rod 220. When the magnetic rod 220 is moved out of the magnetic-resistance sleeve 230, the magnetic beads and / or the adsorbed substances of the magnetic beads gathered on the bottom surface of the magnetic-resistance sleeve 230 are released to the corresponding accommodation positions. The magnetic rod 220, the magnetic beads and the magnetic-resistance sleeve 230 can be used to adsorb and release nucleic acids in the sample, thereby realizing the movement of nucleic acid molecules.
[0076] Each first robot arm 200 can move the magnetic blocking sleeve 230 and the magnetic rod 220 in multiple directions, for example, lift the magnetic blocking sleeve 230 and / or the magnetic rod 220 in the gravity direction, move the magnetic blocking sleeve 230 and the magnetic rod 220 in the horizontal direction, and / or move the magnetic blocking sleeve 230 and / or the magnetic rod 220 in other directions.
[0077] In some embodiments, the magnetic blocking sleeve 230 and the magnetic rod 220 are detachably connected to the second end of the corresponding first robotic arm 200 , respectively, so that the magnetic blocking sleeve 230 and / or the magnetic rod 220 in each first robotic arm 200 can be replaced.
[0078] As an example, Figure 5 As shown, the operating component 20 may also include a clamp 240 disposed at the second end of each mechanical arm. The clamp 240 is at least used to detachably connect the magnetic blocking sleeve to the second end 2 of the corresponding mechanical arm 200. The clamping and releasing of the magnetic blocking sleeve by the clamp 240 is controlled by the control device 100, so that the magnetic blocking sleeve 230 can be separated from the corresponding mechanical arm or moved with the corresponding mechanical arm according to the operation requirements of the extraction step. For example, when the magnetic blocking sleeve 230 is released by the clamp, it can fall into the corresponding sample container accommodating position and wait for the mechanical arm assigned by the control device 100 to move it. Based on this, each magnetic blocking sleeve can be transferred between different first mechanical arms 200.
[0079] However, the present disclosure is not limited thereto, and the magnetic bar or the magnetic blocking sleeve may also be connected to the corresponding first mechanical arm in other ways. For example, the magnetic bar and / or the magnetic blocking sleeve may be directly fixedly connected to the second end 2 of the first mechanical arm and cannot be detached.
[0080] As an example, each first robot arm 200 can drive the magnetic blocking sleeve 230 to stir in the corresponding accommodation position, so as to fully stir the content in the corresponding accommodation position to make it uniform / react fully.
[0081] The sample container 210 is, for example, arranged horizontally (the plane where the x-axis and the y-axis are located as shown in the figure is, for example, a plane perpendicular to the direction of gravity), and may include a plurality of mutually isolated accommodation positions, each accommodation position being, for example, distributed in an array of multiple rows by multiple columns. As an example, the sample container is, for example, a 96-well plate, each well position being a accommodation position, and its common specifications include, for example, 12x8 accommodation positions. In some examples, depending on the different movement methods, each accommodation position in the sample container may also be arranged and distributed in an array in the form of concentric circles, staggered columns, etc., and the present disclosure does not limit the implementation and distribution methods of each accommodation position in the sample container.
[0082] As an example, Figure 6As shown, the sample container 210 can be divided into a plurality of working areas, including: a first containing area, including at least one containing position, the containing position in the first containing area contains a lysate for implementing the lysis step; a second containing area, including at least one containing position, the containing position in the second containing area contains a cleaning solution for implementing the cleaning / washing step; and a third containing area, including at least one containing position, the containing position in the third containing area contains a purification buffer. Based on this, each robotic arm can use the magnetic rod 220 and the magnetic sleeve 230 to transfer the magnetic beads adsorbed with nucleic acid molecules between different working areas and / or different robotic arms.
[0083] Further, the sample container 210 can be, for example, a 96-well plate (including 12 columns, 8 wells in each column). The sample area is, for example, located at the edge of the 96-well plate, so as to facilitate the addition of new samples, and the sample area occupies, for example, the 1st to 3rd columns of wells; the first accommodation area for performing the lysis step occupies, for example, the 4th to 6th columns of wells, each of which can be pre-injected with a lysis solution (for example, including 20 microliters of proteinase K, 10 microliters of RNAse and 400 microliters of CTAB lysis solution); the second accommodation area for performing the cleaning / washing step occupies, for example, the 7th to 9th columns of wells, each of which can be pre-injected with a cleaning solution (for example, including 400 microliters of deproteinized solution); the third accommodation area for performing the purification step occupies, for example, the 10th to 12th columns of wells, each of which can be pre-injected with a purification buffer (for example, TE solution). In this example, the number of samples that each robotic arm can process at a time is, for example, 8 or 16 or 24, which is an integer multiple of the number of accommodation positions provided by a single column of wells in the sample area.
[0084] In some optional examples, such as Figure 6 As shown, the sample container 210 may also include a sample area for storing samples to be processed by the current robot arm.
[0085] like Figures 4 to 6 As shown, the magnetic blocking sleeve 230 can be placed in the corresponding accommodation position and / or taken out from the corresponding accommodation position under the drive of the corresponding first mechanical arm 200, and the corresponding first mechanical arm 200 can drive the magnetic blocking sleeve 230 to move up and down (for example, in the direction of gravity) in the corresponding accommodation position to stir the contents in the corresponding accommodation position. In some examples, the corresponding first mechanical arm 200 can also drive the magnetic blocking sleeve 230 to move horizontally, rotate and / or move around the axis in the corresponding accommodation position, so as to achieve more sufficient stirring of the contents in the corresponding accommodation position.
[0086] like Figure 4As shown, the diameter of the magnetic rod 220 is smaller than the inner diameter of the magnetic-resistance sleeve, so that the magnetic rod 220 can be set in the magnetic-resistance sleeve 230, and can move up and down in the magnetic-resistance sleeve 230 driven by the corresponding first mechanical arm 200. The bottom end of the magnetic rod 220 has a magnetic pole 221, so when the bottom end of the magnetic rod 220 is located at the bottom of the magnetic-resistance sleeve 230, the magnetic beads in the corresponding accommodation position can be gathered at the bottom of the magnetic-resistance sleeve 230 under the action of magnetic force. In some preferred embodiments, part of the side wall of the magnetic rod 220 is also provided with a magnetic-resistance coating 222, which is located above the magnetic pole and is used to shield the magnetic lines of force to reduce the adsorption of magnetic beads at adjacent positions. In some examples, the magnetic-resistance coating can cover the entire side wall of the magnetic rod 220 located above the magnetic pole. In other examples, such as Figure 4 As shown, the magnetic resistance coating can be evenly covered on the lower half side wall of the magnetic rod 220 located above the magnetic pole. Since the upper half of the magnetic rod 220 has little effect on the adsorption and release of the magnetic beads in the corresponding accommodating position, this example can reasonably reduce the coverage area of the magnetic resistance coating and reduce costs.
