WO2023143526A1 - 一种标记物捕获装置 - Google Patents

一种标记物捕获装置 Download PDF

Info

Publication number
WO2023143526A1
WO2023143526A1 PCT/CN2023/073588 CN2023073588W WO2023143526A1 WO 2023143526 A1 WO2023143526 A1 WO 2023143526A1 CN 2023073588 W CN2023073588 W CN 2023073588W WO 2023143526 A1 WO2023143526 A1 WO 2023143526A1
Authority
WO
WIPO (PCT)
Prior art keywords
magnetic
sleeve
attachment
marker
capture device
Prior art date
Application number
PCT/CN2023/073588
Other languages
English (en)
French (fr)
Inventor
蒋霆辉
梁晓飞
张慧欣
沈天皓
陆珺
刘艳
Original Assignee
上海欣光层生物医疗科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN202320112750.2U external-priority patent/CN219921096U/zh
Application filed by 上海欣光层生物医疗科技有限公司 filed Critical 上海欣光层生物医疗科技有限公司
Publication of WO2023143526A1 publication Critical patent/WO2023143526A1/zh

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/02—Instruments for taking cell samples or for biopsy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/24—Apparatus for enzymology or microbiology tube or bottle type
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/26—Inoculator or sampler
    • 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
    • G01N1/40—Concentrating samples

Definitions

  • the utility model belongs to the field of medical equipment, in particular to a marker capturing device.
  • CTCs Circulating Tumor Cells
  • CTCs are extremely rare in blood
  • enrichment becomes a challenge.
  • the detection of CTCs at home and abroad is basically limited to the blood collection test mode of traditional laboratory medicine, the enrichment efficiency is low, and it is difficult to reflect the general condition of tumor patients and the heterogeneity of tumors.
  • the common bottleneck of this model is that the amount of blood sample is too small. How to break through the bottleneck of small sample volume and enrich more CTCs is of great significance to the dynamic monitoring of tumor hematogenous metastasis and the development of liquid biopsy technology.
  • the purpose of this utility model is to design a device introduced into the body, which can collect CTCs from a large amount of meridian blood, and greatly improve the enrichment efficiency of CTCs.
  • the utility model provides a marker capture device, including a sleeve assembly and a magnetic assembly;
  • the sleeve assembly includes an outer sleeve and an attachment sleeve disposed inside the outer sleeve, the outer surface of the attachment sleeve is provided with grooves;
  • the outer sleeve and the attachment sleeve can slide relatively, so that at least part of the groove is exposed outside the outer sleeve, and the end of the attachment sleeve exposed to the outer sleeve is a closed end;
  • the magnetic assembly is disposed within the attachment sleeve to capture a magnetically labeled marker into the groove.
  • the closed end is an arc-shaped end face.
  • one end of the attachment sleeve located in the outer sleeve is an open end, and the magnetic component is placed in the attachment sleeve through the open end.
  • the depth of the groove is 1/2-3/4 of the wall thickness of the attachment sleeve.
  • the grooves are threaded grooves, linear grooves or grid grooves.
  • the magnetic assembly includes a magnetic bead chain composed of several magnetic beads arranged in sequence, and a metal wire connecting the magnetic bead chain in series; the adjacent magnetic poles of two adjacent magnetic beads have the same polarity, A gap exists between two adjacent magnetic beads.
  • the metal wire is provided with a limiting structure at positions outside the magnetic beads at both ends of the magnetic bead chain.
  • the end faces of the magnetic beads are arc-shaped end faces.
  • an intermediate body is provided between two adjacent magnetic beads, and an end face of the intermediate body facing the magnetic bead is an arc-shaped end face.
  • one or more sets of magnetic components are arranged in the attachment sleeve.
  • the attachment sleeve of the utility model is provided with a groove outside, which provides accommodating space for markers such as CTCs, helps to maintain the original state and activity of the marker, and markers trapped in the groove can avoid being damaged by contact.
  • the outer sleeve can also protect the markers in the groove if it is scratched and falls off when it touches the outer sleeve, the blood vessel wall or the subcutaneous tissue.
  • the magnetic device of the present invention includes a magnetic bead chain composed of magnetic beads arranged in sequence.
