WO2019010677A1 - 声波均质模块及生物样本制备系统 - Google Patents

声波均质模块及生物样本制备系统 Download PDF

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Publication number
WO2019010677A1
WO2019010677A1 PCT/CN2017/092819 CN2017092819W WO2019010677A1 WO 2019010677 A1 WO2019010677 A1 WO 2019010677A1 CN 2017092819 W CN2017092819 W CN 2017092819W WO 2019010677 A1 WO2019010677 A1 WO 2019010677A1
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Prior art keywords
module
biological sample
sonic
piezoelectric
sleeve
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PCT/CN2017/092819
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English (en)
French (fr)
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王俊超
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王俊超
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Application filed by 王俊超 filed Critical 王俊超
Priority to PCT/CN2017/092819 priority Critical patent/WO2019010677A1/zh
Priority to US16/630,842 priority patent/US11340147B2/en
Priority to EP17917876.9A priority patent/EP3653697B1/en
Priority to CN201780093041.1A priority patent/CN110914405A/zh
Publication of WO2019010677A1 publication Critical patent/WO2019010677A1/zh

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    • 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
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/06—Hydrolysis; Cell lysis; Extraction of intracellular or cell wall material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/20—Mixing the contents of independent containers, e.g. test tubes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
    • B01F31/85—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations with a vibrating element inside the receptacle
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1006—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
    • C12N15/1013—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers by using magnetic beads
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
    • G01N2001/2866—Grinding or homogeneising

Definitions

  • This invention relates to a sonic homogenization module and, more particularly, to a sonic homogenization module for use in an automated biological sample preparation system.
  • a general biological sample preparation system such as an automated nucleic acid extraction device, mainly uses a stirring sleeve to swing above and below, and disturbs the mixed biological sample, but it should be noted that this stirring method is more disturbing to the biological sample in the sample tank. Large, so that adjacent samples are prone to cross-contamination due to sample splash, which leads to misjudgment.
  • the well-known biological sample preparation system must use a larger volume of the sample tank, and the volume of the device cannot be reduced.
  • One aspect of the present invention relates to a sonic homogenization module that integrates acoustic waves and/or ultrasonic techniques to agitate biological samples at high frequencies to achieve the goal of adequately mixing the samples and avoiding cross-contamination.
  • the sonic homogenization module is used in conjunction with a biological sample preparation system.
  • the sonic homogenization module comprises a sleeve connector, a magnetic Rod, piezoelectric conduction component and driver.
  • the sleeve connector includes a receiving portion and a through portion.
  • the magnetic bar is used to pierce the through portion of the sleeve connector, the piezoelectric conduction component is disposed at the receiving portion of the sleeve connector; and the driver is electrically coupled to the piezoelectric conduction component to cause the piezoelectric conduction component to emit ultrasonic waves shock.
  • the vibration is at a frequency of 100 kilohertz (KHz) to 1 megahertz (MHz).
  • the acoustic wave homogenizing module further includes a vibration motor disposed in the accommodating portion and adjacent to the driver.
  • the driver is disposed at a receiving portion of the sleeve connector.
  • the acoustic homogenization module further includes a test sleeve, the upper end of which is sleeved under the sleeve connecting portion, and wherein the vibration generated by the piezoelectric conducting component can be transmitted through the test sleeve In the biological sample.
  • the magnetic bar can be threaded through the test sleeve.
  • the piezoelectric conducting component is disposed at a bottom of the receiving portion and adjacent to the through portion. In another embodiment of the present invention, the piezoelectric conducting component is disposed at a bottom of the receiving portion and disposed around the through portion.
  • Another aspect of the present invention relates to a biological sample preparation system, comprising the acoustic wave homogenization module according to any one of the above embodiments; and a displacement module electrically coupled to a driver of the acoustic homogenization module and configured to move Acoustic homogenization module.
  • the biological sample preparation system further comprises a test sleeve, the upper end of which is sleeved under the insertion portion of the sleeve connector.
  • the biological sample preparation system may further include the same groove, wherein the sample slot includes a plurality of accommodating spaces, and wherein the displacement module is configured to move the test sleeve of the sonic homogenization module into the accommodating spaces, Perform homogenous agitation.