[0087] In some embodiments, the bottom of the magnetic blocking sleeve 230 may be planar, which helps to increase the aggregation of magnetic beads at the bottom of the magnetic blocking sleeve 230 , thereby improving the magnetic bead collection efficiency.
[0088] In addition, in some optional embodiments, the nucleic acid extraction system 1000 may also include one or more of the following components:
[0089] The motion controller, for example, uses a trapezoidal speed-up and speed-down control algorithm to control the movement speed of the robot arm. The trapezoidal speed-up and speed-down control algorithm can control the change of the movement speed according to a trapezoidal curve or a trapezoidal S-curve, so as to reduce the jitter and vibration caused by the movement and improve the accuracy of the movement and speed control.
[0090] The temperature controller, which is arranged on each rotating disk, can be used to detect and adjust the temperature of one or more accommodating positions respectively to adapt the temperature environment required for the corresponding extraction step. The temperature controller, for example, includes a plurality of temperature sensors, which can be respectively arranged in different accommodating areas (including one or more accommodating positions) of the sample container, and the temperature controller can also include a plurality of temperature adjustment modules, so that the ambient temperature of each accommodating area can be adjusted based on the temperature detected by each temperature sensor, so that the solution and / or sample in the accommodating area is heated or cooled, so that the ambient temperature of different accommodating areas meets the reaction temperature requirements of each extraction step. In some examples, one or more sample containers can be placed in the accommodating space of the temperature controller or on the surface of the temperature controller. In some optional examples, in some examples, at least a portion of the temperature controller, for example, adopts a metal structure (for example, an aluminum alloy).
[0091] The liquid crystal display is used to display various information of the nucleic acid extraction system 1000, such as working status (working attributes of sub-nodes, working progress, sensor data such as temperature, estimated working time / waiting time, etc.) and / or error information.
[0092] The networking controller is used to support the communication between each mechanical arm 200 and the control device 100, so that each mechanical arm 200 can package relevant information and upload it to the control device 100, and the control device 100 can send control information to the mechanical arm 200. In some examples, the networking controller is used to implement basic network communication protocols, which are used to link device nodes into a local area network. In some examples, the networking controller can, for example, connect to the network through a local WiFi connection. In some other examples, the networking controller can also achieve communication based on a wired connection.
[0093] The power supply is used to supply power to at least the mechanical arms and the rotating disk. The power supply can also supply power to other components, such as the above-mentioned networking controller, liquid crystal display, temperature controller, and motion controller.
[0094] According to actual needs, the nucleic acid extraction system 1000 may also include other mechanical components known to those skilled in the art, such as guide rails, springs, blocking plates, connecting shafts, outer shells surrounding the above-mentioned components, etc., and may also include other electronic components known to those skilled in the art, such as various sensors such as liquid level sensors, memories, etc.
[0095] Combine the following Figure 5 The working principle of each robot arm 200 is described.
[0096] A first robot arm 200 selected as a target robot arm by the control device 100 is used, for example, to perform a cracking step:
[0097] First, a sample (for example, in a suspension state) is added to the first receiving position of the sample container 210. The first receiving position may be located at Figure 7 The sample area or first receiving area for performing lysis is shown.
[0098] Samples include, for example, cell-containing liquid samples and cell-free liquid samples, wherein the cell-containing liquid samples include cells, whole blood, and animal tissue homogenate, and the cell-free liquid samples include serum, plasma, tissue extract, swab wash, urine, and virus culture fluid.
[0099] Taking the first accommodating position in the first accommodating area as an example, the first accommodating position may be filled with a lysis solution for rupturing cells and cell nuclei in the sample, separating nucleic acids (DNA / RNA) from nucleoproteins, and deforming and precipitating nucleoproteins, thereby lysing and separating the nucleic acids in the sample.
[0100] A plurality of magnetic beads are automatically added to the lysate by the second robotic arm 200, and the first intermediate substance (the intermediate substance after lysis, such as impurities including nucleic acid and protein particles) in the first accommodation position can be adsorbed by the magnetic beads. The magnetic beads are nanomagnetic beads, for example, they can be silicon oxide nanomagnetic beads with superparamagnetism prepared by improving and modifying the surface of superparamagnetic nanoparticles using nanotechnology, and the diameter is, for example, about 100 to 800 nm, and can have a core-shell structure (i.e., having a superparamagnetic core and a silicon oxide shell). The magnetic beads can specifically identify nucleic acid molecules at the microscopic interface and efficiently bind to them. Due to the superparamagnetism, under the action of Chaotropic salts (guanidine hydrochloride, guanidine isothiocyanate, etc.) and an external magnetic field, the magnetic beads can be used to separate nucleic acids (DNA and / or RNA) from samples such as blood, animal tissues, food, and pathogenic microorganisms.
[0101] Subsequently, the selected first robot arm 200 performs a stirring operation so that the magnetic blocking sleeve 230 is stirred in the first receiving position driven by the movable structure 240 (for example, moving up and down in the first receiving position for a duration of, for example, 10-15 minutes), in order to achieve uniform stirring so that the first intermediate substance in the first receiving position can be fully adsorbed on each magnetic bead.
[0102] Before or after stirring, the selected first robot arm 200 performs an adsorption operation to move the magnetic rod 220 downward to the bottom of the magnetic blocking sleeve 230 , so that the magnetic beads adsorbed with the first intermediate substance in the first accommodating position can be gathered at the bottom of the magnetic blocking sleeve 230 .
[0103] Then, the first robot 200 selected as the target robot by the control device 100 performs a subsequent cleaning step, for example. The cleaning step is used to remove impurities other than nucleic acids contained in the first intermediate substance, and may include multiple sub-steps (e.g., a first cleaning sub-step for removing impurities such as proteins, a second cleaning sub-step for removing impurities such as salt ions, etc.).
[0104] As an example, see Figure 6 In the cleaning step, the selected first robot arm 200 performs the following operations, for example:
[0105] First, the selected first robot arm 200 performs a moving operation, which is used to make the magnetic blocking sleeve 230 and the magnetic rod 220 simultaneously lifted and moved from the first accommodation position to the second accommodation position under the drive of the moving structure 240, so that the magnetic beads adsorbed with the first intermediate substance move from the first accommodation position to the second accommodation position following the magnetic blocking sleeve 230 and the magnetic rod 220 under the action of magnetic force. The bottom of the magnetic blocking sleeve 230 and the magnetic rod 220 falls into the bottom of the second accommodation position, so that the magnetic beads and the first intermediate substance adsorbed thereon are added to the second accommodation position.
[0106] The second containing position contains a first cleaning solution (for example, a deproteinizing agent such as a chaotropic salt) for removing impurities.
