WO2018076592A1 - 一种用于血液液体活检的体内收集装置 - Google Patents

一种用于血液液体活检的体内收集装置 Download PDF

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WO2018076592A1
WO2018076592A1 PCT/CN2017/076351 CN2017076351W WO2018076592A1 WO 2018076592 A1 WO2018076592 A1 WO 2018076592A1 CN 2017076351 W CN2017076351 W CN 2017076351W WO 2018076592 A1 WO2018076592 A1 WO 2018076592A1
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catheter
collection device
catheter body
vivo
needle
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PCT/CN2017/076351
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English (en)
French (fr)
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刘和平
姜结根
洪林
万阳
夏黎明
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广州益养生物科技有限公司
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Publication of WO2018076592A1 publication Critical patent/WO2018076592A1/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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/06—Tubular
    • 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
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • 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
    • C12M47/04—Cell isolation or sorting
    • 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

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  • the present invention relates to a medical device, and in particular to an in vivo collection device for blood liquid biopsy.
  • the method for collecting tumor cells commonly used in the prior art is: collecting 7.5 ml peripheral blood of a patient, collecting tumor cells by using ferrofluid, and then using a series of monoclonal antibody immunohistochemistry and nucleic acid dye to find tumor cells.
  • the disadvantages of this method are as follows: 1.
  • the tumor cells in the circulating blood of patients with solid tumors are extremely rare (about 1 tumor cell / 10 6 -10 7 white blood cells), which is difficult to capture and identify; 2. Many operation steps, complicated operation; The experimental cost is high, and the experimental instrument is extremely expensive; 4.
  • the tumor cells identified by the separation and capture are difficult to be used for downstream analysis, such as genetic analysis, in vitro culture, drug sensitivity test, and the like.
  • a catheter comprising a catheter body and a collecting device, the end of the catheter body being connected to the collecting device.
  • the collection device is a cell collection device.
  • the collecting device is a blood circulation tumor cell collecting device.
  • the cell collector of the present invention can collect cells, especially tumor cells, in vivo, and improves the disadvantages of the prior art in collecting cells in vitro, which is extremely difficult, cumbersome, has many steps, high technical cost, and extremely expensive instruments, so that the captured Tumor cells can be used for downstream analysis, such as genetic analysis, in vitro culture, drug susceptibility testing, and the like.
  • Her2 the human epidermal growth factor receptor 2 (HER2) gene, is an important prognostic factor for breast cancer.
  • HER2-positive (overexpressed or expanded) breast cancer has a special clinical manifestation and biological behavior, and the treatment pattern is also very different from other types of breast cancer, which encodes a transmembrane receptor with a relative molecular mass of 185 kDa.
  • a body-like protein with tyrosine kinase activity is an important prognostic factor for breast cancer.
  • MUC1 a high glycosylation (glycation greater than 50%) and high molecular weight (Mr) expressed by the muc1 gene >200kDa) Protein, also known as the membrane protein, is a transmembrane molecule. It plays an important role in epithelial renewal and differentiation, maintaining epithelial integrity and cancer occurrence and metastasis. Due to the abnormal expression of MUC1 in tumor tissues, it has become an important tumor biomarker. MUC1 is widely distributed and abnormally abundantly expressed on the surface of adenocarcinoma cells, and glycosylation is incomplete, thus exposing the hidden epitopes under normal conditions and becoming targets of immune cell attack.
  • GPC glypicans
  • GPC1-6 GPCs are anchored to the cell membrane by glycosylphosphatidylinositol (GPI), which regulates many cellular signaling pathways (such as Wnt, Hedgehog, FGF, etc.) and tissue and organogenesis.
  • GPI glycosylphosphatidylinositol
  • EpCAM an epithelial cell adhesion molecule
  • EpCAM an epithelial cell adhesion molecule
  • Molecules play a role in the process of carcinogenesis of the epithelium.
  • the collecting device is one of a nylon bag, a porous umbrella collecting device and a cylindrical collecting device, and the collecting device may be sleeved in the catheter body or the catheter is taken out In vitro.
  • the outer surface of the collection device is coupled to an antibody layer for capturing cells.
