WO2024092506A1 - 样本处理模块 - Google Patents

样本处理模块 Download PDF

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Publication number
WO2024092506A1
WO2024092506A1 PCT/CN2022/128981 CN2022128981W WO2024092506A1 WO 2024092506 A1 WO2024092506 A1 WO 2024092506A1 CN 2022128981 W CN2022128981 W CN 2022128981W WO 2024092506 A1 WO2024092506 A1 WO 2024092506A1
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WO
WIPO (PCT)
Prior art keywords
sample processing
processing module
spiral tube
hollow spiral
lifting plate
Prior art date
Application number
PCT/CN2022/128981
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English (en)
French (fr)
Inventor
王俊超
Original Assignee
信任生医股份有限公司
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Publication date
Application filed by 信任生医股份有限公司 filed Critical 信任生医股份有限公司
Priority to PCT/CN2022/128981 priority Critical patent/WO2024092506A1/zh
Publication of WO2024092506A1 publication Critical patent/WO2024092506A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/04—Solvent extraction of solutions which are liquid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/06—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor

Definitions

  • the present invention relates to a sample processing module, in particular to a sample processing module suitable for automated biological sample processing program equipment.
  • nucleic acids e.g., deoxyribonucleic acid (DNA) or ribonucleic acid (RNA)
  • DNA deoxyribonucleic acid
  • RNA ribonucleic acid
  • the current device includes three sets of driving devices, which are used to drive the movement of the magnetic component, the movement of the sleeve, and the rotation of the sleeve.
  • the magnetic component is controlled to capture magnetic beads through magnetic force, and the sample is processed and stirred through the sleeve. Therefore, the automated nucleic acid extraction equipment of the prior art is large in size and requires a large space to place the equipment, resulting in certain restrictions on the conditions of use.
  • the present invention provides a sample processing module, which can achieve the functions of moving up and down and rotating the sleeve through a single driving member.
  • One aspect of the present invention is related to a sample processing module for use with a sleeve, wherein the sample processing module includes a first lifting plate, a fixed plate, a hollow spiral tube and a first driving member.
  • the first lifting plate includes a through hole and a first screw hole arranged on one side of the through hole.
  • the fixed plate is provided with a second screw hole and is arranged opposite to the first lifting plate.
  • the hollow spiral tube includes a hollow body and a threaded portion arranged on the outer surface of the hollow body, wherein the hollow spiral tube has an upper end and a lower end, wherein the upper end is coupled with the through hole of the first lifting plate, and the lower end is detachably coupled with the sleeve, and the hollow spiral tube is screwed with the second screw hole of the fixed plate through the threaded portion, so that the hollow spiral tube is penetrated on the fixed plate.
  • the first driving member includes a first driving rod and a first motor, wherein the first driving rod is screwed with the first screw hole of the first lifting plate, and the first motor is coupled with the first driving rod to drive the first driving rod, and the first lifting plate and the hollow spiral tube are linked to move up and down along the longitudinal axis, and the hollow spiral tube is rotated when moving.
  • the through holes there are a plurality of through holes on the first lifting plate and the through holes are arranged in a row.
  • the hollow spiral tubes are plural and arranged in a row.
  • the sample processing module further includes a bearing, wherein the hollow spiral tube is coupled to the through hole through the bearing.
  • the sample processing module further includes a second lifting plate, a magnetic rod and a second driving member.
  • the second lifting plate includes a third screw hole.
  • the magnetic rod has an upper end and a lower end, wherein the upper end is coupled to the second lifting plate, and the magnetic rod is configured to penetrate the hollow spiral tube.
  • the second driving member includes a second driving rod and a second motor, wherein the second driving rod is screwed into the third screw hole of the second lifting plate, and the second motor is coupled to the second driving rod to drive the second driving rod, and link the second lifting plate and the magnetic rod to move up and down along the longitudinal axis.
  • Another aspect of the present invention is a biological sample processing device for processing a biological sample, comprising a sample processing module of the present invention, a displacement module and a sample tank.
  • the displacement module is coupled to the sample processing module of the present invention and is used to move the sample processing module in a transverse direction.
  • the sample tank is used to hold the biological sample, and the sample processing module is used to process the biological sample in the sample tank.
  • the biological sample processing module further includes a sleeve, which is detachably coupled to the hollow spiral tube; when the hollow spiral tube in the sample module moves up and down and rotates along the longitudinal axis, the sleeve is simultaneously linked to stir the biological sample.
  • the sleeve is polygonal. More preferably, the sleeve further includes a plurality of convex strips disposed on the outer surface of the sleeve.
  • FIG. 1A is a schematic diagram of a sample processing module 100 according to certain embodiments of the present application.
  • FIG. 1B is a cross-sectional view of the sample processing module 100 along line 1B-1B in FIG. 1A ;
  • FIG. 2 is a schematic diagram of a sample processing module 200 according to another embodiment of the present application.
  • FIG3A is a schematic diagram of a second lifting plate, a magnetic rod and a second driving member according to the embodiment of FIG2 ;
  • FIG3B is a cross-sectional view taken along line 3B-3B in FIG3A ;
  • FIG. 4 is a schematic diagram of a sample processing module 400 according to a specific embodiment of the present application.
  • 5A to 5D are schematic diagrams showing the operation of the sample processing module 400 according to an embodiment of the present application.
  • FIG. 6A and FIG. 6B are schematic diagrams showing the configuration of a biological sample processing device 600 according to different embodiments of the present application.
  • biological sample refers to a biological sample suitable for processing by the biological sample processing device and/or the sample processing module of the present invention.