  • 1A and 1B are respectively a sound wave homogenization module 100 according to different embodiments of the present invention.
  • Figure 1C is a cross-sectional view of the acoustic homogenization module 100 taken along line 1C-1C' of Figure 1B;
  • FIG. 2A is a schematic diagram showing the internal configuration of a sound wave homogenizing module 200 according to another embodiment of the present invention.
  • Figure 2B is a cross-sectional view taken along line 2B-2B' of Figure 2A;
  • Figure 3 is a sound wave homogenization module 300 according to another embodiment of the present invention.
  • FIG. 4 is a schematic diagram showing the hardware configuration of a biological sample preparation system 500 according to an embodiment of the present invention.
  • FIG. 5 is a schematic diagram of the use of the acoustic wave homogenization module 100 of the present invention.
  • sound wave encompasses the frequency range of sound waves and/or ultrasound.
  • molecule refers to a nucleic acid molecule and/or a protein molecule within a biological sample.
  • biological sample refers to a biological sample suitable for use in the sonic homogenization module and/or biological sample preparation system of the present invention, for example, a biological sample for nucleic acid extraction, such as blood, body fluid, Animal tissue, plant tissue, and eukaryotic and/or prokaryotic cells.
  • biological sample preparation system refers to automated preparation equipment on the market for processing the above biological samples, especially automated nucleic acid extraction equipment using a magnetic bead technology platform.
  • the automated nucleic acid extraction equipment on the market mainly uses magnetic bead technology to extract nucleic acid, which uses a magnetic rod to agitate the biological sample in the sample tank to release the nucleic acid; however, the magnetic rod is stirred up and down. It is easy to splash the liquid in the sample tank, resulting in cross-contamination between samples, and even affecting the correctness of the test results in severe cases. Moreover, this up and down agitation mode makes it necessary to take into account the degree of liquid level fluctuation when designing the sample tank, and a larger capacity sample tank design is often used to avoid the above liquid splash.
  • the inventor of the present invention proposed a novel sonic homogenization module which adopts a mild stirring method and transmits high-frequency sound waves or ultrasonic waves, thereby not only reducing the liquid level fluctuation. Amplitude to avoid cross-contamination Occurs, it can make the magnetic beads in the sample suspend, increase the collision frequency of the magnetic beads, and thus improve the efficiency of the magnetic beads to capture the target (such as protein or nucleic acid).
  • FIG. 1A and FIG. 1B are schematic diagrams showing the appearance of a sonic homogenizing module 100 according to various embodiments of the present invention, wherein FIG. 1A is an exploded schematic view and FIG. 1B is an assembled schematic view. Further, in order to more clearly understand the arrangement of each component inside the sonic homogenizing module 100 of the present invention, Fig. 1C is a cross-sectional view taken along line 1C-1C' of Fig. 1B.
  • the acoustic homogenization module 100 of the present invention includes a cannula connector 110, a magnetic bar 120, a piezoelectric conduction component 130, and a driver 140 (Fig. 1C) for driving the piezoelectric conduction component 130.
  • the sonic homogenization module 100 of the present invention needs to be used in conjunction with a biological sample preparation system (for example, an automated nucleic acid extraction device), and the cannula connector 110 and/or the magnetic bar 120 of the sonic homogenization module 100 can be used with A mobile device (not shown) of the well-known biological sample preparation system is coupled to facilitate manipulation of the sonic homogenization module 100 to process biological samples, particularly nucleic acid extraction.
  • a biological sample preparation system for example, an automated nucleic acid extraction device
  • the sleeve connector 110 has a receiving portion 112 and a through portion 114.
  • the receiving portion 112 can be coupled to a moving device of a commonly known biological sample preparation system.
  • the insertion portion 114 allows the magnetic bar 120 to be movably disposed therein.
  • the receiving portion 112 is further provided with a snapping structure (eg, a card slot 145) for coupling with a mobile device generally known as a biological sample preparation system.
  • a snapping structure eg, a card slot 145
  • a mobile device generally known as a biological sample preparation system.
