TWI815219B - Nucleic acid processing device and sample pre-processing module thereof - Google Patents

Nucleic acid processing device and sample pre-processing module thereof Download PDF

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TWI815219B
TWI815219B TW110143190A TW110143190A TWI815219B TW I815219 B TWI815219 B TW I815219B TW 110143190 A TW110143190 A TW 110143190A TW 110143190 A TW110143190 A TW 110143190A TW I815219 B TWI815219 B TW I815219B
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sample
nucleic acid
module
processing device
tank
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TW202321431A (en
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林尚錡
謝明哲
高于凱
邱祈翰
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台達電子工業股份有限公司
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A nucleic acid processing device includes a sample pre-processing module and a nucleic acid purification module. The sample pre-processing module includes a sample chamber, plural liquid storage chambers, a mixing chamber, plural communication channels, and a first connection structure. The sample chamber has a sample loading port for adding a sample into the sample chamber. The plural liquid storage chambers are configured to store plural sample pre-processing reagents, which at least include a lysis buffer and a proteinase solution. The mixing chamber is provided for mixing the sample and the sample pre-processing reagents. The plural communication channels are configured to transmit the sample and the sample pre-processing reagents to the mixing chamber. The first connection structure is detachably connected with a second connection structure of the nucleic acid purification module, so as to transmit the pre-processed sample to the nucleic acid purification module.

Description

核酸處理裝置及其樣本前處理模組Nucleic acid processing device and sample preprocessing module

本案係關於一種核酸處理裝置及其樣本前處理模組,尤指一種核酸處理裝置及其可拆卸式樣本前處理模組。This case relates to a nucleic acid processing device and its sample pre-processing module, especially a nucleic acid processing device and its detachable sample pre-processing module.

隨著全球新冠病毒疫情持續肆虐與加劇,公共衛生是現今全球各國正面臨的艱困挑戰。在傳染性疾病傳播速率快速的情況下,有效防治的策略如快速地進行疑似病例的檢測與確認,進行早期隔離或確認治療的方式,是現在全球檢測醫學所共同努力的目標。因此研發傳染性疾病的「即時就地檢測手段」,是刻不容緩的議題之一。目前雖多使用快篩免疫來進行檢測,但30分鐘的初步篩檢僅適合檢測高濃度抗原/抗體檢體,且僅適用於少數傳染性疾病,因此有其限制性。而採以分子檢測方法,能夠提供高準確度的分析,但就目前技術上,因受限於「大型昂貴機台之需求」與「需專業人員操作複雜程序」之限制,此種檢測技術僅能在具有專業技術人員的生化研發中心或臨床分析實驗室才能夠進行檢測。As the global COVID-19 epidemic continues to rage and intensify, public health is a difficult challenge that countries around the world are facing today. In the context of the rapid spread of infectious diseases, effective prevention and control strategies, such as rapid detection and confirmation of suspected cases, early isolation or confirmation of treatment, are now the goals of global testing medicine. Therefore, the development of "point-of-care on-site detection methods" for infectious diseases is an urgent issue. Although rapid screening immunization is currently used for testing, the 30-minute preliminary screening test is only suitable for detecting high-concentration antigen/antibody specimens and is only applicable to a few infectious diseases, so it has its limitations. The use of molecular detection methods can provide highly accurate analysis. However, currently, due to the limitations of "the demand for large and expensive machines" and "the need for professionals to operate complex procedures", this detection technology can only Testing can only be carried out in biochemical R&D centers or clinical analysis laboratories with professional and technical personnel.

「晶片實驗室」近年來發展已逐漸成熟,其核心概念為把不同檢測儀器設備功能微型化整併於同一檢測平台上,實現所謂「即時就地照護 (Point of Care,POC)」之體外診斷(In Vitro Diagnostics,IVD)的目標,其具有「系統體積小」、「準確性高」、「反應快速」與「可即時診斷」之優勢。基於微流控之技術,目前已可將(1)萃取與純化病原體核酸(DNA or RNA),與(2)進行核酸擴增與檢測等傳統核酸檢測步驟所需的多項昂貴儀器與繁複操作程序,整合於一「生物晶片卡匣」上,搭配全自動核酸分析儀之開發,希冀改善現今傳染性疾病診斷的缺陷,提供即時就地檢測的目標,進而造就全體人類福祉之願景。The development of "Chip Lab" has gradually matured in recent years. Its core concept is to miniaturize and integrate the functions of different testing instruments and equipment on the same testing platform to achieve the so-called "Point of Care (POC)" in vitro diagnosis. (In Vitro Diagnostics, IVD) goal, it has the advantages of "small system size", "high accuracy", "quick response" and "real-time diagnosis". Based on microfluidic technology, it is now possible to combine (1) extraction and purification of pathogenic nucleic acids (DNA or RNA), and (2) nucleic acid amplification and detection, which require many expensive instruments and complicated operating procedures for traditional nucleic acid detection steps. , integrated on a "biochip cassette", and developed with a fully automatic nucleic acid analyzer, it is hoped to improve the shortcomings of current infectious disease diagnosis, provide the goal of real-time on-site detection, and thereby create a vision for the well-being of all mankind.

因應檢測所需的樣本採集,例如不同的樣本態樣或不同的採集方式,通常需要先對樣本進行前處理,才能送入核酸分析儀進行核酸萃取、擴增與檢測。因此,如何簡化樣本前處理所需繁瑣步驟,使樣本採集、保存及運送都更加便捷,是亟待克服的課題。In response to the sample collection required for testing, such as different sample formats or different collection methods, the sample usually needs to be pre-processed before it can be sent to the nucleic acid analyzer for nucleic acid extraction, amplification and detection. Therefore, how to simplify the tedious steps required for sample pre-processing and make sample collection, storage and transportation more convenient is an issue that needs to be overcome urgently.

