A high-throughput, continuously loadable automation system for nucleic acid extraction

Abstract

A high-throughput, continuously loadable automation system for nucleic acid extraction comprises an extraction part with at least three process stations, a magnetic unit for transferring magnetic beads between reagent plates on different process stations via relative movement, and a controller configured to control the system such that while an extraction process is in progress for a first sample plate in one process station, another process station receives a second sample plate to perform a subsequent process therefor.

Description

A HIGH-THROUGHPUT, CONTINUOUSLY LOADABLE AUTOMATION SYSTEM FOR NUCLEIC ACID EXTRACTION

[0001] This disclosure relates to an automated system for nucleic acid extraction. More specifically, this disclosure pertains to a high-throughput nucleic acid extraction automation system that includes an extraction apparatus comprising a plurality of process stations and a control unit, and is capable of continuous loading.

[0002] Molecular diagnostics is a method of determining the presence of diseases or infections by analyzing genetic information contained in samples or biological markers contained in proteins using molecular biological techniques. Due to the nature of infectious disease diagnostics, when a specific infectious disease becomes prevalent, it is required to perform a large number of identical types of tests. Therefore, a centralized model has been mainly used, in which samples collected from local clinics and public health centers are rapidly transported to large-scale diagnostic centers equipped with mass testing systems for molecular testing.

[0003] To apply this centralized diagnostic model, molecular diagnostic automation systems have been developed to process large volumes of samples simultaneously, extract nucleic acids, and perform test reactions. Existing automation systems that process large volumes of samples and perform identical tests have mainly been developed in a batch-type format, requiring operator intervention at the end of each batch. Furthermore, conventional high-throughput extraction systems have been developed based on the assumption of routine testing of identical types of samples using identical test protocols. Therefore, when the extraction of one type of sample is completed and the extraction of another type begins, manual intervention by the operator is required, such as replacing buffers and resetting protocols.

[0004] As the frequency and duration of operator intervention increase relative to the system operation time, the number of systems manageable per operator decreases, leading to increased costs for diagnostic centers.

[0005] Accordingly, there is a need to develop a high-throughput extraction system that can automatically perform various nucleic acid extractions corresponding to various samples for diverse molecular diagnostics, and that supports continuous loading to minimize operator intervention.

[0006] In view of the above background, one embodiment of this disclosure provides a high-throughput nucleic acid extraction automation system capable of continuous loading, which maximizes nucleic acid extraction efficiency.

[0007] However, this disclosure is not limited to the aforementioned objectives, and various modifications may be made without departing from the spirit and scope of this disclosure.

[0008] In order to achieve the above objectives, an aspect of the present disclosure may provide a high-throughput, continuously loadable automation system for nucleic acid extraction including: a loading station configured to receive a sample plate containing a plurality of samples; a supply part configured to provide a plurality of reagent plates with a pre-filled reagent and (ii) magnetic beads; an extraction part including at least three process stations for extracting nucleic acids; a plate transfer unit configured to transfer one of the reagent plates from the supply part to one of the process stations; a magnetic unit including a plurality of magnetic rods to generate magnetic force for collecting the magnetic beads; and a controller.

[0009] The magnetic beads, while being collected by the magnetic unit, may be transferred from a reagent plate on one process station to a reagent plate on another process station via relative movement between the magnetic unit and the process stations.

[0010] The controller may control the automation system such that, while a nucleic acid extraction process is in progress for a first sample plate in one process station, another process station receives a second sample plate to perform a subsequent extraction process therefor.

[0011] The magnetic beads, while being collected by the magnetic unit, may be transferred from a reagent plate on one process station to a reagent plate on another process station via relative movement between the magnetic unit and the process stations.

[0012] The controller may control the automation system such that, while a nucleic acid extraction process is in progress for a first sample plate in one process station, another process station receives a second sample plate to perform a subsequent extraction process therefor.

[0013] The system may further include a waste bin for discarding used reagent plates from the process stations.

[0014] The controller may control the plate transfer unit such that the reagent plate is prepared on a subsequent process station before an operation of the subsequent process station, and the used reagent plate on a current process station is discarded into the waste bin after the operation of the current process station.

[0015] The supply part may be configured to provide a plurality of reagent plate sets according to sample types.

[0016] The controller may be configured to: select, based on sample information of the sample plate provided to the loading station, an extraction protocol corresponding to the sample type and a reagent plate set required therefor from among a plurality of pre-stored extraction protocols corresponding to sample types; select process stations required to perform the selected extraction protocol; control the plate transfer unit to deliver the selected reagent plate set to the selected process stations; and control the selected process stations sequentially according to the selected extraction protocol.

[0017] The system may further include an opening unit configured to open the film of the reagent plate provided by the supply part.

[0018] The reagent plate may be sealed with the film.

[0019] The magnetic unit and the opening unit respectively may include a plurality of elements corresponding to each of wells of the reagent plate.

[0020] The loading station may receive the sample plate containing a lysis buffer, and the supply part provides a first reagent plate including a wash buffer and a second reagent plate including an elution buffer.

[0021] The loading station may receive the sample plate further containing a binding buffer.

[0022] The plate transfer unit may be configured to deliver the sample plate from the loading station to a first process station in the extraction part.

[0023] The magnetic unit may be configured to transfer the magnetic beads into the sample plate on the first process station.

[0024] The plate transfer unit may be configured to deliver the reagent plate from the supply part to a second process station in the extraction part.

[0025] The magnetic unit may be configured to transfer the magnetic beads from the sample plate on the first process station to the reagent plate on the second process station.

[0026] The loading station may be a first process station that operates first among the process stations.

[0027] The magnetic unit may be configured to transfer the magnetic beads into the sample plate on the first process station.

[0028] The system may further include a sample supply unit configured to supply the sample plate to the loading station.

[0029] The magnetic unit may be configured to transfer the magnetic beads into the sample plate on the loading station.

[0030] The magnetic unit may be configured to move in a first direction along which the process stations are arranged and in a second direction along which the supply part and the extraction part are arranged.

[0031] The magnetic unit may be configured to transfer the magnetic beads from the supply part to the sample plate on first process station by moving in the second direction, and transfer the magnetic beads to a reagent plate on a subsequent second process station by moving in the first direction.

[0032] The magnetic unit may further include an image sensor configured to generate an image of an area where the magnetic rods descends.

[0033] The magnetic unit may include a first magnetic unit and a second magnetic unit operating within single extraction part.

[0034] The first magnetic unit may perform preceding steps among the process stations and the second magnetic unit performs subsequent steps among the process stations.

[0035] The first magnetic unit and the second magnetic unit may move such that their paths do not overlap with each other.

[0036] The first magnetic unit may be configured to sequentially cycle through the process stations, and the second magnetic unit is configured to sequentially cycle through the process stations, following the first magnetic unit.

[0037] The process station may include at least one of a function of controlling a temperature of a solution in the sample plate or the reagent plate, and a function of stirring the solution.

[0038] The controller may bre configured to determine a combination of the process stations and sequence of functions performed by the process stations according to the determined extraction protocol.

[0039] At least one of the process stations may be a multifunctional process station including both a temperature control function and a stirring function, and is configured to selectively perform one of the two functions or simultaneously perform both functions.

[0040] The controller may determine one extraction protocol from among a plurality of extraction protocols based on identification information of the sample received at the loading station, and selects at least on of the temperature control function and the stirring function of the multifunctional process station according to the determined extraction protocol.

[0041] The system may further include: a storage device configured to store materials including the reagent plates and the magnetic beads provided by the supply part; and a material transfer unit configured to transfer the materials between the storage device and the supply part.

[0042] The controller may be configured to: determine one extraction protocol from among a plurality of extraction protocols based on identification information of the sample received at the loading station; select the materials required for the determined extraction protocol; and operate the material transfer unit to pick up the required materials from the storage device and transfer them to the supply part.

[0043] The storage device may include a plurality of storage segments arranged in parallel along a first direction.

[0044] The supply part may include a plurality of supply segments arranged in parallel along the first direction.

[0045] The material transfer unit may be configured to move in a first direction and a second direction perpendicular to the first direction, to selectively position itself at each of the storage segments or each of the supply segments by moving along the first direction, and to move between the storage device and the supply part by moving along the second direction.

[0046] The storage device may include a storage area for storing materials and a pickup area where the material transfer unit picks up the materials.

[0047] The controller may be configured to: determine one extraction protocol from among a plurality of extraction protocols based on identification information of the sample received at the loading station; select a required material for the determined extraction protocol; operate the material transfer unit along the first direction to pick up the required material from the pickup area of the storage segment; and operate the material transfer unit along the second direction to transfer a picked-up material to the supply segment of the supply part.

[0048] Some of the storage segments may include a refrigeration function.

[0049] The storage segment and the supply segment corresponding to the same material may be aligned with each other in a second direction perpendicular to the first direction.

[0050] Each of the supply segments may be in a one-to-one correspondence with each of the storage segments.

[0051] The process stations may be arranged sequentially and in parallel along the first direction, and the storage segment, the supply segment, and the process station corresponding to a same material are aligned with each other in a second direction perpendicular to the first direction.

[0052] The sample plate received at the loading station may be a first plate, and the reagent plates include a second plate containing a first wash buffer, a third plate containing a second wash buffer, and a fourth plate containing an elution buffer.

[0053] The process stations may include a first process station configured to bind nucleic acids to the magnetic beads in the first plate, a second process station configured to perform first washing in the second plate, a third process station configured to perform second washing in the third plate, and a fourth process station configured to elute nucleic acids from the magnetic beads in the fourth plate.

[0054] The process stations of the extraction part may be arranged in one direction.

[0055] The controller may be configured to sequentially operate the process stations to perform the nucleic acid extraction process.

[0056] The extraction part may be modularly configured with at least two extraction parts.

[0057] The controller may be configured to: determine one extraction protocol from among a plurality of extraction protocols based on identification information of the sample received at the loading station; and match the sample to the extraction part that performs the determined extraction protocol.

[0058] The controller may be configured to operate the process stations sequentially according to the determined extraction protocol.

[0059] The controller may be configured to operate the process stations in a unidirectional sequence according to the determined extraction protocol.

[0060] The controller may be configured to transfer the magnetic beads sequentially to the process stations according to the determined extraction protocol.

[0061] The extraction part may be configured to allow a new process station to be added and an existing process station to be replaced, without changing the process stations already disposed.

[0062] The system may further include a waste bin for discarding the sample plate and reagent plates.

[0063] The extraction part may further include a buffer station, which is located between the loading station and a first process station, and on which the sample plate received at the loading station is placed before moving to the first process station.

[0064] The loading station, the buffer station, and the process stations may be arranged side-by-side in one direction.

[0065] The buffer station may include a multi-position holder configured to align the sample plate.

[0066] The plate transfer unit may be configured to selectively transfer the sample plate from the loading station to either the buffer station or a first process station that performs an initial process among the process stations.

[0067] The control unit may be configured to control the plate transfer unit to: i) transfer the sample plate from the loading station to a first process station that performs an initial process among the process stations, when the first process station is empty; and ii) transfer the sample plate from the loading station to the buffer station, when the first process station is occupied.

[0068] The plate transfer unit may be configured to transfer the sample plate from the loading station to a first process station that performs an initial process among the process stations.

[0069] The magnetic unit may be configured to transfer the magnetic beads from the supply part to the sample plate on the first process station.

[0070] The system may further include a transfer station, which is located between the supply part and the extraction part, and on which the reagent plate provided from the supply part is placed.

[0071] The plate transfer unit may be configured to transfer the reagent plate from the transfer station to one of the process stations.

[0072] The plate transfer unit may include: a first plate transfer unit configured to transfer the reagent plate from the supply part to the transfer station; and a second plate transfer unit configured to transfer the reagent plate from the transfer station to one of the process stations.

[0073] An aspect of the present disclosure may provide a high-throughput, continuously loadable automation system for nucleic acid extraction including: a sample supply unit configured to supply a sample plate containing a plurality of samples; a supply part providing (i) a plurality of reagent plates with a pre-filled reagent and (ii) magnetic beads; an extraction part including a series of process stations for extracting nucleic acids; a plate transfer unit configured to transfer one of the reagent plates from the supply part to one of the process stations; a magnetic unit including a plurality of magnetic rods configured to generate magnetic force for collecting the magnetic beads; a waste bin for discarding a used reagent plate; and a controller.

[0074] The magnetic unit may be configured to change a position of the magnetic beads between reagent plates, each disposed on a different one of the process stations.

[0075] The controller may be configured to: i) initiate a subsequent nucleic acid extraction process before a preceding process is completed in the extraction part; and ii) control the plate transfer unit to prepare a reagent plate on a subsequent process station prior to an operation thereof, and to discard the used reagent plate from a current process station into the waste bin subsequent to an operation thereof.