  • the biological sample can be a biological sample for nucleic acid extraction, such as culture fluid, blood, body fluid, animal tissue, plant tissue, virus, and eukaryotic and/or prokaryotic cells.
  • the term "displacement module” refers to any mechanical module known in the art for moving a component/module (e.g., the sample processing module of the present invention) longitudinally and/or transversely.
  • the displacement module can be a robotic arm.
  • the automated nucleic acid extraction equipment on the market mainly uses magnetic bead technology to extract nucleic acids.
  • it is crucial to mix the biological samples with extraction reagents and magnetic beads to allow them to react fully. Therefore, two sets of driving parts are usually set in the existing automated nucleic acid extraction equipment, one set is used to grab and move the sample or sleeve, and the other set is used to drive the sleeve to rotate, thereby stirring the mixed solution containing the biological sample, extraction reagent and magnetic beads.
  • the number of driving parts not only increases the maintenance cost of the equipment, but also inevitably increases the volume of the overall equipment, causing the user to provide a larger space to set up the extraction equipment.
  • the present application provides a sample processing module, which can achieve the purpose of moving and driving the sleeve to rotate by using a single driving component through the design and linkage relationship of each component.
  • FIG. 1A and FIG. 1B are schematic diagrams and cross-sectional diagrams of the sample processing module 100, respectively.
  • the sample processing module 100 includes a first lifting plate 120, a fixed plate 140, a hollow spiral tube 160 and a first driving member 180, wherein the first lifting plate 120 is coupled to the first driving member 180 and the hollow spiral tube 160, respectively, and the hollow spiral tube 160 is further coupled to the fixed plate 140.
  • the hollow spiral tube 160 can be controlled to move along the longitudinal axis direction by the first driving member 180, and the hollow spiral tube 160 can be rotated while moving by setting the fixed plate 140.
  • the sample processing module 100 in order to avoid sample contamination, can be used with a sleeve 190 during operation, so that the sleeve 190 and the sample are contacted respectively to avoid cross-contamination between two independent experiments.
  • the configuration of the sleeve 190 can be a polygon or any other configuration that can generate a vortex flow in the liquid when rotating to mix different contents in the liquid evenly.
  • a plurality of convex strips 192 are provided on the outer surface of the sleeve 190 to increase the vortex flow strength in the vertical direction to achieve a better mixing effect.
  • the sleeve 190 is a disposable consumable.
  • Exemplary materials suitable for preparing the sleeve 190 include, but are not limited to, polymethyl methacrylate (PMMA; also known as acrylic), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE; also known as Teflon), thermoplastic polyurethane (TPU), polyetheretherketone (PEEK), polyethylene (PE), polyether-polyamide block copolymer (PEBA), etc.
  • PMMA polymethyl methacrylate
  • PVC polyvinyl chloride
  • PTFE polytetrafluoroethylene
  • TPU thermoplastic polyurethane
  • PEEK polyetheretherketone
  • PE polyethylene
  • PEBA polyether-polyamide block copolymer
  • the first lifting plate 120 includes a through hole 122 for coupling with the upper end 164 of the hollow spiral tube 160, and the first screw hole 124 is used to screw with the first driving member 180. It should be conceivable that when the first driving member 180 drives the first lifting plate 120 to move up and down by screwing with the first screw hole 124, the hollow spiral tube 160 can be linked to rise or fall synchronously with the first lifting plate 120.
  • the hollow spiral tube 160 can be coupled to the through hole 122 by a conventional method.
  • the hollow spiral tube 160 is coupled to the through hole 122 by a bearing 169, so that the hollow spiral tube 160 can rotate in the through hole 122 without falling.
  • a person with ordinary knowledge in the art can adjust the configuration of the first lifting plate 120 according to actual use requirements to set a plurality of through holes 122 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more) to simultaneously operate a plurality of hollow spiral tubes 160.
  • the first lifting plate 120 is provided with 12 through holes 122 respectively coupled to the hollow spiral tubes 160 and arranged in a row (not disclosed in FIG. 2).
  • more than one row of through holes 122 can be set on the first lifting plate 120. For example, two, three, four, five, six, seven, eight or more rows can be set (not shown in the figure).
  • the fixing plate 140 is provided with a second screw hole 144 for screwing with the hollow screw tube 160.
  • the fixing plate 140 may be provided with a plurality of second screw holes 144.
  • the fixing plate 140 may be provided with 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more second screw holes 144 according to the number of hollow screw tubes 160 coupled to the first lifting plate 120, for screwing with the hollow screw tubes 160.
  • the second screw holes 144 on the fixing plate 140 and the through holes 122 on the first lifting plate 120 have the same number and are arranged correspondingly up and down.
  • the height position of the fixing plate 140 on the longitudinal axis does not change as the hollow spiral tube 160 rotates and moves up and down.
  • the fixing plate 140 is coupled to the first driving member 180 to fix its position (not shown in the figure).
  • the hollow spiral tube 160 includes a hollow body 162 and a threaded portion 168 disposed on the outer surface thereof.
  • the hollow spiral tube 160 has an upper end 164 and a lower end 166, wherein the upper end 164 is rotatably connected to the through hole 122 of the first lifting plate 120, and the lower end 166 is detachably coupled to the sleeve 190 through the fixing plate 140, so that the sleeve 190 can be removed and replaced before and after the test ends.
  • the hollow spiral tube 160 is coupled to the through hole 122 by means of a bearing 169, so that the hollow spiral tube 160 can rotate in the through hole 122 without falling off.
