High-throughput, continuously loadable automation system for extracting nucleic acid

Abstract

The present invention relates to a high-throughput nucleic acid extraction automation system, and more particularly to a continuously loadable system including an extraction subsystem having a plurality of extraction units and a controller. In the system, nucleic acid extraction is performed while a sample plate is sequentially transferred among the extraction units. While one extraction unit carries out extraction for a first sample plate, another extraction unit can receive a second sample plate and perform extraction in parallel. This configuration enables continuous sample loading and parallel processing, thereby improving operational efficiency and overall throughput.

Description

HIGH-THROUGHPUT, CONTINUOUSLY LOADABLE AUTOMATION SYSTEM FOR EXTRACTING NUCLEIC ACID

[0001] The present invention relates to a high-throughput nucleic acid extraction automation system. More particularly, the present invention relates to a continuously loadable high-throughput nucleic acid extraction automation system including an extraction subsystem having a plurality of extraction units and a controller.

[0002] Molecular diagnostics is a method of determining the presence or absence of a disease or infection by analyzing biological markers contained in genetic information or proteins within a sample using molecular biological techniques. Because infectious disease diagnosis requires the same type of test to be performed in large quantities when a particular infectious disease is prevalent, a centralized model has mainly been employed, in which specimens collected from local clinics or public health centers are rapidly transported to large-scale testing centers equipped with high-throughput molecular testing systems.

[0003] To support such a centralized testing scheme, molecular testing automation systems have been developed to process large numbers of samples at once for nucleic acid extraction and subsequent reaction assays.

[0004] However, conventional high-throughput automation systems, which process many samples simultaneously and perform the same test, have typically been developed in a batch-type configuration, requiring operator intervention each time a batch is completed.

[0005] Moreover, conventional large-scale extraction systems have generally been designed on the assumption that identical tests are routinely performed on samples of the same type. Therefore, when extraction of one type of sample is completed and extraction of another type begins, manual intervention by the operator is required, such as replacing buffers or resetting the protocol.

[0006] As the number and duration of operator interventions increase relative to the system operation time, the number of systems manageable per operator decreases, which in turn increases the operational cost of the testing center.

[0007] Accordingly, there is a need to develop a high-throughput extraction system capable of automatically performing various nucleic acid extractions corresponding to diverse samples for different molecular tests, while allowing continuous loading to minimize operator intervention.

[0008]

[0009] An object of the present disclosure is to provide a high-throughput, continuously loadable nucleic acid extraction automation system.

[0010] Another object of the present disclosure is to provide a method for operating a continuously loadable high-throughput nucleic acid extraction automation system.

[0011] However, the present invention is not limited to the above-mentioned objects and may be embodied in various modifications without departing from the spirit and scope of the present disclosure.

[0012]

[0013] In order to achieve the above objects of the present disclosure, a high-throughput, continuously loadable nucleic acid extraction automation system according to exemplary embodiments of the present disclosure comprises (a) an extraction subsystem for receiving a sample plate and a material and extracting nucleic acids, wherein the extraction subsystem comprises at least one extraction module, wherein the extraction module comprises (a1) a working station including at least three extraction units configured to extract nucleic acids, each of the at least three extraction units comprising at least one function selected from the group of shaking, heating, and magnetic field generation, wherein each of the at least three extraction units is used once sequentially during extraction of the sample plate; (a2) a multi-channel liquid handling unit; and (a3) a plate transfer unit transferring the sample plate between the extraction units; and (b) a controller, wherein the controller is configured to control the extraction subsystem such that while a nucleic acid extraction process for one sample plate is in progress in one extraction unit among the at least three extraction units, another extraction unit receives another sample plate and performs a nucleic acid extraction process for another sample plate.

[0014] In exemplary embodiments, the extraction subsystem may comprise a plurality of extraction modules.

[0015] In exemplary embodiments, the extraction module may further comprise an additional working station including at least three extraction units configured to extract nucleic acids, and the multi-channel liquid handling unit may be configured to access each of the working stations in the extraction module.

[0016] In exemplary embodiments, the plurality of extraction modules may be configured to perform different extraction protocols.

[0017] In exemplary embodiments, the controller may be configured to determine an extraction module to perform nucleic acid extraction for the sample plate based on identification information of the sample plate, and to control the sample plate to be transferred to the determined extraction module.

[0018] In exemplary embodiments, the controller may be configured to control the plate transfer unit such that, while a nucleic acid extraction process for one sample plate is being performed, the sample plate is sequentially transferred to and received by two or more extraction units among the at least three extraction units.

[0019] In exemplary embodiments, the controller may be configured to control the extraction module such that a part of the nucleic acid extraction process is performed in the extraction unit in which the sample plate is received.

[0020] In exemplary embodiments, the extraction module may be configured to selectively perform two or more extraction protocols, and the controller may be configured to determine an extraction protocol to be used in the extraction module based on a type of sample.

[0021] In exemplary embodiments, the controller may be configured to determine, according to the determined extraction protocol, extraction units to be used for nucleic acid extraction of the sample among the at least three extraction units included in the extraction module.

[0022] In exemplary embodiments, the at least three extraction units may comprise a multifunctional extraction unit configured to perform two or more functions.

[0023] In exemplary embodiments, the multifunctional extraction unit may be configured to selectively perform the two or more functions.

[0024] In exemplary embodiments, the at least three extraction units may comprise two or more of the multifunctional extraction units.

[0025] In exemplary embodiments, the controller may be configured to select, according to the determined extraction protocol, a function to be performed by each of the two or more multifunctional extraction units included in the extraction module.

[0026] In exemplary embodiments, the controller may be configured to change a function of the extraction unit in which the sample plate is received during the nucleic acid extraction process for one sample plate.

[0027] In exemplary embodiments, the controller may be configured to control functions of the at least three extraction units such that two or more extraction protocols are continuously performed in one extraction module.

[0028] In exemplary embodiments, the two or more functions may comprise at least two selected from the group consisting of a heating function, a shaking function, and a magnetic field generation function.

[0029] In exemplary embodiments, the at least three extraction units may comprise an extraction unit including a temperature control means configured to control a temperature of the sample plate.

[0030] In exemplary embodiments, the at least three extraction units may comprise an extraction unit including a driving means configured to move the sample plate to shake a solution in the sample plate.

[0031] In exemplary embodiments, the at least three extraction units may comprise an extraction unit including a magnetic means configured to apply a magnetic force to the sample plate.

[0032] In exemplary embodiments, the working station may be configured such that the at least three extraction units are arranged in a first direction.

[0033] In exemplary embodiments, the plate transfer unit may be configured to move in the first direction and to transfer the sample plate among the at least three extraction units arranged in the first direction.

[0034] In exemplary embodiments, the extraction module may further comprise a supply station configured to accommodate materials.

[0035] In exemplary embodiments, the nucleic acid extraction automation system may further comprise a storage subsystem configured to supply materials for nucleic acid extraction and a transfer subsystem configured to transfer the sample plate and the materials to the extraction subsystem.

[0036] In exemplary embodiments, the storage subsystem may be configured to selectively supply materials for nucleic acid extraction based on the sample plate.

[0037] In exemplary embodiments, the extraction subsystem may receive the sample plate and the materials from the transfer subsystem and extracts nucleic acids.

[0038] In exemplary embodiments, the extraction subsystem may comprise a plurality of extraction modules, and the controller may be configured to control the materials corresponding to extraction protocols performed in the plurality of extraction modules to be provided to each of the extraction modules.

[0039] In exemplary embodiments, the working station may be configured to allow addition or replacement of extraction units without modification of other extraction units included in the working station.

[0040] In exemplary embodiments, the multi-channel liquid handling unit may be configured to access the at least three extraction units of the working station and the materials of the supply station.

[0041] In exemplary embodiments, the supply station may be configured such that two or more materials are arranged in a first direction.

[0042] In exemplary embodiments, the supply station may comprise a positioning guide for each of the two or more materials.

[0043] In exemplary embodiments, the supply station may comprise a cover opening / closing unit for the materials.

[0044] In exemplary embodiments, the plate transfer unit may be configured to sequentially transfer the sample plate once to each of the at least three extraction units arranged in the first direction during a nucleic acid extraction process for one sample plate.

[0045] In exemplary embodiments, the extraction subsystem may be configured to allow addition of extraction modules without modification of other extraction modules included in the extraction subsystem.

[0046] In exemplary embodiments, the nucleic acid extraction automation system may further comprise a waste collection unit configured to collect wastes after use of the materials.

[0047] In exemplary embodiments, the transfer subsystem may comprise a material transfer module configured to transfer the materials of the storage subsystem to the supply station of the extraction module.

[0048] In exemplary embodiments, the transfer subsystem may further comprise a sample transfer module configured to provide the sample plate to the extraction module.

[0049] In exemplary embodiments, the extraction subsystem may comprise two or more extraction modules, the transfer subsystem may comprise two or more material transfer modules, and each extraction module may be assigned with one of the material transfer modules.

[0050] In exemplary embodiments, the material transfer module may comprise two or more material transfer units.

[0051] In exemplary embodiments, the two or more material transfer units may transfer different types of materials.

[0052] In exemplary embodiments, the materials may comprise consumables or reagents.

[0053] In exemplary embodiments, the storage subsystem may comprise a storage area for storing materials and a pickup area for delivering the materials to the transfer subsystem.

[0054] In exemplary embodiments, the storage area may comprise two or more material storage modules.

[0055] In exemplary embodiments, each material storage module may comprise two or more material storage units.

[0056] In exemplary embodiments, the two or more material storage units may store different types of materials.

[0057] In exemplary embodiments, the two or more material storage units may be independently temperature-controlled.

[0058] In order to achieve the other objects of the present disclosure, a method for operating a continuously loadable high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure comprises (a) loading a first sample plate to a first extraction unit of the extraction module; (b) determining an extraction protocol to be performed on the first sample plate; (c) determining, based on the determined extraction protocol, an extraction protocol step to be performed by each of the at least three extraction units; (d) performing a first extraction protocol step on the first sample plate by the first extraction unit; (e) transferring the first sample plate to a second extraction unit and performing a second extraction protocol step on the first sample plate by the second extraction unit; and (f) loading a second sample plate to the first extraction unit of the extraction module. The system comprises an extraction module including at least three extraction units configured to extract nucleic acids, and each of the at least three extraction units comprises at least one function selected from the group consisting of shaking, heating, and magnetic field generation.

[0059]

[0060]

[0061]

[0062] The high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure allows continuous loading of multiple sample plates. Accordingly, even while a nucleic acid extraction process is being performed on a sample, a new sample plate can be received and subjected to nucleic acid extraction.

[0063] The high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure is capable of automatically processing various types of nucleic acid extraction procedures. Therefore, even when different types of sample plates are loaded, nucleic acids can be automatically extracted according to an appropriate extraction process.

[0064] The high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure is a scalable system capable of adding one or more extraction modules without modification of the existing system. Accordingly, the system can be flexibly configured according to operational environments or processing demands.

[0065] However, the effects of the present disclosure are not limited to the effects described above, and the present disclosure may be extended in various ways without departing from the spirit and scope of the present invention.

[0066]

[0067] FIG. 1 is a schematic diagram illustrating a high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure.