  • the adjacent ends of adjacent magnetic beads have the same polarity and repel each other, so that the magnetic field can be evenly distributed over the entire length of the magnetic bead chain, and The surrounding 360° magnetic field is evenly distributed without blind areas, which enhances the adsorption effect of the magnetic bead chain.
  • the magnetic bead chains connected in series can ensure the firm connection of the magnetic bead chains, and the metal wires can be pre-bent into different shapes according to requirements.
  • the capture device of the present utility model has a wide application range. Any substance that can be magnetically marked can be captured by the utility model, and the application range can be extended to the adsorption of viruses, fluids or gas suspensions. , industry or environmental protection has a very high prospect.
  • FIG. 1 is a schematic structural view of a marker capture device of the present invention.
  • Fig. 2 is a schematic diagram of the internal structure of the marker capturing device of the present invention.
  • Fig. 3 is a structural schematic diagram of the magnetic device of the present invention.
  • Fig. 4 is a schematic diagram of an arrangement of magnetic beads.
  • Fig. 5 is a schematic diagram of another arrangement of magnetic beads.
  • FIG. 6 is a schematic diagram of the magnetic field of the cross-section of the magnetic bead shown in FIG. 5 .
  • Fig. 7 is the schematic diagram of the magnetic device of the present invention, wherein, a is the magnetic field schematic diagram of the magnetic bead chain section of the present utility model, b is the magnetic field schematic diagram of the side of the magnetic bead chain of the present utility model, and c is another magnetic device of the present utility model A schematic diagram of the structure.
  • connection should be understood in a broad sense, for example, it can be a fixed connection or a detachable connection , or integrally connected; can be mechanically connected; can be directly connected, can also be indirectly connected through an intermediary, and can be internal communication between two components.
  • installation can be a fixed connection or a detachable connection , or integrally connected; can be mechanically connected; can be directly connected, can also be indirectly connected through an intermediary, and can be internal communication between two components.
  • the marker capture device provided by the utility model includes a sleeve assembly and a magnetic assembly.
  • the sleeve assembly includes an outer sleeve 1 and an attachment sleeve 2 disposed inside the outer sleeve 1 , and a groove 20 is provided on the outer surface of the attachment sleeve 2 .
  • the outer sleeve 1 and the attachment sleeve 2 can slide relatively, so that at least part of the groove 20 is exposed outside the outer sleeve 1 , and one end of the attachment sleeve 2 is exposed outside the outer sleeve 1 is the closed end 21.
  • the magnetic component is arranged in the attachment sleeve 2 .
  • One end of the attachment sleeve 2 inside the outer sleeve 1 is an open end (rear end), through which the magnetic assembly is placed in the attachment sleeve 2 .
  • the CTCs in the blood are magnetically labeled with antibodies through Fe 3 O 4 nanoparticles (the magnetic markers of the utility model are paramagnetic markers).
  • the attachment sleeve 2 is completely inside the outer sleeve 1 .
  • the outer sleeve 1 is retracted, the outer sleeve 1 and the attachment sleeve 2 slide relatively, so that the groove of the attachment sleeve 2 is exposed outside the outer sleeve 1, and the attachment sleeve 2 is exposed to the outer sleeve 1
  • the other end is used as the front end of the attachment sleeve 2.
  • the magnetic force of the magnetic component disposed in the attachment sleeve 2 can penetrate the attachment sleeve 2 and radiate outwards, attracting the magnetically marked CTCs to the outer periphery of the attachment sleeve 2 .
  • CTCs have a tendency to approach the magnetic assembly, and the outer surface of the attachment sleeve 2 is provided with a groove 20, and the bottom of the groove 20 is closer to the magnetic assembly 2, so the magnetic force at the bottom of the groove 20 is stronger, therefore, CTCs can be captured and Stored in groove 20.
  • Groove 20 provides accommodation space for CTCs, which is beneficial to maintain the original state of CTCs and protect cell activity.
  • the outer sleeve 1 is pushed forward, and the outer sleeve 1 and the attachment sleeve 2 slide relatively, so that the attachment sleeve 2 is completely located in the outer sleeve 1 . Since the CTCs can always be attracted in the groove 20 under the magnetic force of the magnetic assembly, during the relative sliding process of the outer sleeve 1 and the attached sleeve 2, the edge of the outer sleeve 1 will not scratch the CTCs, and will not cause CTCs fall off.