本案之一目的在於提供一種樣本前處理模組,其可取代樣本送入核酸分析儀前的手動操作,簡化樣本前處理所需繁瑣步驟,使樣本採集、保存及運送都更加便捷。One of the purposes of this case is to provide a sample pre-processing module that can replace the manual operation before the sample is sent to the nucleic acid analyzer, simplify the tedious steps required for sample pre-processing, and make sample collection, storage and transportation more convenient.

本案之另一目的在於提供一種核酸處理裝置,包括可拆卸式樣本前處理模組,其可與核酸純化模組連接,用以將經前處理後之樣本輸送至核酸純化模組,以利後續核酸萃取、擴增與檢測。Another purpose of this case is to provide a nucleic acid processing device, including a detachable sample pre-treatment module, which can be connected to a nucleic acid purification module to transport the pre-processed sample to the nucleic acid purification module to facilitate subsequent Nucleic acid extraction, amplification and detection.

為達上述目的,本案提供一種核酸處理裝置,包括樣本前處理模組及核酸純化模組,其中樣本前處理模組包括:樣本槽,具有加樣口,供樣本添加至樣本槽中;複數個儲液槽,架構於儲存複數個前處理試劑,前處理試劑至少包括裂解液及蛋白酶;混合槽,架構於供樣本及前處理試劑進行混合;複數個連通管道,架構於輸送樣本及前處理試劑至混合槽;以及第一連接結構,係可拆卸地與核酸純化模組之第二連接結構連接,架構於將經前處理後之樣本輸送至核酸純化模組。In order to achieve the above purpose, this case provides a nucleic acid processing device, including a sample pre-processing module and a nucleic acid purification module. The sample pre-processing module includes: a sample tank with a sample addition port for adding samples to the sample tank; a plurality of A storage tank is configured to store a plurality of pre-processing reagents, which at least include lysis solution and protease; a mixing tank is configured to mix samples and pre-processing reagents; a plurality of connecting pipes is configured to transport samples and pre-processing reagents to the mixing tank; and the first connection structure is detachably connected to the second connection structure of the nucleic acid purification module, and is configured to transport the pre-processed sample to the nucleic acid purification module.

在一實施例中,樣本槽容置有樣本保存液,例如病毒運送保存液、通用運送保存液、細菌運送保存液、或組織細胞保存液。In one embodiment, the sample tank contains a sample preservation solution, such as a virus transport preservation solution, a universal transport preservation solution, a bacterial transport preservation solution, or a tissue cell preservation solution.

在一實施例中,前處理試劑更包括核酸助沈劑,例如載體RNA、乙醇、或肝醣。In one embodiment, the pretreatment reagent further includes a nucleic acid precipitation aid, such as carrier RNA, ethanol, or glycogen.

在一實施例中,第一連接結構為凸部,第二連接結構為凹部。In one embodiment, the first connection structure is a convex part, and the second connection structure is a concave part.

在一實施例中,核酸處理裝置更包括蓋體,蓋合於樣本前處理模組及核酸純化模組之上。蓋體包括一跨接氣動閥,架構於驅動樣本由樣本前處理模組流向核酸純化模組。In one embodiment, the nucleic acid processing device further includes a cover covering the sample pretreatment module and the nucleic acid purification module. The cover body includes a crossover pneumatic valve, which is configured to drive the sample to flow from the sample pretreatment module to the nucleic acid purification module.

在一實施例中,樣本前處理模組與外部裂解模組連接。外部裂解模組可為超聲波裂解模組、加熱裂解模組、光驅動裂解模組、磁驅動粒子研磨模組、或機械研磨模組。In one embodiment, the sample pretreatment module is connected to an external lysis module. The external cleavage module can be an ultrasonic cleavage module, a heating cleavage module, a light-driven cleavage module, a magnetically driven particle grinding module, or a mechanical grinding module.

在一實施例中,核酸處理裝置更包括核酸擴增模組,其係與核酸純化模組及外部主動供能模組連接。外部主動供能模組可為超聲波混合模組、磁驅動粒子擾動模組、光驅動引致加熱模組、或電感式加熱模組。In one embodiment, the nucleic acid processing device further includes a nucleic acid amplification module connected to the nucleic acid purification module and the external active power supply module. The external active energy supply module can be an ultrasonic hybrid module, a magnetically driven particle disturbance module, a light-driven heating module, or an inductive heating module.

在一實施例中,樣本為拭子、尿液、血液、痰液、糞便、或唾液。In one embodiment, the sample is a swab, urine, blood, sputum, stool, or saliva.

為達上述目的,本案更提供一種樣本前處理模組,包括:樣本槽,具有加樣口,供樣本添加至樣本槽中;複數個儲液槽,架構於儲存複數個前處理試劑,前處理試劑至少包括裂解液及蛋白酶;混合槽,架構於供樣本及前處理試劑進行混合;複數個連通管道,架構於輸送樣本及前處理試劑至混合槽;以及輸出結構,架構於將經前處理後之樣本輸出。In order to achieve the above purpose, this case also provides a sample pre-processing module, including: a sample tank with a sample addition port for adding samples to the sample tank; a plurality of liquid storage tanks structured to store a plurality of pre-treatment reagents. The reagents at least include lysis solution and protease; a mixing tank, structured for mixing samples and pre-processing reagents; a plurality of connecting pipes, structured for transporting samples and pre-processing reagents to the mixing tank; and an output structure, structured for mixing the pre-processed reagents sample output.