[0068] FIG. 2 is a schematic diagram illustrating another exemplary embodiment of the high-throughput nucleic acid extraction automation system according to the present disclosure.

[0069] FIG. 3 is a schematic diagram illustrating an extraction module of the high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure.

[0070] FIG. 4 is a schematic diagram illustrating processing units arranged on a working station of the high-throughput nucleic acid extraction automation system and an exemplary continuous loading method using the same.

[0071] FIG. 5 is a schematic diagram illustrating the working station and extraction units according to exemplary embodiments of the present disclosure.

[0072] FIG. 6 is a schematic diagram illustrating a supply station and the arrangement of reagents and consumables mounted thereon according to another exemplary embodiment of the present disclosure.

[0073] FIG. 7 is a schematic diagram illustrating the structure of a storage subsystem according to exemplary embodiments of the present disclosure.

[0074] FIG. 8 is a schematic diagram illustrating a structure of a storage subsystem configured to supply materials to each extraction module in a high-throughput nucleic acid extraction automation system having a plurality of extraction modules according to exemplary embodiments of the present disclosure.

[0075] FIG. 9 is a schematic diagram illustrating a material transfer module of a transfer subsystem according to exemplary embodiments of the present disclosure.

[0076] FIG. 10 is a schematic diagram illustrating a sample transfer module of a transfer subsystem according to exemplary embodiments of the present disclosure.

[0077] FIG. 11 is a block diagram illustrating a control configuration of a controller according to exemplary embodiments of the present disclosure.

[0078]

[0079] Hereinafter, exemplary embodiments of the nucleic acid extraction automation system according to the present disclosure will be described in detail with reference to the accompanying drawings. In the accompanying drawings, the same or similar reference numerals denote the same or similar elements throughout.

[0080] The specific structural or functional descriptions set forth in this specification are merely illustrative examples provided for better understanding of the embodiments of the present disclosure. The embodiments of the present disclosure may be implemented in various forms, and should not be construed as limited to the embodiments described herein. It should be understood that all modifications, equivalents, and substitutions that fall within the spirit and scope of the present disclosure are included. When an element is described as being "connected to" or "in contact with" another element, it should be understood that the element may be directly connected to or in direct contact with the other element, or connected or in contact indirectly through another intervening element. Likewise, when an element is described as being "directly connected to" or "directly in contact with" another element, it should be understood that there is no intervening element. Other expressions describing relationships between elements, such as "between" and "directly between," or "adjacent to" and "directly adjacent to," shall be interpreted in the same manner.

[0081] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the present disclosure. Singular expressions include plural forms unless the context clearly indicates otherwise. The terms "comprise," "include," and "have" or variations thereof as used herein specify the presence of stated features, integers, steps, operations, elements, or combinations thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, or combinations thereof.

[0082] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Terms defined in generally used dictionaries shall be interpreted as having meanings consistent with the contextual meaning of the related technology and are not to be interpreted in an overly idealized or formal sense unless explicitly defined in the present application.

[0083] Terms such as "first", "second", and "third" may be used to describe various elements, but such elements are not limited by these terms. These terms are used merely to distinguish one element from another. For example, within the scope of the present disclosure, a first element may be referred to as a second or third element, and similarly, the second or third element may be referred to interchangeably.

[0084]

[0085] According to one aspect of the present disclosure, there is provided a high-throughput, continuously loadable nucleic acid extraction automation system comprising:

[0086] (a) an extraction subsystem for receiving a sample plate and a material and extracting nucleic acids;

[0087] wherein the extraction subsystem comprises at least one extraction module,

[0088] wherein the extraction module comprises:

[0089] (a1) a working station including at least three extraction units configured to extract nucleic acids,

[0090] each of the at least three extraction units comprising at least one function selected from the group of shaking, heating, and magnetic field generation,

[0091] wherein each of the at least three extraction units is used once sequentially during extraction of the sample plate;

[0092] (a2) a multi-channel liquid handling unit; and

[0093] (a3) a plate transfer unit transferring the sample plate between the extraction units; and

[0094] (b) a controller,

[0095] wherein the controller is configured to control the extraction subsystem such that while a nucleic acid extraction process for one sample plate is in progress in one extraction unit among the at least three extraction units, another extraction unit receives another sample plate and performs a nucleic acid extraction process for another sample plate.

[0096]

[0097] The term sample refers to a substance that contains or is presumed to contain an analyte. The sample includes biological samples (for example, cells, tissues, or body fluids obtained from biological sources) and non-biological samples (for example, food, water, or soil).

[0098] The biological sample may include, but is not limited to, viruses, bacteria, tissues, cells, blood (including whole blood, plasma, and serum), lymph, bone marrow fluid, sputum, swabs, aspirates, bronchoalveolar lavage fluid, nasal washings, milk, urine, feces, ocular fluid, saliva, semen, brain extracts, cerebrospinal fluid (CSF), synovial fluid, appendix, spleen, and tonsil tissue extracts, amniotic fluid, and ascitic fluid.

[0099] In addition, the sample may include naturally occurring nucleic acid molecules isolated from a biological source as well as synthetic nucleic acid molecules.

[0100] In one embodiment, the term sample may include substances used for storage, processing, or detection of the sample. The sample may include additional substances such as amplification reagents, detection reagents, preservatives, water, deionized water, saline, pH buffer, acidic solution, or basic solution, but is not limited thereto.

[0101]

[0102] The nucleic acid extraction automation system according to the present disclosure extracts nucleic acids from the sample. The term nucleic acid extraction refers to the process of separating and purifying nucleic acids such as DNA or RNA from a biological sample (e.g., blood, tissue, cell culture fluid, swab, or stool) or a material containing the same. This process may include steps such as disruption (lysis) of cell membranes, removal of impurities such as proteins, and selective separation and recovery of nucleic acids.

[0103] A nucleic acid extraction automation system according to one embodiment of the present disclosure may extract nucleic acids from samples through a multi-step extraction method. The composition of extraction steps, the reagents used in each step, and the extraction procedure may vary depending on the type of sample.

[0104] The multi-step extraction method may be a magnetic bead-based extraction method. Magnetic beads are particles comprising a magnetic material that adheres to a magnet, and whose surface is coated with chemical functional groups or functional polymer materials capable of reversibly binding to nucleic acids depending on conditions such as pH. The magnetic beads can be moved or separated to a desired position using an external magnet, and impurities not bound to the beads can be easily removed through washing steps.

[0105] In one embodiment of the present disclosure, the multi-step extraction method may be a liquid-transfer-based extraction method. The liquid transfer method involves exposing magnetic beads to an extraction solution to allow binding with nucleic acids, immobilizing the magnetic beads in a tube using a magnet, removing the liquid in the tube, and then adding the next processing buffer to proceed with the extraction process.

[0106] In another embodiment, the multi-step extraction method may be a bead-transfer-based extraction method. The bead transfer method separates nucleic acids by physically moving the magnetic beads. Specifically, magnetic beads are exposed to an extraction solution to bind nucleic acids, and a magnetic rod equipped with a cover tip is inserted into the solution to collect and separate the magnetic beads, which are then transferred into a subsequent processing buffer to continue the extraction process.

[0107] The multi-step extraction method may include a lysis step. The lysis step involves breaking down cell walls or membranes through physical or chemical means to release internal materials containing nucleic acids. The lysis step of the present disclosure may include mixing a lysis buffer with the sample. If the sample already contains lysed cells with exposed nucleic acids, the multi-step extraction method may omit the lysis step.

[0108] The multi-step extraction method may include a binding step. The binding step involves mixing magnetic beads with the cell lysate to allow nucleic acids to bind to the magnetic beads. A binding buffer may be added to the cell lysate for this purpose.

[0109] The lysis step and the binding step may be performed together in a single extraction step. A buffer mixture containing both a lysis buffer and a binding buffer may be placed in one extraction chamber and mixed with the sample and the magnetic beads.

[0110] The multi-step extraction method may include a washing step. The washing step involves removing proteins or other cellular components except for nucleic acids to purify the nucleic acids. The washing step of the present disclosure may include mixing the magnetic beads with a wash buffer and then separating the magnetic beads from the wash buffer.

[0111] Depending on the sample, the multi-step extraction method may include two or more washing steps. In such cases, the wash buffers used in the two or more washing steps may differ in composition. In the multi-step extraction method performed in the nucleic acid extraction automation system of the present disclosure, each of the two or more washing steps may be defined as a separate extraction step.

[0112] The multi-step extraction method may include an elution step. The elution step involves separating and recovering nucleic acids from the magnetic beads. The elution step of the present disclosure may include mixing the magnetic beads with an elution buffer and then separating the magnetic beads from the elution buffer.

[0113] According to one embodiment, the high-throughput nucleic acid extraction automation system of the present disclosure may be a system configured to extract nucleic acids according to the multi-step extraction method, wherein the multi-step extraction method comprises at least one of a lysis and / or binding step, a washing step, and an elution step.

[0114]

[0115] Extraction Module

[0116] The high-throughput nucleic acid extraction automation system of the present disclosure includes an extraction module. FIG. 3 is a schematic diagram illustrating the extraction module of the high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure, and FIG. 5 is a diagram illustrating the working station and extraction units according to exemplary embodiments of the present disclosure.

[0117] The extraction module 1000 may include a working station 1100, a multi-channel liquid handling unit 1300, and a plate transfer unit 1400. The working station 1100 is a module configured to receive a sample plate 500 and extract nucleic acids from samples contained therein. The multi-channel liquid handling unit 1300 is a multi-dispensing unit configured to simultaneously supply samples or reagents to a plurality of positions. The plate transfer unit 1400 is a unit configured to transfer the sample plate 500 between extraction units 1110.

[0118] The sample plate refers to a support comprising a plurality of receptacles or wells arranged at regular intervals to simultaneously accommodate, process, and transfer a plurality of samples or solutions. The number of the receptacles or wells may be, for example, 6, 8, 12, 24, 48, 96, or 384. The sample plate may have a standardized footprint to be compatible with the automation system. The sample plate may include identification information recognizable by an identification information reader of the automation system. The identification information may be, for example, a barcode, 2D code, or RFID. In addition, a rack-type plate configured to stably support and fix individual sample containers containing samples in a predetermined array may also be regarded as a sample plate within the scope of the present disclosure, provided that it performs the same functions such as simultaneous transfer, processing, and identification.

[0119] According to one embodiment, the extraction module 1000 may include a plurality of working stations 1100. When the extraction module 1000 includes the plurality of working stations 1100, the multi-channel liquid handling unit 1300 and the plate transfer unit 1400 may be configured to access all of the plurality of working stations 1100. According to one embodiment, the extraction module 1000 may further comprise an additional working station including at least three extraction units 1110 configured to extract nucleic acids, and the multi-channel liquid handling unit may be configured to access each of the working stations included in the extraction module 1000. Each working station 1100 independently receives a sample plate and performs nucleic acid extraction. By sharing one multi-channel liquid handling unit among the working stations, the overall system structure can be simplified, and manufacturing costs can be reduced.

[0120] The working station 1100 may include three or more extraction units 1110. The working station 1100 performs a nucleic acid extraction process for extracting nucleic acids from the samples contained in the sample plate 500. Each extraction unit 1110 receives the sample plate and performs at least part of the nucleic acid extraction process. The number of extraction units 1110 included in one working station 1100 may be, for example, three or more, or five or more, and may be 20 or less, 15 or less, 13 or less, or 11 or less.