  • the capture device as a whole is removed from the capture position.
  • the attachment sleeve 2 is completely inside the outer sleeve 1, and the CTCs stored in the groove 20 are covered and protected by the outer sleeve 1, and will not be scraped off by the blood vessel wall or subcutaneous tissue, and all are attracted and captured by the magnetic assembly All CTCs can be stored in the groove 20 through the capture device of the present utility model, and be taken out of the capture position in good condition.
  • the closed end 21 is an arc-shaped end surface, and the edge of the arc-shaped end surface is round and smooth.
  • the arc-shaped end surface will not damage human tissues or blood vessels. damage to the wall.
  • the closed end 21 includes a closed end cap 210 , and the closed end cap 210 also has an arc-shaped end surface.
  • the closed end cap 210 has a hemispherical structure.
  • the depth of the groove 20 is 1/2-3/4 of the wall thickness of the attachment sleeve 2 .
  • the groove 20 is a thread groove, a linear groove or a grid groove.
  • the number of grooves is 8-12.
  • the magnetic assembly includes a magnetic bead chain composed of several magnetic beads 3 arranged in sequence, and a metal wire 4 connected in series to the magnetic bead chain, and the adjacent two adjacent magnetic beads 3
  • the polarities of the magnetic poles are the same, so that there is a gap 5 between two adjacent magnetic beads 3 .
  • the magnetic bead 3 is a permanent magnetic material such as NdFeB.
  • the magnetic beads 3 include N poles and S poles.
  • the ways in which the magnetic beads 3 are arranged in sequence may be as follows: (1) As shown in Figure 4, two adjacent magnetic beads are arranged vertically (that is, the arrangement direction of the magnetic beads is consistent with the connection direction from the N pole to the S pole in each magnetic bead), and the adjacent magnetic poles of the adjacent magnetic beads The polarity is opposite, that is, the adjacent magnetic beads attract each other. This arrangement makes the magnetic field appear only at the two ends of the entire magnetic bead chain, and the magnetic field formed by the magnetic beads in the middle disappears due to mutual coupling, and the magnetism of the entire magnetic bead chain is very low.
  • the adjacent magnetic poles of adjacent magnetic beads 3 have the same polarity, that is, the adjacent magnetic beads 3 repel each other. Therefore, the magnetic field of the present invention can be evenly distributed over the entire length of the magnetic bead chain, and the 360° magnetic field distribution around the magnetic bead chain has no magnetic blind area, which enhances the attraction effect of the magnetic bead chain to markers, as shown in Figure 7 a And shown in Figure 7b. Adjacent magnetic beads 3 repel each other to form a small gap 5, so that the magnetic bead chain can bend smoothly.
  • the arrangement of the utility model cannot make the adjacent magnetic beads 3 naturally attract each other to form a string, so the magnetic bead chain of the utility model is connected in series through the metal wire 4, and the metal wire 4 can be made of nickel-titanium alloy to firmly connect several magnetic beads 3 , It is not easy to break the chain, and Nitinol is a memory alloy, which can be pre-bent into different shapes to meet the needs of different curvatures.
  • the magnetic beads 3 are provided with through holes, and the metal wires 4 pass through the through holes of the magnetic beads 3 in sequence to connect several magnetic beads 3 in series to form a magnetic bead chain.
  • a position limiting structure 6 is provided outside the magnetic beads at both ends of the magnetic bead chain.
  • the size of the limiting structure is larger than the size of the through hole of the magnetic beads 3, so that the magnetic beads 3 connected in sequence are locked between the limiting structures 6 at both ends. Therefore, even if adjacent magnetic beads 3 repel each other, several magnetic beads 3 can still be kept in the attachment sleeve 2 after being connected in series through the metal wire 4 .
  • the magnetic beads 3 are bar-shaped, and the end faces thereof are arc-shaped end faces, so that the magnetic beads 3 are sausage-shaped.
  • the smooth arc-shaped end face has a larger bending space, which can further increase the degree of compliance between adjacent magnetic beads 3 .