體現本案特徵與優點的一些實施例將在後段的說明中詳細敘述。應理解的是本案能夠在不同的態樣上具有各種的變化,其皆不脫離本案的範圍,且其中的說明及圖式在本質上為說明之用,而非用以限制本案。Some embodiments embodying the features and advantages of the present invention will be described in detail in the following description. It should be understood that this case can have various changes in different aspects without departing from the scope of this case, and the descriptions and drawings are essentially for illustrative purposes rather than limiting this case.

本案主要提供一種樣本前處理模組,包括多個槽體及前處理試劑,其可取代樣本送入核酸分析儀前的手動操作,便於樣本採集、保存及運送。特別是,本案之樣本前處理模組係可拆卸地與核酸純化模組連接,用以將經前處理後之樣本輸送至核酸純化模組,以利後續核酸萃取、擴增與檢測。另一方面,本案亦提供一種核酸處理裝置,包括樣本前處理模組及核酸純化模組,其中,樣本前處理模組及核酸純化模組具有相對應的連接結構,使樣本前處理模組可拆卸地與核酸純化模組連接。This case mainly provides a sample pre-processing module, which includes multiple tanks and pre-processing reagents. It can replace the manual operation before the sample is sent to the nucleic acid analyzer, and facilitates sample collection, storage and transportation. In particular, the sample pre-processing module in this case is detachably connected to the nucleic acid purification module to transport the pre-processed sample to the nucleic acid purification module to facilitate subsequent nucleic acid extraction, amplification and detection. On the other hand, this case also provides a nucleic acid processing device, including a sample preprocessing module and a nucleic acid purification module. The sample preprocessing module and the nucleic acid purification module have corresponding connection structures, so that the sample preprocessing module can Detachably connected to the nucleic acid purification module.

第1圖顯示本案核酸處理裝置之組裝示意圖,第2圖顯示蓋體分離之核酸處理裝置示意圖。核酸處理裝置主要包括樣本前處理模組1及核酸純化模組2,樣本前處理模組1用於對樣本進行初萃等前處理,並與核酸純化模組2連接,以將經前處理後之樣本輸送至核酸純化模組2進行純化,以完成核酸萃取,俾利後續擴增與檢測等流程。Figure 1 shows a schematic diagram of the assembly of the nucleic acid processing device in this case, and Figure 2 shows a schematic diagram of the nucleic acid processing device with lid separation. The nucleic acid processing device mainly includes a sample pre-processing module 1 and a nucleic acid purification module 2. The sample pre-processing module 1 is used to perform pre-processing such as primary extraction on the sample, and is connected to the nucleic acid purification module 2 to convert the pre-processed The sample is transported to the nucleic acid purification module 2 for purification to complete the nucleic acid extraction to facilitate subsequent amplification and detection processes.

在一實施例中,核酸處理裝置更包括蓋體3,蓋合於樣本前處理模組1及核酸純化模組2之上,且有對應樣本前處理模組1及核酸純化模組2之槽體的氣動開口31及輸液管道32。氣動開口31可與壓電式微型泵浦連接,以提供氣體壓力源,並由電磁閥控制氣體輸入各槽體之開關,以驅動流體在槽體間的流動。In one embodiment, the nucleic acid processing device further includes a cover 3 that covers the sample pretreatment module 1 and the nucleic acid purification module 2, and has a slot corresponding to the sample pretreatment module 1 and the nucleic acid purification module 2. The pneumatic opening 31 and the infusion pipe 32 of the body. The pneumatic opening 31 can be connected to a piezoelectric micropump to provide a gas pressure source, and a solenoid valve controls the switch of gas input into each tank to drive the flow of fluid between the tanks.

在一實施例中,核酸處理裝置更包括核酸擴增模組4,設置於核酸純化模組2下方並與核酸純化模組2連接,用以收集萃取完成之核酸溶液,並進行後續的核酸擴增與檢測。在一實施例中,核酸擴增模組4包括收集管件41,其可為離心管(eppendorf tube),但不以此為限。In one embodiment, the nucleic acid processing device further includes a nucleic acid amplification module 4, which is disposed below the nucleic acid purification module 2 and connected to the nucleic acid purification module 2 to collect the extracted nucleic acid solution and perform subsequent nucleic acid amplification. Increase and detect. In one embodiment, the nucleic acid amplification module 4 includes a collection tube 41, which may be a centrifuge tube (eppendorf tube), but is not limited thereto.

第3圖顯示核酸處理裝置之***圖。樣本前處理模組1包括外殼11及其所包覆的槽體結構12。核酸純化模組2包括外殼21及其所包覆的槽體結構22、反應管柱23及分配組件24。第4圖及第5圖則進一步顯示樣本前處理模組1之槽體結構12與核酸純化模組2之槽體結構22於不同視角的***圖。樣本前處理模組1之槽體結構12包括樣本槽121、複數個儲液槽122、混合槽123、複數個連通管道124、及第一連接結構125。樣本槽121具有加樣口1211,供樣本添加至樣本槽121中。複數個儲液槽122架構於儲存複數個前處理試劑。混合槽123架構於供樣本及前處理試劑進行混合。複數個連通管道124架構於輸送樣本及前處理試劑至混合槽123。第一連接結構125係可拆卸地與核酸純化模組2連接,架構於將經前處理後之樣本輸送至核酸純化模組2,俾利進行完整的核酸萃取流程。Figure 3 shows an exploded view of the nucleic acid processing device. The sample preprocessing module 1 includes a shell 11 and a tank structure 12 covered by it. The nucleic acid purification module 2 includes a shell 21 and a covered tank structure 22 , a reaction column 23 and a distribution component 24 . Figures 4 and 5 further show exploded views of the tank structure 12 of the sample pretreatment module 1 and the tank structure 22 of the nucleic acid purification module 2 from different angles. The tank structure 12 of the sample preprocessing module 1 includes a sample tank 121, a plurality of liquid storage tanks 122, a mixing tank 123, a plurality of communication pipes 124, and a first connection structure 125. The sample tank 121 has a sample adding port 1211 for adding samples to the sample tank 121 . A plurality of liquid storage tanks 122 are configured to store a plurality of pretreatment reagents. The mixing tank 123 is configured for mixing samples and pretreatment reagents. A plurality of connecting pipes 124 are structured to transport samples and pretreatment reagents to the mixing tank 123 . The first connection structure 125 is detachably connected to the nucleic acid purification module 2, and is structured to transport the pre-processed sample to the nucleic acid purification module 2 to facilitate a complete nucleic acid extraction process.