[0121] According to one embodiment, the working station 1100 may be configured to allow addition or replacement of extraction units without changing other extraction units included in the same working station. Each extraction unit 1110 included in the working station 1100 of the present disclosure may be a modular extraction unit. The working station 1100 may be configured such that one of the extraction units 1110 installed therein can be removed or a new extraction unit 1110 can be added without modifying other extraction units 1110.

[0122] The working station 1100 may include a mounting base 1120. The extraction units 1110 may be positioned on the mounting base 1120. A guide 1121 may be formed on the mounting base 1120 to position the extraction units at designated locations. The guide 1121 may be a structure protruding from the upper surface of the mounting base 1120, or it may be formed as a recess in the upper surface of the mounting base 1120.

[0123] The mounting base 1120 may have a flat upper surface so that the plurality of extraction units 1110 can be positioned substantially at the same height. This simplifies control of the plate transfer unit 1400 that transfers the sample plate 500 mounted on the extraction units 1110, thereby enabling the controller to stably control the plate transfer unit 1400.

[0124] According to one embodiment, the three or more extraction units 1110 may be arranged in a first direction in the working station 1100. The first direction may be a horizontal straight direction; in other words, the three or more extraction units 1110 may be aligned in a single linear direction within the working station 1100.

[0125] According to one embodiment, the plate transfer unit 1400 may be configured to move in the first direction and transfer the sample plate between the three or more extraction units arranged in the first direction.

[0126] The plate transfer unit 1400 transfers the sample plate 500 between the extraction units 1110. The plate transfer unit 1400 may include a plate holder 1410 and a drive unit 1420. The plate holder 1410 holds the sample plate 500 accurately and stably immobilizes it during transfer. The plate holder 1410 may be a gripper. The plate holder 1410 may include a pressure control function to prevent damage to the plate. Alternatively, the plate holder 1410 may employ a vacuum adsorption mechanism to create a vacuum on the surface of the sample plate 500, thereby holding and transferring the sample plate 500. The drive unit 1420 may include various motors and rail systems. The motor may be, for example, a servo motor or a step motor. The drive unit 1420 may include a linear actuator, or the drive unit 1420 may include a ball screw or a lead screw. Accordingly, the drive unit 1420 can finely adjust the movement of the plate holder 1410 to accurately transfer the sample plate 500 to a target position.

[0127] The extraction unit 1110 of the present disclosure allows at least a part of the nucleic acid extraction process to be carried out on a sample plate 500 received in the extraction unit. The extraction unit 1110 may be configured to apply at least one of physical, thermal, and electromagnetic stimuli to the sample plate 500.

[0128] FIG. 5 is a diagram illustrating the working station and extraction units according to exemplary embodiments of the present disclosure. Referring to FIG. 5(A), the extraction unit 1110 may provide various functions. The extraction unit 1110 may include one or more functions selected from a group consisting of shaking, heating, and magnetic field generation.

[0129] The extraction unit 1110-4 may include temperature control means 1111. The temperature control means 1111 may be a plate including a resistance heating wire or a plate including a Peltier element. By using the extraction unit 1110-4 that includes the temperature control means 1111, the temperature of a solution contained in the sample plate 500 can be controlled. According to one embodiment, the three or more extraction units may include an extraction unit including the temperature control means configured to control the temperature of the sample plate.

[0130] The extraction unit 1110-2 may provide a shaking function. To this end, the extraction unit 1110-2 may include driving means 1112. The driving means 1112 may include a platform on which the sample plate is placed, and the platform may have a rubber coating to prevent the plate from slipping. The driving means 1112 may include a motor that moves the platform. The motor may be a DC motor, a servo motor, or a step motor. Power from the motor enables a vibration mechanism to oscillate the platform regularly. The driving means 1112 may include a damper to block vibrations and noise other than the intended oscillation. According to one embodiment, the three or more extraction units may include an extraction unit 1110-2 that includes the driving means 1112 to move the sample plate to shake a solution in the sample plate.

[0131] The extraction unit 1110-3 may provide a magnetic field generation function. To this end, the extraction unit 1110-3 may include magnetic means 1113. The magnetic means 1113 may be a substrate on which a plurality of permanent magnets are arranged. When the sample plate is placed in the extraction unit 1110-3, the magnetic means 1113 may be configured such that a permanent magnet is positioned close to each sample well of the sample plate. The magnetic means 1113 may alternatively be a substrate on which electromagnets are arranged. Because the magnetic field generated by an electromagnet can be controlled, the electromagnet can be conveniently used together with other functional means within a single extraction unit. According to one embodiment, the three or more extraction units 1110 may include an extraction unit 1110-3 that includes the magnetic means 1113 configured to apply magnetic force to the sample plate.

[0132] According to one embodiment, the extraction unit 1110-8 may include a guide 1114. The guide 1114 enables the sample plate 500 positioned on the upper surface of the extraction unit 1110-9 to be placed at a defined position so that heating and pipetting can be performed properly, and also prevents the sample plate 500 from leaving the extraction unit 1110-9 during shaking.

[0133] The extraction unit 1110 of the present disclosure may be a multi-function extraction unit capable of performing multiple functions. The multi-function extraction unit may be configured to provide two or more functions. FIG. 5(A) shows various exemplary multi-function extraction units. For example, the extraction unit 1110-5 may include the drive means 1112 and the magnetic means 1113. The extraction unit 1110-6 may include the drive means 1112 and the temperature control means 1111. The extraction unit 1110-7 may include all of the drive means 1112, the magnetic means 1113, and the temperature control means 1111. According to one embodiment, the two or more functions may include two or more functions selected from a group consisting of a heating function, a shaking function, and a magnetic field generation function. The extraction unit 1110-1 may be configured not to include the temperature control means 1111, the drive means 1112, and the magnetic means 1113, and to merely provide a space on which the sample plate 500 is placed.

[0134] According to one embodiment, the three or more extraction units may include a multi-function extraction unit configured to provide two or more functions. The high-throughput nucleic acid extraction automation system may include the multi-function extraction unit configured to provide two or more functions described above, whereby the extraction module 1000 can carry out various nucleic acid extraction processes with a smaller number of extraction units. The number of multi-function extraction units included in the extraction module 1000 of the high-throughput nucleic acid extraction automation system is not particularly limited. For example, the extraction module 1000 may include one to five multi-function extraction units. Alternatively, all extraction units 1110 included in the extraction module 1000 may be multi-function extraction units.

[0135] According to one embodiment, the three or more extraction units may include two or more of the multi-function extraction units. At least one of the three or more extraction units included in the extraction module 1000 may provide two or more functions, or two or more extraction units included in the extraction module 1000 may provide two or more functions.

[0136] According to one embodiment, the multi-function extraction unit may be configured to selectively perform the two or more functions. The multi-function extraction unit may perform two or more functions simultaneously; for example, the sample plate may be heated while being shaken. Alternatively, the multi-function extraction unit may be configured to selectively perform only one of the provided functions; for example, after mixing magnetic beads with a sample solution by shaking, the magnetic beads may be immobilized by using the magnetic means.

[0137] According to one embodiment, while a nucleic acid extraction process for one sample plate is in progress, the sample plate may be sequentially transferred to and received by two or more of the three or more extraction units such that the nucleic acid extraction process proceeds.

[0138] Hereinafter, with reference to FIGS. 1, 3, and 4, an example will be described in which a nucleic acid extraction process is performed by the plurality of extraction units 1110 at the working station 1100 of the extraction module 1000 of the present disclosure. FIG. 3 is a schematic diagram illustrating the extraction module of the high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure. FIG. 4 is a diagram illustrating processing units arranged at the working station of the high-throughput nucleic acid extraction automation system and an exemplary continuous loading method using the same.

[0139] Referring to FIG. 4(A), eleven extraction units 1110 may be arranged from extraction unit 0 (1110a) to extraction unit 10 (1110k). A sample plate 500, 510 may be provided to the working station 1100 of the extraction module 1000 by the sample transfer module 3200. The plate transfer unit 1400 transfers the sample plate 500, 510 that has arrived at the working station 1100 of the extraction module 1000 via the sample transfer module 3200 to the extraction unit 0 (1110a).

[0140] When the nucleic acid extraction process for the sample plate 500, 510 starts, the sample plate 500, 510 waiting at the extraction unit 0 (1110a) is moved to the extraction unit 1 (1110b), and reagents necessary for extraction may be dispensed. Reagents 620 and consumables 610 may be located at the supply station 1200. Details of the supply station 1200 will be described later. The reagents 620 required for extraction may be dispensed onto the sample plate 500, 510 by the multi-channel liquid handling unit 1300. The sample plate 500, 510 may be sequentially transferred by the plate transfer unit 1400 from the extraction unit 0 (1110a) to the extraction unit 10 (1110k). The reagent 620 dispensed onto the sample plate 500, 510 at the extraction unit 1 may include, for example, a lysis buffer, magnetic beads, a binding buffer, and an internal control. The extraction unit 1 (1110b) provides a shaking function and can oscillate the solution in the sample plate such that samples contained in the sample plate 500, 510 are lysed by the lysis buffer to expose nucleic acids, and the nucleic acids bind to the magnetic beads.

[0141] The sample plate 500, 510 for which the reaction at the extraction unit 1 (1110b) is completed may be moved to the extraction unit 2 (1110c). The extraction unit 2 (1110c) includes the magnetic means 1113 to generate a magnetic field, whereby the magnetic beads in the sample plate 500, 510 can be immobilized on the bottom surface of the sample plate. The multi-channel liquid handling unit 1300 may aspirate and remove solutions from the sample plate 500, 510 located at the extraction unit 2 (1110c).

[0142] The sample plate 500, 510 from which the lysis buffer and binding buffer have been removed may be moved to the extraction unit 3 (1110d). A first wash buffer may be dispensed onto the sample plate located at the extraction unit 3 (1110d). The extraction unit 3 (1110d) provides a shaking function and can oscillate the solution in the sample plate such that the samples contained in the sample plate 500, 510 are washed by the first wash buffer.

[0143] The sample plate 500, 510 for which the reaction at the extraction unit 3 (1110d) is completed may be moved to the extraction unit 4 (1110e). The extraction unit 4 (1110e) includes the magnetic means 1113 to generate a magnetic field, whereby the magnetic beads in the sample plate 500, 510 can be immobilized on the bottom surface of the sample plate. The multi-channel liquid handling unit 1300 may aspirate and remove the solution (the first wash buffer) from the sample plate 500, 510 located at the extraction unit 4 (1110e).

[0144] The sample plate 500, 510 from which the first wash buffer has been removed may be moved to the extraction unit 5 (1110f). A second wash buffer may be dispensed onto the sample plate located at the extraction unit 5 (1110f). The extraction unit 5 (1110f) provides a shaking function and can oscillate the solution in the sample plate such that the samples contained in the sample plate 500, 510 are washed by the second wash buffer.

[0145] The sample plate 500, 510 for which the reaction at the extraction unit 5 (1110f) is completed may be moved to the extraction unit 6 (1110g). The extraction unit 6 (1110g) includes the magnetic means 1113 to generate a magnetic field, whereby the magnetic beads in the sample plate 500, 510 can be immobilized on the bottom surface of the sample plate. The multi-channel liquid handling unit 1300 may aspirate and remove the solution (the second wash buffer) from the sample plate 500, 510 located at the extraction unit 6 (1110g).