  • the threaded portion 168 is used to be screwed with the second screw hole 144 of the fixing plate 140.
  • a person skilled in the art may select hollow spiral tubes 160 with different pitches according to actual use requirements to change the rotation speed (i.e., the speed at which the sample is stirred). For example, if a hollow spiral tube 160 with a narrower pitch is used, its rotation speed may be increased; if the sample is to be stirred slowly, a hollow spiral tube 160 with a wider pitch may be used instead.
  • the first driving member 180 includes a first driving rod 182 and a first motor 184, wherein the first driving rod 182 is coupled to the first motor 184 and driven to rotate by the first motor 184.
  • the first motor 184 can be any well-known electrical device for converting electrical energy into mechanical energy to drive other devices.
  • the first motor 184 can be a synchronous motor, an induction motor, a reversible motor, a stepping motor, a servo motor, a linear motor or other types of motors.
  • the outer surface of the first driving rod 182 is provided with a thread 183, which is screwed into the first screw hole 124 of the first lifting plate 120. Therefore, when the first motor 184 drives the first driving rod 182 to rotate, the thread in the first screw hole 124 will climb or descend along the thread on the outer surface of the first driving rod 182, thereby driving the first lifting plate 120 to move up and down, and linking the hollow spiral tube 160 to move up and down along the longitudinal axis. At the same time, through the second screw hole 144 on the fixed plate 140, the hollow spiral tube 160 is rotated clockwise or counterclockwise while moving, and drives the sleeve 190 to rotate synchronously to stir the sample.
  • Such a configuration allows the sample processing module 100 of the present invention to drive the sleeve 190 to move and rotate with only one set of driving components (i.e., the first driving component 180), which is one of the advantages of the present invention.
  • the sample processing module 200 of the present invention may further include a second lifting plate 230, a magnetic rod 250 and a second driving member 270, so as to be applied to the experimental procedures of the magnetic bead technology platform, wherein the components of the sample processing module 100 described in FIG. 1 are not described in detail here.
  • the structure and actuation of the second lifting plate 230, the magnetic rod 250 and the second driving member 270 are similar to those of the first lifting plate 220, the first driving member 280 and the hollow spiral tube 260.
  • FIG. 3A is a schematic diagram of the assembly of the second lifting plate 230, the magnetic rod 250 and the second driving member 270 according to these embodiments; and FIG. 3B is a cross-sectional view of FIG. 3A to further illustrate the configuration relationship of each component.
  • the second driving member 270 includes a second driving rod 272 and a second motor 274, wherein the second driving rod 272 is coupled to the second motor 274, and a thread 273 is provided on its outer surface.
  • a third screw hole 232 is provided on one side of the second lifting plate 230 for screwing with the screw rod 272 of the second driving member 270, and the other side is provided for coupling with the magnetic rod 250.
  • the magnetic rod 250 has an upper end 252 and a lower end 254, wherein the upper end 252 is connected to the lower side of the second lifting plate 230, and the lower end 254 is used to pass through the hollow spiral tube 260 and the sleeve 290.
  • the diameter of the magnetic rod 250 is smaller than the diameter of the through hole 222, the hollow spiral tube 260 and the sleeve 290, so that the magnetic rod 250 can pass through the through hole 222 and pass through the hollow spiral tube 260 and the sleeve 290 (please refer to FIG. 2).
  • the second lifting plate 230 can be moved up and down along the second screw rod 272 by the second driving member 270.
  • the second motor 274 can be any well-known electrical device used to convert electrical energy into mechanical energy to drive other devices.
  • the second motor 274 can be a synchronous motor, an induction motor, a reversible motor, a stepper motor, a servo motor, a linear motor or other types of motors.
  • the first driving member 280 drives the first lifting plate 220 to move the hollow spiral tube 260 vertically up and down, and the bottom of the hollow spiral tube 260 can be detachably connected to a sleeve 290.
  • the second driving member 270 drives the second lifting plate 230 to move up and down, and the linked magnetic rod 250 moves up and down along the longitudinal axis, and is inserted into the hollow spiral tube 260 and the sleeve 290.
  • the sample processing module 200 proposed by the present invention can complete the sample processing steps through the above configuration, and those with ordinary knowledge in the relevant technical field can understand that the sample processing module of the present invention can be used to process a large number of biological samples to improve the inspection efficiency.
  • FIG. 4 is a sample processing module 400 according to a specific embodiment of the present application, which can process multiple samples at the same time. Therefore, in this embodiment, the sample processing module 400 is provided with a plurality of hollow screws 430 and a plurality of magnetic rods 460. Structurally, the first lifting plate 410 is provided with a plurality of through holes 422 respectively coupled to the upper ends of the hollow screws 430, and the lower end of the hollow screw 430 can be detachably connected to the sleeve 490 as needed, wherein the connection method is the same as that shown in FIG. 1, and is not further described here. The upper ends of the plurality of magnetic rods 460 are connected to the lower part of the second lifting plate 450.
  • the number of magnetic rods 460 and hollow spiral tubes 430 is the same.
  • the first lifting plate 410 is connected to 12 hollow spiral tubes 430, wherein the hollow spiral tubes 430 are arranged in a row, and the second lifting plate 450 is provided with a corresponding number of 12 magnetic rods 460 and are also arranged in a row, and each magnetic rod 460 is configured to be respectively inserted into the hollow spiral tube 430 and the sleeve 490, and driven to move up and down along the longitudinal axis.