在一實施例中,樣本前處理模組1具有樣本保存液,用以於運送過程中穩定保存樣本。樣本保存液可依樣本種類而選擇,例如但不限於病毒運送保存液(viral transport medium,VTM)、通用運送保存液(universal transport medium,UTM)、細菌運送保存液(bacterial transport medium,BTM)、或組織細胞保存液。In one embodiment, the sample preprocessing module 1 has a sample preservation solution for stably preserving the sample during transportation. The sample preservation medium can be selected according to the type of sample, such as but not limited to viral transport medium (VTM), universal transport medium (UTM), bacterial transport medium (BTM), or tissue cell preservation solution.

在一實施例中,樣本保存液可預先儲存於樣本槽121中,供採檢拭子直接***。在另一實施例中,樣本保存液已儲存在採樣管中,故可將樣本保存液從採樣管移至樣本槽121即可。In one embodiment, the sample preservation solution can be pre-stored in the sample tank 121 for direct insertion of the sampling swab. In another embodiment, the sample preservation solution has been stored in the sampling tube, so the sample preservation solution can be moved from the sampling tube to the sample tank 121 .

樣本前處理主要是於核酸萃取前先將樣本裂解,以將固體組織及細胞之細胞壁與細胞膜完全破壞,藉此釋出樣本中的核酸,包括DNA及RNA,以使後續萃取步驟較容易且有效率。前處理試劑至少包括裂解液及蛋白酶。裂解液可破細胞或破菌,以使細胞裂解並釋出核酸。蛋白酶則可分解蛋白質,並將DNA或RNA自蛋白質上分離。Sample pretreatment mainly involves lysing the sample before nucleic acid extraction to completely destroy the cell walls and membranes of solid tissues and cells, thereby releasing the nucleic acids in the sample, including DNA and RNA, so that subsequent extraction steps are easier and more efficient. efficiency. Pretreatment reagents include at least lysis solution and protease. The lysis solution can disrupt cells or bacteria to lyse cells and release nucleic acids. Proteases break down proteins and separate DNA or RNA from proteins.

在一實施例中,前處理試劑更包括核酸助沈劑,例如但不限於載體RNA (Carrier RNA)、乙醇、或肝醣(glycogen)。核酸助沈劑有助於DNA或RNA的有效沈澱,可提升核酸回收率。In one embodiment, the pretreatment reagent further includes a nucleic acid precipitation aid, such as but not limited to carrier RNA, ethanol, or glycogen. Nucleic acid precipitation aid helps in the effective precipitation of DNA or RNA and can improve the recovery rate of nucleic acid.

經樣本前處理模組1進行初萃後之樣本將接著送入核酸純化模組2中進行純化,以完成核酸的萃取。因此,樣本前處理模組1及核酸純化模組2具有相對應的連接結構,包括樣本前處理模組1上的第一連接結構125及核酸純化模組2上的第二連接結構25。在一實施例中,第一連接結構125為一凸部,且具有與混合槽123連通之傳液管道1251;而第二連接結構25為一凹部,可直接與第一連接結構125對接,使初萃後之樣本可由樣本前處理模組1送入核酸純化模組2。當然,樣本前處理模組1及核酸純化模組2之連接態樣不限於前述凸部與凹部之實施例,其他任何可對接及拆卸的連接結構皆可適用於本案。The sample after initial extraction by the sample pretreatment module 1 will then be sent to the nucleic acid purification module 2 for purification to complete the extraction of nucleic acids. Therefore, the sample pretreatment module 1 and the nucleic acid purification module 2 have corresponding connection structures, including the first connection structure 125 on the sample pretreatment module 1 and the second connection structure 25 on the nucleic acid purification module 2 . In one embodiment, the first connection structure 125 is a convex part and has a liquid transmission pipe 1251 connected with the mixing tank 123; and the second connection structure 25 is a concave part that can be directly connected with the first connection structure 125, so that The sample after initial extraction can be sent to the nucleic acid purification module 2 from the sample pretreatment module 1. Of course, the connection mode of the sample pretreatment module 1 and the nucleic acid purification module 2 is not limited to the above embodiment of the convex part and the concave part, and any other connection structure that can be docked and detached can be applied to this case.

在一實施例中,如第1圖及第2圖所示,蓋體3蓋合於樣本前處理模組1及核酸純化模組2之上,且包括一頂面及四側壁,其中四側壁可貼合於樣本前處理模組1及核酸純化模組2組裝後之外殼,故蓋體3係跨接並套合樣本前處理模組1及核酸純化模組2,且更包括跨接氣動閥33,架構於驅動樣本由樣本前處理模組1流向核酸純化模組2。In one embodiment, as shown in Figures 1 and 2, the cover 3 covers the sample pretreatment module 1 and the nucleic acid purification module 2, and includes a top surface and four side walls, wherein the four side walls It can fit into the assembled shell of the sample pretreatment module 1 and the nucleic acid purification module 2. Therefore, the cover 3 is connected to and fitted with the sample pretreatment module 1 and the nucleic acid purification module 2, and also includes a crossover pneumatic The valve 33 is configured to drive the sample to flow from the sample pretreatment module 1 to the nucleic acid purification module 2.