  • the acoustic homogenization module 100 of the present invention disposes the driver 140 and the piezoelectric conduction component 130 under the accommodating portion 112, wherein the piezoelectric conduction
  • the component 130 and the driver 140 are electrically coupled to each other and drive the piezoelectric conduction component 130 through the driver 140 to generate a vibration frequency of sound waves and/or ultrasonic waves to disturb the biological sample.
  • the acoustic homogenization module 100 of the present invention can generate a vibration frequency between 100 kHz and 1,000 kHz (ie, 1 MHz), for example, 100, 101, 102, 103, 104, 105, 106, 107, 108.
  • the acoustic homogenization module 100 of the present invention additionally includes a test sleeve 150 that is sleeved under the through portion 114 of the sleeve connector 110 for contacting the biological sample.
  • the acoustic waves or ultrasonic waves generated by the piezoelectric conduction component 130 can be conducted through the cannula connector 110 and through the test cannula 150 to the biological sample, disturbing the magnetic beads and/or molecules in the biological sample. .
  • the piezoelectric conducting component 130 is disposed at the bottom of the receiving portion 112 of the sleeve connector 110 and adjacent to the through portion 114 . It should be noted that the piezoelectric conduction component 130 does not directly contact the magnetic bar 120.
  • the acoustic homogenization module 100 of the present invention provides a vibration source to the adjacent test sleeve 150 by the piezoelectric conduction component 130 disposed in the sleeve connector 110 through the configuration of the structure, and is then conducted from above the test sleeve 150.
  • this method not only enables the sonic homogenization module 100 to be fastened to the mobile device of the biological sample preparation system through the accommodating portion 112, so that it is not easy to slip, and can also effectively stir the biological sample to avoid liquid between the samples. Splash.
  • the vibration source ie, the driver 140 and the piezoelectric conduction component 130
  • the sonic homogenization module 100 of the present invention is highly maneuverable, and can be applied to a plurality of sample slots of different configurations.
  • One of the advantages of the present invention is that the sound waves and/or ultrasonic waves are effectively conducted into the sample tank to achieve the mixing effect.
  • FIG. 2A is a schematic diagram showing the internal configuration of the acoustic wave homogenizing module 200 according to another embodiment of the present invention
  • FIG. 2B is a cross-sectional view taken along line 2B-2B' of FIG. 2A.
  • the components of the sonic homogenization module 200 of this embodiment are substantially the same as the sonic homogenization module 100, and therefore, the same components are not described herein.
  • the piezoelectric conduction component 230 and the driver 240 of the acoustic homogenization module 200 are also disposed at the bottom of the receiving portion 212 of the sleeve connector 210.
  • the portion is disposed around the through portion 214 to increase the contact area of the piezoelectric conducting component 230 with the sleeve connector 210, thereby improving vibration efficiency.
  • the magnetic bar 220 can be penetrated into the portion 214, and the piezoelectric conduction component 230 does not directly contact the magnetic bar 220.
  • FIG. 3 illustrates a sound wave homogenization module 300 in accordance with another embodiment of the present invention.
  • the sonic homogenization module 300 integrates two vibration techniques, namely a vibration motor and a sonic vibration module, to provide amplitudes of different intensities to extract nucleic acids in the biological sample.
  • the present acoustic homogenization module 300 is provided with a sleeve connector 310, a magnetic bar 320, a piezoelectric conduction assembly 330, a driver 340, a test sleeve 350, and a vibration motor 360.
  • the sleeve connector 310 has the same structure as the sleeve connector 110 shown in the above embodiment, and is provided with a receiving portion 312 and a penetrating portion 314.
  • the acoustic wave vibration module is composed of a driver 340 and a piezoelectric conducting component 330. .
  • the accommodating portion 312 is internally loaded with a driver 340, a vibration motor 360 and a piezoelectric conducting component 330.
  • the piezoelectric conducting component 330 is disposed at the bottom of the accommodating portion 312 and electrically coupled to the piezoelectric conducting component 330.
  • the vibration motor 360 and the driver 340 are adjacent to each other.
  • a specific vibration module that is, a vibration motor or a sonic vibration module may be selected according to the purpose of sample processing. It should be understood by those skilled in the art that the configuration of the driver 340 and the vibration motor 360 assembly can be adjusted according to the actual use condition; in addition, the driver 340 can also be disposed outside the sleeve connector 310.