[0107] Then, the selected first mechanical arm 200 performs a release operation to allow the magnetic bar 220 to move upward (away from the second accommodation position) driven by the moving structure 240, so that the magnetic bar 220 and the magnetic blocking sleeve 230 produce relative displacement, resulting in a change in the magnetic field. Based on this, the magnetic beads and the first intermediate substance adsorbed thereon are separated from the magnetic blocking sleeve and fall into the second accommodation position.
[0108] Furthermore, the selected first robot arm 200 performs a stirring operation, so that the magnetic blocking sleeve 230, driven by the moving structure 240, fully stirs the contents in the second accommodation position to remove at least part of the impurities contained in the first intermediate substance, thereby obtaining a second intermediate substance. The second intermediate substance is also adsorbed on each magnetic bead. As an example, the magnetic blocking sleeve 230 moves up and down along the direction of gravity under the drive of the moving structure 240.
[0109] Before or after stirring, the selected first robotic arm 200 can perform an adsorption operation to allow the magnetic rod 220 to move downward to the bottom of the magnetic-blocking sleeve 230 driven by the moving structure 240, so that the magnetic field changes, so that the magnetic beads adsorbed with the second intermediate substance in the second containing position can gather at the bottom of the magnetic-blocking sleeve 230.
[0110] Afterwards, the selected first robot arm 200 performs the moving operation again to lift and move the magnetic-blocking sleeve 230 and the magnetic rod 220 to the third accommodating position at the same time, so that the magnetic beads adsorbed with the second intermediate substance are moved to the third accommodating position along with the magnetic-blocking sleeve 230 and the magnetic rod 220 under the action of magnetic force, so as to facilitate the next cleaning sub-step.
[0111] The third containing position is filled with a second cleaning solution for removing impurities (for example, an ethanol solution with a concentration of 70%, for removing salt ions and small molecular impurities, etc.).
[0112] Subsequently, the selected first robot arm 200 performs a release operation again, thereby driving the magnetic rod 220 to move upward (away from the third accommodation position), so that the magnetic rod 220 and the magnetic blocking sleeve 230 are relatively displaced. Therefore, based on the change in the magnetic field, the magnetic beads and the second intermediate substance adsorbed thereon are separated from the magnetic blocking sleeve 230 and fall into the third accommodation position.
[0113] Furthermore, the selected first robot arm 200 performs a stirring operation again, so that the magnetic blocking sleeve 230 fully stirs the contents in the third accommodation position to remove impurities such as salt ions contained in the second intermediate substance, thereby obtaining a third intermediate substance. The third intermediate substance is adsorbed on each magnetic bead. As an example, the magnetic blocking sleeve 230 moves up and down along the direction of gravity under the drive of the selected first robot arm 200.
[0114] Before or after stirring, the selected first robot arm 200 can perform an adsorption operation to move the magnetic rod downward to the bottom of the magnetic-blocking sleeve 230, so that the magnetic field changes, so that the magnetic beads adsorbed with the third intermediate substance (as the intermediate substance after cleaning / washing) in the third containing position can be gathered at the bottom of the magnetic-blocking sleeve.
[0115] However, the embodiments of the present disclosure are not limited thereto, and the cleaning / washing step may include only one sub-step (for example, using a mixed cleaning solution for cleaning / washing), or may include more than two sub-steps, so as to use a variety of cleaning solutions for cleaning / washing in steps.
[0116] Then, the selected first robot arm 200 performs, for example, a subsequent purification step, which is used to obtain a relatively pure nucleic acid extract and separate the nucleic acid extract from the magnetic beads.
[0117] As an example, see Figure 6 In the purification step, the first robot arm 200 selected as the target robot arm by the control device 100 performs the following operations, for example:
[0118] First, the selected first robot arm 200 performs a moving operation to simultaneously lift the magnetic blocking sleeve 230 and the magnetic rod 220 and move them from the third accommodation position to the fourth accommodation position, so that the magnetic beads adsorbed with the first intermediate substance move from the third accommodation position to the fourth accommodation position under the action of magnetic force following the magnetic blocking sleeve 230 and the magnetic rod 220. The bottom of the magnetic blocking sleeve 230 and the magnetic rod 220 falls into the bottom of the fourth accommodation position, so that the magnetic beads together with the adsorbed third intermediate substance are added to the fourth accommodation position.
[0119] The fourth containing position is filled with a purification buffer, which may be 400 uL of a TE solution, for example, including Tris (trishydroxymethylaminomethane) and EDTA, which helps inhibit nuclease activity so that the purified nucleic acid extract can be well stored.
[0120] Subsequently, the selected first mechanical arm 200 performs a release operation to allow the magnetic bar 220 to move upward (away from the fourth accommodation position) under the drive of the selected first mechanical arm 200, so that the magnetic bar 220 and the magnetic blocking sleeve 230 produce relative displacement, resulting in a change in the magnetic field. Based on this, the magnetic beads and the third intermediate substance adsorbed thereon are separated from the magnetic blocking sleeve 230 and fall into the fourth accommodation position.
[0121] Furthermore, the selected first robot arm 200 performs a stirring operation, so that the magnetic blocking sleeve 230 can fully stir the contents in the fourth accommodation position under the drive of the selected first robot arm 200 to remove at least part of the impurities contained in the third intermediate substance, thereby obtaining a nucleic acid extract separated from the magnetic beads. As an example, the magnetic blocking sleeve 230 moves up and down along the direction of gravity under the drive of the selected first robot arm 200.
[0122] Before or after stirring, the selected first robotic arm 200 can automatically perform a recovery operation, so that the magnetic rod 220 is driven by the selected first robotic arm 200 to move downward to the bottom of the magnetic blocking sleeve 230, so that the magnetic field changes, so that the magnetic beads in the fourth accommodating position can gather at the bottom of the magnetic blocking sleeve 230.
[0123] Afterwards, the selected first robot arm 200 performs the moving operation again, so that the magnetic blocking sleeve 230 and the magnetic rod 220 are simultaneously lifted and moved to the fifth receiving position under the drive of the selected first robot arm 200, so that the magnetic beads are moved to the fifth receiving position for recovering the magnetic beads following the magnetic blocking sleeve 230 and the magnetic rod 220 under the action of magnetic force.
[0124] As an alternative embodiment, the second robot arm 200 may be used to recover the magnetic beads.
[0125] Based on the nucleic acid extraction system 1000 provided in the embodiment of the present disclosure, the above steps can be automatically performed under the control of the control device 100.
[0126] Among the above steps, the lysis step takes a longer time (eg, about 10-20 minutes), while the washing step (eg, about 5-10 minutes) and the purification step (eg, about 5-10 minutes) take a shorter time.