  • the outer surface of the collection device is coupled to an antibody layer for capturing blood circulating tumor cells.
  • the antibody layer is a monoclonal antibody layer comprising, but not limited to, at least one of a Her2 monoclonal antibody, a MUCl monoclonal antibody, a GPC1 monoclonal antibody, and an EpCAM monoclonal antibody.
  • the catheter body is a hollow structure, and the catheter includes a pull wire, one end of the pull wire is connected to the inner surface of the nylon bag, and the other end is extended from the catheter body.
  • the collection device is an exosomes or a nucleic acid collection device.
  • the collecting device is a porous nucleic acid binding device.
  • the collection device is a porous cylinder formed by loading of silica or other nucleic acid binding medium nanoparticles.
  • the catheter body is a plastic catheter body.
  • the present invention provides an in vivo collection device for blood liquid biopsy comprising the above described guide a tube and a venous puncture needle capable of arranging the catheter, the catheter body being positioned within the venipuncture needle when the venipuncture needle is sheathed, and the collection device extending from the catheter front end.
  • the catheter further includes a catheter hub disposed at an end of the catheter body; the catheter hub of the catheter and the end of the venipuncture needle when the venipuncture needle is sheathed Abut.
  • the invention has the beneficial effects that the invention provides an in vivo collection device for blood liquid biopsy, which can be used for collecting cells, exosomes and nucleic acids in vivo, especially circulating tumor cells (circulating tumor) Cells, CTCs), for collecting blood circulation tumor cells, the in vivo collection device can capture as many tumors as possible in comparison to prior art techniques for collecting and collecting tumor cells in vitro.
  • the cells are; the in vivo collection device is simple, safe, easy to operate, and low in cost; and the captured tumor cells can be used for downstream analysis, such as genetic analysis, in vitro culture, drug susceptibility testing, etc.; more importantly, the in vivo collection device passes through After improvement, it can be used to block the transfer of tumor cells through the bloodstream.
  • Figure 1 is a schematic structural view 1 of a catheter according to Embodiment 1 of the present invention.
  • Figure 2 is a schematic structural view 2 of the catheter according to Embodiment 1 of the present invention.
  • FIG. 3 is a schematic structural view of an embodiment of a venipuncture needle according to the present invention.
  • FIG. 4 is a schematic structural view of an in vivo cell collection device for blood liquid biopsy according to Embodiment 1 of the present invention.
  • Figure 5 is a schematic structural view of a catheter according to Embodiment 2 of the present invention.
  • FIG. 6 is a schematic structural view of an in vivo nucleic acid collection device for blood liquid biopsy according to Embodiment 2 of the present invention.
  • the catheter body 1, the catheter body, 2, the cell collection device, 3, the antibody layer, 4, the wire, 5, the catheter seat, 6, the needle of the venipuncture needle, 7, the needle of the venous needle, 8, the nucleic acid collection device .
  • An embodiment of the catheter of the present invention comprises a catheter body 1 and a cell collection device 2, the end of which is connected to the cell collection device 2.
  • Setting the catheter body 1 is to facilitate the collection of cells by the cell collection device 2 in vivo, for example, to enable the cell collection device 2 to be used in conjunction with a venipuncture needle.
  • the cell collection device 2 is a blood circulation tumor cell collection device.
  • the cell collection device 2 is one of a nylon bag, a porous umbrella-shaped collecting device, and a cylindrical collecting device, and the cell collecting device 2 can be sleeved in the catheter body 1 or taken out of the catheter Outside the body 1.
  • the cell collection device 2 can be used to collect circulating tumor cells.
  • the outer surface of the cell collection device 2 is coupled to an antibody layer 3 for capturing circulating tumor cells.
  • the antibody layer 3 is a monoclonal antibody layer.
  • the monoclonal antibody layer comprises, but is not limited to, at least one of a Her2 monoclonal antibody, a MUCl monoclonal antibody, a GPC1 monoclonal antibody, and an EpCAM monoclonal antibody.
  • the catheter body 1 is a hollow structure, and the catheter includes a pull wire 4, one end of which is connected to the inner surface of the cell collecting device 2, and the other end protrudes from the catheter body 1.