  • the sample processing module 400 of the present invention is applicable to the technology of extracting nucleic acids in samples by magnetic beads, and for the convenience of explanation, this figure is illustrated in a side view schematic diagram, which simplifies the operation mode of the sample processing module 400.
  • a plurality of samples containing nucleic acids to be extracted are added to the sample tank (or any container that can be used to hold these reactants), and are mixed with extraction reagents (e.g., lysis buffer, binding buffer, washing buffer or washing buffer) and/or magnetic beads as needed according to the steps.
  • extraction reagents e.g., lysis buffer, binding buffer, washing buffer or washing buffer
  • the step of taking the sleeve 490 is first performed to start the first driving member 440, so that the first lifting plate 410 begins to descend and is detachably connected to the upper end of the sleeve 490.
  • the first driving member 440 is activated to drive the sleeve 490 to descend and contact the sample in the sample tank.
  • the hollow spiral tube 430 is driven to rotate and drive the sleeve 490 to rotate synchronously ( Figure 5A).
  • the first driving member 440 drives the first lifting plate 410 to rise, so that the sleeve 490 rises and rotates in the opposite direction ( Figure 5B), and the above actions are repeated to perform the mixing step in the sample tank (that is, repeating the steps of Figures 5A and 5B).
  • the second driving member 470 is activated to lower the magnetic bar 460 and pass it into the hollow spiral tube 430 and the sleeve 490 (FIG. 5C).
  • the magnetic beads are attracted by the magnetic force of the magnetic bar 460 and attached to the outside of the sleeve 490, preferably gathered at the bottom of the sleeve 490.
  • the second driving member 470 is activated to raise the magnetic bar 460 away from the sleeve 490, and the magnetic beads will be suspended in the sample again. If the magnetic beads need to be removed from the sample, the first driving member 440 and the second driving member 470 can be activated at the same time to move the sleeve 490 and the magnetic bar 460 out of the sample, so that the magnetic beads can be removed.
  • the biological sample processing device 600 is an automated nucleic acid (e.g., RNA or DNA) extraction system that can simultaneously process multiple biological samples.
  • the biological sample processing device 600 includes a sample processing module 620 as described in any embodiment of the present application, and a displacement module 640 coupled to the sample processing module 620 to move the sample processing module 620 laterally.
  • the biological sample processing device also includes a sample slot 660, wherein the sample slot 660 is used to hold different biological samples and/or extraction reagents required for different steps.