核酸純化模組2之槽體結構22具有多個槽體及槽體連通管道。多個槽體包括樣本槽、儲液槽、及廢液槽,其中樣本槽架構於承接來自樣本前處理模組1的樣本;儲液槽可為多個,架構於儲存清洗緩衝液及沖提緩衝液等;廢液槽架構於儲存反應後的廢液。反應管柱23設置於槽體結構22中,且具有核酸抓取材料。槽體連通管道則架構於輸送流體於各槽體及反應管柱23之間。來自樣本前處理模組1的樣本將被送入反應管柱23,使核酸與反應管柱23中的核酸抓取材料結合,再經清洗緩衝液的清洗,藉此移除殘留的蛋白質及細胞殘渣,最後由沖提緩衝液將核酸沖提分離出來,並由分配組件24將萃取完成之核酸溶液送入核酸擴增模組4的收集管件41。The tank structure 22 of the nucleic acid purification module 2 has a plurality of tanks and channels connecting the tanks. The plurality of tanks include a sample tank, a liquid storage tank, and a waste tank. The sample tank is structured to receive samples from the sample pretreatment module 1; there can be multiple liquid storage tanks, and is structured to store cleaning buffers and rinsing buffers. Buffer, etc.; the waste liquid tank is structured to store the waste liquid after the reaction. The reaction column 23 is arranged in the tank structure 22 and has nucleic acid capture material. The tank communication pipeline is structured to transport fluid between each tank and the reaction column 23 . The sample from the sample preprocessing module 1 will be sent to the reaction column 23, so that the nucleic acid is combined with the nucleic acid capture material in the reaction column 23, and then washed with the washing buffer to remove residual proteins and cells. The residue is finally eluted and separated with the eluting buffer, and the extracted nucleic acid solution is sent to the collection tube 41 of the nucleic acid amplification module 4 through the distribution component 24 .

在一實施例中,如第6圖所示,為增加破細胞或破菌效率,本案之樣本前處理模組1可與外部裂解模組5連接以提升裂解效率。舉例來說,外部裂解模組5可為但不限於超聲波裂解模組、加熱裂解模組、光驅動裂解模組、磁驅動粒子研磨模組、或機械研磨模組。In one embodiment, as shown in Figure 6, in order to increase the efficiency of cell or bacteriolysis, the sample pretreatment module 1 of this case can be connected to an external lysis module 5 to improve the lysis efficiency. For example, the external cleavage module 5 may be, but is not limited to, an ultrasonic cleavage module, a heating cleavage module, a light-driven cleavage module, a magnetically driven particle grinding module, or a mechanical grinding module.

在一實施例中,如第6圖所示,核酸擴增模組4可與外部主動供能模組6連接以提升試劑效率。舉例來說,外部主動供能模組6可為但不限於超聲波混合模組、磁驅動粒子擾動模組、光驅動引致加熱模組、或電感式加熱模組。In one embodiment, as shown in Figure 6, the nucleic acid amplification module 4 can be connected to an external active power supply module 6 to improve reagent efficiency. For example, the external active energy supply module 6 may be, but is not limited to, an ultrasonic mixing module, a magnetically driven particle perturbation module, a light-driven induced heating module, or an inductive heating module.

在一實施例中,核酸擴增模組4可與核酸檢測裝置連接,以進行完整的核酸分析流程。舉例來說,樣本前處理模組1與核酸純化模組2及核酸擴增模組4接合後,即可放入自動核酸分析儀,以進行樣本前處理、核酸萃取、核酸擴增、與核酸檢測等流程,並取得分析結果。In one embodiment, the nucleic acid amplification module 4 can be connected to a nucleic acid detection device to perform a complete nucleic acid analysis process. For example, after the sample pretreatment module 1 is connected to the nucleic acid purification module 2 and the nucleic acid amplification module 4, it can be placed in an automatic nucleic acid analyzer to perform sample preprocessing, nucleic acid extraction, nucleic acid amplification, and nucleic acid analysis. Detection and other processes and obtain analysis results.

在一實施例中,樣本前處理模組1可適用的檢體樣本包括但不限於拭子、尿液、血液、痰液、糞便、及唾液等,且樣本前處理模組1中所包含的前處理試劑可針對不同的樣本來調整試劑配方。In one embodiment, the specimen samples that the sample preprocessing module 1 can be applied to include but are not limited to swabs, urine, blood, sputum, feces, saliva, etc., and the sample preprocessing module 1 includes Pretreatment reagents can adjust reagent formulas for different samples.