  • FIG. 4 is a schematic diagram showing the hardware configuration of a biological sample preparation system 500 according to an embodiment of the present invention.
  • the biological sample preparation system 500 includes a power supply module 550, a displacement module 560, and at least one acoustic homogenization module 100.
  • the sonic homogenization module 100 is the acoustic homogenization module 100 shown in FIGS. 1A-1C.
  • the biological sample preparation system 500 of the present invention is coupled to the displacement module 560 and the acoustic homogenization module 100 for providing the energy required for driving the components of the device (FIG. 4).
  • the displacement module 560 is an automated robotic arm that can drive the acoustic homogenization module 110 of the present invention to move laterally and/or longitudinally in a three-dimensional space.
  • the displacement module 560 can be provided with a magnetic lifting module (not shown) for driving the magnetic rod 120 to move up and down linearly.
  • the biological sample preparation system 500 of the present invention is a fully automated nucleic acid extraction (for example, ribose nucleic acid (RNA) or deoxyribose nucleic acid (DNA)) system, which is capable of efficiently producing a high purity nucleic acid product.
  • RNA ribose nucleic acid
  • DNA deoxyribose nucleic acid
  • the biological sample is usually processed in conjunction with the test cannula 150 to avoid cross-contamination between samples.
  • the test cannula 150 is a disposable object.
  • the biological sample preparation system 500 can further include the same local tank 580, and the sample tank 580 is provided with a plurality of accommodating spaces 582. It should be understood by those skilled in the art that the required reagents can be filled in a plurality of accommodating spaces of the sample tank according to the purpose of preparation of the biological sample, for example, magnetic beads, lysis buffer, and binding buffer. A binding buffer, a wash buffer, and/or an eluent buffer.
  • the displacement module 560 ie, the automated robot arm
  • the sonic homogenization module 100 of the present invention utilizes a vibrating motor and/or ultrasonic waves to achieve the technical efficiency of homogenizing the magnetic beads and/or nucleic acid molecules within the perturbed sample, rather than driving the agitation through the displacement module 560 using prior art techniques.
  • the rod (corresponding to the test sleeve) is moved up and down for mixing, and the technical means proposed by the invention can effectively reduce the volume of the sample tank accommodation space, and can also reduce the risk of cross-contamination.
  • the acoustic wave homogenization module 100 of the present invention transmits the seismic wave emitted by the piezoelectric conduction component 130 to the biological sample in the accommodating space 582 through the test sleeve 150, so that the magnetic beads 584 in the biological sample are suspended. Increasing the collision frequency between each other can effectively improve the efficiency of nucleic acid extraction.
  • the magnetic rods 120 can be moved into the test sleeve 150 through the insertion portion 114 through the displacement module 560 to perform sample magnetization, and the magnetic rod 120 moves upward through the displacement module 560 to leave the test.
  • a person skilled in the art can configure the displacement module 560, the magnetic lift module 570 and the magnetic lift module 570 in the biological sample preparation system 500 according to the steps of extracting nucleic acid according to the magnetic beads. The operation and arrangement of the components of the plurality of sonic homogenization modules 100.
  • the biological sample preparation system 500 of the present invention may be provided with a plurality of acoustic wave homogenization modules 100 side by side, and each of the modules is coupled to the displacement module 560 to improve the preparation efficiency.