  • the process of extracting the cell collecting device 2 from the vein easily causes the circulating tumor cells on the cell collecting device 2 to fall off and contaminate other cells, and the setting of the wire is
  • the circulating tumor cells on the cell collection device 2 are prevented from falling off during the process of pulling out the cell collection device 2 and preventing contamination of other cells.
  • 1 and 2 are two state diagrams of the catheter of the present embodiment. A schematic view of the catheter after the cell collection device 2 is blown out from the catheter body 1 is shown in FIG. 1 , and the cell collection device 2 is pulled into the catheter body 1 .
  • the schematic diagram of the catheter is shown in Figure 2.
  • the catheter body 1 is a plastic catheter body. It is also set as a plastic catheter body to facilitate the use of the venipuncture needle and to facilitate the retention of the patient.
  • the present embodiment also provides an in vivo cell collection device for blood liquid biopsy, as shown in FIGS. 3 and 4, comprising the catheter described above and a venipuncture needle capable of arranging the catheter, the venous needle When the catheter is sheathed, the catheter body 1 is positioned within the venipuncture needle and the cell collection device 2 projects from the catheter tip.
  • the venous puncture needle includes a needle core 7 of a venous puncture needle and a needle tube 6 of a venipuncture needle sleeved on the needle core 7 of the venous puncture needle, and the catheter is to be sheathed when the venous puncture needle tube is to be placed
  • the catheter is inserted into the needle 6 of the venipuncture needle from the end of the needle 6 of the venipuncture needle.
  • the catheter body 1 is located within the needle tube 6 of the venipuncture needle, and the cell collection device 2 projects from the front end of the catheter 1.
  • the catheter further includes a catheter hub 5 disposed at an end of the catheter body; the vein
  • the catheter hub 5 of the catheter abuts against the distal end of the venipuncture needle.
  • the catheter hub 5 of the catheter abuts the end of the needle 6 of the venipuncture needle.
  • the catheter hub 5 is provided for cooperation with the syringe.
  • the syringe can be attached to the catheter hub 5 to blow the cell collection device out of the catheter body 1.
  • the catheter holder 5 can also be omitted.
  • the cell collection device 2 can be blown out of the catheter body 1 by means of other air blowing means attached to the catheter body 1.
  • the nylon bag can be blown out of the catheter body 1 and floated in the superior vena cava so that the antibody on the nylon bag contacts the cells in the blood, and the length of the nylon bag can reach 10 cm;
  • An embodiment of the catheter of the present invention includes a catheter body 1 and a nucleic acid collection device 8, the end of which is coupled to the nucleic acid collection device 8.
  • the catheter body 1 is provided for the convenience of the nucleic acid collection device 8 to collect nucleic acids in vivo, for example, to enable the nucleic acid collection device 8 to be used in conjunction with a venipuncture needle.
  • nucleic acid collection device 8 is a porous nucleic acid binding device.
  • the nucleic acid collection device 8 is a porous cylinder formed by loading of silica nanoparticles.
  • the use of silica to collect nucleic acids in vivo is set to be porous in order to expand the contact area of the collection medium of silica with blood to facilitate the collection of more nucleic acids.
  • the catheter body 1 is a plastic catheter body. It is also set as a plastic catheter body to facilitate the use of the venipuncture needle and to facilitate the retention of the patient.
  • the present invention provides an in vivo nucleic acid collection device for blood liquid biopsy, as shown in Figures 3 and 6, Including the catheter described above and a venous puncture needle capable of arranging the catheter, the catheter body 1 is located in the venous puncture needle when the venipuncture needle is sheathed, and the nucleic acid collection device 8 Extending from the front end of the catheter 1.
  • the venous puncture needle includes a venipuncture needle core 7 and a venipuncture needle needle 6 that is sleeved with the venipuncture needle core 7 from the vein when the venous puncture needle tube is sleeved with the catheter
  • the venipuncture needle core 7 is pulled out from the end of the puncture needle needle 6, and the catheter is inserted into the venipuncture needle tube 6 from the end of the venipuncture needle tube 6, and the catheter body 1 is located in the venipuncture needle Inside the needle tube 6, and the nucleic acid collection device 8 projects from the front end of the catheter 1, as shown in FIG.