[0076] An aspect of the present disclosure may provide a high-throughput, continuously loadable automation system for nucleic acid extraction including: a loading station configured to receive a sample plate containing a plurality of samples; a supply part providing (i) a plurality of empty plates, (ii) magnetic beads, and (iii) at least one reagents; an extraction part including at least three process stations for extracting nucleic acids; a multi-channel pipette unit; a plate transfer unit configured to transfer one of the empty plates from the supply part to one of the process stations; a magnetic unit including a plurality of magnetic rods configured to generate magnetic force for collecting the magnetic beads; and a controller.

[0077] The multi-channel pipette unit may be configured to transfer one of the reagents from the supply part to the empty plate placed on one of the process stations.

[0078] The magnetic unit may be configured to change a position of the magnetic beads between reagent plates filled with the reagent, each disposed on a different one of the process stations.

[0079] The controller may be configured to control the automation system such that, while a nucleic acid extraction process is in progress for a first sample plate in one process station, another process station is capable of receiving a second sample plate to perform a nucleic acid extraction process therefor.

[0080] An aspect of the present disclosure may provide a method for operating a high-throughput, continuously loadable automation system for nucleic acid extraction, the automation system including: an extraction part including a series of process stations for extracting nucleic acids; a supply part for supplying a plurality of multi-well plates provided with a pre-filled reagent and magnetic beads; a plate transfer unit; and a magnetic unit, and the method includes the steps of: (a) loading a multi-well plate including a sample onto the extraction part; (b) determining an extraction protocol for a sample in the multi-well plate loaded onto the extraction part among a plurality of extraction protocols according to a sample type, and determining a protocol step for each of the process stations to perform the extraction protocol; (c) placing a multi-well plate provided with the reagent, using the plate transfer unit, from the supply part to one of the process stations, wherein the multi-well plate is prepared in state filled with a reagent selected based on the sample; (d) transferring the magnetic beads, using the magnetic unit, from the supply part to the multi-well plate on the process station; (e) changing the position of the magnetic beads, using the magnetic unit, from a first process station, where a protocol step is completed, to a second process station, where a subsequent protocol step will proceed; and (f) discarding used multi-well plate, using the plate transfer unit, from the first process station into a waste bin after the transfer of magnetic beads is completed.

[0081] A first multi-well plate may include a first sample and a second multi-well plate including a second sample are sequentially loaded onto the extraction part.

[0082] While a first extraction protocol for the first sample proceeds in one process station, a second extraction protocol for the second sample simultaneously may proceed in another process station of the same extraction part.

[0083] The supply part may be configured to provide a magnetic rod sleeve that is coupled to a magnetic rod of the magnetic unit.

[0084] The magnetic unit may couple the magnetic rod sleeve before starting the extraction protocol, and discards the magnetic rod sleeve into the waste bin after the extraction protocol is completed.

[0085] The first extraction protocol and the second extraction protocol proceeding in the extraction part may be performed by a single magnetic unit.

[0086] Wherein the magnetic unit may include a first magnetic unit that performs the first extraction protocol and a second magnetic unit that performs the second extraction protocol.

[0087] The multi-well plate loaded onto the extraction part in step may include the sample, a lysis buffer, and a binding buffer.

[0088] The multi-well plate loaded onto the extraction part may include the sample in a lysed state.

[0089] The supply part may be configured to provide multi-well plates respectively containing a wash buffer and an elution buffer.

[0090] According to an embodiment of the present disclosure, the nucleic acid extraction automation system is capable of continuously loading sample plates containing samples. This allows the system to receive new sample plates and prepare or initiate nucleic acid extraction even while an extraction process is being performed on other samples.

[0091] The nucleic acid extraction automation system according to one embodiment of this disclosure is capable of automatically processing various types of nucleic acid extraction procedures. Therefore, even when sample plates of different types are loaded, the system can automatically extract nucleic acids according to the appropriate extraction protocol.

[0092] Furthermore, the nucleic acid extraction automation system according to one embodiment of this disclosure is a scalable system that allows one or more extraction parts to be added without changing the overall system configuration. Accordingly, the system can be flexibly configured in response to environmental changes.

[0093] The effects of the present disclosure are not limited to the foregoing, and should be understood to include all effects that may be inferred from the detailed description of the present disclosure or the configuration described in claims.

[0094] FIG. 1 is a conceptual diagram illustrating the connection structure of an automation system for nucleic acid extraction according to the first embodiment.

[0095] FIG. 2 is a conceptual diagram illustrating the planar layout of the automation system for nucleic acid extraction according to the first embodiment.

[0096] FIG. 3 illustrates an embodiment in which the extraction part in FIG. 2 is configured in a modular manner.

[0097] FIG. 4 illustrates an embodiment in which the first transfer unit is omitted from FIG. 2.

[0098] FIG. 5 illustrates an embodiment in which the storage device is omitted from FIG. 2.

[0099] FIG. 6 illustrates an embodiment in which a plurality of magnetic units are provided.

[0100] FIG. 7 is a modified embodiment of FIG. 6.

[0101] FIG. 8 illustrates an embodiment in which an opening unit is provided.

[0102] FIG. 9 illustrates an embodiment in which the supply part and the extraction part are spatially separated.

[0103] FIG. 10 is a modified embodiment of FIG. 9.

[0104] FIG. 11 is a conceptual diagram illustrating the connection structure of the automation system for nucleic acid extraction according to the second embodiment.

[0105] FIG. 12 is a conceptual diagram illustrating the planar layout of the automation system for nucleic acid extraction according to the second embodiment.

[0106] FIG. 13 is a modified embodiment of FIG. 12.

[0107] Hereinafter, the present disclosure will be described in detail with reference to embodiments and example drawings. The embodiments are for illustrative purposes only, and it should be apparent to those of skill in the art that the scope of the present disclosure is not limited to the embodiments.

[0108] In addition, in adding reference numerals to the components of each drawing, it should be noted that same reference numerals are assigned to same components as much as possible even though they are shown in different drawings. In addition, in describing the embodiments of the present disclosure, when it is determined that a detailed description of a related well-known configuration or function interferes with the understanding of the embodiments of the present disclosure, the detailed description thereof will be omitted.

[0109] In addition, in describing the components of the embodiments of the present disclosure, terms such as first, second, A, B, (a), (b), (i), (ii), etc. may be used. These terms are only for distinguishing the components from other components, and the nature or order of the components is not limited by the terms.

[0110] In this specification, specific structural or functional descriptions are provided only to illustrate exemplary embodiments of the disclosure. The embodiments may be implemented in various forms and should not be construed as limited to those described herein. It should be understood that all modifications, equivalents, and substitutions that fall within the spirit and scope of the disclosure are encompassed.

[0111] When a component is described as being "connected," "coupled" or "fastened" to other component, the component may be directly connected or fastened to the other component, but it will be understood that another component may be "connected," "coupled" or "fastened" between the components. Similarly, when a component is described as being “directly connected,” “directly coupled,” or “directly linked,” it should be understood that no intermediate component exists. Other expressions describing relationships between components, such as “between,” and “directly between,”, or “adjacent to,” and “directly adjacent to,” should be interpreted in the same manner.

[0112] adjacent to,” should be interpreted in the same manner.

[0113] The terminology used in this specification is intended only to describe exemplary embodiments and is not meant to limit the scope of the disclosure. Unless clearly stated otherwise, singular expressions include plural forms. Terms such as “include,” “comprise,” or “have” are intended to indicate the presence of stated features, numbers, steps, operations, components, parts, or combinations thereof, but do not preclude the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0114] Unless otherwise defined, all terms used herein, including technical and scientific terms, have the same meaning as commonly understood by those skilled in the art to which this disclosure pertains. Terms defined in commonly used dictionaries should be interpreted consistently with their ordinary meanings in the relevant technical context and should not be interpreted in an overly formal or idealized manner unless explicitly defined herein.

[0115] Terms such as first, second, and third may be used to describe various components, but such components are not limited by these terms. These terms are used merely to distinguish one component from another. For example, without departing from the scope of the disclosure, a first component may be referred to as a second or third component, and similarly, a second or third component may be interchangeably referred to as a first component.

[0116] As used herein, the term "sample" may include a biological sample (e.g., cells, tissues, and fluids from a biological source) and a non-biological sample (e.g., food, water, and soil). Examples of the biological sample may include viruses, bacteria, tissues, cells, blood (e.g., whole blood, plasma, or serum), lymph, bone marrow fluid, saliva, sputum, swab, aspiration, milk, urine, feces, ocular fluid, semen, brain extract, spinal fluid, joint fluid, thymic fluid, bronchoalveolar lavage fluid, ascites, and amniotic fluid. In addition, the sample may include natural nucleic acid molecules isolated from a biological source, and synthetic nucleic acid molecules. According to an embodiment of the present disclosure, the sample may include an additional substance such as water, deionized water, saline solution, pH buffer, acid solution, or alkaline solution.

[0117] In this specification, directions may be defined based on the drawings. The transverse direction may refer to the x-axis direction or the first direction, the longitudinal direction may refer to the y-axis direction or the second direction, and the height direction may refer to the z-axis direction, which is perpendicular to the x-y plane, or the third direction. However, these directions are exemplary and the embodiments of this disclosure are not limited thereto. For example, the embodiments may include directions that are not perpendicular to each other, curved or circular directions, or even zigzag directions.

[0118] According to one embodiment of this disclosure, the nucleic acid extraction automation system (10) may be configured such that a plurality of devices are provided in a modular structure and can be combined. Furthermore, each device may also comprise a plurality of sub-devices provided in a modular structure.

[0119] As used herein, the term “modular” refers to a structure in which a device is composed of multiple independent yet interchangeable modules, each performing a unique function while operating as part of the overall system. These modules may be added, removed, replaced, or expanded as needed, allowing flexible adjustment of the device's design and functionality.

[0120] Specifically, when a modular structure is adopted, the following advantages may be obtained. First, scalability may be achieved by easily expanding the performance or functionality of the device through the addition or replacement of modules. Second, flexibility may be ensured by allowing individual modules to be replaced without stopping the entire system when a specific module fails or becomes unnecessary. Third, maintainability may be improved by enabling maintenance work to be performed more easily through module-level management. Fourth, reusability may be achieved by allowing the same module to be reused in other devices or systems. Lastly, design simplification may be realized by dividing complex functions into independent modules, thereby simplifying the overall design.

[0121] The overall process of a nucleic acid amplification test system may be broadly divided into pre-treatment, extraction, set-up, and amplification / detection. In some cases, the set-up process may be omitted. Different systems or devices may be organically connected for each process.

[0122] The nucleic acid extraction automation system according to one embodiment may be positioned downstream of the pre-treatment system and upstream of the set-up system or the amplification / detection system.

[0123] The nucleic acid extraction automation system according to one embodiment may receive a deep well plate (DWP) containing dispensed samples that have completed pre-treatment and automatically perform the nucleic acid extraction process. This system adopts a magnetic bead transfer method without a separate liquid handling unit, thereby simplifying the structure and minimizing the risk of cross-contamination. Hereinafter, this method is referred to as the “bead transfer” method.

[0124] [Bead Transfer Method]

[0125] The bead transfer method according to one embodiment is characterized by collecting magnetic beads bound to nucleic acids using magnetic force and physically transferring the beads to the wells of the next process. This is typically performed by a transfer head including magnetic force means such as a magnetic rod or pin tool.

[0126] The specific nucleic acid extraction process may include the following steps:

[0127] A) Lysis step: A lysis buffer is added to each well of a first DWP containing samples (e.g., blood, cell suspension, etc.) to disrupt cell and nuclear membranes and release nucleic acids (DNA, RNA, etc.).

[0128] B) Binding step: Magnetic beads and a binding buffer (e.g., containing high salt and alcohol) are added to each well of the first DWP. Under specific conditions, nucleic acids selectively bind (adsorb) to the surface of the magnetic beads (e.g., silica-coated). The binding step may be divided into the buffer addition step and the bead addition step.

[0129] C) Washing step: (i) Insert magnetic force means (e.g., magnetic rod) of the transfer head into each well of the first DWP containing suspended magnetic beads bound to nucleic acids. (ii) Apply magnetic force to capture the beads on the surface of the rod. (iii) Withdraw the magnetic force means from each well and transfer the captured beads to the wells of a second DWP pre-dispensed with wash buffer 1. (iv) Release the beads into the wash buffer by deactivating or reducing the magnetic force, then mix to remove impurities (proteins, salts, etc.) not bound to the beads. (v) If necessary, repeat steps (i) to (iv) in third and fourth DWPs containing different wash buffers (e.g., wash buffer 2) to enhance washing precision.