根據本案之構想,採檢後之初始樣本,例如來自拭子或採樣管之樣本,首先會經加樣口1211送入樣本前處理模組1之樣本槽121,且由於樣本槽121中具有樣本保存液,因此樣本可於運送過程被穩定地保存。再者,由於前處理試劑,例如裂解液、蛋白酶、及核酸助沈劑等,已預先儲存於樣本前處理模組1之儲液槽122中,故無需再手動添加,可簡化樣本前處理所需繁瑣步驟,使樣本採集、保存及運送都更加便捷。由於樣本前處理模組1為可拆卸結構,故可直接用於第一線的採集,待採集完成即可將樣本前處理模組1運送至檢驗室,由檢驗室人員將樣本前處理模組1與核酸純化模組2接合,再送入自動核酸分析儀中,進行後續的樣本前處理、核酸萃取、核酸擴增、與核酸檢測等流程。亦即,透過自動核酸分析儀的流體控制模組,可先將樣本與前處理試劑於樣本前處理模組1中混合進行裂解初萃,再將初萃後的樣本送入核酸純化模組2中,將核酸進一步純化提取出來,再進行核酸擴增與檢測。According to the concept of this case, the initial sample after collection, such as a sample from a swab or a sampling tube, will first be sent to the sample slot 121 of the sample pre-processing module 1 through the sampling port 1211, and since there is a sample in the sample slot 121 Preservation solution, so samples can be stably preserved during transportation. Furthermore, since the pretreatment reagents, such as lysis buffer, protease, and nucleic acid precipitation aid, etc., have been pre-stored in the reservoir 122 of the sample pretreatment module 1, there is no need to add them manually, which can simplify the sample pretreatment process. No cumbersome steps are required, making sample collection, storage and transportation more convenient. Since the sample pre-processing module 1 is a detachable structure, it can be directly used for front-line collection. Once the collection is completed, the sample pre-processing module 1 can be transported to the laboratory, and the laboratory personnel will transport the sample pre-processing module 1 to the laboratory. 1 is connected to the nucleic acid purification module 2, and then sent to the automatic nucleic acid analyzer for subsequent sample preprocessing, nucleic acid extraction, nucleic acid amplification, and nucleic acid detection. That is, through the fluid control module of the automatic nucleic acid analyzer, the sample and pre-treatment reagents can be mixed in the sample pre-treatment module 1 for lysis and preliminary extraction, and then the sample after the initial extraction can be sent to the nucleic acid purification module 2 In the process, the nucleic acid is further purified and extracted, and then nucleic acid amplification and detection are performed.

再者,由於不同的檢體樣本會需要不同的前處理試劑配方,因此,將樣本前處理模組1設計成可拆卸式卡匣,即可因應不同的樣本而配置不同的前處理試劑,且可配合第一線的採集、保存與運送。相較於全自動分析儀因應不同樣本需要全面更動卡匣設計,本案之可拆卸式樣本前處理模組1在應用上更加彈性,故大大增加了其應用價值。Furthermore, since different specimen samples require different pre-processing reagent formulas, the sample pre-processing module 1 is designed as a detachable cassette, so that different pre-processing reagents can be configured according to different samples, and Can cooperate with front-line collection, storage and transportation. Compared with fully automatic analyzers that completely change the cassette design in response to different sample needs, the detachable sample preprocessing module 1 in this case is more flexible in application, thus greatly increasing its application value.

此外,當檢體樣本為固態樣本(例如糞便)時,本案之樣本前處理模組1更可提供濾除大顆粒的結構設計,例如,在樣本槽121底部設置過濾膜,以濾除樣本中的雜質顆粒,以利後續的樣本處理程序。In addition, when the specimen sample is a solid sample (such as feces), the sample preprocessing module 1 of this case can also provide a structural design to filter out large particles. For example, a filter membrane is provided at the bottom of the sample tank 121 to filter out the particles in the sample. of impurity particles to facilitate subsequent sample processing procedures.

另一方面,除前述實施例示範之第一連接結構外,亦可另外設計轉接頭或直接透過軟管傳輸,使樣本前處理模組可適用於各種態樣之核酸分析儀。舉例來說,第一連接結構實質上為一輸出結構,經套接一軟管(作為第二連接結構)並注入核酸純化模組之加樣口,即可同樣達成樣本前處理模組與核酸純化模組之間的流體輸送。在一實施例中,也可將樣本前處理模組的輸出結構設置在蓋體上,例如在蓋體上設置液體流道,以將經樣本前處理模組進行初萃後的樣本導入核酸純化模組之加樣口。On the other hand, in addition to the first connection structure demonstrated in the foregoing embodiments, an additional adapter can also be designed or the sample preprocessing module can be directly transmitted through a hose, so that the sample preprocessing module can be applied to various types of nucleic acid analyzers. For example, the first connection structure is essentially an output structure. By connecting a hose (as the second connection structure) and injecting it into the sample port of the nucleic acid purification module, the sample pretreatment module and the nucleic acid can be connected in the same way. Fluid transfer between purification modules. In one embodiment, the output structure of the sample pre-processing module can also be provided on the cover. For example, a liquid channel is provided on the cover to introduce the sample after initial extraction by the sample pre-processing module into nucleic acid purification. The sample adding port of the module.

第7圖顯示本案另一實施例之樣本前處理模組的示意圖,第8圖顯示第7圖之樣本前處理模組的***圖。在另一實施例中,樣本前處理模組7包括外殼71、槽體結構72、蓋體73、輸出結構74、及採集管件75。本實施例的槽體結構72與前述槽體結構12相同,故不再贅述。蓋體73上設有氣動開口731及輸液管道732,架構於驅動流體在槽體間的流動。輸出結構74與蓋體73上的輸液管道732連通,以將經前處理後之樣本輸出。採集管件75與輸出結構74連接,以承接經輸出結構74輸出之樣本。舉例來說,採集管件75可為公規品,例如5ml或10ml試管。因此,根據本實施例之構想,經樣本前處理模組7進行初萃後的樣本可透過輸出結構74直接導入採集管件75,即可供檢驗室人員進一步將採集管件75內的樣本送入各種態樣之核酸分析儀進行後續的核酸萃取、擴增與檢測等流程。Figure 7 shows a schematic diagram of a sample pre-processing module according to another embodiment of the present invention, and Figure 8 shows an exploded view of the sample pre-processing module in Figure 7 . In another embodiment, the sample preprocessing module 7 includes a housing 71 , a tank structure 72 , a cover 73 , an output structure 74 , and a collection tube 75 . The trough structure 72 of this embodiment is the same as the trough structure 12 described above, so the details will not be described again. The cover 73 is provided with a pneumatic opening 731 and a liquid infusion pipe 732 to drive the flow of fluid between the tanks. The output structure 74 is connected to the infusion pipe 732 on the cover 73 to output the pre-processed sample. The collection pipe 75 is connected to the output structure 74 to receive the sample output through the output structure 74 . For example, the collection tube 75 can be a standard product, such as a 5ml or 10ml test tube. Therefore, according to the concept of this embodiment, the sample after initial extraction by the sample preprocessing module 7 can be directly introduced into the collection pipe 75 through the output structure 74, which can be used by laboratory personnel to further send the samples in the collection pipe 75 into various The state-of-the-art nucleic acid analyzer performs subsequent nucleic acid extraction, amplification and detection processes.