[0127] The traditional scheme adopts a linear working method, that is, each sample completes the lysis, washing and purification steps in the same extraction device used to perform the extraction task linearly. Assuming that the lysis step takes 20 minutes, the washing step takes 5 minutes, and the purification step takes 5 minutes, 4 extraction devices are running at the same time and each extraction device can process 8 samples at a time, based on the traditional linear working method, it takes 30 minutes to process 32 samples, and 60 minutes to process 33 samples, that is, the waiting time for the sample extraction results is 30 minutes and 60 minutes respectively, and one sample needs to wait for 30 minutes before it can be processed. It can be seen that the traditional scheme has low efficiency in nucleic acid extraction and inflexible resource allocation. New samples can only be added after the previous batch of samples has been extracted.
[0128] The present invention manages and allocates sample extraction tasks based on a sample queue, so that idle robotic arms can be used to perform at least one extraction step in an extraction task for a new sample, thereby coordinating multiple robotic arms based on a serial, parallel or pipeline working mode. Assuming that the time required for the lysis step is 20 minutes, the time required for the washing step is 5 minutes, and the time required for the purification step is 5 minutes, 4 robotic arms are running simultaneously and each robotic arm can process 8 samples at a time, based on the assembly-line working mode proposed in the embodiment of the present disclosure, after the robotic arm responsible for the lysis step completes the lysis step of the first batch of samples, it can immediately start to perform the lysis step on the second batch of samples, and at the same time, other robotic arms responsible for the washing and purification steps can continue to perform the washing and purification steps on the first batch of samples that have completed the lysis in parallel, so that the time required to process the first 32 samples is 30 minutes, and the time required to process 33 samples is 50 minutes, that is, the waiting time for the sample extraction results is 30 minutes and 50 minutes respectively, among which the 33rd sample only needs to wait 20 minutes to start processing. Compared with the traditional solution that simply uses a parallel method, the embodiment of the present disclosure based on the assembly-line working mode can improve the extraction efficiency by about 11%. Based on the traditional solution of using a single extraction device to execute each step in series, assuming that 16 samples can be processed each time, then completing the extraction of all 33 samples requires executing three batches of extraction tasks, which takes a total of 90 minutes. The sample waiting times are 30 minutes, 60 minutes, and 90 minutes, respectively. Compared with this serial single extraction device working mode, the embodiment of the present disclosure improves the extraction efficiency by 50% based on the assembly line working mode.
[0129] Therefore, the embodiments of the present disclosure improve the efficiency of nucleic acid extraction, resource utilization, and allow real-time allocation of newly added samples.
[0130] Figure 7 The following is a flow chart of the nucleic acid extraction control method according to an embodiment of the present disclosure. The nucleic acid extraction control method is implemented based on the hardware provided in any of the above embodiments and / or other hardware structures known to those skilled in the art.
[0131] In step S100, a list of manageable devices is read. The list of manageable devices is stored in a memory included in the control device, or in a memory communicatively coupled to the control device. The list of manageable devices is used to indicate each child node (i.e., each robotic arm) that can be managed in the nucleic acid extraction system, and may include identification codes of n child nodes (e.g., the serial number of each robotic arm), where n is a natural number greater than 1. The identification code of each robotic arm may be set and assigned by the control device, or may be uploaded by each child node to the control center (the control device as the parent node).
[0132] In step S200, the working mode of each sub-node is configured. If it is configured as the first working mode, then step S300 is continued to be performed, so that each sub-node can independently perform the various steps required for the nucleic acid extraction task on the assigned sample in series; if it is configured as the second working mode, then step S400 is continued to be performed, so that each sub-node can collaboratively and in parallel perform the various steps required for the nucleic acid extraction task.
[0133] In the first working mode, each robot arm as a sub-node in the nucleic acid extraction system works independently of each other, that is, each robot arm is configured to serially perform the above-mentioned lysis, cleaning and purification steps on the corresponding one or more samples. In other words, in the first working mode, each sample completes the lysis, cleaning and purification steps under the operation of the same robot arm, and the n robot arms indicated by the manageable device list are simply combined into an integrated workstation, which achieves the requirement of improving the nucleic acid extraction speed by executing the nucleic acid extraction tasks in parallel.
[0134] As an example, Figure 7 As shown, step S300 may include sub-steps S310 to S350.
[0135] In step S310, the sample queue is read. The sample queue is used to indicate the sequence number and quantity of samples to be extracted. The sample queue is configured to have a first-in-first-out property, that is, the sample added to the sample queue first will be assigned to the corresponding robot arm before the sample added to the sample queue later, so as to perform the extraction task first. However, the embodiments of the present disclosure are not limited to this, and the order of the sample queue can also be managed by setting a priority.
[0136] In step S320, the samples in the sample queue are allocated to the target child nodes in the idle state.
[0137] In step S330, the target subnode is driven to perform the extraction task on the corresponding sample, and the working attribute of the target subnode is configured to be a non-idle state. After a target subnode completes the extraction task, the working attribute of the target subnode is restored to the idle state.
[0138] In step S340, it is determined whether the extraction task is completed. If it is completed, the process returns to step S310 to continue reading the sample queue to process the newly added sample; if it is not completed, step S350 is executed.
[0139] As an example, step S340 may start execution after step S320 is executed for a period of time (for example, the estimated time for the preset extraction task), and may obtain the work attributes fed back by each target subnode by querying each target subnode, and determine whether each target subnode has been restored to an idle state based on the work attributes fed back by each target subnode.
[0140] In step S350, the state of the target subnode is polled until the target subnode completes the extraction task and then returns to step S310. For example, the state of the target subnode can be inquired at intervals, and the state fed back by the target subnode can be used to determine whether the target subnode has completed the extraction task. For example, the control device can send a state inquiry request to each mechanical arm as the target subnode, and each mechanical arm as the target subnode feeds back a state response (including the state information of the mechanical arm) to the control device in response to the state inquiry request, so that the control device can obtain the state information of each mechanical arm and determine whether each mechanical arm as the target subnode is in an idle state. In some alternative embodiments, the control device can also determine whether each mechanical arm is in an idle state based on the operation time required for each extraction step.
[0141] In some examples, each sub-node may also actively provide a data packet to the control device, where the data packet is at least used to indicate whether the corresponding sub-node is in an idle state.
[0142] In the first working mode, each target sub-node independently extracts nucleic acid from the sample assigned to the sub-node. Based on this, the corresponding target sub-node can be matched at any time for the sample newly added to the sample queue. Therefore, according to the different sample addition times, there can be a time difference in the time when each sub-node starts the nucleic acid extraction task, so that the entire nucleic acid extraction system allows the sample to be "tested and tested at any time", and in the case of idle sub-nodes, there is no need to wait for all sub-nodes to complete the extraction task, which improves the efficiency of nucleic acid extraction and resource utilization, and reduces the waiting time required for multiple batches of nucleic acid extraction tasks.