[0130] D) Elution step: (i) Capture the washed magnetic beads from the final wash DWP using magnetic force means. (ii) Transfer the beads to each well of a fifth DWP containing elution buffer (e.g., low-salt buffer or nuclease-free water). (iii) Release the beads into the elution buffer and elute pure nucleic acids from the beads under specific conditions (e.g., heating or room temperature incubation). (iv) Finally, fix the empty beads to the side or bottom of the well using magnetic force means and safely recover only the supernatant containing nucleic acids, i.e., the eluate.

[0131]

[0132] Most conventional automated nucleic acid extraction devices use a “liquid transfer” method. In this method, magnetic beads remain fixed in each well of a DWP throughout the process, and a plate magnet placed outside the well is used to fix the beads to the side wall. Then, a pipette tip is used to aspirate and remove the solution (e.g., lysis solution, wash solution) from the well and dispense new solutions (e.g., wash buffer, elution buffer).

[0133] This conventional liquid transfer method may cause the following problems. First, during the aspiration process, some magnetic beads that are not firmly fixed by magnetic force may be aspirated into the pipette tip and lost, which may directly lead to a decrease in the final yield of nucleic acids. Second, during the repeated aspiration and dispensing of sample solutions, aerosols may be generated, which may become a major cause of cross-contamination between wells. Third, ethanol-based wash buffers used in the washing step may be difficult to completely remove using pipettes. If a small amount of wash buffer remains on the bottom of the well or on the bead pellet, it may interfere with the subsequent elution process, thereby reducing the purity of the nucleic acids and inhibiting molecular diagnostic reactions such as PCR.

[0134] In contrast, the bead transfer method according to this disclosure actively transfers the magnetic beads themselves to the wells of the next process, thereby fundamentally resolving the problems of the conventional technology and providing the following advantages. First, since there is no step of aspirating or removing liquid, magnetic force means forcibly collect and transfer the beads, so the risk of bead loss during the process is very low, and a high and consistent nucleic acid recovery rate can be ensured. Second, since the sample-containing solution is not directly pipetted, and only the beads are separated and moved to the next well containing clean buffer, the generation of aerosols is significantly reduced, and the risk of cross-contamination between samples is remarkably decreased. Third, because the beads are completely withdrawn from the solution of the previous well and transferred to the next well, the carry-over of residual liquid is extremely low. In particular, when transferring from the final wash well to the elution well, the carry-over of ethanol components is minimized, allowing the acquisition of high-purity nucleic acids that do not inhibit subsequent reactions. Fourth, the liquid transfer method requires complex pipetting steps to aspirate and dispense the liquid in all 96 wells (as an example), whereas the bead transfer method can simultaneously collect beads from all wells using 96 magnetic rods and transfer them collectively to the next plate. This simplifies the process steps and significantly shortens the overall nucleic acid extraction time. Fifth, since there is no need to aspirate or dispense liquid at each step, the use of expensive automated pipette tips can be drastically reduced, thereby lowering operational costs.

[0135]

[0136] The nucleic acid extraction automation system according to one embodiment includes: (i) a first embodiment that does not include a dispensing unit, and (ii) a second embodiment that includes a dispensing unit.

[0137] In the first embodiment that does not include a dispensing unit, a first DWP is received in which a sample that has completed pre-treatment is contained, and lysis buffer and binding buffer have already been added. Therefore, in the first embodiment, there is no need to separately prepare the lysis buffer and the binding buffer. In addition, the first embodiment may prepare a pre-filled DWP in which reagents and beads are pre-dispensed into each well. The pre-filled DWP is prepared for single use.

[0138] In the second embodiment that includes a dispensing unit, a first DWP containing a sample that has completed pre-treatment is received, and lysis buffer and binding buffer are added. Therefore, in the second embodiment, the lysis buffer and the binding buffer must be separately prepared. Furthermore, in the second embodiment, reagents and beads may be prepared in bulk. Here, “bulk” refers to a state in which multiple doses are prepared in a single container. The dispensing unit dispenses each reagent and bead into each well of an empty DWP.

[0139]

[0140] [First Embodiment]

[0141] FIG. 1 is a conceptual diagram illustrating the connection structure of an automation system for nucleic acid extraction according to a first embodiment. And FIG. 2 is a conceptual diagram illustrating the planar layout of the automation system for nucleic acid extraction according to the first embodiment.

[0142] The automation system for nucleic acid extraction (10) according to the first embodiment includes: a loading station to which samples are supplied; a supply part that supplies materials; an extraction part configured to extract nucleic acids; a plate transfer unit that transfers plates; a waste bin that discards used plates; and a magnetic unit that collects magnetic beads.

[0143] The loading station is configured to receive a sample plate accommodating a plurality of samples. The supply part is configured to supply a plurality of reagent plates pre-filled with reagents and magnetic beads. The extraction part includes at least three or more process stations to extract nucleic acids. The plate transfer unit is configured to transfer reagent plates from the supply part to one of the process stations. The magnetic unit includes a plurality of magnetic rods that generate magnetic force to collect magnetic beads.

[0144] The automation system for nucleic acid extraction (10) according to the first embodiment includes one or more transfer units. The transfer unit is capable of transferring plates. The plates transferred by gripping with the transfer unit include sample plates, bead plates, reagent plates, and sleeve plates.

[0145] The transfer unit according to one embodiment may be used to grip and relocate sample plates, bead plates, and reagent plates. Additionally, the transfer unit may be combined with an orthogonal axis transfer mechanism and may move in a first direction and a second direction.

[0146] The transfer unit may include a gripper that grips the plate and a transfer rail that horizontally moves the gripper. For example, the transfer unit may grip and transfer a deep well plate or a 96-well plate. The transfer unit includes a gripper that stably grips and holds the plate, thereby physically transferring the plate containing samples or reagents.

[0147] The gripper may include a pair of jaws or a pin structure that grips the side flange or specific portion of a standard plate (e.g., ANSI / SLAS standard plate). The gripper may be mechanically driven by a pneumatic cylinder, motor, or solenoid to grip and release the plate. The gripping part of the gripper may include an elastic member (e.g., rubber, silicone pad) or a specific concave-convex structure to increase friction with the plate and prevent slipping during transfer.

[0148] The transfer unit may further include a lifting drive part that moves vertically (Z-axis) to pick up or place the plate from or onto a station. The lifting drive part may perform operations such as descending to grip the plate and then ascending, or descending to release the plate and then ascending again.

[0149] The gripper may be mounted on a transfer mechanism that allows precise movement in the first and second directions. The transfer unit may include a first direction rail (X-axis direction rail) and a second direction rail (Y-axis direction rail). The transfer mechanism may include one or more step motors or servo motors, and a belt-pulley system, ball screw, or linear motor for power transmission. The transfer mechanism moves the gripper (and the plate gripped thereby) to a preset coordinate, i.e., the exact location of each process station or plate storage area, according to signals from the controller.

[0150] The transfer mechanism of the transfer unit may include a gantry structure and an articulated robot arm.

[0151] The transfer unit may be implemented in the form of a gantry structure or a Cartesian coordinate robot. Specifically, the gantry structure includes a first axis (X-axis) guide rail fixedly installed on the upper part of the housing or frame of the device, and a second axis (Y-axis) beam linearly movable along the first axis guide rail. The second axis beam is coupled with the gripper, and a third axis (Z-axis) actuator is slidably installed on the gripper. Each axis (X, Y, Z) is precisely driven by an independent drive motor (e.g., step motor or servo motor) and a power transmission member (e.g., belt-pulley system, ball screw, or lead screw).

[0152] Since this gantry structure is based on a Cartesian coordinate system, the gripper can be accurately aligned to a specific position on the X-Y plane. The gantry structure has the advantages of relatively simple and robust construction and ensures high positional accuracy over a wide working area.

[0153] The transfer unit may be implemented in the form of an articulated robot arm. Specifically, the articulated robot arm includes a fixed base and a plurality of links rotatably connected by a plurality of joints. Typically, a 4-axis, 5-axis, or 6-axis robot arm may be used. A gripper is mounted on the end-effector of the robot arm.

[0154] Each joint of the articulated robot arm is precisely angle-controlled by a built-in servo motor and reducer. The articulated robot arm controls the position and orientation of the end-effector through complex calculations by the controller based on robot kinematics. This structure provides a higher degree of freedom (DOF) compared to the gantry structure. Therefore, it is advantageous for flexible and rapid movement between multiple stations arranged in a complex manner within the device, not only for simple planar movement. Additionally, it enables complex motions such as tilting or rotating the gripper at a specific angle as needed, thereby maximizing process flexibility.

[0155] The transfer unit may transfer plates between the supply part (210) and the extraction part (220). Specifically, the transfer unit may transfer plates from the supply segment (211) of the supply part (210) to the process station (222) of the extraction part (220). The transfer unit may also transfer plates from the storage segment (130) of the storage device (100) to the supply segment (211) of the supply part (210).

[0156] The transfer unit may transfer sample plates to the loading station (221). The transfer unit may transfer sample plates from the loading station (221) to the first buffer station (226) or the first process station (222a). The transfer unit may transfer plates from the last process station (222e) to the second buffer station (227) or the completion station (228).

[0157] The transfer unit may discard plates that have completed processing at the process station (222) into the waste bin (229).

[0158] The transfer unit according to one embodiment may be provided as a single unit. One transfer unit may transfer all of the sample plates, bead plates, reagent plates, and sleeve plates. One transfer unit may move to the storage device (100), supply part (210), loading station (221), and process station (222).

[0159] The transfer unit according to another embodiment may include two or more units divided by function. The transfer unit according to the first embodiment may include: a first transfer unit (310) that loads sample plates into the loading station (221); a second transfer unit (320) that delivers materials between the storage device (100) and the supply part (210); and a plate transfer unit (240) that delivers materials from the supply part (210) to the extraction part (220).

[0160] Alternatively, the transfer units may be integrated or separated by function.

[0161]

[0162] The automation system for nucleic acid extraction (10) according to the first embodiment includes various stations.

[0163] A station refers to a designated position or area within the automation system for nucleic acid extraction where a plate (e.g., DWP) is placed to perform a specific process or to wait. A station receives a plate transferred by the first transfer unit (310) or the plate transfer unit (240), and places the plate at a predetermined location so that other functional modules, such as the magnetic unit (250), can access the sample within the plate and perform operations.

[0164] The automation system for nucleic acid extraction may include various types of stations depending on their purpose and function. For example, the stations may include: a loading station (221), where a sample plate containing samples is introduced into the system; one or more process stations (222), where actual unit processes of biomolecule extraction such as lysis & binding, washing, and elution are performed; buffer stations (226, 227), where plates temporarily wait according to the workflow; and a completion station (228), where plates containing extracted molecules (e.g., nucleic acids) wait to be discharged.

[0165] The loading station (221) may function as an access point where a user or the first transfer unit (310) loads a sample plate into the system. The completion station (228) may function as a discharge point where completed plates are retrieved.

[0166] The buffer stations (226, 227) may be passive stations without any processing function, simply holding plates. These stations improve operational efficiency by allowing plates to wait after a preceding process until the next process station becomes available, or to wait before a process begins or before being discharged after completion.

[0167] The process stations (222) may include specific functions tailored to the characteristics of the unit process being performed. For example, a process station (222) may include a heating means (e.g., heating block) to maintain the sample or reaction solution in the plate at a specific temperature. It may also include agitation means (e.g., orbital shaker, linear shaker) to shake or agitate the plate to promote mixing of samples and reagents or resuspension of magnetic beads. Additionally, a process station (222) may serve as an area where magnetic separation is performed by the magnetic unit (250) approaching to capture and release magnetic beads.

[0168] These stations preferably include structures that ensure plates are always placed in accurate and stable positions. To achieve this, a station may include a plate positioning structure and a plate fixing structure.

[0169] The positioning structure guides the plate to be placed at a precisely predetermined location on the X-Y plane when the first transfer unit (310) or the plate transfer unit (240) places the plate on the station (400). This may be implemented using corner guides that engage with the corners or specific shapes of the plate, guide pins that fit into holes on the bottom surface of the plate, or pocket-shaped recesses that match the outer shape of the plate. Such positioning structures are essential to ensure that each well of a 96-well plate is precisely aligned with the 96 magnetic rods of the magnetic unit (250).

[0170] The fixing structure physically holds the plate in place to prevent it from shifting or vibrating due to external forces (e.g., vibration from agitation means, contact force during approach / retreat of the magnetic unit). This may be implemented using mechanical clamps that press the top or side flange of the plate, spring-loaded latches using elastic force, or auto-locking mechanisms driven by solenoids or motors.

[0171]

[0172] The sample plate may be a multi-well plate in which multiple samples are aliquoted. The multi-well plate includes a deep well plate (DWP) and a 96-well plate. The sample plate is prepared in a state where preprocessing is completed and aliquoting into each well is finished by a preprocessing device.