綜上所述,本案提供一種可拆卸式樣本前處理模組,其可取代樣本送入核酸分析儀前的手動操作,簡化樣本前處理所需繁瑣步驟,使樣本採集、保存及運送都更加便捷。又,樣本前處理模組可與核酸純化模組連接,用以將經前處理後之樣本輸送至核酸純化模組,以利後續核酸萃取、擴增與檢測。再者,由於不同的檢體樣本會需要不同的前處理試劑配方,因此,將樣本前處理模組設計成可拆卸式卡匣,即可因應不同的樣本而配置不同的前處理試劑,故在應用上更加彈性,也大大增加了其應用價值。To sum up, this case provides a detachable sample pre-processing module, which can replace the manual operation before the sample is sent to the nucleic acid analyzer, simplify the tedious steps required for sample pre-processing, and make sample collection, storage and transportation more convenient. . In addition, the sample pre-processing module can be connected to the nucleic acid purification module to transport the pre-processed sample to the nucleic acid purification module to facilitate subsequent nucleic acid extraction, amplification and detection. Furthermore, since different specimen samples require different pre-processing reagent formulas, the sample pre-processing module is designed as a detachable cassette, which can configure different pre-processing reagents according to different samples. Therefore, in It is more flexible in application and greatly increases its application value.

縱使本發明已由上述實施例詳細敘述而可由熟悉本技藝人士任施匠思而為諸般修飾,然皆不脫如附申請專利範圍所欲保護者。Even though the present invention has been described in detail through the above embodiments, it can be modified in various ways as desired by those skilled in the art, without departing from the intended protection within the scope of the appended patent application.

1:樣本前處理模組 11:外殼 12:槽體結構 121:樣本槽 1211:加樣口 122:儲液槽 123:混合槽 124:連通管道 125:第一連接結構 1251:傳液管道 2:核酸純化模組 21:外殼 22:槽體結構 23:反應管柱 24:分配組件 25:第二連接結構 3:蓋體 31:氣動開口 32:輸液管道 33:跨接氣動閥 4:核酸擴增模組 41:收集管件 5:外部裂解模組 6:外部主動供能模組 7:樣本前處理模組 71:外殼 72:槽體結構 73:蓋體 731:氣動開口 732:輸液管道 74:輸出結構 75:採集管件 1: Sample preprocessing module 11: Shell 12: Tank structure 121:Sample slot 1211: Sample adding port 122:Liquid storage tank 123: Mixing tank 124: Connecting pipes 125: First connection structure 1251: Liquid transfer pipeline 2: Nucleic acid purification module 21: Shell 22: Tank structure 23: Reaction column 24: Assign components 25: Second connection structure 3: Cover 31:Pneumatic opening 32:Infusion pipeline 33: Jumper pneumatic valve 4: Nucleic acid amplification module 41:Collect pipe fittings 5:External cracking module 6: External active energy supply module 7: Sample pre-processing module 71: Shell 72: Tank structure 73: Cover 731:Pneumatic opening 732:Infusion pipeline 74:Output structure 75:Collect pipe fittings

第1圖顯示本案核酸處理裝置之組裝示意圖。 第2圖顯示蓋體分離之核酸處理裝置示意圖。 第3圖顯示核酸處理裝置之***圖。 第4圖及第5圖顯示樣本前處理模組之槽體結構與核酸純化模組之槽體結構於不同視角的***圖。 第6圖顯示核酸處理裝置與外部模組連接示意圖。 第7圖顯示本案另一實施例之樣本前處理模組的示意圖。 第8圖顯示第7圖之樣本前處理模組的***圖。 Figure 1 shows the assembly diagram of the nucleic acid processing device in this case. Figure 2 shows a schematic diagram of the nucleic acid processing device for lid separation. Figure 3 shows an exploded view of the nucleic acid processing device. Figures 4 and 5 show exploded views of the tank structure of the sample pretreatment module and the tank structure of the nucleic acid purification module from different perspectives. Figure 6 shows a schematic diagram of the connection between the nucleic acid processing device and the external module. Figure 7 shows a schematic diagram of a sample pre-processing module according to another embodiment of the present invention. Figure 8 shows an exploded view of the sample pre-processing module in Figure 7.