[0146] The sample plate 500, 510 from which the second wash buffer has been removed may be moved to the extraction unit 7 (1110h). The extraction unit 7 (1110h) provides a heating function and dries the magnetic beads remaining after removal of the second wash buffer.

[0147] The sample plate 500, 510 for which drying at the extraction unit 7 (1110h) is completed may be moved to the extraction unit 8 (1110i). A third wash buffer may be dispensed onto the sample plate located at the extraction unit 8 (1110i). The extraction unit 8 (1110i) includes the magnetic means 1113 to generate a magnetic field, whereby the magnetic beads in the sample plate 500, 510 can be immobilized on the bottom surface of the sample plate. The multi-channel liquid handling unit 1300 may aspirate and remove the third wash buffer from the sample plate 500, 510 located at the extraction unit 8 (1110i).

[0148] The sample plate 500, 510 from which the third wash buffer has been removed at the extraction unit 8 (1110i) may be moved to the extraction unit 9 (1110j). An elution buffer may be dispensed onto the sample plate located at the extraction unit 9 (1110j). The extraction unit 9 (1110j) provides shaking and heating functions and can oscillate the solution in the sample plate such that nucleic acids bound to the magnetic beads contained in the sample plate 500, 510 are eluted from the magnetic beads by the dispensed elution buffer.

[0149] The sample plate 500, 510 for which the reaction at the extraction unit 9 (1110j) is completed may be moved to the extraction unit 10 (1110k). The extraction unit 10 (1110k) includes the magnetic means 1113 to generate a magnetic field, whereby the magnetic beads in the sample plate 500, 510 can be immobilized on the bottom surface of the sample plate. In this way, the nucleic acid extraction process is completed, and the extracted nucleic acids may be transferred to a suitable container, or, with the magnetic beads captured, may be used in a subsequent step such as a PCR test.

[0150] When the multi-function extraction units having multiple functions of the present disclosure are used, the same nucleic acid extraction process can be performed with a smaller number of extraction units. FIG. 2 is a schematic diagram illustrating the high-throughput nucleic acid extraction automation system according to other exemplary embodiments of the present disclosure. Hereinafter, with reference to FIGS. 1 and 2, an example will be described in which the nucleic acid extraction process is carried out by a plurality of extraction units 1110 at the working station 1100 of the extraction module 1000 in another embodiment in which a multi-function extraction unit is actively utilized.

[0151] At the working station 1100 of FIG. 2, seven extraction units 1110 may be arranged from extraction unit 20 (1110m) to extraction unit 26 (1110s). A sample plate 500 may be provided to the working station 1100 of the extraction module 1000 by the sample transfer module 3200. The plate transfer unit 1400 transfers the sample plate 500 that has arrived at the working station 1100 of the extraction module 1000 via the sample transfer module 3200 to the extraction unit 20 (1110m).

[0152] When the nucleic acid extraction process for the sample plate 500 starts, the sample plate 500 waiting at the extraction unit 20 (1110m) is moved to the extraction unit 21 (1110n), and reagents required for extraction may be dispensed. Reagents 620 and consumables 610 may be located at the supply station 1200. The reagents 620 required for extraction may be dispensed onto the sample plate 500 by the multi-channel liquid handling unit 1300. The sample plate 500 may be sequentially transferred by the plate transfer unit 1400 from the extraction unit 20 (1110m) to the extraction unit 26 (1110s). The reagent 620 dispensed onto the sample plate 500 at the extraction unit 21 stage may include, for example, a lysis buffer, magnetic beads, a binding buffer, and an internal control. The extraction unit 21 (1110n) has a shaking function and may be a multi-function extraction unit including magnetic means 1113 capable of generating a magnetic field.

[0153] With the sample plate 500 positioned at the extraction unit 21 (1110n), the lysis buffer and the binding buffer may be dispensed onto the sample plate 500, and the solution in the sample plate may be shaken so that nucleic acids bind to the magnetic beads. Thereafter, the shaking function of the extraction unit 21 (1110n) is stopped, the magnetic means 1113 is actuated to immobilize the magnetic beads to the bottom of the sample plate, and the multi-channel liquid handling unit 1300 is operated to aspirate and remove the solutions (the lysis buffer and binding buffer) from the sample plate 500 located at the extraction unit 21 (1110n). With the sample plate 500 remaining at the extraction unit 21 (1110n), a first wash buffer is dispensed, and the shaking function and the actuation of the magnetic means 1113 are sequentially performed, thereby washing the magnetic beads and removing the first wash buffer. Thereafter, with the sample plate 500 positioned at the extraction unit 21 (1110n), a second wash buffer is dispensed, and the shaking function and the actuation of the magnetic means 1113 are sequentially performed, thereby washing the magnetic beads and removing the second wash buffer.

[0154] The sample plate 500 from which the second wash buffer has been removed may be moved to the extraction unit 22 (1110o). The extraction unit 22 (1110o) provides a heating function and dries the magnetic beads remaining after removal of the second wash buffer.

[0155] The sample plate 500 for which drying at the extraction unit 22 (1110o) is completed may be moved to the extraction unit 23 (1110p). A third wash buffer may be dispensed onto the sample plate located at the extraction unit 23 (1110p). The extraction unit 23 (1110p) includes the magnetic means 1113 to generate a magnetic field, whereby the magnetic beads in the sample plate 500 can be immobilized on the bottom surface of the sample plate. The multi-channel liquid handling unit 1300 may aspirate and remove the third wash buffer from the sample plate 500 located at the extraction unit 23 (1110p).

[0156] The sample plate 500 from which the third wash buffer has been removed at the extraction unit 23 (1110p) may be moved to the extraction unit 24 (1110q). An elution buffer may be dispensed onto the sample plate located at the extraction unit 24 (1110q). The extraction unit 24 (1110q) provides shaking and heating functions and can oscillate the solution in the sample plate such that nucleic acids bound to the magnetic beads contained in the sample plate 500 are eluted from the magnetic beads by the dispensed elution buffer.

[0157] The sample plate 500 for which the reaction at the extraction unit 24 (1110q) is completed may be moved to the extraction unit 25 (1110r). The extraction unit 25 (1110r) includes the magnetic means 1113 to generate a magnetic field, whereby the magnetic beads in the sample plate 500 can be immobilized on the bottom surface of the sample plate. In this way, the nucleic acid extraction process is completed, and the extracted nucleic acids may be transferred to a suitable container or, with the magnetic beads captured, may be used in a subsequent step such as a PCR test. By using the multi-function extraction unit, the number of extraction units used in one extraction module of the present disclosure can be reduced.

[0158] As described above, the high-throughput nucleic acid extraction automation system of the present disclosure performs the nucleic acid extraction process while sequentially transferring the sample plate between a plurality of extraction units. Each extraction unit is responsible for a part of the nucleic acid extraction process, and upon completion of the responsible process, the sample plate is transferred to the next extraction unit. This unique operation of the system enables continuous loading in a high-throughput nucleic acid extraction system and allows a various extraction protocols to be executed. Operations of the high-throughput nucleic acid extraction automation system of the present disclosure are controlled by a controller.

[0159]

[0160] Controller

[0161] FIG. 11 is a block diagram illustrating a control configuration of a controller according to exemplary embodiments of the present disclosure. The controller 400 may control the transfer subsystem 300 to transfer the sample plate 500 and materials 600 required for nucleic acid extraction. The controller 400 may control the storage subsystem 200 to provide the materials 600 required for nucleic acid extraction to the transfer subsystem. The controller may control the extraction module 1000 so that nucleic acid extraction is performed. The extraction subsystem 100 may include a plurality of extraction modules 1000, and the controller 400 may independently control each of the plurality of extraction modules 1000.

[0162] According to one embodiment, the controller may control the extraction module so that a portion of the nucleic acid extraction process is performed at an extraction unit in which the sample plate is received. The nucleic acid extraction process in the high-throughput nucleic acid extraction automation system described above may be controlled by the controller. The controller may determine an extraction protocol for the sample plate and may define in advance extraction protocol steps to be performed by respective extraction units. When the nucleic acid extraction process is in progress, the controller may control transfer of the sample plate to a specific extraction unit according to a predetermined schedule and may control the extraction unit at which the sample plate is positioned to perform a corresponding part of the process.

[0163] According to one embodiment, while the nucleic acid extraction process for one sample plate is in progress, the controller may control the plate transfer unit so that the sample plate is sequentially transferred to and received by two or more of the three or more extraction units. As described above, the controller can control the system such that a plurality of extraction units individually perform respective portions of the nucleic acid extraction process.

[0164] According to one embodiment, the extraction module may be configured to selectively perform two or more extraction protocols, and the controller may determine which extraction protocol is to be used in the extraction module according to the type of sample. The plurality of extraction units 1110 included in the extraction module 1000 can all be controlled independently. Therefore, various extraction protocols can be executed.

[0165] As used herein, an "extraction protocol" is a procedure that specifies a series of process steps to be performed to separate and purify nucleic acids from a sample and the operating conditions for each step. The extraction protocol may include a sequence of steps of the nucleic acid extraction process and the execution order thereof. The extraction protocol may include process parameters such as time, temperature, shaking conditions, dispense volume, aspiration volume, and flow rate of the liquid handling unit, timing and intensity of application and release of a magnetic field, and the like for each step. The extraction protocol may include specifications of reagents and consumables. An "extraction process" is a collective concept for a set of processes that can be performed to separate and purify nucleic acids from a specimen; that is, it refers to a process framework that defines the types of steps and their interrelationships. The extraction protocol is a specific implementation of the extraction process. Accordingly, even for the same extraction process, multiple different extraction protocols may be derived depending on the type of sample type, the reagent used, and the state of the device.

[0166] Referring to FIG. 3, the extraction module 1000 may include an identification information reader 1500 configured to read identification information of the sample plate 500. The identification information reader 1500 may be a barcode reader, a QR code reader, a camera for recognizing identification information, or an RFID reader. The identification information reader may read the identification information of the sample plate 500 delivered by the sample transfer module 3200 and may receive sample data corresponding to the sample contained in the sample plate. The sample data may include information required to extract nucleic acids from the sample; for example, information on reagents necessary for nucleic acid extraction of the sample, information on the extraction module 1000 that is to receive the sample plate, or information indicating whether the sample contained in the sample plate is subject to urgent testing.

[0167] When the sample plate 500 is provided to the extraction module 1000 by the sample transfer module 3200, information on the sample plate 500 is delivered to the controller 400 by the identification information reader 1500, and the controller 400 may determine an extraction protocol to be used in the extraction module according to the type of sample. According to one embodiment, in accordance with the determined extraction protocol, the controller 400 may determine, among the three or more extraction units included in the extraction module, which extraction units will be used for nucleic acid extraction of the sample. The nucleic acid extraction process described above with reference to FIG. 4 is a process in which all extraction units from extraction unit 0 (1110a) to extraction unit 10 (1110k) are used. However, depending on the type of sample, a nucleic acid extraction process that uses only one or two of three wash buffers may be performed. In such a case, the nucleic acid extraction process may be performed by using only some of the extraction units 1110 installed at the working station 1100. For example, among the extraction units 1110a-1110k installed at the working station 1100 of FIG. 4, the extraction units 5 (1110f) and 6 (1110g) may not be used. In this case, according to the determined extraction protocol, the controller 400 may determine, among the extraction units 1110a-1110k, which extraction units will be used for nucleic acid extraction of the sample.