[0173] The automation system for nucleic acid extraction according to the first embodiment may receive a sample plate in which each well contains a sample along with lysis buffer and binding buffer. The preprocessing device, which is a preceding stage of the automation system, may pre-add lysis buffer and binding buffer to the plate containing the sample. Additionally, Proteinase K (PK) and Internal Control (IC) may be pre-added to the plate containing the sample by the preprocessing device.

[0174] The automation system for nucleic acid extraction according to the first embodiment may omit the dispensing unit for adding lysis buffer, binding buffer, PK, and IC. By omitting the dispensing unit, the equipment becomes smaller and lighter, the cost is reduced, and the system operation becomes simpler with shortened process time.

[0175]

[0176] The first transfer unit (310) that loads the sample plate onto the loading station (221) may also be referred to as a sample supply unit. The sample supply unit (310) picks up the prepared sample plate and places it onto the loading station (221). The sample supply unit (310) may be a component of the preprocessing device, a component of the automation system for nucleic acid extraction, or a separate transfer robot provided between the preprocessing device and the automation system.

[0177] The first transfer unit (310) may use a fixed-path transfer method without a gripper that grips the plate. The first transfer unit (310) may deliver the plate by sliding or rolling along a predetermined path. This transfer mechanism may use a belt conveyor, rail and chain / timing belt, or roller conveyor.

[0178] In this case, the loading station (221) may be a predetermined position provided within the transfer path of the first transfer unit (310), and may be referred to as a loading position. The first transfer unit (310) may include an optical sensor to detect the plate or a stopper or pin structure to physically fix the plate at the correct position to accurately determine the loading position.

[0179] Once the first transfer unit (310) delivers the plate to the loading station (221) or loading position, the plate transfer unit (240) may pick up the plate and deliver it to the first buffer station (226) or the first process station (222a).

[0180] The supply part may supply: a bead plate containing magnetic beads, a reagent plate containing reagents, and a sleeve plate containing magnetic rod sleeves that couple with magnetic rods. The magnetic rod sleeve includes a spin tip.

[0181] The bead plate, reagent plate, and sleeve plate may all be provided as multi-well plates and may be supplied as single-use units. Each well of the sample plate, bead plate, reagent plate, and sleeve plate may correspond to one another. The sample plate, bead plate, and reagent plate may all be provided as 96-well deep well plates, although the depth of the wells may differ.

[0182] The bead plate and reagent plate supplied to the supply part are pre-filled with beads or reagents. These plates are sold and transported with the well openings sealed by film or caps. The bead plate and reagent plate supplied to the supply part may be in a state where the film or cap is removed. Alternatively, the automation system for nucleic acid extraction may include a separate film remover or cap opener to automatically open the bead plate and reagent plate.

[0183] The extraction part includes a plurality of process stations that perform the extraction protocol. The extraction part includes a series of process stations that execute the extraction protocol. For example, the extraction part includes at least three or more process stations. Each process station is configured to operate independently and may be arranged in sequence according to the order of the extraction protocol. For example, the process stations may be arranged in a single row.

[0184] The term “extraction protocol” refers to a set of sequentially defined operations required to effectively isolate and purify nucleic acids from a specific type of sample (e.g., whole blood, serum, saliva, tissue, cells, virus, etc.). Depending on the type or characteristics of the sample, the preprocessing steps, reagent composition (e.g., lysis buffer, binding buffer, washing buffer, elution buffer), reagent volume, reaction time, incubation temperature, and magnetic bead handling conditions required for nucleic acid extraction may vary.

[0185] The automation system for nucleic acid extraction according to one embodiment may store multiple extraction protocols optimized for various sample types in the form of a database or allow users to set them. The controller obtains or receives the sample type information when the sample is loaded into the extraction part, selects the optimal extraction protocol corresponding to the sample type from the prepared protocols, and sequentially controls the operation of each process station, plate transfer unit, and magnetic unit according to the order and conditions defined in the selected protocol to perform the automated nucleic acid extraction process.

[0186]

[0187] Referring to FIG. 1, the automation system for nucleic acid extraction (10) according to the first embodiment may include a storage device (100), an extraction device (200), a transfer unit (300), and a controller (400). In one example, the storage device (100) and the extraction device (200) may be arranged adjacent to each other or may be integrated. Alternatively, the storage device (100) may be a component of the extraction device (200).

[0188] The storage device (100) may include a storage area (110) and a pickup area (120). The storage area (110) may store materials used in the nucleic acid extraction process. The pickup area (120) may be provided in front of or above the storage area (110), and may be accessible by the transfer unit (300).

[0189] The storage device (100) may include a plurality of storage segments (130). Different storage segments (130) may store different materials, and some segments may store the same material. For example, the plurality of storage segments (130) may be arranged side by side in a first direction.

[0190] The storage device (100) may include a temperature control unit. The plurality of storage segments (130) may include one or more segments that are independently temperature-controlled.

[0191] Materials stored in the storage device (100) may include magnetic rod sleeves, reagent plates, magnetic beads, and distilled water. The reagent plates may include plates that respectively contain washing buffer 1, washing buffer 2, distilled water, and elution buffer. Each reagent plate may contain a single-use quantity of reagent and may be provided as disposable.

[0192] In this specification, the term “reagent plate” is used to distinguish it from a sample plate containing samples. A reagent plate refers to a plate pre-filled with reagents. Hereinafter, the reagent plate and the sample plate are collectively referred to as “plate.”

[0193] The plate may have a strip shape, square shape, or ring shape. The wells of the plate may be arranged in a column direction, in both row and column directions, or in a curved direction.

[0194] The plate may include at least eight wells. For example, the plate may include: an 8-well strip with eight wells arranged in a row, an 8-well plate with two columns and four rows, a 12-well strip with twelve wells in a single column, a 16-well plate with two columns and eight rows or four columns and four rows, a 24-well plate with three columns and eight rows or six columns and four rows, a 32-well plate with four columns and eight rows, a 48-well plate with six columns and eight rows, a 96-well plate with twelve columns and eight rows, a 384-well plate with twenty-four columns and sixteen rows. Other configurations with various numbers of columns and shapes may also be provided.

[0195] The shape of the sample plate and the reagent plate may be the same. For example, both the sample plate and the reagent plate may be deep well plates (DWP). Specifically, both may be 96-well DWP with wells arranged in rows and columns.

[0196] According to one embodiment, the storage segments (130) may include: a storage segment (1301) for racks holding magnetic rod sleeves, a storage segment (1302) for plates containing magnetic beads, a storage segment (1303) for plates containing washing buffer 1, a storage segment (1304) for plates containing washing buffer 2, a storage segment (1305) for plates containing distilled water (D.W.) used for magnetic beads, a storage segment (1306) for plates containing elution buffer.

[0197] In this specification, the term “reagent plate” may be used to distinguish it from a “sample plate” that contains samples. A reagent plate refers to a plate pre-filled with reagents. Hereinafter, the reagent plate and the sample plate are collectively referred to as a “plate.”

[0198] The magnetic rod sleeve is a consumable that is detachably coupled to the magnetic unit (250) and surrounds the magnetic rod to prevent contamination. It includes a tubular body with a hollow interior into which the magnetic rod is inserted. The sleeve protects the magnetic rod from direct contact with samples or reagent solutions and is provided as disposable to fundamentally prevent cross-contamination between samples.

[0199] The magnetic unit (250) may be configured to mix magnetic beads and reagents in a solution. Typically, the magnetic unit (250) reciprocates the magnetic rod sleeve vertically to generate vortex flow and agitate the solution.

[0200] The magnetic rod sleeve includes a spin tip. The spin tip is coupled to the drive shaft of the magnetic unit (250) and enables rotational motion. When the spin tip rotates while coupled to the magnetic unit (250), it generates a strong vortex that uniformly disperses the magnetic beads in the solution for agitation. For example, it may agitate a bead-containing solution to equalize bead density.

[0201] In this specification, the term “reagent” may be used to exclude magnetic beads. Reagents may include washing buffer and elution buffer.

[0202] Magnetic beads are magnetic particles designed to bind nucleic acids by coating their surface with specific chemical groups, and are used in automated nucleic acid extraction processes. Depending on the coating material, magnetic beads may include silica-coated beads, carboxyl-functionalized beads, and streptavidin-coated beads. Depending on their size, magnetic beads may include nanobeads and microbeads.

[0203] The transfer unit (300) may include: a first transfer unit (310) that transfers samples to the extraction device (200), and a second transfer unit (320) that transfers materials from the storage device (100) to the extraction device (200).

[0204] The first transfer unit (310) includes a sample supply unit. It may receive a sample plate from a preprocessing device, where preprocessing has been completed, and deliver it to the automation system for nucleic acid extraction (10). The first transfer unit (310) may be a gripper that moves along a transfer rail (311) and grips and places the sample plate. Referring to FIG. 2, the transfer rail (311) extends in a second direction (vertical direction in the drawing). However, the extension direction and installation position of the transfer rail (311) may vary as needed.

[0205] The sample plate received by the first transfer unit (310) is preprocessed and pre-filled with reagents. In one embodiment, the sample plate may contain lysed samples. In another embodiment, the sample plate may contain samples along with lysis buffer and binding buffer.

[0206] The first transfer unit (310) may place the gripped sample plate onto the loading station (221). The sample plate at the loading station (221) may be moved to the first buffer station (226) of the extraction part (220). According to one embodiment, the first transfer unit (310) may move the sample plate from the loading station (221) to the first buffer station (226) while gripping it, or may place the sample plate on the loading station (221) and then push it to the first buffer station (226). For example, the first transfer unit (310) may include a pusher that pushes the sample plate.

[0207] When the loading station (221) is empty, the first transfer unit (310) may place another sample plate onto the loading station (221). By moving the sample plate brought by the first transfer unit (310) to the first buffer station (226), the transfer rail (311) becomes free of sample plates, allowing the first transfer unit (310) to continuously transfer additional sample plates. In another embodiment, multiple first buffer stations (226) may be provided.

[0208] The second transfer unit (320) may deliver materials from the storage device (100) to the supply part (210) of the extraction device (200). The second transfer unit (320) may be a gripper that moves along transfer rails (321, 322) and grips and places plates containing materials.

[0209] According to one embodiment, the transfer rails of the second transfer unit (320) may include: a first transfer rail (321) extending in a first direction, and a second transfer rail (322) extending in a second direction. The second transfer unit (320) may move in the first direction from the storage device (100) to the storage segment (130) storing the target material, receive the material, and then move in the second direction to place the material onto the corresponding supply segment (211). The second transfer unit (320) may replenish the supply segment (211) with materials required during the nucleic acid extraction process.

[0210]

[0211] The extraction device (200) may include one or more extraction modules (201). When a plurality of extraction modules (201) are provided, two or more extraction modules (201-1, 201-2) may be connected in series or in parallel. The term “connected in series” means that a single sample may sequentially pass through two or more extraction modules (201-1, 201-2) during the extraction process. The term “connected in parallel” means that two or more samples may undergo extraction processes independently in respective extraction modules (201-1, 201-2).

[0212] Each extraction module (201) may include a supply part (210), an extraction part (220), a plate transfer unit (240), a magnetic unit (250), and a controller.

[0213] According to one embodiment, the supply part (210) may receive materials from the storage device (100) and supply them to the extraction part (220). The supply part (210) may be used to prepare materials required for the extraction process in advance, thereby reducing process time. The supply part (210) may be positioned adjacent to the extraction part (220). For example, the storage device (100), the supply part (210), and the extraction part (220) may be arranged in sequence along a second direction.

[0214] Materials stored in the supply part (210) may include magnetic rod sleeves, reagent plates, magnetic beads, and distilled water. The reagent plates may include plates respectively containing washing buffer 1, washing buffer 2, distilled water, and elution buffer. Each reagent plate may contain a single-use quantity of reagent and may be provided as disposable.

[0215] The supply part (210) may include a plurality of supply segments (211). Different supply segments (211) may prepare different materials, and some supply segments (211) may prepare the same material. The plurality of supply segments (211) may be arranged side by side in a first direction.

[0216] The supply part (210) may include a temperature control unit. The plurality of supply segments (211) may include one or more segments that are independently temperature-controlled.

[0217] The plurality of storage segments (130) of the storage device (100) and the plurality of supply segments (211) of the supply part (210) may be arranged side by side in the first direction. One or more storage segments (130) and one or more supply segments (211) may be provided to match each other. The matched storage segments (130) and supply segments (211) may be positioned at the shortest distance, for example, aligned along the same line in the second direction.