[0143] In some embodiments, in the first working mode, the nucleic acid extraction control method of the disclosed embodiment can also select the number of matching target sub-nodes according to the number interval of the number of samples in the sample queue. Based on this, as an example, Figure 8 A flow chart showing an example of a control method according to an embodiment of the present disclosure is shown. Figure 8 As shown, the above step S320 may further include sub-steps S321 to S325.
[0144] In step S321, the required number of child nodes k is determined according to the number interval of the number of samples m in the sample queue. Both m and k are natural numbers greater than 0.
[0145] For example, if it is detected that the number of samples X0 in the sample queue is greater than 0 and less than the first threshold value (i.e., the number of samples X0 is in the first number interval), the required number of child nodes k=1 is determined, and only one idle child node is required to receive the samples in the current sample queue; if it is detected that the number of samples X0 in the sample queue is greater than / or equal to the first threshold value and less than the second threshold value (i.e., the number of samples X0 is in the second number interval), the required number of child nodes k=2 is determined; and so on. Furthermore, if it is detected that the number of samples X0 in the sample queue is zero, it means that the sample queue is empty, and the number of samples in the sample queue can be detected after waiting for a period of time.
[0146] In this embodiment, the boundary values of each quantity interval such as the first threshold value and the second threshold value can be determined according to the number of accommodation positions included in each sample container. For example, the boundary values of each quantity interval are set to integer multiples of the number of accommodation positions provided by the sample container in each row / column, and the boundary value of each quantity interval is less than / equal to the total number of accommodation positions provided by the sample container for performing the lysis step.
[0147] by Figure 6 The 96-well plate shown is used as an example of a sample container. Each column of the 96-well plate provides 8 accommodating positions, and 3 columns of accommodating positions in the 96-well plate are used to perform the lysis step. The first threshold is set to 8, the second threshold is set to 16, and the third threshold can also be set to 24.
[0148] In step S322, according to the required number of child nodes k, it is determined whether there are enough idle child nodes available for allocation. If yes, step S323 is executed in sequence; if not, step S324 is executed to wait for other child nodes to be released to idle state.
[0149] In step S323, the samples indicated by the sample queue are allocated to k target child nodes in an idle state.
[0150] When it is necessary to distribute samples in the sample queue to multiple sub-nodes, the samples may be distributed evenly to each sub-node, or unequally to each sub-node according to actual needs, which is not limited in this embodiment.
[0151] In some examples, in the waiting step S324, at least one child node A with a shorter waiting time may be estimated by a time optimization algorithm. w , and assign the current sample to child node A wThe waiting queue is thus conducive to parallel waiting. w After completing the current extraction task, the samples in the waiting queue will be matched to child node A in turn. w The robotic arm where it is located is used to continue executing step S323.
[0152] However, the embodiments of the present disclosure are not limited thereto, and the waiting step S324 may also simply execute a waiting step, that is, waiting until one or more child nodes are released to an idle state, and then taking the child node as the target child node, and continuing to execute step S323.
[0153] In some optional embodiments, such as Fig. 9 As shown, in order to avoid unreasonable sub-node allocation caused by new samples being added to the sample queue immediately after the sample number is detected, step S320 may also include sub-step S325, which is used to wait for a preset time (for example, 10 minutes) after the sample is assigned to the corresponding target sub-node, and then re-detect the sample number. If the number of samples in the sample queue changes (for example, new samples are added to the sample queue within the preset time), it is necessary to reallocate samples and sub-nodes according to the updated sample number and the above method, that is, return to step S321; if the number of samples in the sample queue does not change, continue to execute step S330 to drive each target sub-node to start executing the extraction task.
[0154] In the second working mode, based on the preset control mechanism, the various robotic arms as sub-nodes work in coordination and in parallel, and each sample can complete the lysis, cleaning and purification steps respectively under the operation of one or more robotic arms, rather than being limited to completing all the steps for nucleic acid extraction based on the same robotic arm. Based on this assembly-line second working mode, the efficiency of nucleic acid extraction can be improved by executing each step in parallel.
[0155] In some examples, in the second working mode, n robotic arms as child nodes can be pre-divided into at least two groups, and these at least two groups of robotic arms cooperate to perform lysis, cleaning and purification steps for each sample. For example, the first group of robotic arms among the n robotic arms is used to perform the lysis step, the second group of robotic arms is used to perform the cleaning step, and the third group of robotic arms is used to perform the purification step, and each group of robotic arms includes one or more robotic arms. In some examples, since the time occupied by the lysis step is longer than the time occupied by the cleaning step and the purification step, the number of robotic arms included in the first group of robotic arms can be greater than the number of robotic arms included in the second group of robotic arms and / or the third group of robotic arms, for example, the number of robotic arms included in the first group of robotic arms is greater than / equal to the sum of the number of robotic arms included in the second group and the third group of robotic arms, and each robotic arm in the first group of robotic arms can perform the lysis step on different samples in parallel to improve the lysis efficiency, balance the time occupied by each step in the extraction task, and optimize the waiting time, thereby improving the efficiency of nucleic acid extraction.
[0156] In some other examples, in the second working mode, the samples in the sample queues may be allocated according to whether each node is in an idle state and the number of samples in each queue. Figure 8 .
[0157] In step S410, each sub-sample queue is read. The sample queue is used to indicate the sequence number and quantity of the samples to be extracted. Each sample queue is configured to have a first-in-first-out property, that is, the sample added to the sample queue first will be assigned to the corresponding robot arm before the sample added to the sample queue later, so as to perform the extraction task first. However, the embodiment of the present disclosure is not limited to this, and the order of the sample queue can also be managed by setting a priority.
[0158] Different from step S310 in the first working mode, in the second working mode, the sample queue may include multiple sub-sample queues, which are respectively used to sort the samples to be executed in each step. For example, the multiple sub-sample queues include: a lysis sample queue, which is used to sort the samples to be executed in the lysis step; a washing sample queue, which is used to sort the samples to be executed in the washing step; and a purification sample queue, which is used to sort the samples to be executed in the purification step.
[0159] In step S420, for each sample queue, a subnode allocation algorithm is executed to determine a target subnode for receiving a corresponding sample in each subsample queue, and the working attributes of the target subnode are configured according to the steps required to be executed by the sample.
[0160] In step S430, the target subnode is driven to perform a corresponding step (e.g., lysis step / cleaning step / purification step) on the corresponding sample, and the working attribute of the target subnode is configured to a working state corresponding to the step (e.g., lysis working state / cleaning working state / purification working state). After a target subnode completes a corresponding step, the working attribute of the target subnode is restored to an idle state.
[0161] For example, for samples in the lysis sample queue, the working attribute of the corresponding target subnode is configured as the lysis working state, and after the target subnode completes the lysis step, its working attribute is restored to the idle state, and the target subnode is added to the idle subnode queue for activation.
[0162] In step S440, it is determined whether the corresponding step executed by the target child node is finished. If it is finished, it returns to step S410 to continue reading each sample queue to process the newly added sample; if it is not finished, it executes step S450.