[0168] The controller 400 of the present disclosure may also be configured to control functions of a multi-function extraction unit. According to one embodiment, in accordance with the determined extraction protocol, the controller may select respective functions to be performed by two or more multi-function extraction units included in the extraction module. A multi-function extraction unit can perform two or more functions simultaneously. As described above with reference to FIG. 2, for example, the extraction unit 24 (1110q) is a multi-function extraction unit having shaking and heating functions. According to the extraction protocol, the controller may control the extraction unit 24 (1110q) to be used as the extraction unit responsible for a shaking step or as the extraction unit responsible for a heating step in the present nucleic acid extraction process.

[0169] According to another embodiment, while the nucleic acid extraction process for one sample plate is in progress, the controller may control the function of the extraction unit in which the sample plate is received to be changed. During one nucleic acid extraction process, a multi-function extraction unit may use two or more functions in sequence. As described above with reference to FIG. 2, the extraction unit 21 (1110n) has a shaking function and a magnetic field generation function. With the sample plate 500 positioned at the extraction unit 21 (1110n), a lysis buffer and a binding buffer may be dispensed onto the sample plate 500, and the solution in the sample plate may be shaken so that nucleic acids bind to magnetic beads. Thereafter, the controller may stop the shaking function of the extraction unit 21 (1110n), actuate the magnetic means 1113 to immobilize the magnetic beads to the bottom of the sample plate, and operate the multi-channel liquid handling unit 1300 to aspirate and remove solutions from the sample plate 500. With the sample plate 500 remaining at the extraction unit 21 (1110n), a first wash buffer may be dispensed, and the controller 400 may controls the shaking function of the extraction unit 21 (1110n) and the magnetic means 1113 of the extraction unit 21 (1110n) to operate sequentially, thereby washing the magnetic beads and removing the first wash buffer. Thereafter, with the sample plate 500 still positioned at the extraction unit 21 (1110n), a second wash buffer is dispensed, and the controller controls the shaking function of the extraction unit 21 (1110n) and the magnetic means 1113 of the extraction unit 21 (1110n) to operate sequentially, thereby washing the magnetic beads and removing the second wash buffer. To this end, during the nucleic acid extraction process for one sample plate, the controller 400 may control the extraction unit so that its function is changed.

[0170] In addition, the high-throughput nucleic acid extraction automation system 10 of the present disclosure also enables continuous loading. The continuous loading means that an operator can additionally load a new sample plate even while the system is performing the nucleic acid extraction process for previously loaded sample plates, without waiting for the currently running batch to be completed. This continuous loading function minimizes system downtime and enables random-access processing of samples even in environments where the arrival timing of samples is irregular. Accordingly, compared with conventional nucleic acid extraction systems, sample-handling efficiency is improved and throughput can be maximized. In addition, the continuous loading function minimizes operator intervention so that one operator can operate multiple systems simultaneously or perform unattended operation for extended periods.

[0171] FIG. 4 is a diagram illustrating processing units arranged at the working station of the high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure and an exemplary continuous loading method using the same. According to one embodiment, while the nucleic acid extraction process for one sample plate 500 is in progress at one extraction unit among the three or more extraction units 1110, the controller 400 controls another extraction unit 1110 to receive another sample plate 500 and carry out a nucleic acid extraction process.

[0172] FIG. 4(B) illustrates that the first sample plate 510 is mounted on the extraction unit 0 (1110a) of the working station 1100. When the nucleic acid extraction process for the first sample plate 510 starts, the first sample plate 510 positioned on the extraction unit 0 (1110a) is moved to the extraction unit 1 (1110b), and reagents necessary for extraction may be dispensed. When the process at the extraction unit 1 (1110b) is completed and the first sample plate 510 is moved to the extraction unit 2 (1110c), a second sample plate 520 may be mounted on the extraction unit 0 (1110a) of the same working station 1100 (see FIG. 4(C)). At the extraction unit 2 (1110c), magnetic beads in the first sample plate 510 are immobilized on the bottom surface of the sample plate, and the lysis buffer and the binding buffer contained in the first sample plate 510 may be removed. The first sample plate 510 from which the lysis buffer and binding buffer have been removed may be moved to the extraction unit 3 (1110d). A first wash buffer may be dispensed onto the first sample plate 510 positioned at the extraction unit 3 (1110d). In addition, the second sample plate 520 is moved to the extraction unit 1 (1110b) so that the nucleic acid extraction process can proceed for the second sample plate 520 (see FIG. 4(D)). In this manner, two or more sample plates can be continuously processed in one extraction module 1000. In conventional batch-type high-throughput extraction devices, when nucleic acid extraction for one sample plate is completed, the processed sample plate is removed from the device, and a new sample plate is then received for subsequent extraction and processed. In the system of the present disclosure, the nucleic acid extraction process for a sample plate proceeds while the sample plate is sequentially transferred to and received by two or more extraction units among the three or more extraction units., Therefore, while the nucleic acid extraction process for one sample plate is in progress at one extraction unit, another extraction unit can receive a different sample plate and perform a nucleic acid extraction process in parallel.

[0173] Accordingly, even while the nucleic acid extraction automation system 10 is performing extraction from samples, an operator can load a new cartridge containing samples without interrupting the nucleic acid extraction process. Thus, system efficiency can be maximized and operator intervention is minimized.

[0174] According to one embodiment, the three or more extraction units 1110 may be configured to be used once sequentially while the nucleic acid extraction process for one sample plate is in progress. The plate transfer unit 1400 may, while the nucleic acid extraction process for one sample plate is in progress, sequentially transfer the sample plate once to each of the three or more extraction units arranged in a first direction. The extraction units 1110 of the present disclosure may be arranged side-by-side in the first direction, and the sample plate may be sequentially transferred to the extraction units 1110 in the first direction while the nucleic acid extraction process proceeds. With this extraction method accompanied by one-way sample transfer, nucleic acid extraction processes for different types of samples can be performed successively in one extraction module 1000.

[0175] Various extraction reagents may be prepared at the supply station 1200, and an extraction unit 1110 that has completed performance of the nucleic acid extraction process for the first sample plate 510 may not be used again for the first sample plate 510. Therefore, the controller 400 may control the extraction unit 1110 for which the process for the first sample plate 510 has been completed so that an extraction protocol for the second sample plate 520 is performed. According to one embodiment, the controller may control functions of the three or more extraction units such that two or more extraction protocols are performed continuously in one extraction module.

[0176]

[0177] Supply station, multi-channel liquid handling unit, plate transfer unit, and identification information reader

[0178] With reference to FIG. 3, the extraction module 1000 may include a supply station 1200, a multi-channel liquid handling unit 1300, a plate transfer unit 1400, and an identification information reader 1500. FIG. 6 is a schematic diagram illustrating the supply station and an arrangement of reagents and consumables mounted thereon according to other exemplary embodiments of the present disclosure.

[0179] The supply station 1200 is configured so that materials 600, 610, 620 required for nucleic acid extraction are placed thereon. The materials 600 include consumables 610 such as pipette tips and reagents 620 required for extraction.

[0180] According to one embodiment, the high-throughput nucleic acid extraction automation system may further include a storage subsystem 200 that supplies materials for nucleic acid extraction and a transfer subsystem 300 that transfers the sample plate 500 and the materials 600 to the extraction subsystem 100. These will be described again later.

[0181] According to one embodiment, the extraction module 1000 may further include the supply station 1200 configured to accommodate the materials. The extraction subsystem 100 receives the sample plate and the materials from the transfer subsystem 300 and can extract nucleic acids. The received sample plate 500 may be placed at the working station 1100, and the received materials 600 may be placed at the supply station 1200.

[0182] According to one embodiment, the supply station 1200 may be configured such that two or more of the materials 600 are arranged in a first direction. In this way, the supply station 1200 and the working station 1100 can be arranged in parallel so that the materials 600 are efficiently provided to the working station 1100.

[0183] According to one embodiment, the supply station 1200 may include a mounting base 1220. The mounting base 1220 provides spaces in which the materials 600 can be placed.

[0184] According to one embodiment, the supply station 1200 may include a positioning guide 1210 for each of the two or more materials 600. The positioning guide 1210 allows the materials 600 to be placed at defined positions. The positioning guide 1210 may be a recess formed on an upper surface of the mounting base 1220 of the supply station 1200. Alternatively, the positioning guide 1210 may be a wall or a structure protruding from the upper surface of the mounting base 1220. The positioning guide 1210 may be formed to match the size of each material 600. For example, a positioning guide 1210-1 for the consumables 610 and a positioning guide 1210-2 for the reagents 620 may differ in size or shape.

[0185] A plurality of materials 600 may be placed at the supply station 1200. The number and types of materials placed at the supply station 1200 may vary depending on the type of samples processed by the extraction module 1000. FIG. 6(A) illustrates an exemplary configuration of materials that may be arranged at the supply station 1200. For example, the supply station 1200 may be configured to accommodate nine types of reagents 620. The reagent 620-1 may be proteinase K, the reagent 620-2 may be an internal control, the reagent 620-3 may be a lysis buffer, the reagent 620-4 may be magnetic beads, the reagent 620-5 may be a binding buffer, the reagent 620-6 may be a washing buffer 1, the reagent 620-7 may be a washing buffer 2, the reagent 620-8 may be a washing buffer 3, and the reagent 620-9 may be an elution buffer.

[0186] According to one embodiment, the supply station 1200 may include a cover opening / closing unit 1230 for the materials 600. Although covers are depicted for the reagent 620-1 and the reagent 620-9, the reagents that require covers are not limited to these; any reagent left on the supply station may be protected from contamination by using a cover. The cover opening / closing unit 1230 may be configured to separate such covers from the reagents and store them, and then re-cap the reagents after operation of the extraction module 1000 is completed. The cover opening / closing unit 1230 may include a gripper capable of picking up a cover. The cover opening / closing unit 1230 may include a shelf for storing covers and a drive unit for moving the gripper.

[0187] According to one embodiment, the mounting base 1220 may include temperature control means 1240. When a reagent requires refrigeration rather than storage at room temperature, prolonged placement at the supply station 1200 may degrade the reagent performance. To prevent this, temperature control means 1240 may be installed at locations where reagents requiring refrigeration are placed so that their temperatures are maintained at a low level. The temperature control means 1240 may be a cooling device equipped with a thermoelectric element such as a Peltier element. The temperature control means 1240 may include a heat-pipe-based cooling structure, a liquid-circulation cooling structure, or a compact compressor-type refrigeration unit. As a result, a stable low-temperature environment can be maintained for reagents exposed at the supply station 1200 for extended periods, thereby minimizing deterioration of reagent characteristics and improving system reliability and reproducibility.

[0188] According to one embodiment, the extraction module 1000 may include the multi-channel liquid handling unit 1300. The multi-channel liquid handling unit may be a liquid-handling device that performs aspiration, dispensing, mixing, and the like through multiple liquid channels. The multi-channel liquid handling unit 1300 may be configured to access the three or more extraction units 1110 of the working station and the materials 600 at the supply station 1200.