12:槽體結構 12: Tank structure

121:樣本槽 121:Sample slot

1211:加樣口 1211: Sample adding port

122:儲液槽 122:Liquid storage tank

123:混合槽 123: Mixing tank

124:連通管道 124: Connecting pipes

125:第一連接結構 125: First connection structure

1251:傳液管道 1251: Liquid transfer pipeline

22:槽體結構 22: Tank structure

25:第二連接結構 25: Second connection structure

Claims (14)

一種核酸處理裝置,包括一樣本前處理模組及一核酸純化模組,其中該樣本前處理模組包括:一樣本槽,具有一加樣口,供一樣本添加至該樣本槽中;複數個儲液槽,架構於儲存複數個前處理試劑,該前處理試劑至少包括一裂解液及一蛋白酶;一混合槽,架構於供該樣本及該前處理試劑進行混合;複數個連通管道,架構於輸送該樣本及該前處理試劑至該混合槽;以及一第一連接結構,係可拆卸地與該核酸純化模組之一第二連接結構連接,架構於將經前處理後之該樣本輸送至該核酸純化模組。 A nucleic acid processing device, including a sample pre-processing module and a nucleic acid purification module, wherein the sample pre-processing module includes: a sample tank with a sample adding port for adding a sample to the sample tank; a plurality of A storage tank is structured to store a plurality of pre-treatment reagents, the pre-treatment reagents at least include a lysis solution and a protease; a mixing tank is structured to mix the sample and the pre-treatment reagent; a plurality of connecting pipes is structured in Transport the sample and the pre-treatment reagent to the mixing tank; and a first connection structure is detachably connected to a second connection structure of the nucleic acid purification module, and the structure is used to transport the pre-processed sample to The nucleic acid purification module. 如請求項1所述之核酸處理裝置,其中該樣本槽容置一樣本保存液。 The nucleic acid processing device of claim 1, wherein the sample tank contains a sample preservation solution. 如請求項2所述之核酸處理裝置,其中該樣本保存液為一病毒運送保存液、一通用運送保存液、一細菌運送保存液、或一組織細胞保存液。 The nucleic acid processing device of claim 2, wherein the sample preservation solution is a virus transport preservation solution, a universal transport preservation solution, a bacterial transport preservation solution, or a tissue cell preservation solution. 如請求項1所述之核酸處理裝置,其中該前處理試劑更包括一核酸助沈劑。 The nucleic acid processing device of claim 1, wherein the pretreatment reagent further includes a nucleic acid precipitation aid. 如請求項4所述之核酸處理裝置,其中該核酸助沈劑為載體RNA、乙醇、或肝醣。 The nucleic acid processing device of claim 4, wherein the nucleic acid precipitation aid is carrier RNA, ethanol, or glycogen. 如請求項1所述之核酸處理裝置,其中該第一連接結構為一凸部,該第二連接結構為一凹部。 The nucleic acid processing device of claim 1, wherein the first connection structure is a convex part, and the second connection structure is a concave part. 如請求項1所述之核酸處理裝置,更包括一蓋體,蓋合於該樣本前處理模組及該核酸純化模組之上。 The nucleic acid processing device of claim 1 further includes a cover covering the sample pretreatment module and the nucleic acid purification module. 如請求項7所述之核酸處理裝置,其中該蓋體包括一跨接氣動閥,架構於驅動該樣本由該樣本前處理模組流向該核酸純化模組。 The nucleic acid processing device of claim 7, wherein the cover includes a crossover pneumatic valve configured to drive the sample to flow from the sample preprocessing module to the nucleic acid purification module. 如請求項1所述之核酸處理裝置,其中該樣本前處理模組與一外部裂解模組連接。 The nucleic acid processing device of claim 1, wherein the sample pretreatment module is connected to an external lysis module. 如請求項9所述之核酸處理裝置,其中該外部裂解模組為一超聲波裂解模組、一加熱裂解模組、一光驅動裂解模組、一磁驅動粒子研磨模組、或一機械研磨模組。 The nucleic acid processing device of claim 9, wherein the external lysis module is an ultrasonic lysis module, a heating lysis module, a light-driven lysis module, a magnetically driven particle grinding module, or a mechanical grinding module group. 如請求項1所述之核酸處理裝置,更包括一核酸擴增模組,其係與該核酸純化模組及一外部主動供能模組連接。 The nucleic acid processing device of claim 1 further includes a nucleic acid amplification module connected to the nucleic acid purification module and an external active power supply module. 如請求項11所述之核酸處理裝置,其中該外部主動供能模組為一超聲波混合模組、一磁驅動粒子擾動模組、一光驅動引致加熱模組、或一電感式加熱模組。 The nucleic acid processing device of claim 11, wherein the external active energy supply module is an ultrasonic mixing module, a magnetically driven particle perturbation module, a light-driven induced heating module, or an inductive heating module. 如請求項1所述之核酸處理裝置,其中該樣本為一拭子、一尿液、一血液、一痰液、一糞便、或一唾液。 The nucleic acid processing device of claim 1, wherein the sample is a swab, urine, blood, sputum, stool, or saliva. 一種樣本前處理模組,與一核酸純化模組並用,該樣本前處理模組包括:一樣本槽,具有一加樣口,供一樣本添加至該樣本槽中;複數個儲液槽,架構於儲存複數個前處理試劑,該前處理試劑至少包括一裂解液及一蛋白酶;一混合槽,架構於供該樣本及該前處理試劑進行混合;複數個連通管道,架構於輸送該樣本及該前處理試劑至該混合槽;以及一第一連接結構,係可拆卸地與該核酸純化模組之一第二連接結構連接,架構於將經前處理後之該樣本輸送至該核酸純化模組。 A sample pre-processing module is used together with a nucleic acid purification module. The sample pre-processing module includes: a sample tank with a sample adding port for adding a sample to the sample tank; a plurality of liquid storage tanks, a structure Store a plurality of pre-processing reagents, which at least include a lysis solution and a protease; a mixing tank configured for mixing the sample and the pre-processing reagent; and a plurality of connecting pipes configured for transporting the sample and the pre-processing reagent. Pretreatment reagents are supplied to the mixing tank; and a first connection structure is detachably connected to a second connection structure of the nucleic acid purification module, and is structured to transport the sample after pretreatment to the nucleic acid purification module. .
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