  • the catheter body 1 and the nucleic acid collection device 8 were pulled out together.
  • the nucleic acid adhered to the nucleic acid collection device 8 is eluted for analysis and identification and a series of downstream tests.

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Abstract

提供了一种导管，包括导管本体和收集装置，该导管本体的前端与收集装置连接。还提供了一种用于血液液体活检的体内收集样本装置，该体内收集装置用于在体内收集细胞、外泌体(exosomes)和核酸，尤其是血液循环肿瘤细胞(circulating tumor cells，CTCs)。相较于现有技术中采集外周血体外分离捕获肿瘤细胞技术而言，该体内收集装置可以捕获富集尽可能多的肿瘤细胞；该收集装置经过改进后，还可以用于阻断肿瘤细胞经血流转移。

Description

一种用于血液液体活检的体内收集装置 技术领域
本发明涉及一种医疗器械，具体涉及一种用于血液液体活检的体内收集装置。
背景技术
目前现有技术中普遍使用的收集肿瘤细胞的方法为：采集病人7.5ml外周血离心，利用免疫磁流体(ferrofluid)捕获肿瘤细胞，然后利用一系列单抗免疫组化和核酸染料发现肿瘤细胞。但是此方法的缺点为：1.实体瘤患者循环血中肿瘤细胞极为罕见(约1个肿瘤细胞/106-107白细胞)，难以捕获发现和鉴定；2.操作步骤多，操作繁琐；3.实验成本高，实验仪器极其昂贵；4.分离捕获鉴定到的肿瘤细胞难以用于下游分析，如基因分析、体外培养、药敏试验等。
发明内容
本发明的目的在于克服现有技术存在的不足之处而提供了一种导管和用于血液液体活检的体内收集装置。
为实现上述目的，所采取的技术方案：一种导管，包括导管本体和收集装置，所述导管本体的末端与所述收集装置连接。
作为本发明的优选实施方式，所述收集装置为细胞收集装置。
作为本发明的优选实施方式，所述收集装置为血液循环肿瘤细胞收集装置。本发明所述细胞收集器可在体内收集细胞，尤其是肿瘤细胞，改进了现有技术中体外收集细胞的操作极度困难、繁琐、步骤多、技术成本高、仪器极其昂贵等缺点，使得捕获的肿瘤细胞可以用于下游分析，如基因分析、体外培养、药敏试验等。
Her2，人类表皮生长因子受体2(human epidermalgrowth factor receptor-2，HER2)基因，是重要的乳腺癌预后判断因子。HER2阳性(过表达或扩增)的乳腺癌，其临床特点和生物学行为有特殊表现，治疗模式也与其他类型的乳腺癌有很大的区别，其编码相对分子质量为185kDa的跨膜受体样蛋白，具有酪氨酸激酶活性。
MUC1，是由muc1基因表达的一种高糖基化(糖化大于50％)、高分子量(Mr ＞200kDa)蛋白，又称附膜蛋白，是跨膜分子。它在上皮更新与分化，维持上皮完整性和癌的发生与转移等方面都起到重要的作用。由于MUC1在肿瘤组织中的异常表达，使其成为一种重要肿瘤生物学标志物。MUC1广泛分布并异常丰富地表达于腺癌细胞表面，而且糖基化不完全，因此暴露出正常情况下隐蔽的抗原表位，成为免疫细胞攻击靶点。
GPC，磷脂酰肌醇蛋白聚糖(glypicans)是硫酸肝素二大家族之一。在哺乳动物中发现了6种GPCs，分别称为GPC1-6。GPCs通过糖基磷脂酰肌醇(GPI)锚定在细胞膜上，调节许多细胞信号通路(如Wnt，Hedgehog，FGF等信号传递)和组织器官发生。在癌症发生时，癌细胞上GPCs质与量都会发生变化而成为重要的癌性标志物。