[0189] With reference to FIG. 1, the multi-channel liquid handling unit 1300 may include a multi-channel liquid handler. The multi-channel liquid handling unit 1300 includes a liquid handling unit actuator 1310 that controls movement of the multi-channel liquid handler. The liquid handling unit actuator 1310 controls movement of the multi-channel liquid handling unit 1300. Specifically, the liquid handling unit actuator 1310 supports at least three motions among X-, Y-, and Z-axis translations and rotational motion to achieve precise movements of the liquid handling unit. Alternatively, the liquid handling unit actuator 1310 may be a robotic arm.

[0190] According to one embodiment, the multi-channel liquid handling unit 1300 may be, for example, a multi-channel dispenser unit. The multi-channel dispenser unit may be a multi-dispenser configured to simultaneously supply a particular reagent (e.g., a washing buffer or an elution buffer) to a plurality of positions. By means of a nozzle array, multi-channel dispensing can be performed, allowing the same solution can be uniformly delivered at high speed. The multi-channel dispenser unit may be configured to connect to a fixed reagent supply line or to a cartridge-type reagent pack.

[0191] According to one embodiment, the multi-channel liquid handling unit 1300 may be a multi-channel pipettor. The multi-channel pipettor may include one or more multi-channel pipet units and a motion unit. A multi-channel pipet unit may include a multi-channel pipet head and a pipet body. The multi-channel pipet head mounts pipette tips and can aspirate and discharge liquid. The multi-channel pipet head may be coupled to the pipet body so as to be movable in a vertical direction. The pipet body transmits power to, and controls, the multi-channel pipet head.

[0192] The extraction module 1000 may include a plate transfer unit 1400. The plate transfer unit 1400 transfers the sample plate 500 between extraction units 1110. The plate transfer unit 1400 may include a plate holder 1410 and a drive unit 1420. The plate holder 1410 is configured to hold the sample plate 500 and may be in the form of a gripper. The plate holder 1410 may include a support for the sample plate. The drive unit 1420 moves the plate holder 1410. The drive unit 1420 may include linear rails and guides and, for example, may employ a belt-drive mechanism. The drive unit 1420 may include a step motor or a servo motor.

[0193] The extraction module 1000 may include the identification information reader 1500 configured to read identification information of the sample plate 500. The identification information reader 1500 may be a barcode reader, a QR code reader, a camera for recognizing identification information, or an RFID reader. The identification information reader 1500 may read identification information of the sample plate 500 brought by the sample transfer module 3200 and may receive sample data associated with the sample contained in the sample plate. The sample data may include information required to extract nucleic acids from the sample. For example, the sample data may include information on reagents required for nucleic acid extraction of the sample, information on the extraction module 1000 that will receive the sample plate, or information indicating whether the sample plate contains a sample for urgent testing.

[0194] As described above, the extraction module 1000 may include a plurality of working stations 1100. Each of the plurality of working stations 1100 included in one extraction module 1000 may include three or more extraction units 1110 and may perform an independent extraction operation.

[0195] In the extraction module 1000 including a plurality of working stations 1100, at least one of the supply station 1200, the multi-channel liquid handling unit 1300, the plate transfer unit 1400, and the identification information reader 1500 may be configured to operate for all of the plurality of working stations 1100. Specifically, in the extraction module 1000 including a plurality of working stations 1100, the supply station 1200 may be configured to provide the materials 600 to all of the plurality of working stations 1100. In the extraction module 1000 including a plurality of working stations 1100, the multi-channel liquid handling unit 1300 may be configured to access each of the plurality of working stations 1100. In the extraction module 1000 including a plurality of working stations 1100, the plate transfer unit 1400 may be configured to transfer the sample plates 500 located at the respective working stations 1100 among the extraction units 1110 of the plurality of working stations 1100. In the extraction module 1000 including a plurality of working stations 1100, the identification information reader 1500 may be configured to read identification information of all sample plates 500 loaded to the plurality of working stations 1100.

[0196]

[0197] Extraction subsystem

[0198] The high-throughput nucleic acid extraction automation system of the present disclosure includes an extraction subsystem. The extraction subsystem receives a sample plate and materials and extracts nucleic acids.

[0199] The extraction subsystem is a collective concept of extraction modules. One extraction module may constitute the extraction subsystem, or a plurality of extraction modules may constitute the extraction subsystem.

[0200] With reference to FIG. 11, according to one embodiment, the extraction subsystem may include a plurality of extraction modules. By way of example, FIG. 11 illustrates four extraction modules 1000a-1000d included in the extraction subsystem 100, but the number of extraction modules 1000 included in the extraction subsystem 100 is not particularly limited.

[0201] According to one embodiment, the plurality of extraction modules 1000 may be configured to perform different extraction protocols. The controller 400 may independently control each of the first through fourth extraction modules 1000a to1000d. The controller 400 may control the allocation of sample plates 500 containing different types of samples to the first through fourth extraction modules 1000a to1000d, and may control the extraction modules 1000a to 1000d to perform nucleic acid extraction processes for the respective allocated sample plates 500 according to different extraction protocols.

[0202] According to one embodiment, the controller may control the provision of materials corresponding to extraction protocols performed at the plurality of extraction modules to the respective extraction modules. The extraction protocol may vary depending on the type of sample, and the extraction reagents used in the extraction protocol may also differ depending on the sample type. With reference to FIG. 10, the controller 400 may receive information regarding the samples of the first through fourth extraction modules 1000a to 1000d and may control the storage subsystem 200 so that the reagents 620 required for each extraction module are prepared. The controller 400 may further control the transfer subsystem 300 to deliver the reagents 620 prepared for each of the first through fourth extraction modules 1000a to 1000d to the respective extraction modules.

[0203] According to one embodiment, based on identification information of the sample plate 500, the controller 400 may determine the extraction module 1000 at which nucleic acid extraction for the sample plate 500 is to be performed, and may control transfer of the sample plate 500 to the determined extraction module 1000. When a plurality of extraction modules 1000 are respectively performing extraction processes for different samples, the compositions of reagents held in their respective supply stations 1200 may differ from one another. Accordingly, when a new sample plate 500 is received by the system, it is efficient to transfer the sample plate 500 to an extraction module 1000 that can perform nucleic acid extraction for the sample without replacing the reagents stocked in its supply station 1200. With reference to FIG. 10, the sample transfer module 3200 is configured to access all of the plurality of extraction modules 1000a to 1000c. Accordingly, the controller 400 may control the sample transfer module 3200 to transfer the sample plate 500 to the determined extraction module 1000.

[0204] According to one embodiment, the extraction subsystem may be configured to allow additional extraction modules to be installed without changing other extraction modules already included in the extraction subsystem. Owing to its modular design, the extraction module 1000 of the present disclosure can be flexibly expanded and adapted to various testing environments. For example, the extraction subsystem 100 may include two or more extraction modules 1000. In such a case, since each extraction module 1000 is independently controlled and operated, the configuration of extraction units included in each of two or more extraction modules 1000 may differ. In addition, because the extraction modules 1000 have a modular structure, the extraction subsystem 100 of the present disclosure allows additional installation or replacement of extraction modules 1000 without modification of other devices constituting the extraction subsystem.

[0205] According to one embodiment, among the plurality of extraction modules 1000, a component included in one extraction module 1000 may be configured to access another extraction module 1000. For example, the multi-channel liquid handling unit 1300 included in one of the plurality of extraction modules 1000 may be configured to access another extraction module 1000. Specifically, the multi-channel liquid handling unit 1300 included in one extraction module 1000 may access a sample plate mounted at an extraction unit 1110 of another extraction module 1000 to aspirate and discard spent liquids after a reaction or to dispense a fresh reagent. Alternatively, the plate transfer unit 1400 included in one of the plurality of extraction modules 1000 may be configured to access another extraction module 1000. Specifically, the plate transfer unit 1400 included in one extraction module 1000 may access a sample plate mounted on an extraction unit 1110 of another extraction module 1000 and transfer it to a different extraction unit 1110. As a result, by sharing functional units among extraction modules 1000, the system can operated more efficiently.

[0206]

[0207] Storage subsystem

[0208] The high-throughput nucleic acid extraction automation system 10 of the present disclosure may include a storage subsystem 200 that supplies materials for nucleic acid extraction.

[0209] FIG. 7 is a schematic diagram illustrating a structure of the storage subsystem according to exemplary embodiments of the present disclosure. FIG. 8 is a schematic diagram illustrating a structure of the storage subsystem for supplying materials to respective nucleic acid modules in a high-throughput nucleic acid extraction automation system having a plurality of nucleic acid modules according to exemplary embodiments of the present disclosure.

[0210] The storage subsystem 200 stores materials 600 and supplies them to the extraction subsystem 100. According to one embodiment, the materials 600 may include consumables 610 or extraction reagents 620. The consumables 610 may include pipette tips and nucleic acid tubes. The extraction reagents 620 may include at least one of proteinase K, an internal control, a lysis buffer, magnetic beads, a binding buffer, a washing buffer 1, a washing buffer 2, a washing buffer 3, and an elution buffer.

[0211] According to one embodiment, the storage subsystem 200 may include a storage area 210 for storing the materials 600 and a pickup area 220 for delivering the materials 600 to the transfer subsystem 300.

[0212] The storage area 210 is an area for storing the materials 600. The storage area 210 may be configured to store the consumables 610 and the reagents 620 used in the high-throughput nucleic acid extraction automation system of the present disclosure. The consumables and the reagents may be stored in respective separate spaces because optimal storage conditions for the consumables and reagents differ from each other. To this end, according to one embodiment, the storage area 210 may include two or more material storage modules 2100. Referring to FIG. 7, a first material storage module 2100a may store the consumables 610, and a second material storage module 2100b may store the reagents 620. In addition, among the reagents 620, some may require refrigeration or freezing depending on type, whereas others can be stored at room temperature. Therefore, according to one embodiment, the material storage module 2100 may include two or more material storage units 2110. The two or more material storage units 2110 may store different kinds of materials, and their temperature of each may be independently controlled. For example, a first reagent 620a may be a reagent stored at room temperature, and a second reagent 620b may be a refrigerated reagent. In this case, a first material storage unit 2110a may be a material storage unit that maintains room temperature, and a second material storage unit 2110b may be a material storage unit configured to maintain 4 ℃.

[0213] The storage subsystem 200 may include the storage area 210 for storing the materials 600 and the pickup area 220 for delivering the materials 600 to the transfer subsystem 300. The pickup area 220 is an area in which the materials 600 to be transferred to the extraction subsystem 100 are positioned. A material transfer module 3100 of the transfer subsystem 300 may pick up the materials 600 from the pickup area 220 and supply them to the supply station 1200 of an extraction module.