  • an intermediate body 7 is provided between two adjacent magnetic beads 3 , and mutual repulsion still exists between adjacent magnetic beads 3 after being separated by the intermediate body 7 .
  • the end face of the intermediate body 7 facing the magnetic bead is an arc-shaped end face.
  • the intermediate body 7 is a spherical iron ball or steel ball. The existence of the intermediate body 7 causes the gap between adjacent magnetic beads 3 to release the magnetic field of the magnetic beads more fully, and the radiation range of such a magnetic field is larger.
  • the smooth intermediate body 7 can also further increase the degree of compliance between adjacent magnetic beads 3 . At this time, the end faces of the magnetic beads 3 can be arc-shaped or flat.
  • the metal wire 4 can be a single strand, bent into a helical shuttle-shaped basket, or double or multiple strands juxtaposed to naturally form a basket shape.
  • the attachment sleeve 2 one or more sets of magnetic components are provided. Whether it is the magnetic field radiation attraction or the basket configuration, the capture range in the blood vessel section can be expanded to achieve the goal of "three-dimensional capture".
  • the magnetic assembly in the attachment sleeve 2 is taken out from the opening at the rear end of the attachment sleeve 2, and the CTCs located in the groove 20 naturally fall or are eluted due to loss of attraction, In this way, further detection, identification, collection and culture of the adsorbed CTCs can be realized.
  • the magnetic assembly is inserted into the attachment sleeve 2, and the attachment sleeve 2 isolates the CTCs from the magnetic assembly, so that the CTCs do not directly contact the magnetic assembly, preventing the CTCs from being directly adsorbed on the magnetic assembly, resulting in cells that cannot be washed after capture. take off.
  • the attraction between the CTCs and the magnetic component can be eliminated by pulling out the magnetic component from the attachment sleeve 2 , without using forced demagnetization methods such as high temperature demagnetization, which avoids damage to the cells.
  • the magnetic assembly is always wrapped in the cannula assembly and does not come into contact with blood or tissue, so it can also be reused.
  • the capture device of the present invention can capture the magnetically marked markers into the groove of the attachment sleeve by using the magnetic assembly arranged in the attachment sleeve.
  • the capture device can not only be used to enrich circulating tumor cells (CTCs), but also capture any material that can be magnetically labeled, such as viruses, suspended matter in fluid, etc., so that the markers can be separated.
  • Step 1 5-8 mg of magnetic enhancer (superparamagnetic particles) was intravenously injected 20-30 minutes before the operation to mark CTCs.
  • Step 2 Puncture the femoral vein in the groin under local anesthesia, introduce a catheter sheath, and establish a venous channel; perform inferior vena cava contrast, and judge the capture device and capture position according to the shape of the inferior vena cava.
  • the aorta, superior vena cava, or blood vessels downstream of the tumor can also be selected as the capture location as needed.
  • Step 3 Guide the capture device through the catheter sheath into the capture position of the inferior vena cava through the guide wire, retreat the outer sleeve 1, expose the groove 20 of the attachment sleeve 2, start to absorb and capture CTCs, and capture the CTCs as the attachment sleeve 2 Attachment segment; preferably, the attachment sleeve 2 containing the entire length of the magnetic bead chain has grooves 20 on its outer surface, and this part of the grooves 20 is completely exposed to the blood flow as an attachment segment.
  • Step 4 the capture time is designed to be half an hour. Human blood circulates once every 3 minutes on average, and half an hour is equivalent to 10 cycles. If the total blood volume of the human body is 5,000ml, half an hour is equivalent to filtering 50,000ml of blood, which is 10,000 times the volume of blood samples collected in traditional laboratory medicine.
  • Step 5 after the capture is completed, the outer sleeve 1 is pushed forward, the attachment section of the attachment sleeve 2 is completely put into the outer sleeve 1, and then the capture device is taken out as a whole.
  • Step 6 push out the attachment section of the attachment sleeve 2 from the front end of the outer sleeve 1, and place it in a test tube containing reagents, pull out the magnetic assembly from the rear end of the attachment sleeve 2, cut off the attachment section of the attachment sleeve 2, CTCs were obtained by placing them in test tubes containing reagents.