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Abstract

一种声波均质模块（100、200、300）和含该声波均质模块的生物样本制备系统（500）。声波均质模块（100、200、300）包括套管连接件（110、210、310）、磁棒（120、220、320）、压电传导组件（130、230、330）和驱动器（140、340）。套管连接件（110、210、310）具一容置部（112、212、312）和一穿设部（114、214、314）。磁棒（120、220、320）用以穿设套管连接件（110、210、310）的穿设部（114、214、314）。压电传导组件（130、230、330）设于套管连接件（110、210、310）的容置部（112、212、312）。驱动器（140、340）与压电传导组件（130、230、330）电性耦接，使压电传导组件（130、230、330）以100千赫兹至1兆赫兹的频率震动。

Description

声波均质模块及生物样本制备系统 技术领域
本发明是有关于一种声波均质模块，且特别是有关于一种供自动化生物样本制备系统使用的声波均质模块。
背景技术
市面上有多种用以制备生物样本(如，核酸)的设备，特别是基于磁珠技术平台而开发的生物样本制备系统。一般的生物样本制备系统，例如自动化核酸萃取设备，主要是利用搅拌套管以上下摆动的方式，扰动混合生物样本，但需要注意的是，此一搅拌方式对样本槽中的生物样本扰动程度较大，使得邻近样本间容易因样本飞溅造成交叉污染，进而产生误判。同时，为了避免搅动过程因液面起伏使样本溢出，通常熟知的生物样本制备系统必须使用更大体积的样本槽，也使得设备体积无法缩小。
有鉴于此，为了避免交叉污染的产生，提升生物样本设备的制备效能，本领域亟需一种改良的声波均质模块，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内容的简化摘要，以使阅读者对本申请内容具备基本的理解。此发明内容并非本申请内容的完整概述，且其用意并非在指出本发明实施例的重要/关键组件或界定本发明的范围。
本发明的一态样是有关于一种声波均质模块，整合声波和/或超声波技术于高频进行生物样本搅拌，达到充分混合样本且避免交叉污染发生的目的。
依据本发明一实施方式，所述声波均质模块是用以搭配一生物样本制备系统使用。在结构上，所述声波均质模块包含套管连接件、磁 棒、压电传导组件和驱动器。所述套管连接件含一容置部和一穿设部。磁棒用以穿设套管连接件的穿设部，压电传导组件设于套管连接件的容置部；以及驱动器与压电传导组件电性耦接，使该压电传导组件发出超声波震动。在一具体的实施方式中，以一100千赫兹(KHz)-1兆赫兹(MHz)的频率震动。
依据本发明另一实施方式，所述声波均质模块，还包含一震动马达设于容置部中，且与所述驱动器相邻。
依据本发明一具体的实施方式，所述驱动器设于套管连接件的容置部。
依据本发明另一实施方式，所述声波均质模块还包含一试验套管，其上端与套管连接件穿设部下方套接，且其中压电传导组件所产生震动可通过试验套管传导至生物样本中。
在本发明一实施方式中，所述磁棒可穿设于试验套管中。
在本发明另一实施方式中，所述压电传导组件设于容置部的底部且邻近穿设部。在本发明另一实施方式中，所述压电传导组件设于该容置部的底部且环绕穿设部设置。
本发明另一态样是关于一种生物样本制备系统，其包含上述任一实施方式所述的声波均质模块；以及一位移模块，与声波均质模块的驱动器电性耦接，并用以移动声波均质模块。
依据本发明一实施方式，所述生物样本制备系统还包含一试验套管，其上端与套管连接件的穿设部下方套接。再者，所述生物样本制备系统可还包含一样本槽，其中样本槽包含多个容置空间，且其中位移模块用以移动该声波均质模块的试验套管于该些容置空间中，进行均质搅拌。
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，所附图式的说明如下：
图1A和图1B分别为依据本发明不同实施方式所示的声波均质模块100；
图1C为图1B中沿着1C-1C’线所示的声波均质模块100的剖视图；
图2A为依据本发明另一实施方式所示的声波均质模块200的内部配置示意图；
图2B为图2A中沿着2B-2B’线的剖视图；
图3为依据本发明另一实施方式所示的声波均质模块300；
图4为依据本发明一实施方式所示的生物样本制备系统500的硬件配置示意图；以及