  • the overall operation of the biological sample processing device 600 is substantially the same as that described in FIGS. 5A to 5D , except that the biological sample processing device includes a displacement module 640, which can move the sample processing module between sample slots containing different reaction reagents and extend into the holes for magnetic attraction and/or mixing, so as to automatically complete the entire extraction process and obtain nucleic acid products.
  • a displacement module 640 which can move the sample processing module between sample slots containing different reaction reagents and extend into the holes for magnetic attraction and/or mixing, so as to automatically complete the entire extraction process and obtain nucleic acid products.
  • FIG. 6B is a biological sample processing device 600 according to another embodiment of the present invention.
  • the biological sample processing device 600 further includes a cannula box including a plurality of cannulas 680 for use by the sample processing module 620.
  • the configuration of the cannula 680 and the sample processing module 620 is as described in FIGS. 1 to 4 , and thus will not be further described here.
  • the present application provides a sample processing module and a biological sample processing device comprising the sample processing module, the advantage of which is that longitudinal movement and rotational stirring can be completed through a single driving module, thereby achieving the purpose of reducing the maintenance cost of the automated nucleic acid extraction device and reducing the size of the device.

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Abstract

一种样本处理模块（100），包含一第一升降板（120）、一固定板（140）、一中空螺管（160）以及一第一驱动件（180），第一升降板（120）是与第一驱动件（180）及中空螺管（160）耦接，其中中空螺管（160）进一步与固定板（140）螺合，据以使中空螺管（160）可于升降时同步旋转。

Description

样本处理模块 技术领域
本发明涉及一种样本处理模块，特别是一种适用于自动化生物样本处理程序设备的样本处理模块。
背景技术
核酸(例如脱氧核糖核酸(deoxyribonucleic acid,DNA)或核糖核酸(ribonucleic acid,RNA))萃取为进行分子生物学、遗传学、医学及流行病学等多种研究以及临床诊断的首要步骤。随着核酸萃取的技术愈趋成熟，市面上已有许多萃取套组及自动化萃取设备，以达到快速且大量萃取核酸的目的。
近年来，自动化核酸萃取设备不断推陈出新，特别是采用磁珠技术平台的自动化核酸萃取设备。一般来说，目前的装置包含三组驱动装置，分别为用于驱动磁性组件移动，驱动套管移动和驱动套管旋转等三组驱动装置，其中操控磁性组件透过磁力进行磁珠捕捉，及透过套管处理样本并进行搅拌。因此，先前技术自动化核酸萃取设备体积较大，需要占用较大的空间来放置设备，导致使用条件受到一定限制。
有鉴于此，为了改善自动化核酸萃取设备的缺陷，本领域亟需一种改良的装置及/或设备，以改善先前技术的不足。
发明内容
发明内容旨在提供本申请的简化摘要，以使阅读者对本申请具备基本的理解。此发明内容并非本申请的完整概述，且其用意并非在指出本发明实施例的重要/关键元件或界定本发明的范围。
为解决先前技术所存在的问题，本发明提供一种样本处理模块，其透过单一驱动件即可完成套管上下移动及旋转的功能。
本发明之一态样系有关于一种样本处理模块用以搭配一套管使用，其中样本处理模块包含一第一升降板、一固定板、一中空螺管以及一第一驱动件。所述第一升降板包含一贯穿孔以及设置于所述贯穿孔一侧的第一螺孔。所述固定板设有一第二螺孔，且与所述第一升降板相对设置。所述中空螺管包含一中空本体及一设置于中空本体之外表面的螺纹部，其中中空螺管具有上端及下端，其上端是与第一升降板的贯穿孔耦接，下端则是与所述套管可拆卸地耦接，且中空螺管是藉由所述螺纹部与固定板的第二螺孔螺合，使中空螺管穿设于固定板上。所述第一驱动件包含第一驱动杆及第一马达，其中第一驱动杆是与第一升降板的第一螺孔螺合，第一马达是与第一驱动杆耦接，用以驱动所述第一驱动杆，并连动第一升降板及中空螺管沿着纵轴方向上下移动，且于移动时旋转所述中空螺管。