  • step 3 to step 6 can be repeated several times, so that the CTCs can be captured and separated from the blood.
  • the marker capture device provided by the utility model has a groove outside the attachment sleeve, which provides a storage space for the marker, helps to maintain the original state and activity of the marker, and sinks into the groove
  • the marker can avoid falling off due to scratching caused by touching the outer sleeve, blood vessel wall or subcutaneous tissue, and the outer sleeve can also protect the marker in the groove.
  • Its magnetic device includes a magnetic bead chain composed of magnetic beads arranged in sequence.
  • the adjacent ends of adjacent magnetic beads have the same polarity and repel each other, so that the magnetic field can be evenly distributed over the entire length of the magnetic bead chain, and the surrounding 360° magnetic field is evenly distributed There is no blind area, which enhances the adsorption effect of the magnetic bead chain, and the metal wire ensures the suppleness and firmness of the magnetic bead chain.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Sustainable Development (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • General Physics & Mathematics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Analytical Chemistry (AREA)

Abstract

一种标记物捕获装置，包括套管组件和磁性组件；套管组件包括外套管（1）和设于外套管（1）内的附着套管（2），附着套管（2）的外表面设有凹槽（20）；外套管（1）与附着套管（2）能够相对滑动，使至少部分凹槽（20）暴露于外套管（1）之外，附着套管（2）暴露于外套管（1）外的一端为封闭端（21）；磁性组件设于附着套管（2）内，以将被磁性标记的标记物捕获至凹槽（20）中。该捕获装置适用范围广，凡是能够被磁性标记的物质，均可被捕获，适用范围可拓展至病毒、流体或气体悬浮物的吸附等，在医学、生物学、工业或环保领域具有极高的前景。

Description

一种标记物捕获装置 技术领域
本实用新型属于医疗器械领域，具体涉及一种标记物捕获装置。
 背景技术