[0214] When the extraction subsystem 100 includes a plurality of extraction modules 1000, the storage subsystem 200 may include a single pickup area 220, and the transfer subsystem 300 may be configured to transfer the materials 600 to each of the plurality of extraction modules 1000. Alternatively, the storage subsystem 200 may include a plurality of pickup areas 220 respectively corresponding to the plurality of extraction modules 1000. Referring to FIG. 8, when the extraction subsystem 100 includes first through third extraction modules 1000a to 1000c, the storage subsystem 200 may include first through third pickup areas 220a to 220c configured to provide the consumables 610 and the reagents 620 required for the supply stations 1200a, 1200b, and 1200c of the respective extraction modules. Because sufficient space is required in the storage area 210 to store various materials 600, the storage area 210 may be positioned apart from the extraction modules 1000 or may be implemented below or above the installation space of the extraction module 1000. Accordingly, when the pickup areas 220a to 220c are positioned adjacent to the supply stations 1200a to 1200c of the respective extraction modules 1000a to 1000c, the materials 600 required for each extraction module 1000 can be supplied rapidly.

[0215]

[0216] Transfer subsystem

[0217] FIG. 9 is a schematic diagram illustrating a material transfer module of a transfer subsystem according to exemplary embodiments of the present disclosure. FIG. 10 is a schematic diagram illustrating a sample transfer module of the transfer subsystem according to exemplary embodiments of the present disclosure. FIG. 1 is a schematic diagram illustrating a high-throughput nucleic acid extraction automation system according to exemplary embodiments of the present disclosure.

[0218] The high-throughput nucleic acid extraction automation system may include a transfer subsystem 300. The transfer subsystem 300 transfers the sample plate 500 and materials 600 to the extraction subsystem 100.

[0219] The transfer subsystem 300 may include a material transfer module 3100 and a sample transfer module 3200. The material transfer module 3100 may transfer the materials 600 from the storage subsystem 200 to the supply station 1200 of the extraction module 1000. The sample transfer module 3200 may be configured to provide the sample plate 500 to the extraction module 1000 (see FIG. 1).

[0220] According to one embodiment, the extraction subsystem may include two or more extraction modules, and the transfer subsystem may include two or more material transfer modules, each of which may be assigned to each extraction module. Referring to FIG. 9, the material transfer module 3100 may include two or more material transfer units 3110a and 3110b that transfer materials from a pickup area 220 of the storage subsystem 200 to the supply station 1200 of the extraction module 1000. The two or more material transfer units 3110a and 3110b may transfer different types of materials. Although consumables 610 and reagents 620 may be transferred by a single device, separate transfer devices may be required in some cases. For example, in a high-throughput extraction system, a large amount of consumables 610 is used, so rapid transfer of the consumables 610 is required, whereas the reagents 620 used in the high-throughput extraction system may be heavy and have wide openings, and thus may require more careful handling during transfer. The material transfer module 3100 may include a first material transfer unit 3110a for transferring the consumables 610 and a second material transfer unit 3110b for transferring the reagents 620. The material transfer module 3100 may include a gripper, a lift, or an articulated robotic arm.

[0221] Referring to FIGS. 1 and 10, the sample transfer module 3200 provides the sample plate 500 to the working station 1100 of the extraction module 1000. The provided sample plate may be delivered to an extraction unit of the working station 1100 by the plate transfer unit 1400 of the extraction module 1000. A single sample transfer module 3200 may deliver a plurality of sample plates 500 to the respective extraction modules 1000a to 1000c.

[0222] The sample transfer module 3200 of the present disclosure may include a carrier. The carrier is a mechanism that continuously transports articles using power and may include a lift and / or a conveyor. The lift may vertically transport the sample plate, and the conveyor may transport the sample plate in a horizontal or inclined direction. The carrier may be implemented as a conveyor alone or as a combination of a conveyor and a lift. The sample plate of the present disclosure may be transferred by the sample transfer module 3200 while being accommodated in a pallet. The pallet of the present disclosure may be a customized pallet configured to receive the sample plate. When transferred in a state accommodated in the pallet, precise positioning of the sample plate can be achieved.

[0223] Referring to FIG. 1, the high-throughput nucleic acid extraction automation system 10 may include a waste collection unit 700. The waste collection unit 700 may be an area where the materials 600 are discarded after use. The waste collection unit 700 may include a waste liquid reservoir 710 and a solid waste reservoir 720. The waste liquid reservoir 710 is where used reagents 620 are discarded, and the solid waste reservoir 720 is where consumables 610 may be discarded. In one embodiment, the waste liquid reservoir 710 and the solid waste reservoir 720 may include sliding doors configured to open and close their openings. The sliding doors seal the interiors of the waste liquid reservoir 710 and the solid waste reservoir 720 to prevent contamination. For example, the sliding doors may open when the system of the present disclosure is started and may close when the system is shut down.

[0224]

[0225] Operation Method

[0226] According to one aspect of the present disclosure, a method for operating a high-throughput, continuously loadable nucleic acid extraction automation system is provided. The system includes an extraction module including at least three extraction units configured to extract nucleic acids, and each of the at least three extraction units comprises at least one function selected from the group consisting of shaking, heating, and magnetic field generation. The method comprises:

[0227] (a) loading a first sample plate to a first extraction unit of the extraction module;

[0228] (b) determining an extraction protocol to be performed on the first sample plate;

[0229] (c) determining, based on the determined extraction protocol, an extraction protocol step to be performed by each of the at least three extraction units;

[0230] (d) performing a first extraction protocol step on the first sample plate by the first extraction unit;

[0231] (e) transferring the first sample plate to a second extraction unit and performing a second extraction protocol step on the first sample plate by the second extraction unit; and

[0232] (f) loading a second sample plate to the first extraction unit of the extraction module.

[0233] The continuously loadable high-throughput nucleic acid extraction automation system (hereinafter, "the system") of the present disclosure includes an extraction module configured to perform nucleic acid extraction. The extraction module includes at least three extraction units. For example, the extraction module may include 3 to 5, 3 to 7, 3 to 9, 3 to 11, or 3 to 20 extraction units. Each extraction unit may have at least one of a shaking function, a heating function, and a magnetic field generation function. The magnetic field generation function may be used, for example, for a magnetic bead-based nucleic acid capture operation during a washing step or an elution step. The shaking function may be used, for example, for mixing magnetic beads and a solution. The heating function may be used, for example, for a lysis operation or a drying operation. The at least three extraction units may include, for example, a first extraction unit and a second extraction unit.

[0234] As described above, an extraction protocol is a procedure that defines a series of process steps to be performed to separate and purify nucleic acids from a sample and the corresponding operating conditions for each step. An extraction protocol step is an individual process unit that constitutes the extraction protocol, in which a specific function (e.g., heating, shaking, or application of a magnetic field) and the corresponding operating conditions are specified, and which is defined to be executable by a single extraction unit. The extraction protocol may include, for example, a first extraction protocol step and a second extraction protocol step.

[0235] As described above, a sample plate may include a plurality of sample wells and may be assigned identification information such as a barcode, a 2D code, or RFID. The system may further include, optionally, a plate transfer unit, materials storage means, a waste collection unit, and various sensors.

[0236] (a) loading a first sample plate to a first extraction unit of the extraction module.

[0237] After reading identification information of the first sample plate, the controller may check the operational status of available extraction units, determine an appropriate first extraction unit, and control loading of the first sample plate onto the determined extraction unit. For example, the loading operation may involve the plate transfer unit 1400 picking up the first sample plate from the sample transfer module 3200 and placing the first sample plate at an extraction unit 1110n (see FIG. 2). The first extraction unit refers to the extraction unit that performs the first extraction protocol step during the execution of the corresponding extraction protocol. The first extraction unit may vary depending on the sample plate.

[0238] (b) determining an extraction protocol to be performed on the first sample plate.

[0239] Based on the identification information of the first sample plate, the controller may select or construct an appropriate extraction protocol in consideration of the type and target of the sample contained in the first sample plate. For example, depending on the type of sample(e.g., nasopharyngeal swab, urine) contained in the first sample plate or the type of target to be extracted (e.g., virus-derived nucleic acid, microorganism-derived nucleic acid), the kinds of extraction reagents used and the parameters of the protocol may differ. The protocol may be a predefined standard protocol, or an adaptive protocol dynamically assembled and modified by the controller based on sample information, reagent availability, and the operational status of the device.

[0240] (c) determining, based on the determined extraction protocol, extraction protocol steps to be performed by each of the at least three extraction units.

[0241] For a given sample plate, the determined extraction protocol may be executed while the sample plate is sequentially transferred among a plurality of extraction units. To this end, the determined extraction protocol may be provided in a form decomposed into a plurality of extraction protocol steps. Alternatively, the controller 400 may decompose the determined extraction protocol into component stages to generate extraction protocol steps. When the controller 400 generates the extraction protocol steps, it may configure them in consideration of the operational status of the extraction module. For example, when a large number of sample plates must be processed by one extraction module, the number of extraction units used for extraction may be increased to minimize the residence time of each sample plate at a single extraction unit. In a continuously loadable extraction system, the shorter the residence time of a sample plate at a single extraction unit, the greater the number of samples that can be processed per unit time. If some extraction units are not operating normally, the extraction protocol steps may be configured such that the extraction proceeds without using those extraction units.

[0242] Next, the extraction units that will perform the extraction protocol steps are determined, and the extraction protocol steps are mapped to the determined extraction units. Preference may be given to mapping an extraction unit capable of performing the functions required by the respective extraction protocol step. Transfer paths and waiting times for the respective steps may also be considered.

[0243] According to one embodiment, the extraction protocol steps to be performed by each of the at least three extraction units may be determined such that the at least three extraction units are used once sequentially. With reference to FIG. 2, for the first sample plate 500, the first extraction protocol step may be assigned to the first extraction unit 1110n, and the second through fourth extraction protocol steps may be sequentially assigned to the second extraction unit 1110o, the third extraction unit 1110p, and the fourth extraction unit 1110q. In this case, not all extraction units 1110 included in the extraction module must be used, and some extraction units may remain unassigned depending on the selected extraction protocol. The expression "the at least three extraction units are used once sequentially" means, for example, that the first and third extraction protocol steps are not redundantly assigned to the same extraction unit (e.g., the first extraction unit 1110n), but rather that the first through fourth extraction protocol steps are respectively assigned to the first through fourth extraction units 1110n to 1110q.

[0244] As described above, when the extraction protocol steps are determined such that the at least three extraction units are used once sequentially, it becomes easier to configure processing of multiple sample plates during continuous loading.

[0245] That is, once the first extraction protocol step for the first sample plate is completed at the first extraction unit, allocation of the first extraction unit to a second sample plate is automatically enabled, since the first extraction unit will no longer be reused for the first sample plate. In addition, the waiting time or transfer path of the second sample plate can be easily set to match the timing at which the first sample plate is transferred to the next extraction unit, thereby simplifying overall procedure setup and minimizing idle time of the extraction units. Consequently, simultaneous continuous processing of two or more sample plates within a single extraction module is facilitated, thereby improving throughput and sample-handling efficiency.

[0246] (d) performing a first extraction protocol step on the first sample plate by the first extraction unit.

[0247] The first extraction unit performs the first extraction protocol step on the first sample plate in accordance with parameters included in the assigned first extraction protocol step. The first extraction protocol step may include dispensing a reagent required for the first sample plate; for example, dispensing magnetic beads to the first sample plate, or dispensing a binding buffer to the first sample plate. In preparation for this, the first extraction protocol step may further include preparing the reagent required for the first sample plate.

[0248] (e) transferring the first sample plate to a second extraction unit and performing a second extraction protocol step on the first sample plate by the second extraction unit.