依据本申请某些实施方式，所述第一升降板上的贯穿孔为复数个且呈列设置。
依据本申请较佳的实施方式，所述中空螺管为复数根且呈列设置。
依据本申请另一实施方式，所述样本处理模块更包含一轴承，其中中空螺管是透过轴承与贯穿孔耦接。
依据本申请又一实施方式，所述样本处理模块更包含一第二升降板、一磁棒以及一第二驱动件。所述第二升降板包含一第三螺孔。所述磁棒具有上端及下端，其中上端与第二升降板耦接，且所述磁棒经配置用以穿设所述中空螺管。所述第二驱动件包含第二驱动杆及第二马达，其中所述第二驱动杆与第二升降板的第三螺孔螺合，第二马达则与第二驱动杆耦接，用以驱动第二驱动杆，并连动第二升降板和磁棒沿着纵轴方向上下移动。
本发明的另一态样系关于一种用以处理一生物样本的生物样本处理设备，包含本发明样本处理模块、一位移模块以及一样本槽。所述位移模块与本发明样本处理模块耦接，用以于横轴方向移动所述样本处理模块。所述样本槽用以盛装生物样本，其中所述样本处理模块用以处理样本槽内的生物样本。
依据本申请一实施方式，所述生物样本处理模块更包含一套管，其与中空螺管可拆卸地耦接；当所述样本模块中的中空螺管沿着纵轴方向上下移动旋转时，同时连动所述套管搅拌生物样本。依据本申请较佳的实施方式，所述套管为多边形。更佳地，所述套管更包含复数个凸条设置于套管的外表面上。
在参阅下文实施方式后，本发明所属技术领域中具有通常知识者当可轻易了解本发明的基本精神及其他发明目的，以及本发明所采用的技术手段与实施态样。
附图说明
为让本发明的上述与其他目的、特征、优点与实施例能更明显易懂，本发明的附图说明如下：
图1A为依据本申请某些实施方式所绘示的样本处理模块100的示意图；
图1B为图1A的样本处理模块100中沿1B-1B线的剖面图；
图2为依据本申请另一实施方式所绘示的样本处理模块200的示意图；
图3A为依据图2的实施方式所绘示的第二升降板、磁棒及第二驱动件的示意图；
图3B为图3A中沿3B-3B线的剖面图；
图4为依据本申请特定实施方式所绘示的样本处理模块400的示意图；
图5A至图5D为依据本申请实施方式所绘示的样本处理模块400的作动示意图；以及
图6A及图6B为依据本申请不同实施方式所绘示的生物样本处理设备600的配置示意图。
根据惯常的作业方式，图中各种特征与元件并未依比例绘制，其绘制方式是为了以最佳的方式呈现与本发明相关的具体特征与元件。此外，在不同图式间，以相同或相似的元件符号来指称相似的元件/ 部件。
附图标记说明：100、200、400、620-样本处理模块；120、220、410-第一升降板；122、222、422-贯穿孔；124-第一螺孔；140、240、420-固定板；144-第二螺孔；160、260、430-中空螺管；162-中空本体；164-上端；166-下端；168-螺纹部；169-轴承；180、280、440-第一驱动件；182-第一驱动杆；183-螺纹；184-第一马达；190、290、490、680-套管；192-凸条；230、450-第二升降板；232-第三螺孔；250、460-磁棒；252-上端；254-下端；270、470-第二驱动件；272-第二驱动杆；273-螺纹；274-第二马达；600-生物样本处理设备；640-位移模块；660-样本槽。
具体实施方式
为了使本申请的叙述更加详尽与完备，下文针对了本发明的实施态样与具体实施例提出了说明性的描述；但这并非实施或运用本发明具体实施例的唯一形式。实施方式中涵盖了多个具体实施例的特征以及用以建构与操作这些具体实施例的方法步骤与其顺序。然而，亦可利用其他具体实施例来达成相同或均等的功能与步骤顺序。
除非本说明书另有定义，此处所用的科学与技术词汇的含义与本新型所属技术领域中具有通常知识者所理解与惯用的意义相同。此外，在不和上下文冲突的情形下，本说明书所用的单数名词涵盖该名词的复数型；而所用的复数名词时亦涵盖该名词的单数型。
所述「生物样本」一词，是指适用于本发明生物样本处理设备及/或样本处理模块所处理的生物样本。在一实施方式中，所述生物样本可以是用以进行核酸萃取的生物样本，如，培养液、血液、体液、动物组织、植物组织、病毒，以及真核和/或原核细胞。
在本申请中「位移模块」一词，是指任一种本领域习知用以沿着纵向和/或横向移动一组件/模块(例如，本发明样本处理模块)的机械模块。在非限制的实施方式中，所述位移模块可以是机器手臂。
除非本说明书另有定义，此处所用的科学与技术词汇的含义与本 发明所属技术领域中具有通常知识者所理解与惯用的意义相同。此外，在不和上下文冲突的情形下，本说明书所用的单数名词涵盖该名词的复数型；而所用的复数名词时亦涵盖该名词的单数型。
目前市面上的自动化核酸萃取设备主要采用磁珠技术来萃取核酸，为了达到自生物样本内萃取目标核酸的目的，将生物样本与萃取试剂以及磁珠等混合使其充分反应至关重要，因此现有的自动化核酸萃取设备内通常会设置两组驱动件，一组用以抓取和移动样本或套管，另一组用以驱动套管旋转，据以搅拌包含生物样本、萃取试剂及磁珠的混合液。然而，驱动件的数量除了提高设备的维护成本外，必然地增加整体设备的体积，造成使用者需提供更大的空间以设置萃取设备。
为了解决前述自动化核酸萃取设备的缺陷，本申请提供一种样本处理模块，藉由各构件的设计及连动关系，可利用单一驱动组件即可达到移动和驱动套管旋转的目的。
图1A及图1B分别为所述样本处理模块100的示意图及剖面图，为了清楚说明所述样本处理模块100的每个元件的构型及配置方式，请同时参见图1A及图1B。如图所示，所述样本处理模块100包含一第一升降板120、一固定板140、一中空螺管160以及一第一驱动件180，其中所述第一升降板120分别与第一驱动件180及中空螺管160耦接，且所述中空螺管160进一步与固定板140耦接。这样的配置方式，可透过第一驱动件180来控制中空螺管160沿着纵轴方向移动，并藉由设置固定板140使中空螺管160于移动的同时旋转。在一实施方式中，为了避免样本污染，所述样本处理模块100于操作时可搭配一套管190使用，让套管190与样本分别接触，以避免先后两次的独立实验之间交互污染。
在本申请实施方式中，所述套管190的构型可以是多边形或其他自转时可于液体内产生回旋流，使液体中不同内容物混合均匀的任一种构型。较佳地，所述套管190的外表面设置复数个凸条192，以增加垂直方向的回旋流强度，使混合效果更好。