EpCAM，上皮细胞粘附分子(Epithelial cell adhesion molecule)，是一种由GA-733-2基因编码的分子量为40kDa的跨膜糖蛋白，作为嗜同种的钙非依赖性的上皮细胞间粘附分子在上皮癌变过程中发挥着作用。
作为本发明的优选实施方式，所述收集装置为尼龙袋、多孔性伞形收集装置和圆柱形收集装置中的一种，所述收集装置可套设在所述导管本体内或脱出所述导管本体外。
作为本发明的优选实施方式，所述收集装置的外表面偶联用于捕获细胞的抗体层。
作为本发明的优选实施方式，所述收集装置的外表面偶联用于捕获血液循环肿瘤细胞的抗体层。优选地，所述抗体层为单克隆抗体层，所述单克隆抗体层包含但不限于Her2单克隆抗体、MUC1单克隆抗体、GPC1单克隆抗体和EpCAM单克隆抗体中的至少一种。
作为本发明的优选实施方式，所述导管本体为中空结构，所述导管包括拉线，所述拉线的一端与尼龙袋的内表面连接，另一端伸出所述导管本体。
作为本发明的优选实施方式，所述收集装置为外泌体或核酸收集装置。
作为本发明的优选实施方式，所述收集装置为多孔型核酸结合装置。
作为本发明的优选实施方式，所述收集装置为由二氧化硅或其他核酸结合介质纳米颗粒装填形成的多孔圆柱体。
作为本发明的优选实施方式，所述导管本体为塑料导管本体。
本发明提供了一种用于血液液体活检的体内收集装置，包括上述所述的导 管以及能够套设所述导管的静脉穿刺针，所述静脉穿刺针套设所述导管时，所述导管本体位于所述静脉穿刺针内，且所述收集装置从所述导管前端伸出。
作为本发明的优选实施方式，所述导管还包括设置在所述导管本体末端的导管座；所述静脉穿刺针套设所述导管时，所述导管的导管座与所述静脉穿刺针的末端抵接。
本发明的有益效果在于：本发明提供了一种用于血液液体活检的体内收集装置，该体内收集装置可以用于在体内收集细胞、外泌体和核酸，尤其是血液循环肿瘤细胞(circulating tumor cells，CTCs)，用于收集血液循环肿瘤细胞时，该体内收集装置相较于现有技术中采集外周血体外分离捕获肿瘤细胞技术而言，该体内收集装置可以捕获富集尽可能多的肿瘤细胞；并且该体内收集装置简便、安全、易操作、成本低；并且捕获的肿瘤细胞可用于下游分析，如基因分析、体外培养、药敏试验等；更为重要的是，此体内收集装置经过改进后，可以用以阻断肿瘤细胞经血流转移。
附图说明
图1为本发明实施例1所述导管的结构示意图1；
图2为本发明实施例1所述导管的结构示意图2；
图3为本发明所述静脉穿刺针的一种实施例的结构示意图；
图4为本发明实施例1所述用于血液液体活检的体内细胞收集装置的结构示意图；
图5为本发明实施例2所述导管的结构示意图；
图6为本发明实施例2所述用于血液液体活检的体内核酸收集装置的结构示意图；
图中，1、导管本体，2、细胞收集装置，3、抗体层，4、拉线，5、导管座，6、静脉穿刺针的针管，7、静脉穿刺针的针芯，8、核酸收集装置。
具体实施方式
为更好的说明本发明的目的、技术方案和优点，下面将结合具体实施例对本发明作进一步说明。
实施例1
本发明所述导管的一种实施例，如图1和图2所示，包括导管本体1和细胞收集装置2，所述导管本体1的末端与所述细胞收集装置2连接。设置所述导管本体 1是为了方便所述细胞收集装置2在体内收集细胞，例如使细胞收集装置2能够与静脉穿刺针配合使用。
进一步地，所述细胞收集装置2为血液循环肿瘤细胞收集装置。
进一步地，所述细胞收集装置2为尼龙袋、多孔性伞形收集装置和圆柱形收集装置中的一种，所述细胞收集装置2可套设在所述导管本体1内或脱出所述导管本体1外。所述细胞收集装置2可以用于收集循环肿瘤细胞。