图5为本发明声波均质模块100的使用示意图。
根据惯常的作业方式，图中各种特征与组件并未依比例绘制，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组件。此外，在不同图式间，以相同或相似的组件符号来指称相似的组件/部件。
具体实施方式
为了使本公开内容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。
虽然用以界定本发明较广范围的数值范围与参数皆是约略的数值，此处已尽可能精确地呈现具体实施例中的相关数值。然而，任何数值本质上不可避免地含有因个别测试方法所致的标准偏差。在此处，「约」通常是指实际数值在一特定数值或范围的正负10％、5％、1％或0.5％之内。或者是，「约」一词代表实际数值落在平均值的可接 受标准误差之内，视本发明所属技术领域中具有通常知识者的考虑而定。除了实验例之外，或除非另有明确的说明，当可理解此处所用的所有范围、数量、数值与百分比(例如用以描述材料用量、时间长短、温度、操作条件、数量比例及其他相似者)均经过「约」的修饰。因此，除非另有相反的说明，本说明书与附随申请专利范围所公开的数值参数皆为约略的数值，且可视需求而更动。至少应将这些数值参数理解为所指出的有效位数与套用一般进位法所得到的数值。
所述「声波」一词，涵盖声波和/或超声波的频率范围。
在此所述「分子」是指生物样本内的核酸分子和/或蛋白质分子。
所述「生物样本」一词，是指适用于本发明声波均质模块和/或生物样本制备系统处理的生物性样本，例如，用以供核酸萃取的生物性样本，如，血液、体液、动物组织、植物组织，以及真核和/或原核细胞。
在本文中「生物样本制备系统」一词是指市面上用以处理上述生物样本的自动化制备设备，尤其是采用磁珠技术平台的自动化核酸萃取设备。
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，其是利用磁棒上、下搅动样本槽内的生物样本使核酸释出；然而，此一利用磁棒上、下搅动的方式容易使样本槽内的液体飞溅，导致样本间交叉污染，严重时甚至会影响检验结果的正确性。再者，此种上、下搅动方式使得在设计样本槽时，必需将液面起伏程度纳入考虑，往往会采用较大容量的样本槽设计，以避免上述液体飞溅情况。
为了解决前述搅拌生物样本衍生的样本交叉污染问题，本案发明人提出一种新颖的声波均质模块，其采用温和的搅拌方式，并透过高频的声波或超声波传导，不仅能降低液面起伏幅度以避免交叉污染的 发生，更能够让样本中磁珠悬浮，提升磁珠碰撞频率，进而提升磁珠捕捉目标物(如，蛋白质或核酸)的效率。
图1A和图1B为依据本发明不同实施方式所绘示的声波均质模块100的外观示意图，其中图1A为分解示意图，而图1B为组装示意图。再者，为更清楚得知本发明声波均质模块100内部每一组件的配置方式，图1C为沿着图1B上第1C-1C’线所示的剖视图。
请同时参见图1A至图1C。在结构上，本发明声波均质模块100包括套管连接件110、磁棒120、压电传导组件130和用以驱动所述压电传导组件130的驱动器140(图1C)。需要注意的是，本发明声波均质模块100需搭配生物样本制备系统(例如，自动化核酸萃取设备)使用，所述声波均质模块100的套管连接件110和/或磁棒120可与通常熟知的生物样本制备系统的移动装置(图中未绘示)耦接，以利操控声波均质模块100来处理生物样本，特别是核酸萃取。
如图1C所示，在结构上所述套管连接件110本体具有一容置部112和一穿设部114，其中容置部112可与通常熟知的生物样本制备系统的移动装置耦接，穿设部114则可容许磁棒120活动地穿设其中。依据某些特定实施方式，所述容置部112上方更设有卡合结构(如，卡槽145)，以与通常熟知生物样本制备系统的移动装置耦接。所属技术领域具有通常知识者应当可以理解，本发明套管连接件110与移动装置(图中未绘示)的构型，可依据实际使用状况及其通常经验修改使套管连接件110可与移动装置彼此卡合。
此外，为解决先前技术造成生物样本交叉污染的问题并提供最佳的声波传导效率，本发明声波均质模块100将驱动器140和压电传导组件130配置于容置部112下方，其中压电传导组件130与驱动器140彼此电性耦接，并透过驱动器140驱动压电传导组件130，使其产生声波和/或超声波的震动频率，来扰动生物样本。依据一具体实施方式中，本发明声波均质模块100可产生介于100KHz-1,000KHz(即，1MHz)的震动频率，例如，100、101、102、103、104、105、106、107、108、109、110、110、120、130、140、150、160、170、180、 190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990和1,000KHz。