依据本申请较佳的实施方式，所述套管190为一次性耗材，适用以制备所述套管190的例示性材质包含，但不限于，聚甲基丙烯酸甲酯(poly methyl methacrylate，PMMA；或称为压克力(acrylic))、聚氯乙烯(poly vinyl chloride，PVC)、聚四氟乙烯(polytetrafluoroethylene，PTFE；或称铁氟龙)、热塑性聚胺酯(thermoplastic polyurethane，TPU)、聚醚醚酮(polyetheretherketone，PEEK)、聚乙烯(polyethylene，PE)、聚醚-聚酰胺嵌段共聚物(polyether block amide，PEBA)等。
依据本申请实施方式，所述第一升降板120包含一贯穿孔122用以与中空螺管160的上端164耦接，以及第一螺孔124用以与第一驱动件180螺合。应可想见，当第一驱动件180藉由与第一螺孔124螺合来驱动第一升降板120上下移动时，可连动所述中空螺管160连同第一升降板120同步上升或下降。在可任选的实施方式中，可利用习知的方法将中空螺管160与贯穿孔122耦接。在本申请较佳的实施方式中，中空螺管160是利用轴承169与贯穿孔122耦接，使中空螺管160可于贯穿孔122内旋转且不会掉落。
依据本申请实施方式，本领域具有通常知识者可依据实际使用需求调整第一升降板120的构型，以设置复数个贯穿孔122(例如2、3、4、5、6、7、8、9、10、11、12或更多)，据以同时操作复数根中空螺管160。在一实施方式中，第一升降板120上是设有12个贯穿孔122分别与中空螺管160耦接，并呈列设置(图2中未揭示)。依据使用目的不同，亦可于第一升降板120上设置一列以上的贯穿孔122，举例来说，可以设置二、三、四、五、六、七、八或更多列(图中未绘示)。
所述固定板140上设置有第二螺孔144与中空螺管160螺合。在较佳的实施方式中，所述固定板140可设置复数个第二螺孔144，举例来说，所述固定板140可依据与第一升降板120的耦接的中空螺管160的数量设置2、3、4、5、6、7、8、9、10、11、12或更多个第二螺孔144，用以螺合该些中空螺管160。在较佳的实施方式中，所述固定板140上的第二螺孔144与第一升降板120上的贯穿孔122有相 同的数量且上下相对应设置。
依据本申请实施方式，在样本处理模块100的操作过程中，固定板140于纵轴上的高度位置不会随着中空螺管160旋转上下移动而改变。在非限制性实施方式中，是将所述固定板140与第一驱动件180耦接，据以固定其位置(图中未绘示)。
所述中空螺管160包含中空本体162以及设置于其外表面的螺纹部168。在结构上，中空螺管160具有上端164和下端166，所述上端164是与第一升降板120的贯穿孔122可旋转地相接，下端166通过固定板140，用以与套管190可拆卸式地耦接，以便在试验结束及开始前卸除及更换所述套管190。如上述，在本申请较佳的实施方式中，中空螺管160是利用轴承169与贯穿孔122耦接，使中空螺管160可于贯穿孔122内旋转且不会掉落。所述螺纹部168用以与固定板140的第二螺孔144螺合。
在非必要的实施方式中，本领域具有通常知识者可依据实际使用需求，选择螺距不同的中空螺管160，据以改变旋转速度(亦即搅拌样本时的速度)，例如，若使用螺距较窄的中空螺管160，可提高其旋转速度；若欲缓慢搅拌样本时，则改以螺距较宽的中空螺管160。
所述第一驱动件180包含一第一驱动杆182以及一第一马达184，其中第一驱动杆182是与第一马达184耦接，并藉由第一马达184驱动其旋转。依据本申请实施方式，所述第一马达184可以是任一种熟知用以将电能转化成机械能来驱动其他装置的电气设备，举例来说，第一马达184可以是同步马达、感应马达、可逆马达、步进马达、伺服马达、线性马达或其他种类的马达。
在一实施方式中，所述第一驱动杆182的外表面设有螺纹183，与第一升降板120的第一螺孔124螺合。因此，第一马达184驱动第一驱动杆182旋转，第一螺孔124内的螺纹就会顺着第一驱动杆182外表面的螺纹爬升或下降，据以带动第一升降板120上下移动，并连动中空螺管160沿着纵轴方向上下移动，同时藉由固定板140上的第二螺孔144，使中空螺管160于移动同时进行顺时针或逆时针旋转， 并带动套管190同步旋转来搅拌样本。这样的配置方式，使得本发明样本处理模块100仅需一组驱动件(亦即，第一驱动件180)即可驱动套管190移动及旋转，此为本发明优势之一。
请参见图2依据本申请某些另一实施方式，本发明样本处理模块200除了包含第1图所述样本处理模块100的构件外，可更包含第二升降板230、磁棒250及第二驱动件270，据以应用于磁珠技术平台的实验程序，其中第1图所述样本处理模块100的构件在此不另赘述。原则上，该第二升降板230、磁棒250及第二驱动件270的结构及作动方式与第一升降板220、第一驱动件280及中空螺管260类似。
具体而言，请同时参见图3A和图3B，其中图3A为依据该些实施方式所绘示的第二升降板230、磁棒250及第二驱动件270的组装示意图；图3B为图3A的剖面图，以进一步说明各构件的配置关系。所述第二驱动件270包含一第二驱动杆272及一第二马达274，其中该第二驱动杆272是与第二马达274耦接，且其外表面设有螺纹273。
所述第二升降板230上的一侧设置一第三螺孔232，用以与第二驱动件270的螺杆272螺接，另一侧设以与磁棒250耦接。所述磁棒250具有上端252和下端254，其中上端252与第二升降板230的下方相接，下端254用以穿设于中空螺管260以及套管290内。在构型上，依据一较佳的实施方式，所述磁棒250的直径小于贯穿孔222、中空螺管260以及套管290的直径，使磁棒250可通过贯穿孔222穿设于中空螺管260以及套管290内(请参照图2)。于实际作动时，藉由第二驱动件270能够使第二升降板230沿着第二螺杆272上下移动。依据本申请实施方式，所述第二马达274可以是任一种熟知用以将电能转化成机械能来驱动其他装置的电气设备，举例来说，第二马达274可以是同步马达、感应马达、可逆马达、步进马达、伺服马达、线性马达或其他种类的马达。
在实际作动时，第一驱动件280透过驱动第一升降板220连带中空螺管260沿着纵向上下移动，中空螺管260的下方可用以与一套管290可拆卸式的相接。第二驱动件270驱动第二升降板230升降，连 动磁棒250沿着纵轴方向上下移动，穿设于中空螺管260及套管290中，本发明所提出的样本处理模块200透过上述配置能够完成样本处理步骤，且所属技术领域中具有通常知识者当可理解可利用本发明样本处理模块，来处理大量的生物样本，以提升检验效率。