[0163] As an example, step S440 may start execution after step S420 has been executed for a period of time (for example, a preset step execution estimated time), and may obtain the working attributes fed back by each target subnode by querying each target subnode, and determine whether each target subnode has been restored to an idle state based on the working attributes fed back by each target subnode.
[0164] In step S450, the state of the target subnode is polled until the target subnode completes the corresponding step and then returns to step S410. For example, the state of the target subnode can be inquired at intervals, and whether the target subnode has completed the corresponding step can be judged based on the state fed back by the target subnode. For example, the control device can send a state inquiry request to each mechanical arm as the target subnode, and each mechanical arm as the target subnode feeds back a state response (including the state information of the mechanical arm) to the control device in response to the state inquiry request, so that the control device can obtain the state information of each mechanical arm and judge whether each mechanical arm as the target subnode is in an idle state.
[0165] In the second working mode, for different steps in the extraction task, sub-nodes can be flexibly selected for parallel execution, and a sub-node allocation algorithm can be used to implement a mode similar to assembly line operation, so that the entire nucleic acid extraction system allows samples to be "tested as they are", which is conducive to the concurrent execution of nucleic acid extraction tasks and nucleic acid extraction steps, improves nucleic acid extraction efficiency and resource utilization, and reduces the waiting time required for nucleic acid extraction tasks.
[0166] In some embodiments, the subnode allocation algorithm can determine the target subnode according to the number interval of the number of samples in each sample queue. Specifically, the subnode allocation algorithm can determine the number interval of the number of samples in each sample queue, and determine the subnode for receiving the corresponding sample according to the number interval. Based on this, as an example, the above step S420 can further include sub-steps S421 to S425. Fig.10 This is explained.
[0167] Taking the first sample queue as an example, Fig.10 A schematic diagram showing a flow chart of a subnode allocation algorithm according to an embodiment of the present disclosure.
[0168] In step S421, the required number of child nodes k is determined according to the number interval of the number of samples m in the first sample queue. Both m and k are natural numbers greater than 0.
[0169] For example, if it is detected that the number of samples X1 in the first sample queue is greater than 0 and less than the first threshold (i.e., the number of samples X1 is in the first number interval), the required number of child nodes k=1 is determined, and only one idle child node is required to receive the samples in the current sample queue; if it is detected that the number of samples X1 in the sample queue is greater than / or equal to the first threshold and less than the second threshold (i.e., the number of samples X1 is in the second number interval), the required number of child nodes k=2 is determined; and so on. Furthermore, if it is detected that the number of samples X1 in the first sample queue is zero, it means that the sample queue is empty, and the number of samples in the first sample queue can be detected after waiting for a period of time.
[0170] In step S422, based on the required number of child nodes k, it is determined whether there are enough idle child nodes available for allocation. If yes, step S423 is executed in sequence; if not, step S424 is executed to wait for other child nodes to be released to an idle state.
[0171] In step S423, the samples indicated by the first sample queue are allocated to k target child nodes in an idle state.
[0172] When it is necessary to distribute samples in the sample queue to multiple sub-nodes, the samples may be distributed evenly to each sub-node, or unequally to each sub-node according to actual needs, which is not limited in this embodiment.
[0173] In some examples, in the waiting step S424, at least one child node A with a shorter waiting time may be estimated by a time optimization algorithm. w , and assign the current sample to child node A w The waiting queue is thus conducive to parallel waiting.w After completing the current extraction task, the samples in the waiting queue will be added to the child node A in turn. w The robotic arm where it is located is used to continue executing step S423.
[0174] However, the embodiments of the present disclosure are not limited thereto, and the waiting step S424 may also simply execute a waiting step, that is, waiting until one or more child nodes are released to an idle state, and then taking the child node as the target child node, and continuing to execute step S423.
[0175] In some optional embodiments, such as Fig.10 As shown, in order to avoid unreasonable sub-node allocation caused by new samples joining the sample queue immediately after the sample number is detected, step S420 may also include sub-step S425, which is used to wait for a preset time (for example, 10 minutes) after the sample is assigned to the corresponding target sub-node, and then re-detect the sample number. If the number of samples in the sample queue changes (for example, there are new samples added to the first sample queue within the preset time), it is necessary to reallocate samples and sub-nodes according to the updated sample number and the above method, that is, return to step S421; if the number of samples in the first sample queue does not change, continue to execute step S430 to drive each target sub-node to start executing the corresponding first step.
[0176] In step S500, Figure 8 As shown, the nucleic acid extraction system can be manually stopped from receiving samples and / or the nucleic acid extraction system can be stopped from executing extraction tasks / extraction steps.
[0177] Fig.11 A flowchart showing an example of a sub-node allocation algorithm according to an embodiment of the present disclosure is shown.
[0178] In such Fig.10 In the example shown, if it is detected that the number of samples X1 in the first sample queue (for example, the lysis sample queue / cleaning sample queue / purification sample queue) is greater than 0 and less than the first threshold (that is, the number of samples X1 is in the first number interval), the samples in the current first sample queue are assigned to the idle child node A. k1 , and the child node A k1 The working attribute of is configured as the corresponding first working state (for example, the lysis state); if it is detected that the number of samples X1 in the first sample queue is greater than / or equal to the first threshold and less than the second threshold (that is, the number of samples X1 is in the second number interval), the samples in the current first sample queue are assigned to the child node A in the idle state k1 and child node A k2 , and the child node A k1 and child node A k2The working attribute of is configured as the corresponding first working state; and so on. Furthermore, if it is detected that the number of samples X1 in the first sample queue is zero, it means that the first sample queue is empty, and the number of samples in the first sample queue can be detected after waiting for a period of time.
[0179] In this embodiment, the boundary values of each quantity interval such as the first threshold value and the second threshold value can be determined according to the number of accommodation positions included in each sample container. For example, the boundary values of each quantity interval are set to integer multiples of the number of accommodation positions provided by the sample container in each row / column.
[0180] Taking a 96-well plate as a sample container as an example, each column of the 96-well plate provides 8 accommodating positions, then the first threshold is set to 8, the second threshold is set to 16, the third threshold can also be set to 24, and the fourth threshold can also be set to 32.
[0181] The working modes of this embodiment mainly include the first working mode and the second working mode, but the present invention is not limited thereto. For example, the working mode configurable in step S200 may also include a mixed working mode, in which a part of the manageable n robotic arms may be configured as the first working mode, and another part of the robotic arms may be configured as the second working mode, so as to adjust the mode configuration of each robotic arm according to actual needs.
[0182] Fig.12 An exemplary flowchart of the time optimization algorithm of the embodiment of the present disclosure is shown.
[0183] Based on the above embodiment, if the number of child nodes in the idle state is less than the number of target child nodes required for the number interval in which the sample number is located, a time optimization algorithm may be executed. The time optimization algorithm is used to estimate the waiting time required for each child node, and select the child node that is about to be released to the idle state as the target child node according to the waiting time.