进一步地，所述细胞收集装置2的外表面偶联用于捕获循环肿瘤细胞的抗体层3。优选地，所述抗体层3为单克隆抗体层。优选地，所述单克隆抗体层包含但不限于Her2单克隆抗体、MUC1单克隆抗体、GPC1单克隆抗体和EpCAM单克隆抗体中的至少一种。
进一步地，所述导管本体1为中空结构，所述导管包括拉线4，所述拉线4的一端与细胞收集装置2的内表面连接，另一端伸出所述导管本体1。采用所述细胞收集装置2在静脉内收集完循环肿瘤细胞后，从静脉拔出所述细胞收集装置2的过程中容易使细胞收集装置2上的循环肿瘤细胞脱落及污染其他细胞，设置拉线是为了将细胞收集装置2拉入导管本体1内，使得细胞收集装置2上的循环肿瘤细胞在拔出细胞收集装置2的过程中不脱落及防止污染其他细胞。图1和图2为本实施例所述导管的两种状态图，将细胞收集装置2从导管本体1吹出后的导管示意图如图1所示，将细胞收集装置2拉入导管本体1内的导管示意图如图2所示。
进一步地，所述导管本体1为塑料导管本体。设置为塑料导管本体还是为了方便与静脉穿刺针配合使用及方便留置病人体内。
本实施例还提供了一种用于血液液体活检的体内细胞收集装置，如图3和4所示，包括上述所述的导管以及能够套设所述导管的静脉穿刺针，所述静脉穿刺针套设所述导管时，所述导管本体1位于所述静脉穿刺针内，且所述细胞收集装置2从所述导管前端伸出。具体地，所述静脉穿刺针包括静脉穿刺针的针芯7以及套设在所述静脉穿刺针的针芯7上的静脉穿刺针的针管6，当所述静脉穿刺针管要套设所述导管时，从所述静脉穿刺针的针管6的末端拔出所述静脉穿刺针的针芯7，将所述导管从所述静脉穿刺针的针管6的末端插入所述静脉穿刺针的针管6，所述导管本体1位于所述静脉穿刺针的针管6内，且所述细胞收集装置2从所述导管1前端伸出。
进一步地，所述导管还包括设置在所述导管本体末端的导管座5；所述静脉 穿刺针套设所述导管时，所述导管的导管座5与所述静脉穿刺针的末端抵接。具体地，所述导管的导管座5与所述静脉穿刺针的针管6的末端抵接。设置导管座5是为了与注射器配合，当需要将细胞收集装置2吹出导管本体1时，可以将注射器接在导管座5上把细胞收集装置吹出导管本体1；当然，也可以不设置导管座5，可以采用其他的吹气装置接在导管本体1上将细胞收集装置2吹出导管本体1。
本实施例所述体内细胞收集装置的使用方法如下：
(1)拉动拉线4，使尼龙袋收纳于导管本体1的中空结构中，如图2所示；
(2)将静脉穿刺针刺入锁骨下静脉，拔出静脉穿刺针的针芯7；
(3)将导管沿静脉穿刺针的针管6插入锁骨下静脉，可直达上腔静脉。用注射器接在导管座5上可将尼龙袋吹出导管本体1，并飘悬于上腔静脉中，使得尼龙袋上的抗体与血液中的细胞接触，尼龙袋的长度可达10cm；
(4)剪去导管本体末端的导管座5，将静脉穿刺针6小心地拔出，而导管本体1及末端连接的尼龙袋2留置锁骨下静脉中，并将导管本体1用医用胶带固定于体表；
5)留置一段时间后(48～72小时)，拉动拉线4，使尼龙袋收纳于导管本体1的中空结构中，拔出体外。将尼龙袋表面上粘附的细胞洗脱，培养，进行分析鉴定及一系列下游测试。
实施例2
本发明所述导管的一种实施例，如图5所示，包括导管本体1和核酸收集装置8，所述导管本体1的末端与所述核酸收集装置8连接。设置所述导管本体1是为了方便所述核酸收集装置8在体内收集核酸，例如使核酸收集装置8能够与静脉穿刺针配合使用。
进一步地，所述核酸收集装置8为多孔型核酸结合装置。
优选地，所述核酸收集装置8为由二氧化硅纳米颗粒装填形成的多孔圆柱体。采用二氧化硅能够在体内收集核酸，将其设置为多孔是为了扩大二氧化硅这个收集介质与血液的接触面积，以便于收集更多的核酸。