依据某些实施方式，本发明声波均质模块100还额外设有一试验套管150，套接在套管连接件110的穿设部114下方，用以接触生物样本。在实际使用的过程中，所述压电传导组件130所产生的声波或超声波可通过套管连接件110再经由试验套管150传导至生物样本中，扰动生物样本内的磁珠和/或分子。
如图1C所示，所述压电传导组件130设于套管连接件110的容置部112底部，且与穿设部114相邻。需要注意的是，所述压电传导组件130并未直接接触磁棒120。
本发明声波均质模块100通过此一结构的配置，利用设置于套管连接件110内的压电传导组件130提供震动源至相邻的试验套管150，再由试验套管150的上方传导至生物样本中；此一方式不仅让声波均质模块100能够通过容置部112紧固于生物样本制备系统的移动装置上，使其不易滑脱，且亦可有效搅拌生物样本，避免样本间液体飞溅。再者，将震动源(即，驱动器140和压电传导组件130)设于套管连接件110内，使得本发明声波均质模块100具高机动性，能够适用多种不同构造形状的样本槽，将声波和/或超声波有效传导至样本槽中，达到混合的效果，此为本发明优势之一。
图2A为依据本发明另一实施方式所绘示的声波均质模块200的内部配置示意图；以及图2B为图2A中沿着2B-2B’线的剖视图。此实施方式的声波均质模块200的组件原则上与声波均质模块100大致相同，因此，相同组件在此不另赘述。本声波均质模块200的压电传导组件230和驱动器240同样设于套管连接件210的容置部212的底 部，但环绕穿设部214设置，以增加压电传导组件230与套管连接件210的接触面积，由此提升震动效率。此外，同上述实施方式，所述磁棒220可穿设部214中，且压电传导组件230并未直接接触磁棒220。
图3为依据本发明另一实施方式所绘示的声波均质模块300。在此实施方式中，所述声波均质模块300整合二种震动技术，即，震动马达和声波震动模块，以提供不同强度的震幅，来萃取生物样本中的核酸。如图所示，本声波均质模块300设有套管连接件310、磁棒320、压电传导组件330、驱动器340、试验套管350和震动马达360。所述套管连接件310与上述实施方式所示的套管连接件110结构相同，设有一容置部312和一穿设部314，声波震动模块是由驱动器340和压电传导组件330所组成。所述容置部312内部装载有驱动器340、震动马达360和压电传导组件330，所述压电传导组件330设于容置部312底部并与压电传导组件330电性耦接，所述震动马达360和驱动器340彼此相邻。于实际使用的过程中，可依据样本处理的目的，选择特定的震动模块，即，震动马达或声波震动模块。本发明所属技术领域具有通常知识者应当可以理解，可依据实际使用状况来调整所述驱动器340和震动马达360组件的配置方式；此外，所述驱动器340亦可设于套管连接件310外。
图4为依据本发明一实施方式所示的生物样本制备系统500的硬件配置示意图。所述生物样本制备系统500包括一电源供应模块550、位移模块560和至少一声波均质模块100。在此实施方式中，所述声波均质模块100为图1A至图1C所示的声波均质模块100。
具体而言，本发明的生物样本制备系统500电源供应模块550与位移模块560和声波均质模块100的耦接，用以提供本设备各构件驱动时所需的能源(图4)，且所述位移模块560为自动化机械手臂，能带动本发明声波均质模块110于三维空间中横向和/或纵向移动。再者，所述位移模块560可设有磁吸升降模块(图中未绘示)用以驱动磁棒120上、下线性移动。
请同时参见图1A、图1B、图4和图5，在较佳的实施方式中， 本发明的生物样本制备系统500为一全自动化核酸萃取(例如，核醣核酸(ribose nucleic acid；RNA)或脱氧核醣核酸(deoxyribose nucleic acid；DNA))系统，能够有效制备高纯度的核酸产物。
生物样本制备系统500过程中(例如，核酸萃取过程)，通常需搭配试验套管150处理生物样本，避免样本间交叉污染的情况发生。在一较佳的实施方式中，试验套管150为抛弃式的对象。