[0249] When the first extraction protocol step for the first sample plate is completed at the first extraction unit, the first sample plate is transferred to the second extraction unit. The second extraction unit may be the extraction unit designated to perform the second extraction protocol step. The transfer may be performed by the plate transfer unit 1400. The second extraction protocol step may include, for example, operating the magnetic field generation function of the second extraction unit to immobilize magnetic beads on the bottom of the sample plate, removing a reaction solution, and dispensing a washing buffer. Accordingly, the second extraction protocol step may include a step of preparing the washing buffer required for the first sample plate.

[0250] (f) loading a second sample plate to the first extraction unit of the extraction module.

[0251] When the first sample plate is transferred to the second extraction unit, a new sample plate, i.e., a second sample plate, is loaded to the first extraction unit, which has become vacant, and the extraction process proceeds. The second sample plate may undergo the same extraction operation as the first sample plate, or the extraction process may be performed according to an extraction protocol different from that applied to the first sample plate. In addition, a third sample plate and a fourth sample plate may be sequentially introduced in the same manner so that each sample plate simultaneously performs different extraction steps at different extraction units.

[0252] According to the method of the present disclosure, by loading the second sample plate to the first extraction unit in step (f), continuous loading can be achieved within the same extraction module. This is accomplished by immediately reusing the first extraction unit for initial processing step of the next plate while the first sample plate proceeds through subsequent steps at the second extraction unit and beyond. As a result, multiple sample plates are processed in a pipeline manner within a single extraction module, thereby improving throughput and minimizing module idle time.

[0253] While the above description has been made with reference to exemplary embodiments of the present disclosure, it will be understood by those skilled in the art that various modifications and changes can be made without departing from the spirit and scope of the present disclosure as defined by the following claims.

[0254]

[0255] <Cross-Reference to Related Application>

[0256] The application claims priority to Korean Patent Application No. 10-2024-0153029, filed in the Korean Intellectual Property Office on October 31, 2024, the entire disclosure of which is incorporated herein by reference in its entirety.

[0257]

[0258] <List of Reference Signs>

[0259] 10: high-throughput nucleic acid extraction automation system

[0260] 100: extraction subsystem 1000: extraction module

[0261] 1100: working station 1110: extraction unit

[0262] 1111: temperature control means 1112: driving means

[0263] 1113: magnetic means 1114: guide

[0264] 1120: mounting base 1200: supply station

[0265] 1210: positioning guide 1220: mounting base

[0266] 1230: cover opening / closing unit 1240: temperature control means

[0267] 1300: multi-channel liquid handling unit

[0268] 1310: liquid handling unit actuator 1400: plate transfer unit

[0269] 1410: plate holder 1420: drive unit

[0270] 1500: identification information reader 200: storage subsystem

[0271] 210: storage area 2100: material storage module

[0272] 2110: material storage unit 220: pickup area

[0273] 300: transfer subsystem 3100: material transfer module

[0274] 3110: material transfer unit 3200: sample transfer unit

[0275] 400: controller 500: sample plate

[0276] 600: material 610: consumable

[0277] 620: reagent 700: waste collection unit

[0278] 710: waste liquid reservoir 720: solid waste reservoir

Claims

A high-throughput, continuously loadable nucleic acid extraction automation system comprising:(a) an extraction subsystem for receiving a sample plate and a material and extracting nucleic acids;wherein the extraction subsystem comprises at least one extraction module,wherein the extraction module comprises:(a1) a working station including at least three extraction units configured to extract nucleic acids, each of the at least three extraction units comprising at least one function selected from the group of shaking, heating, and magnetic field generation,wherein each of the at least three extraction units is used once sequentially during extraction of the sample plate;(a2) a multi-channel liquid handling unit; and(a3) a plate transfer unit transferring the sample plate between the extraction units, and(b) a controller, wherein the controller is configured to control the extraction subsystem such that while a nucleic acid extraction process for one sample plate is in progress in one extraction unit among the at least three extraction units, another extraction unit receives another sample plate and performs a nucleic acid extraction process for another sample plate.The nucleic acid extraction automation system of claim 1, wherein the extraction subsystem comprises a plurality of extraction modules.The nucleic acid extraction automation system of claim 2, wherein the extraction module further comprises an additional working station including at least three extraction units configured to extract nucleic acids, andwherein the multi-channel liquid handling unit is configured to access each of the working stations in the extraction module.The nucleic acid extraction automation system of claim 2, wherein the plurality of extraction modules are configured to perform different extraction protocols.The nucleic acid extraction automation system of claim 2, wherein the controller is configured to determine an extraction module to perform nucleic acid extraction for the sample plate based on identification information of the sample plate, and to control the sample plate to be transferred to the determined extraction module.The nucleic acid extraction automation system of claim 1, wherein the controller is configured to control the plate transfer unit such that, while a nucleic acid extraction process for one sample plate is being performed, the sample plate is sequentially transferred to and received by two or more extraction units among the at least three extraction units.The nucleic acid extraction automation system of claim 6, wherein the controller is configured to control the extraction module such that a part of the nucleic acid extraction process is performed in the extraction unit in which the sample plate is received.The nucleic acid extraction automation system of claim 6, wherein the extraction module is configured to selectively perform two or more extraction protocols, and the controller is configured to determine an extraction protocol to be used in the extraction module based on a type of sample.The nucleic acid extraction automation system of claim 8, wherein the controller is configured to determine, according to the determined extraction protocol, extraction units to be used for nucleic acid extraction of the sample among the at least three extraction units included in the extraction module.The nucleic acid extraction automation system of claim 8, wherein the at least three extraction units comprise a multifunctional extraction unit configured to perform two or more functions.The nucleic acid extraction automation system of claim 10, wherein the multifunctional extraction unit is configured to selectively perform the two or more functions.The nucleic acid extraction automation system of claim 11, wherein the at least three extraction units comprise two or more of the multifunctional extraction units.The nucleic acid extraction automation system of claim 12, wherein the controller is configured to select, according to the determined extraction protocol, a function to be performed by each of the two or more multifunctional extraction units included in the extraction module.The nucleic acid extraction automation system of claim 10, wherein the controller is configured to change a function of the extraction unit in which the sample plate is received during the nucleic acid extraction process for one sample plate.The nucleic acid extraction automation system of claim 6, wherein the controller is configured to control functions of the at least three extraction units such that two or more extraction protocols are continuously performed in one extraction module.The nucleic acid extraction automation system of claim 10, wherein the two or more functions comprise at least two selected from the group consisting of a heating function, a shaking function, and a magnetic field generation function.The nucleic acid extraction automation system of claim 1, wherein the at least three extraction units comprise an extraction unit including a temperature control means configured to control a temperature of the sample plate.The nucleic acid extraction automation system of claim 1, wherein the at least three extraction units comprise an extraction unit including a driving means configured to move the sample plate to shake a solution in the sample plate.The nucleic acid extraction automation system of claim 1, wherein the at least three extraction units comprise an extraction unit including a magnetic means configured to apply a magnetic force to the sample plate.The nucleic acid extraction automation system of claim 1, wherein the working station is configured such that the at least three extraction units are arranged in a first direction.The nucleic acid extraction automation system of claim 20, wherein the plate transfer unit is configured to move in the first direction and to transfer the sample plate among the at least three extraction units arranged in the first direction.The nucleic acid extraction automation system of claim 1, wherein the extraction module further comprises a supply station configured to accommodate materials.The nucleic acid extraction automation system of claim 22, further comprising a storage subsystem configured to supply materials for nucleic acid extraction and a transfer subsystem configured to transfer the sample plate and the materials to the extraction subsystem.The nucleic acid extraction automation system of claim 23, wherein the storage subsystem is configured to selectively supply materials for nucleic acid extraction based on the sample plate.The nucleic acid extraction automation system of claim 23, wherein the extraction subsystem receives the sample plate and the materials from the transfer subsystem and extracts nucleic acids.The nucleic acid extraction automation system of claim 23, wherein the extraction subsystem comprises a plurality of extraction modules, and the controller is configured to control the materials corresponding to extraction protocols performed in the plurality of extraction modules to be provided to each of the extraction modules.The nucleic acid extraction automation system of claim 1, wherein the working station is configured to allow addition or replacement of extraction units without modification of other extraction units included in the working station.The nucleic acid extraction automation system of claim 22, wherein the multi-channel liquid handling unit is configured to access the at least three extraction units of the working station and the materials of the supply station.The nucleic acid extraction automation system of claim 22, wherein the supply station is configured such that two or more materials are arranged in a first direction.The nucleic acid extraction automation system of claim 29, wherein the supply station comprises a positioning guide for each of the two or more materials.The nucleic acid extraction automation system of claim 22, wherein the supply station comprises a cover opening / closing unit for the materials.The nucleic acid extraction automation system of claim 21, wherein the plate transfer unit is configured to sequentially transfer the sample plate once to each of the at least three extraction units arranged in the first direction during a nucleic acid extraction process for one sample plate.The nucleic acid extraction automation system of claim 1, wherein the extraction subsystem is configured to allow addition of extraction modules without modification of other extraction modules included in the extraction subsystem.The nucleic acid extraction automation system of claim 1, further comprising a waste collection unit configured to collect wastes after use of the materials.The nucleic acid extraction automation system of claim 23, wherein the transfer subsystem comprises a material transfer module configured to transfer the materials of the storage subsystem to the supply station of the extraction module.The nucleic acid extraction automation system of claim 23, wherein the transfer subsystem further comprises a sample transfer module configured to provide the sample plate to the extraction module.The nucleic acid extraction automation system of claim 35, wherein the extraction subsystem comprises two or more extraction modules, the transfer subsystem comprises two or more material transfer modules, and each extraction module is assigned with one of the material transfer modules.The nucleic acid extraction automation system of claim 35, wherein the material transfer module comprises two or more material transfer units.The nucleic acid extraction automation system of claim 38, wherein the two or more material transfer units transfer different types of materials.The nucleic acid extraction automation system of claim 1, wherein the materials comprise consumables or reagents.The nucleic acid extraction automation system of claim 23, wherein the storage subsystem comprises a storage area for storing materials and a pickup area for delivering the materials to the transfer subsystem.The nucleic acid extraction automation system of claim 41, wherein the storage area comprises two or more material storage modules.The nucleic acid extraction automation system of claim 42, wherein each material storage module comprises two or more material storage units.The nucleic acid extraction automation system of claim 43, wherein the two or more material storage units store different types of materials.The nucleic acid extraction automation system of claim 43, wherein the two or more material storage units are independently temperature-controlled.A method for operating a continuously loadable high-throughput nucleic acid extraction automation system, the system comprising an extraction module including at least three extraction units configured to extract nucleic acids, wherein each of the at least three extraction units comprises at least one function selected from the group consisting of shaking, heating, and magnetic field generation,the method comprising:(a) loading a first sample plate to a first extraction unit of the extraction module;(b) determining an extraction protocol to be performed on the first sample plate;(c) determining, based on the determined extraction protocol, an extraction protocol step to be performed by each of the at least three extraction units;(d) performing a first extraction protocol step on the first sample plate by the first extraction unit;(e) transferring the first sample plate to a second extraction unit and performing a second extraction protocol step on the first sample plate by the second extraction unit; and(f) loading a second sample plate to the first extraction unit of the extraction module.

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