图4是依据本申请特定实施方式所绘示的样本处理模块400，可以同时处理复数样本。因此，在此实施例中，所述样本处理模块400设有复数根中空螺管430和复数根磁棒460。在结构上，第一升降板410设有复数个贯穿孔422分别与该些中空螺杆430的上端耦接，且视需要中空螺管430的下端可与套管490可拆卸式地相接，其中所述连接方式与第1图所示相同，在此不另赘述。复数根磁棒460的上端与第二升降板450下方连接。在较佳的实施方式中，磁棒460与中空螺管430的数量相同，如图所示，本实施方式中第一升降板410与12根中空螺管430相接，其中所述中空螺管430呈列设置，以及第二升降板450上设有相对应数量的12根磁棒460且同样呈列设置，且经配置每一磁棒460可分别穿设于中空螺管430及套管490中，经驱动沿着纵轴方向上下移动。
接着，藉由图5A至图5D来进一步说明本发明样本处理模块400的作动方式。
在一实施方式中，本发明样本处理模块400适用于以磁珠来萃取样本中的核酸的技术，且为了方便说明此图以侧视示意图加以说明，简化表示样本处理模块400的作动方式。具体来说，在核酸萃取步骤上，将欲萃取的复数个包含核酸的样本加至样本槽(或任一可用以盛装该些反应物的容器)，依照步骤视需要与萃取试剂(例如，裂解缓冲液、结合缓冲液、冲洗缓冲液或冲提缓冲液)和/或磁珠混合。举例而言，于处理样本前，先进行取用套管490的步骤启动第一驱动件440，使第一升降板410开始下降与套管490的上端可拆卸的连接。接着，于样本处理的步骤上，启动第一驱动件440并带动套管490下降与样本槽中的样本接触，同时藉由中空螺管430与固定板420的配置，驱动中空螺管430自转，并带动套管490同步旋转(图5A)，再藉由第一 驱动件440带动第一升降板410上升，使套管490上升并往相反方向旋转(图5B)，重复上述动作进行样本槽内的混合步骤(亦即重复图5A及图5B的步骤)。再者，可视磁珠萃取法步骤的需要，启动第二驱动件470使磁棒460下降，穿设至中空螺管430及套管490内(图5C)，藉由磁棒460的磁力吸引磁珠，使其贴附于套管490外侧，较佳是聚集于套管490的下方处，若要将磁珠再次悬浮于样本中，启动第二驱动件470使磁棒460上升，远离所述套管490，磁珠将再次悬浮于所述样本中。若需从样本中移除磁珠，可同时启动第一驱动件440及第二驱动件470将所述套管490连同磁棒460移出于样本外，则可将磁珠移除。
图6A及图6B为依据本申请不同实施方式所绘示的生物样本处理设备600的配置示意图。在较佳的实施方式中，所述生物样本处理设备600为一自动化核酸(例如，RNA或DNA)萃取系统，能够同步处理多个生物样本。具体来说，如图6A所示所述生物样本处理设备600包含本申请任一种实施方式所述的样本处理模块620，以及一位移模块640与样本处理模块620耦接，据以横向移动所述样本处理模块620。此外，所述生物样本处理设备亦包含一样本槽660，其中样本槽660用以盛装不同生物样本及/或不同步骤所需的萃取试剂。
所述生物样本处理设备600的整体操作方式与图5A至图5D所述大致相同，惟生物样本处理设备包含位移模块640，可带着样本处理模块于包含不同反应试剂的样本槽间移动，并伸入孔洞中进行磁吸和/或混合，以自动化完成全部的萃取流程，获得核酸产物。
图6B为依据本发明另一实施方式所示的生物样本处理设备600，在此实施方式中，生物样本处理设备600更包含套管匣包含有复数套管680供所述样本处理模块620取用，所述套管680与样本处理模块620的配置方式如第1图至图4所述，故在此不另赘述。
总结上述，本申请提供一种样本处理模块及包含所述样本处理模块的生物样本处理设备，其优势在于透过单一驱动模块即可完成纵向移动和自转搅拌的作动，达到降低自动化核酸萃取设备的维护成本及 缩减设备体积的目的。
虽然上文实施方式中揭露了本发明的具体实施例，然其并非用以限定本发明，本发明所属技术领域中具有通常知识者，在不悖离本发明的原理与精神的情形下，当可对其进行各种更动与修饰，因此本发明的保护范围当以附随申请专利范围所界定者为准。

Claims (10)

  1. 一种样本处理模块，用以搭配一套管使用，其特征在于，包含一第一升降板，包含：
    一贯穿孔；和
    一第一螺孔设于该贯穿孔之一侧；
    一固定板，设有一第二螺孔，且该固定板与该第一升降板相对设置；
    一中空螺管，包含一中空本体及一螺纹部设于该中空本体的外表面，其中该中空螺管具有一上端及一下端，该上端与该贯穿孔耦接，该中空螺管藉由该螺纹部与该固定板的第二螺孔螺合，并使该中空螺管穿设于该固定板上，且该中空螺管的该下端用以与该套管可拆卸地耦接；以及
    一第一驱动件，包含：
    一第一驱动杆，与该第一升降板的第一螺孔螺合；和
    一第一马达，与该第一驱动杆耦接，用以驱动该第一驱动杆连动该第一升降板和该中空螺管沿着纵轴方向上下移动，且该中空螺管于移动时旋转。
  2. 根据权利要求1所述的样本处理模块，其特征在于，更包含：
    一第二升降板，包含一第三螺孔于该第二升降板上；
    一磁棒，具有一上端和一下端，其中该上端与该第二升降板耦接，且该磁棒经配置用以穿设该中空螺管；以及
    一第二驱动件，包含：
    一第二驱动杆，与该第二升降板的第三螺孔螺合；以及
    一第二马达，与该第二驱动杆耦接，用以驱动该第二驱动杆连动该第二升降板和该磁棒沿着纵轴方向上下移动。
  3. 根据权利要求1所述的样本处理模块，其特征在于，更包含一 轴承，其中该中空螺管透过该轴承与该贯穿孔耦接。
  4. 根据权利要求1所述的样本处理模块，其特征在于，其中该中空螺管的下端用以与该套管卡合。
  5. 根据权利要求1所述的样本处理模块，其特征在于，其中该第一升降板上的该贯穿孔为复数个且呈列设置。
  6. 根据权利要求1所述的样本处理模块，其特征在于，其中该中空螺管为复数根且呈列设置。
  7. 一种生物样本处理设备，用以处理一生物样本，其特征在于，包含：
    一如权利要求1所述的样本处理模块；
    一位移模块，与该样本处理模块耦接，并用以于横轴方向移动该样本处理模块；以及
    一样本槽，用以承装该生物样本，其中该样本处理模块用以处理该样本槽内的该生物样本。
  8. 根据权利要求7所述的生物样本处理设备，其特征在于，更包含一套管，用以与该中空螺管可拆卸地耦接，其中当驱动该样本处理模块中的该中空螺管沿着纵轴方向上下移动旋转时，同时搅拌该生物样本。
  9. 根据权利要求8所述的生物样本处理设备，其特征在于，其中该套管为多边形。
  10. 根据权利要求9所述的生物样本处理设备，其特征在于，其中该套管更包含复数个凸条设于该套管的外表面上。
PCT/CN2022/128981 2022-11-01 2022-11-01 样本处理模块 WO2024092506A1 (zh)

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