[0218] According to one embodiment, the supply segments (211) may include: a supply segment (2111) for racks holding magnetic rod sleeves, a supply segment (2112) for plates containing magnetic beads, a supply segment (2113) for plates containing washing buffer 1, a supply segment (2114) for plates containing washing buffer 2, a supply segment (2115) for plates containing distilled water (D.W.) used for magnetic beads, a supply segment (2116) for plates containing elution buffer.

[0219] According to one embodiment, the extraction part (220) may receive materials from the supply part (210) and perform the extraction process. The extraction part (220) may be configured to selectively perform two or more extraction processes. When samples with different extraction protocols are provided to a single extraction part (220), the extraction part (220) may be configured to perform the extraction protocol corresponding to each sample.

[0220] The extraction part (220) may include a plurality of process stations (222: 222a-222e). Each process station (222) may perform one or more extraction processes. Some process stations (222) may perform two or more extraction processes sequentially or selectively.

[0221] Each process station (222) may include a plate fixing unit for securing the plate. The plate fixing unit may adopt a clamp structure. The plate fixing unit may include a structure for positioning the plate and a structure for preventing vertical displacement of the plate. The positioning structure may allow the plate to be guided into the correct position even if the plate transfer unit places it slightly off-center.

[0222] Some process stations (222) may include agitation or thermal control functions.

[0223] The agitation function may include magnetic mixing, shaking, or ultrasonic mixing. Magnetic mixing involves rotating or vibrating a magnet beneath the plate to rotate magnetic beads inside the plate. Shaking involves applying horizontal or rotational vibration to the plate at a specific frequency. Ultrasonic mixing involves applying ultrasound to the plate to generate microbubbles in the liquid within the wells for mixing.

[0224] The thermal control function may include: heating or cooling using a Peltier element, heating using a film heater, heating using an infrared lamp (IR lamp), heating using a heat pipe. Thermal control may be applied to the block on which the plate is placed or to the lid covering the plate.

[0225] According to one embodiment, the plate transfer unit (240) may be used to transfer sample plates, bead plates, and reagent plates. The plate transfer unit (240) may be combined with an orthogonal axis transfer mechanism and may move in a first direction and a second direction.

[0226] The plate transfer unit (240) may include a plate gripper for gripping the plate and plate transfer rails (241, 242) for horizontally moving the gripper. The plate transfer rails may include a first direction rail (241) and a second direction rail (242). For example, the plate gripper may move along the first direction rail (241) to travel between process stations, and along the second direction rail (242) to travel between the supply part (210) and the extraction part (220).

[0227] According to one embodiment, the magnetic unit (250) may be used to separate and purify biomolecules such as nucleic acids and proteins via magnetic beads. The magnetic unit (250) may include 96 magnetic rods corresponding to the standard 96-well plate, and may simultaneously capture and hold magnetic beads using the magnetic rods.

[0228] The magnetic unit (250) may be combined with an orthogonal axis transfer mechanism and may move between multiple process stations arranged within the device. This enables a bead transfer method, where only the magnetic beads are transferred to the next process well, rather than moving the sample solution.

[0229] The magnetic unit (250) may include a magnetic head containing magnetic rods and magnetic transfer rails (251, 252) for horizontally moving the magnetic head.

[0230] The magnetic head may include a plurality of magnetic rods. For example, the magnetic head may include 96 magnetic rods arranged in an 8×12 array corresponding to the positions of the wells in a 96-well plate.

[0231] Each magnetic rod may include a high-strength permanent magnet at its tip or inside, or the rod itself may be made of a magnetic material. The magnetic rod generates a magnetic field to quickly and strongly capture magnetic beads inside the wells. The magnetic rods may be used in combination with disposable magnetic rod sleeves, which cover the outer surface of the rods to prevent direct contact with sample solutions and thereby prevent cross-contamination.

[0232] The magnetic head may further include a lifting drive unit that moves the magnetic rods vertically (Z-axis). The lifting drive unit may perform operations such as descending to capture magnetic beads, ascending, descending to release them at the target station, and ascending again.

[0233] The magnetic transfer rails may include a first direction rail (251) and a second direction rail (252). For example, the magnetic head may move along the first direction rail (251) between process stations, and along the second direction rail (252) between the supply part (210) and the extraction part (220).

[0234] The magnetic head may be mounted on a transfer system that allows precise movement in the first and second directions. The transfer system may include one or more step motors or servo motors, and a belt-pulley system, ball screw, or linear motor for power transmission. The transfer system moves the magnetic head (and the magnetic beads captured therein) to a preset coordinate, i.e., the exact location of each process station where different processes (e.g., binding, washing 1, washing 2, elution) are performed, according to signals from the controller.

[0235] The magnetic beads, while collected by the magnetic unit (250), may be transferred from a reagent plate at one process station (222) to a reagent plate located at another process station (222), based on the relative movement between the magnetic unit (250) and the process stations.

[0236] In one example, the magnetic unit (250) may be movable, and the process stations (222) may be fixed. As the magnetic unit (250) may move from a previous process station to a next process station, the magnetic beads may be transferred between different reagent plates.

[0237] In another example, the process stations (222) may be movable, and the magnetic unit (250) may be fixed. The process stations (222) may move along a circular path, such that when the magnetic unit (250) has captured magnetic beads from a first reagent plate at a previous process station, the process station may move so that a second reagent plate at the next process station is positioned beneath the magnetic unit (250).

[0238] The automation system for nucleic acid extraction (10) may be arranged such that the storage device (100) and the extraction device (200) are aligned in the second direction. The plurality of extraction modules (201) within the extraction device (200) may also be arranged in the second direction. Alternatively, some extraction modules (201) within the extraction device (200) may be continuously connected in the first direction.

[0239] According to one embodiment, the extraction device (200) may include a waste bin (229) for discarding materials. The waste bin (229) may be provided separately for different types of materials. For example, separate waste bins may be provided for discarding spin tips and plates.

[0240] The waste bin (229) may be positioned adjacent to the extraction part (220), allowing used materials in the extraction part (220) to be discarded quickly. For example, the waste bin (229) may be located between the supply part (210) and the extraction part (220). Multiple waste bins (229), separated by material type, may be arranged in the first direction. Alternatively, the waste bin (229) may be located within the extraction part (220), for example, aligned with the process stations (222) or positioned between the process stations (222).

[0241] An additional waste bin (260) may be provided between the storage device (100) and the supply part (210). The waste bin (260) may extend in the first direction and receive discarded materials from the plurality of storage segments (130) or supply segments (211).

[0242] The controller (400) may include a storage device control unit, a transfer unit control unit, and an extraction device control unit. When multiple extraction modules (201) are provided, the extraction device control unit may include multiple control parts. Even if some of the extraction modules (201-1, 201-2) are malfunctioning or under maintenance, the control part responsible for the operating extraction module (201) may continue to function normally.

[0243]

[0244] According to one embodiment, the automation system for nucleic acid extraction (10) is configured to enable continuously loading. The term "continuously loading" refers to a state in which, within a single extraction part (220), the second extraction process for a second sample is being prepared or is in progress before the first extraction process for a first sample is completed. In a broad sense, continuously loading includes loading a second sample into the extraction part (220) before the first extraction process for the first sample is completed. In a narrow sense, continuously loading refers to starting the second extraction process for the second sample before the first extraction process for the first sample is completed within the same extraction part (220).

[0245] The controller (400) may control the system such that, while a nucleic acid extraction process is being performed on a first sample plate at one process station (222), another process station (222) receives a second sample plate for performing an extraction process. Furthermore, the controller (400) may control the system to start a subsequent process before the ongoing nucleic acid extraction process in the extraction part (220) is completed.

[0246] The controller (400) may control the plate transfer unit (240) to prepare a reagent plate on a subsequent process station before the operation of the subsequent process station, and to discard the used reagent plate on the current process station into the waste bin (229) after the operation of the current process station. To implement continuously loading, a reagent plate must be pre-positioned on the subsequent process station, and a new reagent plate must be prepared on the process station where the operation has ended. The plate transfer unit (240) prepares the required reagent plate in advance on the process station and discards the used reagent plate into the waste bin after the process is completed. The plate transfer unit (240) also prepares the required reagent plate in advance on an empty process station.

[0247] The supply part (210) is configured to supply a plurality of reagent plate sets according to the sample type. For example, the plurality of reagent plate sets may be placed on a tray. Based on the sample information of the sample plate provided to the loading station (221), the controller (400) selects an extraction protocol corresponding to the sample type from among a plurality of pre-stored extraction protocols, and selects a reagent plate set required for the selected extraction protocol. The controller (400) then selects the process stations required to perform the selected extraction protocol and controls the plate transfer unit (240) to deliver the selected reagent plate set to the selected process stations. The controller (400) sequentially controls the selected process stations according to the selected extraction protocol.

[0248]

[0249] Next, the extraction method of the automation system for nucleic acid extraction (10) according to the first embodiment will be described.

[0250] The first transfer unit (310) moves along the transfer rail (311) extending in the second direction while holding a sample plate, and places the sample plate on the loading station (221). The first transfer unit (310) may transfer the sample plate from the loading station (221) to the first buffer station (226). This transfer may be performed by the first transfer unit (310) or the plate transfer unit (240). The first transfer unit (310) may move in the first direction to transfer the sample plate to the first buffer station (226), or may push the sample plate using a pusher to move it to the first buffer station (226). When the first process station (222a) becomes vacant, the plate transfer unit (240) transfers the sample plate from the first buffer station (226) to the first process station (222a).

[0251] Alternatively, if the first process station (222a) is vacant, the plate transfer unit (240) may directly transfer the sample plate from the loading station (221) to the first process station (222a).

[0252] The plate transfer unit (240) picks up reagent plates from the supply segment (211) of the supply part (210) and delivers them to the second to fifth process stations (222b-222e) of the extraction part (220). Specifically, the plate transfer unit (240) picks up a plate containing wash buffer 1 from supply segment (2113) and transfers it to the second process station (222b), picks up a plate containing wash buffer 2 from supply segment (2114) and transfers it to the third process station (222c), picks up a plate containing distilled water from supply segment (2115) and transfers it to the fourth process station (222d), and picks up a plate containing elution buffer from supply segment (2116) and transfers it to the fifth process station (222e).

[0253] The plate transfer unit (240) discards the used reagent plates or sample plates from the process stations (222) into the waste bin (229).

[0254] The magnetic unit (250) of the extraction device (200) mounts a magnetic rod sleeve from a rack stored in supply segment (2111) of the supply part (210). The magnetic unit (250) picks up magnetic beads from a plate stored in supply segment (2112) and delivers them to the sample plate on the first process station (222a).

[0255] According to one embodiment, the first process station (222a) may perform one or more functions among shaking and heating. The first process station (222a) may selectively or sequentially perform shaking and heating, or perform both simultaneously.

[0256] After the lysis and binding steps are completed at the first process station (222a), nucleic acids in the sample plate are bound to the magnetic beads. The magnetic unit (250) generates a magnetic field on the sample plate at the first process station (222a) to bind the magnetic beads to the magnetic rod, and then transfers them to the reagent plate on the second process station (222b).

[0257] The plate transfer unit (240) discards the sample plate from the first process station (222a) into the waste bin (229), and delivers a new sample plate waiting at the loading station (221) or the first buffer station (226) to the first process station (222a).

[0258] The reagent plate on the second process station (222b) contains wash buffer 1, and the magnetic beads are transferred from the magnetic rod. The second process station (222b) may perform one or more functions among shaking and incubation. It may selectively or sequentially perform shaking and incubation, or perform both simultaneously.

[0259] After the first wash step is completed at the second process station (222b), the magnetic unit (250) transfers the magnetic beads to the reagent plate on the third process station (222c). The plate transfer unit (240) discards the reagent plate from the second process station (222b) into the waste bin (229), and delivers a new reagent plate to the second process station (222b).

[0260] The reagent plate on the third process station (222c) contains wash buffer 2, and the magnetic beads are transferred from the magnetic rod. The third process station (222c) may perform one or more functions among shaking and incubation. It may selectively or sequentially perform shaking and incubation, or perform both simultaneously.

[0261] After the second wash step is completed at the third process station (222c), the magnetic unit (250) transfers the magnetic beads to the reagent plate on the fourth process station (222d). The plate transfer unit (240) discards the reagent plate from the third process station (222c) into the waste bin (229), and delivers a new reagent plate to the third process station (222c).

[0262] The reagent plate on the fourth process station (222d) contains distilled water, and the magnetic beads are transferred from the magnetic rod. The fourth process station (222d) may perform one or more functions among shaking and incubation. It may selectively or sequentially perform shaking and incubation, or perform both simultaneously.

[0263] The distilled water wash process at the fourth process station (222d) may be selectively performed. Whether the process at the fourth process station (222d) is performed depends on the type of sample in the sample plate. If the process at the fourth process station (222d) is not required, the magnetic rod may move directly from the third process station (222c) to the fifth process station (222e).