癌症的转移很大程度上是由于肿瘤原发灶脱落的癌细胞转移到其它器官，形成新的转移性肿瘤。血行转移则是转移范围最广最快的，被称为终极转移。目前对于癌症相关的一个研究热点就是基于此类具有转移潜能的异常细胞：循环肿瘤细胞（Circulating Tumor Cell，CTCs），即游弋在血液中的癌细胞。另一方面，肿瘤传统病理活检的诸多缺陷始终无法克服，这使CTCs又成为肿瘤液体活检的主要诊断方法之一。并且，CTCs捕获后可以进行各种检测，来获取更多转移相关信息，同时能实时追踪癌症转移方向并评估治疗预后。
然而，由于CTCs在血液中极其稀少，使得富集成为难题。目前国内外的CTCs检测基本还局限于传统检验医学的采血检验模式，富集效率低，也很难反映肿瘤患者的全身情况和肿瘤的异质性。这种模式的共同瓶颈就是采血样本量实在太少。如何突破标本量少的瓶颈，又能富集更多CTCs，这对肿瘤血行转移的动态监测和液体活检技术的发展具有重要意义。
 技术问题
本实用新型的目的是设计一种导入体内的器械，能够从大量经流血液中采集CTCs，大大提高CTCs的富集效率。
 技术解决方案
为了达到上述目的，本实用新型提供了一种标记物捕获装置，包括套管组件和磁性组件；
所述套管组件包括外套管和设于所述外套管内的附着套管，所述附着套管的外表面设有凹槽；
所述外套管与所述附着套管能够相对滑动，使至少部分所述凹槽暴露于所述外套管之外，所述附着套管暴露于所述外套管外的一端为封闭端；
所述磁性组件设于所述附着套管内，以将被磁性标记的标记物捕获至所述凹槽中。
可选地，所述封闭端为弧形端面。
可选地，所述附着套管位于所述外套管内的一端为开口端，所述磁性组件通过所述开口端置于所述附着套管内。
可选地，所述凹槽的深度为所述附着套管管壁厚度的1/2-3/4。
可选地，所述凹槽为螺纹凹槽、直线型凹槽或网格状凹槽。
可选地，所述磁性组件包括由若干依次排列的磁珠组成的磁珠链，以及串联所述磁珠链的金属丝；相邻两个所述磁珠的相邻磁极的极性相同，使相邻两个所述磁珠间存在间隙。
可选地，所述金属丝上，位于所述磁珠链两端的磁珠外侧的位置，设有限位结构。
可选地，所述磁珠的端面为弧形端面。
可选地，相邻两个所述磁珠间设有中间体，所述中间体朝向所述磁珠的端面为弧形端面。
可选地，所述附着套管内，设有一组或多组磁性组件。
 有益效果
本实用新型的技术效果：
（1）本实用新型的附着套管外设有凹槽，为CTCs等标记物提供了容纳空间，有助于保持标记物的原有状态和活性，陷入凹槽中的标记物能够避免因触碰外套管、血管壁或皮下组织造成刮蹭而脱落，外套管也能对凹槽中的标记物起到保护作用。
（2）本实用新型的磁性装置包括由依次排列的磁珠组成的磁珠链，相邻磁珠的相邻端极性相同，相互排斥，使磁场能够均匀分布于磁珠链全长，且周围360°磁场分布均匀无盲区，增强了磁珠链的吸附效果。
（3）相邻磁珠间互斥，能够产生微小间隙，有利于磁珠链的柔顺弯曲。
（4）通过形态可塑的金属丝，譬如镍钛合金丝，串联的磁珠链能保证磁珠链的牢固连接，金属丝能够根据需求被预弯成不同形状。
（5）本实用新型的安全设计，外套管与附着套管完全使用目前血管介入所用导管材料，安全可靠；磁性组件不与血液和人体接触，安全可靠；附着套管的封闭端圆润光滑，操作有超滑导丝的引导，比现有静脉支架等手术安全得多；CTCs捕获术仅为介入二级手术，即住院医师即可独立完成，并且学界将制定专门的安全操作规程，以确保安全性；针对血管操作可能出现的血栓问题，介入医学界已有完全成熟的肝素化操作程序；纳米磁性制剂目前国际上已有获FDA批准的用于磁共振造影剂的制剂，安全可靠。
（6）本实用新型的捕获装置适用范围广，凡是能够被磁性标记的物质，均可通过本实用新型捕获，适用范围可拓展至病毒、流体或气体悬浮物的吸附等，在医学、生物学、工业或环保领域具有极高的前景。
 附图说明
图1为本实用新型的标记物捕获装置的结构示意图。
图2为本实用新型的标记物捕获装置的内部结构示意图。
图3为本实用新型的磁性装置的一种结构示意图。
图4为一种磁珠排列方式的示意图。
图5为另一种磁珠排列方式的示意图。
图6为图5所示的磁珠截面的磁场示意图。
图7为本实用新型的磁性装置示意图，其中，a为本实用新型磁珠链截面的磁场示意图，b为本实用新型磁珠链侧面的磁场示意图，c为本实用新型的磁性装置的另一种结构示意图。
图中，1-外套管，2-附着套管，20-凹槽，21-封闭端，3-磁珠，4-金属丝，5-间隙，6-限位结构，7-中间体。
 本发明的实施方式