[0184] In some examples, the time optimization algorithm can estimate the waiting time for each child node to be released to an idle state based on the execution time required for each pre-stored extraction step. The execution time required for each pre-stored extraction step can be obtained by detecting the execution time of each extraction step during the test phase, or can be manually set.
[0185] In some examples, the time optimization algorithm may be used to establish a sample waiting queue for each child node, so that each child node processes the samples in the corresponding sample waiting queue in turn.
[0186] In some examples, such as Fig.12 As shown, the time optimization algorithm is used to execute steps S610 to S650, for example.
[0187] In step S610, the extraction steps to be performed on the current sample to be distributed are determined.
[0188] In step S620, based on the extraction step, the waiting time required for the global sub-nodes is traversally estimated. For example, step S620 can traversally estimate the waiting time required for the samples to be allocated in various situations, for example, the waiting time required for each sub-node to perform the extraction step / the entire extraction task can be estimated in each working mode (the first working mode and the second working mode).
[0189] It should be noted that the waiting time of the sample referred to in the present disclosure may refer to the time required for the sample to complete all extraction steps from the current time node (for example, the time node of completing the input, the time node of completing the lysis step, etc.).
[0190] In some embodiments, the expected time for each child node to complete the extraction step may also be obtained from each child node to estimate the relevant waiting time.
[0191] In step S630, based on the constraint condition of the shortest waiting time, the target sub-node corresponding to the sample to be allocated is confirmed.
[0192] In some embodiments, steps S620 and S630 may also select the child node with the shortest required waiting time as the target child node by estimating the waiting time of each child node after receiving the sample to be allocated and performing trial and error.
[0193] Fig.13 A flowchart showing an example of a control method according to an embodiment of the present disclosure implementing a stack operation based on a sample queue and a sub-node queue.
[0194] like Fig.13As shown, first check the sample queue and read the sample queue; then read the idle subnode queue for indicating the idle state subnode, and select the idle subnode 1 as the target subnode, the working attribute of which is configured as the lysis working state; assign the current sample to subnode 1, so that subnode 1 can perform the lysis step on the current sample; after subnode 1 completes the lysis step of the current sample, configure the working attribute to the idle state, and rejoin the idle subnode queue; read the idle subnode queue again, and select the idle subnode 2 as the target subnode, the working attribute of which is configured as the cleaning working state; The current sample is assigned to subnode 2 so that subnode 2 can perform the cleaning / washing step on the current sample; after subnode 2 completes the cleaning / washing step of the current sample, the working attribute is configured to the idle state, and it is rejoined to the idle subnode queue; the idle subnode queue is read again, and subnode 3 in the idle state is selected as the target subnode, and the working attribute of the target subnode is configured to the purification working state; the current sample is assigned to subnode 3 so that subnode 3 can perform the purification step on the current sample; after subnode 3 completes the purification step of the current sample, the working attribute is configured to the idle state, and it is rejoined to the idle subnode queue, and the extraction task of the current sample is completed.
[0195] Fig.14 A flowchart showing an example of implementing a stack operation based on a sample queue and a sub-node queue according to an embodiment of the present disclosure is shown.
[0196] like Fig.14 As shown, first check the sample queue; if there are new samples that have not been processed in the sample queue, read the idle sub-node queue, and select the target sub-node in the idle state to perform the lysis step; after the lysis step is completed, read the idle sub-node queue again, and select the target sub-node in the idle state to perform the cleaning / washing step; after the cleaning / washing step is completed, read the idle sub-node queue again, and select the target sub-node in the idle state to perform the purification step; then, recheck the sample queue so that the above process can be performed in sequence for each sample in the sample queue.
[0197] In summary, the nucleic acid extraction scheme of the embodiment of the present disclosure can assign corresponding target robotic arms to samples according to whether each robotic arm is in an idle state, and the control device can control the rotating table and / or the robotic arm to automatically match the samples to be tested to the corresponding target robotic arms in sequence. Therefore, compared with the traditional scheme that does not allow new samples to be added during the working process, the nucleic acid extraction scheme of the embodiment of the present disclosure allows the addition of new samples at any time, and can automatically and in real time use the robotic arm that is currently in an idle state to extract nucleic acids from new samples, which is conducive to realizing "on-demand testing" in the scenario of batch nucleic acid testing, and is conducive to the automatic parallel execution of nucleic acid extraction steps / tasks, reducing waiting time, and improving the efficiency of nucleic acid extraction and resource utilization.
[0198] Compared with the traditional technology that relies on manual labor to add and distribute samples, add and recover magnetic beads, the solution adopted by the present invention can automatically realize functions such as adding, inputting and distributing samples, adding and recovering magnetic beads based on a highly integrated and intelligent nucleic acid extraction system, without the need for human intervention throughout the process, thereby improving the efficiency of nucleic acid extraction and reducing labor costs. Automated control is conducive to the realization of automated data management, and can greatly reduce errors caused by manual operations.
[0199] In some preferred embodiments, in the second working mode, based on a preset control mechanism, each robotic arm as a sub-node works in coordination and in parallel, and each sample can complete the lysis, cleaning and purification steps respectively under the operation of one or more robotic arms, without being limited to completing all the steps for nucleic acid extraction based on the same robotic arm. Based on this pipeline-style second working mode, the efficiency of nucleic acid extraction can be improved by executing each step in parallel.
[0200] In some preferred embodiments, when selecting a target robot for the sample to be assigned, the waiting time required for each sub-node and each working mode can be traversed and estimated and trial-and-error can be performed, and the sub-node with the shortest estimated waiting time can be selected as the target robot for the sample to be assigned based on the time optimization algorithm, thereby further improving the intelligence and automation performance of the nucleic acid extraction system and further improving the efficiency of nucleic acid extraction.
[0201] In some preferred embodiments, a corresponding number of idle target robotic arms can be allocated based on the number of samples to be allocated, so as to rationally allocate system resources, which is conducive to further improving the intelligence and automation performance of the nucleic acid extraction system and improving the efficiency of nucleic acid extraction.
[0202] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the statement "comprise a ..." do not exclude the presence of other identical elements in the process, method, article or device including the elements.
[0203] According to the embodiments of the present invention as described above, these embodiments do not describe all the details in detail, nor do they limit the invention to the specific embodiments described. Obviously, many modifications and changes can be made based on the above description. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can make good use of the present invention and the modified use based on the present invention. The present invention is limited only by the claims and their full scope and equivalents.