再者，本生物样本制备系统500可还包含一样本槽580，且样本槽580上设有复数个容置空间582。本发明技术领域具有通常知识者应当可以理解，可依据生物样本制备的目的于样本槽复数个容置空间中，填充所需的试剂，例如，磁珠、裂解缓冲液(lysis buffer)、结合缓冲液(binding buffer)、冲洗缓冲液(wash buffer)和/或冲提缓冲液(elute buffer)。
于样本实际处理的过程，位移模块560(即，自动化机械手臂)能准确地带动装设有试验套管150的声波均质模块100于样本槽中多个容置空间移动，并伸入至容置空间中进行磁吸或混合。需要注意的是本发明的声波均质模块100是利用震动马达和/或超声波达到均质化扰动样本内的磁珠和/或核酸分子的技术功效，而非利用先前技术通过位移模块560驱使搅拌棒(相当于试验套管)上下移动进行混合，本发明所提出的技术手段能够有效降低样本槽容置空间的体积，亦可降低发生交叉污染的风险。如图5所示，本发明声波均质模块100将压电传导组件130所发出的震波通过试验套管150传导至容置空间582内的生物样本中，使生物样本中的磁珠584悬浮，增加彼此之间的碰撞频率，能够有效提升核酸萃取效率。
另外，于磁吸的过程，能够通过位移模块560将该些磁棒120通过穿设部114进入至试验套管150内进行样本磁吸，当磁棒120通过位移模块560向上移动离开所述试验套管150时，则不进行磁吸，本领域所述技术领域中具有通常知识者可依据磁珠萃取核酸的步骤，加以配置本生物样本制备系统500中位移模块560、磁吸升降模块570和复数个声波均质模块100各构件的作动及配置方式。
此外，为了同时处理多个生物样本，本发明的生物样本制备系统500可设有复数个彼此并排的声波均质模块100，且各该模块与位移模块560耦接，以提升制备效率。
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改与修饰，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。
【符号说明】
主要组件符号列示如下：
100、200、300  声波均质模块
110、210、310  套管连接件
112、212、312  容置部
114、214、314  穿设部
120、220、320  磁棒
130、230、330  压电传导组件
140、340       驱动器
150、250、350  试验套管
360            震动马达
500            生物样本制备系统
550            电源供应模块
560            位移模块。

Claims (11)

  1. 一种声波均质模块，用以处理一生物样本，其特征在于，包含：
    一套管连接件，包含一容置部及一穿设部；
    一磁棒，用以穿设该套管连接件的穿设部；
    一压电传导组件，设于该套管连接件的容置部；以及
    一驱动器，与该压电传导组件电性耦接，使该压电传导组件发出声波震动。
  2. 如权利要求1所述的声波均质模块，其中该震动的频率范围为100千赫兹至1兆赫兹。
  3. 如权利要求1所述的声波均质模块，还包含一震动马达，设于该容置部，且与该驱动器相邻。
  4. 如权利要求1所述的声波均质模块，其中该驱动器设于该套管连接件的容置部。
  5. 如权利要求1所述的声波均质模块，还包含一试验套管，其上端与该套管连接件的穿设部下方套接，且其中该压电传导组件所产生的震动，可通过该试验套管传导至该生物样本中。
  6. 如权利要求5所述的声波均质模块，其中该磁棒可穿设于该试验套管中。
  7. 如权利要求1所述的声波均质模块，其中该压电传导组件设于该容置部的底部且邻近该穿设部。
  8. 如权利要求1所述的声波均质模块，其中该压电传导组件设于该容置部的底部且环绕该穿设部设置。
  9. 一种生物样本制备系统，其特征在于，包含：
    如权利要求1所述的声波均质模块；以及
    一位移模块，与该声波均质模块的驱动器电性耦接，并用以移动该声波均质模块。
  10. 如权利要求9所述的生物样本制备系统，还包含一试验套管，其上端与该套管连接件的穿设部下方套接，且其中该压电传导组件所 产生的震动，可通过该试验套管传导至该生物样本中。
  11. 如权利要求10所述的生物样本制备系统，还包含一样本槽，其中该样本槽包含多个容置空间，且其中该位移模块用以移动该声波均质模块的试验套管于该些容置空间中，进行均质搅拌。
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