下面将结合附图对本实用新型的技术方案进行清楚、完整地描述，显然，所描述的实施例是本实用新型一部分实施例，而不是全部的实施例。基于本实用新型中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本实用新型保护的范围。
在本实用新型的描述中，需要说明的是，术语“上”“下”“左”“右”“垂直”“水平”“内”“外”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本实用新型和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本实用新型的限制。此外，术语“第一”“第二”“第三”仅用于描述目的，而不能理解为指示或暗示相对重要性。
在本实用新型的描述中，需要说明的是，除非另有明确的规定和限定，术语“安装”“相连”“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以具体情况理解上述术语在本实用新型中的具体含义。
本实用新型提供的标记物捕获装置包括套管组件和磁性组件。
如图1所示，套管组件包括外套管1和设于所述外套管1内的附着套管2，所述附着套管2的外表面设有凹槽20。所述外套管1与所述附着套管2能够相对滑动，使至少部分所述凹槽20暴露于所述外套管1之外，所述附着套管2暴露于所述外套管1外的一端为封闭端21。所述磁性组件设于所述附着套管2内。附着套管2位于所述外套管1内的一端为开口端（后端），磁性组件通过所述开口端置于所述附着套管2中。
捕获前，先将血液中的CTCs通过Fe 3O 4纳米颗粒用抗体进行磁性标记（本实用新型的磁性标记物为顺磁性标记物）。初始状态时，附着套管2完全位于外套管1内。捕获装置放置于捕获位置后，后退外套管1，外套管1与附着套管2相对滑动，使附着套管2的凹槽暴露在外套管1之外，以附着套管2暴露于外套管1之外的一端，作为附着套管2的前端。设于附着套管2内的磁性组件的磁力可穿透附着套管2而向外辐射，将被磁性标记的CTCs吸引至附着套管2的外周。CTCs具有向磁性组件靠近的趋势，附着套管2的外表面设有凹槽20，凹槽20的底部更靠近磁性组件2，故凹槽20底部的磁力更强，因此，CTCs能够被捕获并保存于凹槽20中。凹槽20为CTCs提供了容纳空间，有利于保持CTCs的原有状态，保护细胞活性。
捕获结束后，向前推动外套管1，外套管1与附着套管2相对滑动，使附着套管2完全位于外套管1内。由于CTCs在磁性组件的磁力作用下，能够始终被吸引于凹槽20内，在外套管1与附着套管2相对滑动的过程中，外套管1的边缘不会刮蹭CTCs，不会造成CTCs脱落。
最后，将捕获装置整体从捕获位置处移出。移出时，附着套管2完全位于外套管1内，凹槽20中保存的CTCs在外套管1的包覆保护下，不会被血管壁或皮下组织刮蹭而脱落，所有被磁性组件吸引捕获的CTCs均能通过本实用新型的捕获装置保存于凹槽20中，并被完好的带离出捕获位置。
在一些实施例中，所述封闭端21为弧形端面，弧形端面的边缘圆滑，当附着套管2的封闭端21位于外套管1之外时，弧形端面不会对人体组织或血管壁造成损伤。在另一些实施例中，封闭端21包含一封闭端盖210，该封闭端盖210也具有弧形端面，优选地，封闭端盖210为半球形结构。
在一些实施例中，凹槽20的深度为附着套管2管壁厚度的1/2-3/4。凹槽20为螺纹凹槽、直线型凹槽或网格状凹槽。凹槽的数量为8-12条。
如图2和图3所示，磁性组件包括由若干依次排列的磁珠3组成的磁珠链，以及串联所述磁珠链的金属丝4，相邻两个所述磁珠3的相邻磁极的极性相同，使相邻两个所述磁珠3间存在间隙5。磁珠3为钕铁硼等永磁材料。
磁珠3包含N极和S极。磁珠3依次排列的方式可能有以下几种：
（1）如图4所示，相邻两个磁珠纵向排列（即磁珠的排列方向与每个磁珠中N极至S极的连接方向一致），相邻磁珠的相邻磁极的极性相反，即相邻磁珠之间相吸。这种排列方式使磁场只呈现在整条磁珠链的两端，位于中间的磁珠形成的磁场均因相互耦合而消失，整条磁珠链的磁性很低。