Claims
1. An integrated nucleic acid extraction system, wherein: include: pillar; A plurality of rotating tables are distributed around the pillar, and a loading surface of each rotating table is used for placing one or more sample containers; A plurality of first mechanical arms, each of which has a first end connected to the pillar and a second end facing the object-carrying surface, and the second end is provided with an operating component for performing an extraction task, and the operating component is used to attract or release the magnetic beads in the corresponding sample container; A control device, used for allocating the first mechanical arm in an idle state as a target mechanical arm for the sample to be tested in each sample container, and controlling the target mechanical arm to match the position of the sample to be tested according to the position data of the sample to be tested, so that the target mechanical arm performs at least one extraction step of the extraction task on the sample to be tested; A sensor, used for detecting the position of the sample to be tested to obtain the position data; as well as At least one second robotic arm is used to add magnetic beads to each sample container and / or remove or recover the magnetic beads from each sample container under the control of the control device.
2. The nucleic acid extraction system according to claim 1, wherein: The control device drives the target mechanical arm to rotate around the support pillar to an operating position corresponding to the sample to be tested; and / or Each of the rotating tables rotates around its own axis under the control of the control device, so that the sample container located on the loading surface can be rotated to a corresponding operating position.
3. The nucleic acid extraction system according to claim 1, wherein: The first ends of the plurality of first mechanical arms are rotatably connected to the pillar at different heights of the pillar.
4. The nucleic acid extraction system according to claim 3, wherein: Each of the first mechanical arms comprises a first portion, a second portion and a connecting structure for connecting the first portion and the second portion, wherein a non-zero angle is formed between the extension directions of the first portion and the second portion, The first part is connected between the first end of the first robotic arm and the connecting structure, the second part is located between the connecting structure and the second end of the first robotic arm, and the second part is connected to the operating component at the second end of the first robotic arm. The first robotic arms have different lengths so as to allow the first robotic arms to rotate freely around the pillar as the axis without interfering with each other under the control of the control device.
5. The nucleic acid extraction system according to claim 1, wherein: The operating components include: A magnetic rod, used to attract magnetic beads in a corresponding sample container; and A magnetic blocking sleeve is used to isolate the magnetic rod and the magnetic bead. When the magnetic bar is placed in the magnetic blocking sleeve, the magnetic beads and / or adsorbed substances of the magnetic beads gather on the bottom surface of the magnetic blocking sleeve under the gravitational force of the magnetic bar, so that the magnetic beads and / or adsorbed substances of the magnetic beads move with the magnetic blocking sleeve and the magnetic bar. When the magnetic rod is moved out of the magnetic-resistance sleeve, the magnetic beads and / or adsorbates of the magnetic beads gathered on the bottom surface of the magnetic-resistance sleeve are released into the corresponding accommodation positions of the sample containers.
6. The nucleic acid extraction system according to claim 5, wherein: The operating component further comprises a clamp, which is at least used to detachably connect the magnetic blocking sleeve to the corresponding second end of the first mechanical arm, and the clamping and releasing of the magnetic blocking sleeve by the clamp is controlled by the control device.
7. The nucleic acid extraction system according to claim 1, wherein: The at least one second robotic arm is rotatably connected to the support column, and is also used to add one or more reaction liquids required for the extraction task to each sample container under the control of the control device, and / or remove or recover the liquid in each sample container.
8. The nucleic acid extraction system according to claim 7, wherein: At least one of the rotating tables provides a material area for storing the one or more reaction solutions and / or magnetic beads, and each of the second robotic arms is configured under the control of the control device to: Obtaining one of the one or more reaction solutions from the material area and injecting it into a designated position in a designated sample container under the control of the control device; and / or Under the control of the control device, the magnetic beads are moved from the material area to a designated position in a designated sample container, or the magnetic beads are recovered from each sample container to the material area.
9. The nucleic acid extraction system according to claim 1, wherein: Also includes: a communication module, coupled to the sensor, for providing corresponding position data to the control device, so that the control device can record the position information of the sample to be detected and allocate the corresponding target robot arm to it, Each of the rotating tables has an independent number, and each of the sample containers on the rotating tables has an independent number. The position information includes the independent number corresponding to the rotating table where the sample to be detected is located and the independent number corresponding to the sample container where the sample to be detected is located.
10. The nucleic acid extraction system according to claim 1, wherein: The control device comprises: A memory for storing a sample queue of unfinished extraction tasks; and A processor is communicatively coupled to the memory, and is used to independently and parallelly control each of the first robotic arms, and allocate corresponding target robotic arms to samples in the sample queue according to a first-in-first-out principle.
11. The nucleic acid extraction system according to claim 10, wherein: The control device is suitable for: Selecting a working mode, wherein the working mode includes a first working mode and a second working mode, In the first working mode, the control device selects the corresponding target robot arm for the sample to be tested, so that the target robot arm serially performs each extraction step in the extraction task on the sample to be tested. In the second working mode, the control device selects the corresponding target robot arm for each extraction step of the sample to be tested, so as to allow different first robot arms to perform different extraction steps on the sample to be tested.
12. The nucleic acid extraction system according to claim 11, wherein: The control device is also suitable for: In the second working mode, a plurality of sub-sample queues corresponding to the plurality of extraction steps are established and managed, each sub-sample queue being used to record and sort samples for which the extraction step corresponding to the sub-sample queue is to be executed; as well as Based on each sub-sample queue, an allocation algorithm is executed respectively, wherein the allocation algorithm is used to select the corresponding target robot arm for the sample in the sub-sample queue, so that the target robot arm performs the extraction step corresponding to the sample queue on the sample.
13. The nucleic acid extraction system according to claim 12, wherein: Based on each of the subsample queues, the processor executes the allocation algorithm to adapt: According to the quantity interval of the samples in the sub-sample queue, a corresponding number of target robotic arms are selected to perform corresponding extraction steps on the samples to be tested in the sample queue.
14. The nucleic acid extraction system according to claim 13, wherein: If the number of the first robotic arms in the idle state is less than the number of target robotic arms required in the number interval, the processor executes a time optimization algorithm, which is used to estimate the waiting time required for each of the first robotic arms, and selects the first robotic arm that is about to be released to the idle state as the target robotic arm based on the estimated waiting time.
15. The nucleic acid extraction system according to claim 1, wherein: The control device is also suitable for: Dividing the plurality of first mechanical arms into a plurality of groups, each group of first mechanical arms being respectively configured to perform one of a plurality of extraction steps required for the extraction task; as well as For each extraction step of the current sample to be processed, a first robotic arm in an idle state is selected as the target robotic arm from a group of first robotic arms corresponding to the extraction step.
16. The nucleic acid extraction system according to claim 15, wherein: The multiple extraction steps include at least a first extraction step and a second extraction step, the time required to execute the first extraction step is longer than the time required to execute the second extraction step, the multiple first robotic arms include a first group of robotic arms corresponding to the first extraction step and a second group of robotic arms corresponding to the second extraction step, and the number of the first robotic arms included in the first group of robotic arms is greater than the number of the first robotic arms included in the second group of robotic arms.
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