[0264] After the distilled water wash step is completed at the fourth process station (222d), the magnetic unit (250) transfers the magnetic beads to the reagent plate on the fifth process station (222e). The plate transfer unit (240) discards the reagent plate from the fourth process station (222d) into the waste bin (229), and delivers a new reagent plate to the fourth process station (222d).

[0265] The reagent plate on the fifth process station (222e) contains elution buffer, and the magnetic beads are transferred from the magnetic rod. The fifth process station (222e) may perform one or more functions among shaking and heating. It may selectively or sequentially perform shaking and heating, or perform both simultaneously.

[0266] After the elution step is completed at the fifth process station (222e), the nucleic acids are separated from the magnetic beads. The plate transfer unit (240) transfers the processing plate containing the extracted nucleic acids to the second buffer station (227) or the completion station (228).

[0267] The magnetic unit (250) discards the magnetic rod sleeve into the waste bin (229).

[0268] When the completion station (228) is ready, the plate transfer unit (240) transfers the reagent plate from the second buffer station (227) to the completion station (228). The reagent plate on the completion station (228) may be transferred to a PCR setup device or returned to the storage device (100).

[0269]

[0270] FIG. 3 illustrates an embodiment in which the extraction part in FIG. 2 is configured in a modular manner.

[0271] The extraction part may be modularly configured with at least two or more extraction parts.

[0272] The first extraction part (220-1) and the second extraction part (220-2) may be arranged in parallel or side by side. Each of the first extraction part (220-1) and the second extraction part (220-2) includes a loading station (221-1, 221-2), respectively. When the first transfer unit (310) loads a sample plate onto the first loading station (221-1), the extraction process is performed in the first extraction part (220-1). When the first transfer unit (310) loads a sample plate onto the second loading station (221-2), the extraction process is performed in the second extraction part (220-2).

[0273] The first extraction part (220-1) and the second extraction part (220-2) may share the supply part (210) and the plate transfer unit (240). Each of the first extraction part (220-1) and the second extraction part (220-2) may include a magnetic unit (250-1, 250-2).

[0274] The extraction part may be modularly configured with at least two or more extraction parts that perform different extraction protocols. The first extraction part (220-1) and the second extraction part (220-2) may perform extraction processes according to different sample types. The controller may be configured to determine one extraction protocol from among a plurality of extraction protocols based on identification information of the sample transferred by the first transfer unit (310), and to match the sample to the extraction part that performs the determined extraction protocol.

[0275] Referring to FIG. 3, a sample plate for a first type of sample is loaded onto the first loading station (221-1), and a sample plate for a second type of sample is loaded onto the second loading station (221-2). The first extraction part (220-1) and the second extraction part (220-2) independently perform their respective extraction protocols.

[0276] In the first extraction part (220-1), a protocol step is in progress at the first process station (222a-1), and a sample plate is loaded onto the first loading station (221-1). In the second extraction part (220-2), a protocol step is in progress at the fourth process station (222d-1), and a sample plate is placed on the second buffer station (226-2).

[0277]

[0278] FIG. 4 illustrates an embodiment in which the first transfer unit is omitted from FIG. 2.

[0279] In one embodiment, the automation system for nucleic acid extraction may not include a transfer unit for loading sample plates. The sample plate may be manually loaded by an operator or loaded by a transfer unit of a preprocessing device.

[0280]

[0281] FIG. 5 illustrates an embodiment in which the storage device is omitted from FIG. 2.

[0282] In one embodiment, the automation system for nucleic acid extraction may not include a separately provided storage device. In this case, the supply part (210) may store reusable materials and function as a storage unit.

[0283]

[0284] FIG. 6 illustrates an embodiment in which a plurality of magnetic units are provided.

[0285] In one embodiment, the automation system for nucleic acid extraction may include two or more magnetic units (250a, 250b) in a single extraction part. Each magnetic unit (250a, 250b) performs a single extraction protocol for the same sample, but performs different protocol steps.

[0286] Referring to the drawing, the first magnetic unit (250a) performs protocol steps for the first and second process stations (222a, 222b), and the second magnetic unit (250b) performs protocol steps for the third to fifth process stations (222c, 222d, 222e).

[0287]

[0288] FIG. 7 is a modified embodiment of FIG. 6.

[0289] In one embodiment, the automation system for nucleic acid extraction may include two or more magnetic units (250a, 250b) in a single extraction part. Each magnetic unit (250a, 250b) performs an extraction protocol for a different sample. The magnetic units (250a, 250b) move in a manner that prevents interference with each other. For example, the magnetic units may move along a circular path.

[0290] Referring to the drawing, for the first sample, a protocol step is in progress at the fourth process station (222d), and the second magnetic unit (250b) performs the extraction protocol for the first sample. For the second sample, a protocol step is in progress at the first process station (222a), and the first magnetic unit (250a) performs the extraction protocol for the second sample.

[0291]

[0292] FIG. 8 illustrates an embodiment in which an opening unit is provided.

[0293] In one embodiment, the automation system for nucleic acid extraction may further include an opening unit (270) capable of opening a film or cap of a reagent plate. The opening unit (270) includes a peeler or a puncher and may be positioned adjacent to the supply part (210).

[0294] Additionally, in one embodiment, the first process station (222a) may serve as the loading station (221). The loading station (221) may not be separately provided, and the sample plate may be directly loaded onto the first process station (222a). In this case, the station onto which the sample plate is loaded may be referred to as either the loading station (221) or the first process station (222a), depending on the context. That is, this disclosure is not limited to a configuration in which the loading station (221) is provided separately from the process station (222).

[0295]

[0296] FIG. 9 illustrates an embodiment in which the supply part and the extraction part are spatially separated.

[0297] In one embodiment, the automation system for nucleic acid extraction may be configured such that the supply part (210) and the extraction part (220) are spatially separated. The term "spatially separated" includes both separation within a single device and separation into distinct devices.

[0298] The supply part (210) may include a transfer station (245). The third transfer unit (243) picks up materials from the supply segment (211) and places them onto the transfer station (245). The fourth transfer unit (244) picks up the materials placed on the transfer station (245) and transfers them to the required process station (222). In this case, the transfer station (245) may be located within the extraction part (220) or in a separate space between the supply part (210) and the extraction part (220).

[0299] Additionally, the transfer station (245) is not limited to a station for placing materials. For example, the fourth transfer unit (244) may receive materials directly from the third transfer unit (243) while the third transfer unit (243) is holding the materials.

[0300]

[0301] FIG. 10 is a modified embodiment of FIG. 9.

[0302] In one embodiment, the automation system for nucleic acid extraction may include two or more magnetic units (250a, 250b) in a single extraction part. Each magnetic unit (250a, 250b) performs an extraction protocol for a different sample. The magnetic units (250a, 250b) move in a manner that prevents interference with each other. For example, the magnetic units may move along a circular path.

[0303] Referring to the drawing, for the first sample, a protocol step is in progress at the third process station (222c), and the second magnetic unit (250b) performs the extraction protocol for the first sample. The sample plate containing the second sample is loaded onto the loading station (221) and is in a pre-processing state, while the first magnetic unit (250a) is moving toward the first process station (222a).

[0304] Additionally, in one embodiment, the automation system for nucleic acid extraction may include two or more buffer stations (226a, 226b). Providing multiple buffer stations can significantly prevent bottlenecks in the flow of sample plates.

[0305]

[0306] [Second Embodiment]

[0307] FIG. 11 is a conceptual diagram illustrating the connection structure of the automation system for nucleic acid extraction according to the second embodiment, and FIG. 12 is a conceptual diagram illustrating the planar layout of the system.

[0308] The automation system for nucleic acid extraction (11) according to the second embodiment includes a dispensing unit (230). The supply part (210) supplies empty deep-well plates and reagents contained in reagent tubes.

[0309] The dispensing unit (230) aspirates a predetermined amount of reagent from the reagent tube and dispenses it into each well of an empty deep-well plate or a sample plate. The timing of dispensing reagents into the empty deep-well plate may be before or after the plate is transferred to the process station (222). Preferably, to minimize the movement path of the pipette, it is desirable to dispense the reagent before the empty deep-well plate is transferred to the process station (222). In this case, the dispensing unit (230) only needs to move in the first direction over the supply part (210) to dispense the reagent. Conversely, if the reagent is dispensed after the empty deep-well plate is transferred to the process station (222), the dispensing unit (230) must move in both the first and second directions to travel from the supply part (210) to the extraction part (220).

[0310] The dispensing unit (230) may dispense reagents only into the necessary wells of the plate. Compared to the first embodiment, the automation system for nucleic acid extraction (11) of the second embodiment has the advantage of saving reagents when there are wells in the sample plate that do not contain samples. For example, if only 48 or fewer wells of a 96-well plate contain samples, the system (10) of the first embodiment must use a single-use reagent plate, resulting in more than half of the reagents being discarded unused. However, the system (11) of the second embodiment can dispense reagents only into wells containing samples or into corresponding wells of an empty deep-well plate.

[0311] The dispensing unit (230) may include multiple dispensing channels. It may branch a single pneumatic line into multiple channels and perform aspiration or dispensing through each channel by applying negative or positive pressure.

[0312] The dispensing unit (230) includes a movable dispensing unit and a fixed dispensing unit.

[0313] The movable dispensing unit may be implemented in the form of a pipetting head. The pipettor may be coupled to a transport mechanism such as a gantry structure or multi-joint robotic arm, allowing free movement in three-dimensional space. A disposable pipette tip is detachably coupled to the lower end of the pipettor, which fundamentally prevents cross-contamination between reagents or samples. The tip may be loaded from a tip rack provided in the device and ejected into a disposal area.

[0314] The movable dispensing unit may be configured as a single-channel head or a multi-channel head. The multi-channel head may consist of 8 or 12 channels and can dispense reagents simultaneously into one row or column of a deep-well plate, thereby reducing processing time.

[0315] The fixed dispensing unit has the form of a dedicated dispensing station. It is fixedly installed above a specific point along the transport path of the deep-well plate. Unlike the movable dispensing unit that actively moves to the DWP, in the fixed dispensing unit, the DWP must move beneath the dispensing unit.

[0316] The fixed dispensing unit includes a nozzle manifold having multiple fixed nozzles corresponding one-to-one or in groups to the well arrangement of the deep-well plate. Each nozzle (or nozzle group) is connected via tubing to an external bulk reagent container. The precise supply of reagents is controlled by a solenoid valve system that opens and closes the flow path and a metering pump connected upstream of the nozzle manifold.

[0317] Compared to the movable dispensing unit, the fixed dispensing unit does not use disposable tips, reducing consumable costs and is advantageous for high-throughput processing.

[0318] The drawings of the present specification illustrate a movable dispensing unit.

[0319] The dispensing unit (230) may move along transfer rails, which include a first direction rail (231) and a second direction rail (232). For example, the dispensing unit (230) may move along the first direction rail (231) to approach the target material or process station, and move along the second direction rail (232) to travel between the supply part (210) and the extraction part (220).

[0320] In the second embodiment, only samples may be provided to the sample plate loaded onto the loading station (221). After the sample plate containing the sample is transferred from the loading station (221) to the first process station (222a), the required reagents may be dispensed into the sample plate.

[0321] According to one embodiment, the dispensing unit (230) may aspirate reagents from the supply part (210) and dispense them into the sample plate located at the first process station (222a). The reagents delivered to the sample plate may include PK, IC, lysis buffer, and binding buffer.

[0322] According to another embodiment, the dispensing unit (230) may aspirate reagents from the supply part (210) and dispense them into empty deep-well plates located at the second to fifth process stations (222b-222e). The reagent provided to the second process station (222b) may be wash buffer 1, to the third process station (222c) may be wash buffer 2, to the fourth process station (222d) may be distilled water, and to the fifth process station (222e) may be elution buffer.

[0323] The materials stored in the storage device (100) may include empty deep-well plates, dispensing unit tips, magnetic rod sleeves, reagent tubes, magnetic beads, and distilled water. The reagent tubes may include tubes containing PK, IC, lysis buffer, binding buffer, wash buffer 1, wash buffer 2, distilled water, and elution buffer. These reagent tubes may contain multi-dose reagents and be used multiple times.

[0324] According to one embodiment, the storage segment (130) may include: a storage segment (1301) for racks holding magnetic rod sleeves, a storage segment (1302) for plates containing magnetic beads, a storage segment (1312) for tip racks with tips of a first diameter, a storage segment (1313) for tip racks with tips of a second diameter, a storage segment (1309) for PK, a storage segment (1310) for IC, a storage segment (1307) for lysis buffer, a storage segment (1308) for binding buffer, a storage segment (1311) for empty deep-well plates, a storage segment (1303) for wash buffer 1, a storage segment (1304) for wash buffer 2, a storage segment (1305) for distilled water used with magnetic beads, and a storage segment (1306) for elution buffer.