进一步地，所述导管本体1为塑料导管本体。设置为塑料导管本体还是为了方便与静脉穿刺针配合使用及方便留置病人体内。
本发明提供了一种用于血液液体活检的体内核酸收集装置，如图3和6所示， 包括上述所述的导管以及能够套设所述导管的静脉穿刺针，所述静脉穿刺针管套设所述导管时，所述导管本体1位于所述静脉穿刺针内，且所述核酸收集装置8从所述导管1前端伸出。具体地，所述静脉穿刺针包括静脉穿刺针针芯7以及套设所述静脉穿刺针针芯7的静脉穿刺针针管6，当所述静脉穿刺针管套设所述导管时，从所述静脉穿刺针针管6的末端拔出所述静脉穿刺针针芯7，将所述导管从所述静脉穿刺针针管6的末端插入所述静脉穿刺针针管6，所述导管本体1位于所述静脉穿刺针针管6内，且所述核酸收集装置8从所述导管1前端伸出，如图6所示。
本实施例所述体内核酸收集器的使用方法如下：
(1)将静脉穿刺针刺入锁骨下静脉或其他外周静脉，拔出静脉穿刺针针芯7；
(2)将导管沿静脉穿刺针针管6插入锁骨下静脉或其他外周静脉，可直达上腔静脉或其他外周静脉内。核酸收集装置8置于上腔静脉或其他外周静脉中，与血液中的核酸接触，结合收集血液中的核酸；
(3)将静脉穿刺针针管6小心地拔出，而导管本体1和末端的核酸收集装置8留置锁骨下静脉或其它外周静脉中，并将导管本体1用医用胶带固定于体表；
(4)留置一段时间后(48～72小时)，导管本体1和核酸收集装置8连同拔出。将核酸收集装置8上粘附的核酸洗脱，进行分析鉴定及一系列下游测试。
最后所应当说明的是，以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制，尽管参照较佳实施例对本发明作了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的实质和范围。

Claims (12)

  1. 一种导管，其特征在于，包括导管本体和收集装置，所述导管本体的前端与所述收集装置连接。
  2. 根据权利要求1所述的导管，其特征在于，所述收集装置为细胞收集装置。
  3. 根据权利要求2所述的导管，其特征在于，所述收集装置为血液循环肿瘤细胞收集装置。
  4. 根据权利要求1所述的导管，其特征在于，所述收集装置为尼龙袋、多孔性伞形收集装置和圆柱形收集装置中的一种，所述收集装置可套设在所述导管本体内或脱出所述导管本体外。
  5. 根据权利要求4所述的导管，其特征在于，所述收集装置的外表面偶联用于捕获细胞的抗体层。
  6. 根据权利要求5所述的导管，其特征在于，所述收集装置的外表面偶联用于捕获血液循环肿瘤细胞的抗体层。
  7. 根据权利要求4所述的导管，其特征在于，所述导管本体为中空结构，所述导管包括拉线，所述拉线的一端与尼龙袋的内表面连接，另一端伸出所述导管本体。
  8. 根据权利要求1所述的导管，其特征在于，所述收集装置为外泌体或核酸收集装置。
  9. 根据权利要求1所述的导管，其特征在于，所述收集装置为多孔型核酸结合装置。
  10. 根据权利要求1所述的导管，其特征在于，所述收集装置为由二氧化硅纳米颗粒装填形成的多孔圆柱体。
  11. 一种用于血液液体活检的体内收集装置，其特征在于，包括如权利要求1-10任一所述的导管以及能够套设所述导管的静脉穿刺针，所述静脉穿刺针套设所述导管时，所述导管本体位于所述静脉穿刺针内，且所述收集装置从所述导管前端伸出。
  12. 根据权利要求11所述的体内收集装置，其特征在于，所述导管还包括设置在所述导管本体末端的导管座；所述静脉穿刺针套设所述导管时，所述导 管的导管座与所述静脉穿刺针的末端抵接。
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