[0325] In this specification, the term "empty deep-well plate" is used to distinguish it from a sample plate containing samples. It refers to a plate in an empty state. Hereinafter, the term "plate" will be used to collectively refer to both empty deep-well plates and sample plates.

[0326] The tip may be detachably coupled to the dispensing unit (230). While the tip is coupled to the dispensing unit (230), it may aspirate and dispense liquid within the plate. For example, it may aspirate reagents from the supply part (210) and dispense them into the empty deep-well plate in the extraction part (220).

[0327] In this specification, the term "reagent" may be used to exclude magnetic beads. Reagents may include PK (Proteinase K), IC (Internal Control), lysis buffer, binding buffer, washing buffer, and elution buffer. PK is an enzyme that digests proteins during nucleic acid extraction, and IC is a control used to verify accuracy and reliability. PK and IC may be provided in bead or liquid form. Hereinafter, it is assumed that PK and IC are provided in liquid form.

[0328]

[0329] The extraction module (201) may include the supply part (210), extraction part (220), dispensing unit (230), plate transfer unit (240), magnetic unit (250), and controller (400).

[0330] The materials stored in the supply part (210) may include empty deep-well plates, dispensing unit tips, magnetic rod sleeves, reagent tubes, magnetic beads, and distilled water. The reagent tubes may include tubes containing PK, IC, lysis buffer, binding buffer, wash buffer 1, wash buffer 2, distilled water, and elution buffer. These reagent tubes may contain multi-dose reagents and be used multiple times.

[0331] According to one embodiment, the supply segment (211) may include: a supply segment (2111) for racks holding magnetic rod sleeves, a supply segment (2112) for plates containing magnetic beads, a supply segment (2122) for tip racks with tips of a first diameter, a supply segment (2123) for tip racks with tips of a second diameter, a supply segment (2119) for plates containing PK, a supply segment (2120) for plates containing IC, a supply segment (2117) for plates containing lysis buffer, a supply segment (2118) for plates containing binding buffer, a supply segment (2121) for empty deep-well plates, a supply segment (2113) for plates containing wash buffer 1, a supply segment (2114) for plates containing wash buffer 2, a supply segment (2115) for plates containing distilled water used with magnetic beads, and a supply segment (2116) for plates containing elution buffer.

[0332] The dispensing unit (230) of the extraction device (200) mounts tips from the supply segments (2122, 2123) of the supply part (210). It aspirates reagents from the supply segments (2113, 2114, 2115, 2116, 2117, 2118, 2119, 2120) and delivers them to the plates on the process stations (222a-222e) of the extraction part (220). After use, the dispensing unit (230) discards the tips into the waste bin (229).

[0333]

[0334] According to one embodiment, the extraction device (200) may include a waste bin (229) for discarding materials. The waste bin (229) may be provided separately for each type of material. For example, separate waste bins may be provided for spin tips, pipette tips, and plates. Additionally, waste bins may be distinguished by tip type, such as a waste bin for 300 μL tips and another for 1000 μL tips.

[0335]

[0336] FIG. 13 is a modified embodiment of FIG. 12. The embodiments shown in FIGs. 12 and 13 differ in the location of the waste bin (229).

[0337] In the system shown in FIG. 12, the waste bin (229) is located in the space between the supply part (210) and the extraction part (220). Additionally, some waste bins (229) may be located within the extraction part (220). For example, a waste bin (229) for discarding spin tips, which are frequently used by the magnetic unit (250), may be provided in the extraction part (220). The waste bin (229) for spin tips may be located between the first buffer station (226) and the first process station (222a), and may be arranged in a single row alongside the first buffer station (226) and the first process station (222a). When the process stations (222) and waste bins (229) are arranged in a single row, the processing plate (240) or magnetic unit (250) can simultaneously perform transfer and disposal while moving in the first direction, thereby simplifying the movement path.

[0338] In the system shown in FIG. 13, the waste bins (229) may be located within the extraction part (220). The waste bins (229) may be located between process stations (222) or between the first buffer station (226) and the first process station (222a). The waste bins (229) may be arranged in a single row alongside the first buffer station (226) and the first to fifth process stations (222a-222e).

[0339] For example, between the first buffer station (226) and the first process station (222a), waste bins (229) for spin tips, tips of the first diameter, tips of the second diameter, and plates may be located. Between the first process station (222a) and the second process station (222b), a waste bin (229) for plates may be located. Between the third process station (222c) and the fourth process station (222d), a waste bin (229) for plates may be located. Between the second buffer station (227) and the completion station (228), a waste bin (229) for plates may be located.

[0340]

[0341] Next, a method of extraction by the automation system for nucleic acid extraction (11) according to a second embodiment will be described.

[0342] The first transfer unit (310), while holding a sample plate, moves along the transfer rail (311) extending in the second direction and places the sample plate on the loading station (221).

[0343] Then, the first transfer unit (310) may transfer the sample plate from the loading station (221) to the first buffer station (226). At this time, the transfer of the sample plate may be performed by the first transfer unit (310) or the plate transfer unit (240). The first transfer unit (310) may move in the first direction to transfer the sample plate to the first buffer station (226), or may push the sample plate with a pusher to move it to the first buffer station (226).

[0344] When the first process station (222a) becomes vacant, the plate transfer unit (240) transfers the sample plate on the first buffer station (226) to the first process station (222a). Alternatively, if the first process station (222a) is vacant, the plate transfer unit (240) may directly transfer the sample plate from the loading station (221) to the first process station (222a).

[0345] The plate transfer unit (240) receives a plate from the supply segment (2121), which stores empty deep-well plates of the supply part (210), and delivers it to the second to fifth process stations (222b-222e) of the extraction part (220). Then, the dispensing unit (230) aspirates PK from the supply segment (2119) containing PK and delivers it to the sample plate on the first process station (222a); aspirates IC from the supply segment (2120) containing IC and delivers it to the sample plate on the first process station (222a); aspirates lysis buffer from the supply segment (2117) containing lysis buffer and delivers it to the sample plate on the first process station (222a); and aspirates binding buffer from the supply segment (2118) containing binding buffer and delivers it to the sample plate on the first process station (222a).

[0346] The dispensing unit (230) aspirates wash buffer 1 from the supply segment (2113) containing wash buffer 1 and delivers it to the empty deep-well plate on the second process station (222b); aspirates wash buffer 2 from the supply segment (2114) containing wash buffer 2 and delivers it to the empty deep-well plate on the third process station (222c); aspirates distilled water from the supply segment (2115) containing distilled water and delivers it to the empty deep-well plate on the fourth process station (222d); and aspirates elution buffer from the supply segment (2116) containing elution buffer and delivers it to the empty deep-well plate on the fifth process station (222e).

[0347] The plate transfer unit (240) discards the used plates from the process stations (222) into the waste bin (229).

[0348] The magnetic unit (250) of the extraction device (200) mounts a rod sleeve from the supply segment (2111), which stores a rack holding magnetic rod sleeves of the supply part (210). The magnetic unit (250) receives magnetic beads from the plate stored in the supply segment (2112), which contains magnetic beads of the supply part (210), and delivers them to the sample plate on the first process station (222a).

[0349] According to one embodiment, the first process station (222a) may perform one or more functions among shaking and heating. The first process station (222a) may selectively or sequentially perform shaking and heating, or may perform shaking and heating simultaneously.

[0350] When the lysis and binding steps are completed at the first process station (222a), nucleic acids in the sample plate bind to the magnetic beads. The magnetic unit (250) generates a magnetic field on the magnetic rod in the sample plate on the first process station (222a) to bind the magnetic beads, and then transfers them to the plate on the second process station (222b).

[0351] The plate transfer unit (240) discards the sample plate on the first process station (222a) into the waste bin (229), and delivers a new sample plate waiting at the loading station (221) or the first buffer station (226) to the first process station (222a).

[0352] The plate on the second process station (222b) contains wash buffer 1, and the magnetic beads are transferred from the magnetic rod. The second process station (222b) may perform one or more functions among shaking and incubation. The second process station (222b) may selectively or sequentially perform shaking and incubation, or may perform shaking and incubation simultaneously.

[0353] When the first wash step is completed at the second process station (222b), the magnetic unit (250) transfers the magnetic beads to the plate on the third process station (222c). The plate transfer unit (240) discards the plate on the second process station (222b) into the waste bin (229), and delivers a new plate to the second process station (222b).

[0354] The plate on the third process station (222c) contains wash buffer 2, and the magnetic beads are transferred from the magnetic rod. The third process station (222c) may perform one or more functions among shaking and incubation. The third process station (222c) may selectively or sequentially perform shaking and incubation, or may perform shaking and incubation simultaneously.

[0355] When the second wash step is completed at the third process station (222c), the magnetic unit (250) transfers the magnetic beads to the plate on the fourth process station (222d). The plate transfer unit (240) discards the plate on the third process station (222c) into the waste bin (229), and delivers a new plate to the third process station (222c).

[0356] The plate on the fourth process station (222d) contains distilled water, and the magnetic beads are transferred from the magnetic rod. The fourth process station (222d) may perform one or more functions among shaking and incubation. The fourth process station (222d) may selectively or sequentially perform shaking and incubation, or may perform shaking and incubation simultaneously.

[0357] The distilled water washing process at the fourth process station (222d) may be selectively performed. Whether the process at the fourth process station (222d) is performed depends on the type of sample in the sample plate. If the process at the fourth process station (222d) is not required, the magnetic rod may move from the third process station (222c) to the fifth process station (222e).

[0358] When the distilled water washing step is completed at the fourth process station (222d), the magnetic unit (250) transfers the magnetic beads to the plate on the fifth process station (222e). The plate transfer unit (240) discards the plate on the fourth process station (222d) into the waste bin (229), and delivers a new plate to the fourth process station (222d).

[0359] The plate on the fifth process station (222e) contains elution buffer, and the magnetic beads are transferred from the magnetic rod. The fifth process station (222e) may perform one or more functions among shaking and heating. The fifth process station (222e) may selectively or sequentially perform shaking and heating, or may perform shaking and heating simultaneously.

[0360] When the elution step is completed at the fifth process station (222e), nucleic acids are separated from the magnetic beads. The plate transfer unit (240) transfers the processing plate containing the extracted nucleic acids to the second buffer station (227) or the completion station (228).

[0361] The magnetic unit (250) discards the magnetic rod sleeve into the waste bin (229).

[0362] When the completion station (228) becomes ready, the plate transfer unit (240) transfers the plate from the second buffer station (227) to the completion station (228). The plate on the completion station (228) may be transferred to a PCR setup device or returned to the storage device (100).

[0363]

[0364] The above description merely explains the idea of the present disclosure and the present disclosure may be changed and modified in various ways without departing from the scope of the present disclosure by those of skill in the art. Accordingly, the embodiments described herein are provided not to limit, but to merely explain the idea of the present disclosure, and the idea of the present disclosure is not limited by the embodiments. The scope of the present disclosure should be construed by the following claims, and all technical ideas within the equivalent scope should be construed as being included in the scope of the present disclosure.

Claims

1.A high-throughput, continuously loadable automation system for nucleic acid extraction comprising:a loading station configured to receive a sample plate containing a plurality of samples;a supply part configured to provide a plurality of reagent plates with a pre-filled reagent and (ii) magnetic beads;an extraction part comprising at least three process stations for extracting nucleic acids;a plate transfer unit configured to transfer one of the reagent plates from the supply part to one of the process stations;a magnetic unit comprising a plurality of magnetic rods to generate magnetic force for collecting the magnetic beads; anda controller;wherein the magnetic beads, while being collected by the magnetic unit, are transferred from a reagent plate on one process station to a reagent plate on another process station via relative movement between the magnetic unit and the process stations, andwherein the controller controls the automation system such that, while a nucleic acid extraction process is in progress for a first sample plate in one process station, another process station receives a second sample plate to perform a subsequent extraction process therefor.2.The system of claim 1, wherein the magnetic beads, while being collected by the magnetic unit, are transferred from a reagent plate on one process station to a reagent plate on another process station via relative movement between the magnetic unit and the process stations, andwherein the controller controls the automation system such that, while a nucleic acid extraction process is in progress for a first sample plate in one process station, another process station receives a second sample plate to perform a subsequent extraction process therefor.3.The system of claim 1, further comprising a waste bin for discarding used reagent plates from the process stations,wherein the controller controls the plate transfer unit such that the reagent plate is prepared on a subsequent process station before an operation of the subsequent process station, and the used reagent plate on a current process station is discarded into the waste bin after the operation of the current process station.4.The system of claim 1, wherein the supply part is configured to provide a plurality of reagent plate sets according to sample types, andwherein the controller is configured to:select, based on sample information of the sample plate provided to the loading station, an extraction protocol corresponding to the sample type and a reagent plate set required therefor from among a plurality of pre-stored extraction protocols corresponding to sample types;select process stations required to perform the selected extraction protocol;control the plate transfer unit to deliver the selected reagent plate set to the selected process stations; andcontrol the selected process stations sequentially according to the selected extraction protocol.5.The system of claim 1, further comprises an opening unit configured to open the film of the reagent plate provided by the supply part, wherein the reagent plate is sealed with the film,wherein the magnetic unit and the opening unit respectively comprise a plurality of elements corresponding to each of wells of the reagent plate.6.The system of claim 1, wherein the loading station receives the sample plate containing a lysis buffer, and the supply part provides a first reagent plate including a wash buffer and a second reagent plate including an elution buffer.7.The system of claim 6, wherein the loading station receives the sample plate further containing a binding buffer.8.The system of claim 1, wherein the plate transfer unit is configured to deliver the sample plate from the loading station to a first process station in the extraction part, andwherein the magnetic unit is configured to transfer the magnetic beads into the sample plate on the first process station.9.The system of claim 8, wherein the plate transfer unit is configured to deliver the reagent plate from the supply part to a second process station in the extraction part, andwherein the magnetic unit is configured to transfer the magnetic beads from the sample plate on the first process station to the reagent plate on the second process station.10.The system of claim 1, wherein the loading station is a first process station that operates first among the process stations, andwherein the magnetic unit is configured to transfer the magnetic beads into the sample plate on the first process station.11.The system of claim 1, further comprising a sample supply unit configured to supply the sample plate to the loading station,wherein the magnetic unit is configured to transfer the magnetic beads into the sample plate on the loading station.12.The system of claim 1, wherein the magnetic unit is configured to move in a first direction along which the process stations are arranged and in a second direction along which the supply part and the extraction part are arranged, and the magnetic unit is configured to transfer the magnetic beads from the supply part to the sample plate on first process station by moving in the second direction, and transfer the magnetic beads to a reagent plate on a subsequent second process station by moving in the first direction.13.The system of claim 1, wherein the magnetic unit further comprises an image sensor configured to generate an image of an area where the magnetic rods descends.14.The system of claim 1, wherein the magnetic unit comprises a first magnetic unit and a second magnetic unit operating within single extraction part.15.The system of claim 14, wherein the first magnetic unit performs preceding steps among the process stations and the second magnetic unit performs subsequent steps among the process stations, andwherein the first magnetic unit and the second magnetic unit move such that their paths do not overlap with each other16.The system of claim 14, wherein the first magnetic unit is configured to sequentially cycle through the process stations, and the second magnetic unit is configured to sequentially cycle through the process stations, following the first magnetic unit.17.The system of claim 1, wherein the process station includes at least one of a function of controlling a temperature of a solution in the sample plate or the reagent plate, and a function of stirring the solution.18.The system of claim 17, wherein the controller is configured to determine a combination of the process stations and sequence of functions performed by the process stations according to the determined extraction protocol.19.The system of claim 1, wherein at least one of the process stations is a multifunctional process station comprising both a temperature control function and a stirring function, and is configured to selectively perform one of the two functions or simultaneously perform both functions.20.The system of claim 19, wherein the controller determines one extraction protocol from among a plurality of extraction protocols based on identification information of the sample received at the loading station, and selects at least on of the temperature control function and the stirring function of the multifunctional process station according to the determined extraction protocol.21.The system of claim 1, further comprising: a storage device configured to store materials including the reagent plates and the magnetic beads provided by the supply part; anda material transfer unit configured to transfer the materials between the storage device and the supply part.22.The system of claim 21, wherein the controller is configured to:determine one extraction protocol from among a plurality of extraction protocols based on identification information of the sample received at the loading station;select the materials required for the determined extraction protocol; andoperate the material transfer unit to pick up the required materials from the storage device and transfer them to the supply part.23.The system of claim 21, wherein the storage device comprises a plurality of storage segments arranged in parallel along a first direction, andwherein the supply part comprises a plurality of supply segments arranged in parallel along the first direction.24.The system of claim 23, wherein the material transfer unit is configured to move in a first direction and a second direction perpendicular to the first direction, to selectively position itself at each of the storage segments or each of the supply segments by moving along the first direction, and to move between the storage device and the supply part by moving along the second direction.25.The system of claim 24, wherein the storage device comprises a storage area for storing materials and a pickup area where the material transfer unit picks up the materials.26.The system of claim 25, wherein the controller is configured to:determine one extraction protocol from among a plurality of extraction protocols based on identification information of the sample received at the loading station;select a required material for the determined extraction protocol;operate the material transfer unit along the first direction to pick up the required material from the pickup area of the storage segment; andoperate the material transfer unit along the second direction to transfer a picked-up material to the supply segment of the supply part.27.The system of claim 23, herein some of the storage segments include a refrigeration function.28.The system of claim 23, wherein the storage segment and the supply segment corresponding to the same material are aligned with each other in a second direction perpendicular to the first direction.29.The system of claim 23, wherein each of the supply segments is in a one-to-one correspondence with each of the storage segments.30.The system of claim 23, wherein the process stations are arranged sequentially and in parallel along the first direction, and the storage segment, the supply segment, and the process station corresponding to a same material are aligned with each other in a second direction perpendicular to the first direction.31.The system of claim 1, wherein the sample plate received at the loading station is a first plate, and the reagent plates comprise a second plate containing a first wash buffer, a third plate containing a second wash buffer, and a fourth plate containing an elution buffer, andwherein the process stations comprise a first process station configured to bind nucleic acids to the magnetic beads in the first plate, a second process station configured to perform first washing in the second plate, a third process station configured to perform second washing in the third plate, and a fourth process station configured to elute nucleic acids from the magnetic beads in the fourth plate.32.The system of claim 1, wherein the process stations of the extraction part are arranged in one direction, andwherein the controller is configured to sequentially operate the process stations to perform the nucleic acid extraction process.33.The system of claim 1, wherein the extraction part is modularly configured with at least two extraction parts, andwherein the controller is configured to: determine one extraction protocol from among a plurality of extraction protocols based on identification information of the sample received at the loading station; and match the sample to the extraction part that performs the determined extraction protocol.34.The system of claim 33, wherein the controller is configured to operate the process stations sequentially according to the determined extraction protocol.35.The system of claim 33, wherein the controller is configured to operate the process stations in a unidirectional sequence according to the determined extraction protocol.36.The system of claim 35, wherein the controller is configured to transfer the magnetic beads sequentially to the process stations according to the determined extraction protocol.37.The system of claim 1, wherein the extraction part is configured to allow a new process station to be added and an existing process station to be replaced, without changing the process stations already disposed.38.The system of claim 1, further comprising a waste bin for discarding the sample plate and reagent plates.39.The system of claim 1, wherein the extraction part further comprises a buffer station, which is located between the loading station and a first process station, and on which the sample plate received at the loading station is placed before moving to the first process station.40.The system of claim 39, wherein the loading station, the buffer station, and the process stations are arranged side-by-side in one direction.41.The system of claim 39, wherein the buffer station includes a multi-position holder configured to align the sample plate.42.The system of claim 39, wherein the plate transfer unit is configured to selectively transfer the sample plate from the loading station to either the buffer station or a first process station that performs an initial process among the process stations.43.The system of claim 39, wherein the control unit is configured to control the plate transfer unit to: i) transfer the sample plate from the loading station to a first process station that performs an initial process among the process stations, when the first process station is empty; and ii) transfer the sample plate from the loading station to the buffer station, when the first process station is occupied.44.The system of claim 1, wherein the plate transfer unit is configured to transfer the sample plate from the loading station to a first process station that performs an initial process among the process stations, andwherein the magnetic unit is configured to transfer the magnetic beads from the supply part to the sample plate on the first process station.45.The system of claim 1, further comprising a transfer station, which is located between the supply part and the extraction part, and on which the reagent plate provided from the supply part is placed,wherein the plate transfer unit is configured to transfer the reagent plate from the transfer station to one of the process stations.46.The system of claim 45, wherein the plate transfer unit comprises: a first plate transfer unit configured to transfer the reagent plate from the supply part to the transfer station; and a second plate transfer unit configured to transfer the reagent plate from the transfer station to one of the process stations.47.A high-throughput, continuously loadable automation system for nucleic acid extraction comprising:a sample supply unit configured to supply a sample plate containing a plurality of samples;a supply part providing (i) a plurality of reagent plates with a pre-filled reagent and (ii) magnetic beads;an extraction part including a series of process stations for extracting nucleic acids;a plate transfer unit configured to transfer one of the reagent plates from the supply part to one of the process stations;a magnetic unit including a plurality of magnetic rods configured to generate magnetic force for collecting the magnetic beads;a waste bin for discarding a used reagent plate; anda controller;wherein the magnetic unit is configured to change a position of the magnetic beads between reagent plates, each disposed on a different one of the process stations, andwherein the controller is configured to:i) initiate a subsequent nucleic acid extraction process before a preceding process is completed in the extraction part; andii) control the plate transfer unit to prepare a reagent plate on a subsequent process station prior to an operation thereof, and to discard the used reagent plate from a current process station into the waste bin subsequent to an operation thereof.48.A high-throughput, continuously loadable automation system for nucleic acid extraction comprising:a loading station configured to receive a sample plate containing a plurality of samples;a supply part providing (i) a plurality of empty plates, (ii) magnetic beads, and (iii) at least one reagents;an extraction part including at least three process stations for extracting nucleic acids;a multi-channel pipette unit;a plate transfer unit configured to transfer one of the empty plates from the supply part to one of the process stations;a magnetic unit including a plurality of magnetic rods configured to generate magnetic force for collecting the magnetic beads; anda controller;wherein the multi-channel pipette unit is configured to transfer one of the reagents from the supply part to the empty plate placed on one of the process stations,wherein the magnetic unit is configured to change a position of the magnetic beads between reagent plates filled with the reagent, each disposed on a different one of the process stations, andwherein the controller is configured to control the automation system such that, while a nucleic acid extraction process is in progress for a first sample plate in one process station, another process station is capable of receiving a second sample plate to perform a nucleic acid extraction process therefor.49.A method for operating a high-throughput, continuously loadable automation system for nucleic acid extraction,the automation system comprising: an extraction part including a series of process stations for extracting nucleic acids; a supply part for supplying a plurality of multi-well plates provided with a pre-filled reagent and magnetic beads; a plate transfer unit; and a magnetic unit, andthe method comprises the steps of:(a) loading a multi-well plate including a sample onto the extraction part;(b) determining an extraction protocol for a sample in the multi-well plate loaded onto the extraction part among a plurality of extraction protocols according to a sample type, and determining a protocol step for each of the process stations to perform the extraction protocol;(c) placing a multi-well plate provided with the reagent, using the plate transfer unit, from the supply part to one of the process stations, wherein the multi-well plate is prepared in state filled with a reagent selected based on the sample;(d) transferring the magnetic beads, using the magnetic unit, from the supply part to the multi-well plate on the process station;(e) changing the position of the magnetic beads, using the magnetic unit, from a first process station, where a protocol step is completed, to a second process station, where a subsequent protocol step will proceed; and(f) discarding used multi-well plate, using the plate transfer unit, from the first process station into a waste bin after the transfer of magnetic beads is completed.50.The method of claim 49, wherein a first multi-well plate including a first sample and a second multi-well plate including a second sample are sequentially loaded onto the extraction part, andwherein, while a first extraction protocol for the first sample proceeds in one process station, a second extraction protocol for the second sample simultaneously proceeds in another process station of the same extraction part.51.The method of claim 50, wherein the supply part is configured to provide a magnetic rod sleeve that is coupled to a magnetic rod of the magnetic unit, andwherein the magnetic unit couples the magnetic rod sleeve before starting the extraction protocol, and discards the magnetic rod sleeve into the waste bin after the extraction protocol is completed.52.The method of claim 51, wherein the first extraction protocol and the second extraction protocol proceeding in the extraction part are performed by a single magnetic unit.53.The method of claim 51, wherein the magnetic unit comprises a first magnetic unit that performs the first extraction protocol and a second magnetic unit that performs the second extraction protocol.54.The method of claim 49, wherein the multi-well plate loaded onto the extraction part in step (a) includes the sample, a lysis buffer, and a binding buffer.55.The method of claim 49, wherein the multi-well plate loaded onto the extraction part comprises the sample in a lysed state, andwherein the supply part is configured to provide multi-well plates respectively containing a wash buffer and an elution buffer.

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