（2）如图5和图6所示，相邻两个磁珠横向排列（即磁珠的排列方向与每个磁珠中N极至S极的连线方向垂直），相邻磁珠相互颠倒排列。这种排列方式的磁场分布如图6所示，虽然磁珠链的全长均有磁场分布，但磁珠链截面上的磁场不均，呈哑铃状，N极和S极的“腰”间有对称的两个磁盲区，磁盲区的位置吸附效果大大降低。
而且，上述（1）和（2）的磁珠链，相邻磁珠间因磁力作用相互吸引，使相邻磁珠间的连接较为僵硬，当磁珠链弯折时，需要较大的外力以克服相邻磁珠间的吸引力，克服吸引力使相邻磁珠分离并弯折后，容易造成磁珠链断链。磁珠仅靠磁力连接成串，进一步增大了断链的风险。
本实用新型中，如图3和图7的c所示，相邻磁珠3相邻磁极极性相同，即相邻磁珠3之间相互排斥。因此，本实用新型的磁场能够均匀分布于磁珠链的全长，且磁珠链周围360°的磁场分布均无磁盲区，增强了磁珠链对标记物的吸引效果，如图7的a和图7的b所示。相邻磁珠3之间相互排斥，形成微小间隙5，使磁珠链能够柔顺弯曲。本实用新型的排列方式不能使相邻磁珠3自然相吸成串，故本实用新型磁珠链通过金属丝4串联，金属丝4可选择镍钛合金材质，以将若干磁珠3牢固连接，不易断链，且镍钛合金为记忆合金，可以被预先弯曲成不同形状，以适应不同弯度的需求。
磁珠3上设有通孔，金属丝4依次穿过磁珠3的通孔将若干磁珠3串联成磁珠链。金属丝4上，位于磁珠链两端的磁珠外侧的位置，设有限位结构6。限位结构的尺寸大于磁珠3的通孔的尺寸，使依次相连的磁珠3被锁紧在两端的限位结构6之间。因此，即使相邻的磁珠3之间互斥，若干磁珠3仍能经金属丝4串联后始终保持在附着套管2内。
在一些实施例中，如图3所示，磁珠3为条形，其端面为弧形端面，使磁珠3呈香肠形。圆滑的弧形端面具有更大的弯曲空间，能够进一步增加相邻磁珠3间的柔顺程度。
在一些实施例中，如图7的c所示，相邻两个磁珠3间设有中间体7，经中间体7间隔后，相邻磁珠3之间仍存在互斥力。中间体7朝向磁珠的端面为弧形端面，可选地，中间体7为球形的铁珠或钢珠。中间体7的存在造成相邻磁珠3之间的空隙能够更充分地释放磁珠的磁场，这样的磁场辐射范围更大。圆滑的中间体7也能够进一步增加相邻磁珠3间的柔顺程度，此时磁珠3的端面既可以为弧形，也可以为平面。
在一些实施例中，金属丝4可以是单股，弯成螺旋梭形网篮，也可以是双股或多股并列，自然形成网篮状。在附着套管2内，磁性组件设有一组或多组。无论是磁场辐射吸引，还是网篮构型，均可扩大在血管截面中的捕获范实现“立体捕获”的目标。
捕获装置整体从捕获位置处移出后，将附着套管2中的磁性组件由附着套管2后端的开口处取出，位于凹槽20中的CTCs因失去吸引而自然掉落，或被洗脱，如此能够实现对被吸附的CTCs进一步检测、鉴定和收集培养。
本实用新型的捕获装置，磁性组件插入附着套管2内，附着套管2将CTCs和磁性组件隔离，使CTCs不直接接触磁性组件，防止CTCs直接吸附在磁性组件上，导致捕获后细胞无法洗脱。磁性组件从附着套管2内抽出，即可消退CTCs与磁性组件间的吸引，无需使用高温退磁等强制退磁的方式，避免了对细胞的损毁。磁性组件始终在套管组件的包裹中，不与血液或组织接触，故也可以重复使用。
本实用新型的捕获装置利用设置于附着套管内的磁性组件，能够将经过磁性标记的标记物捕获至附着套管的凹槽中。该捕获装置不仅能够用于富集循环肿瘤细胞（CTCs），对于任意能够被磁性标记的物质，例如病毒、流体中的悬浮物等，均能够使用该捕获装置进行捕获，使标记物被分离。
本实用新型的捕获装置的使用方法为：
步骤一，术前20-30分钟静脉注射磁性增强剂（超顺磁微粒）5-8mg，对CTCs进行标记。
步骤二，局麻下在腹股沟穿刺股静脉，引入导管鞘，建立静脉通道；行下腔静脉造影，根据下腔静脉形态以判断捕获装置和捕获位置。也可以根据需要选择主动脉、上腔静脉或肿瘤下游血管等为捕获位置。
步骤三，通过导丝引导捕获装置通过导管鞘进入下腔静脉的捕获位置，后退外套管1，暴露出附着套管2的凹槽20，开始吸附捕获CTCs，捕获了CTCs为附着套管2的附着段；优选地，内含磁珠链全长的附着套管2，其外表面均有凹槽20，这部分凹槽20完全暴露在血流中，作为附着段。
步骤四，捕获时间设计为半小时。人体血液平均3min循环一次，半小时相当于10个周期，以人体总血液量为5000ml计算，半小时相当于过滤50000ml血液，是传统检验医学采血样本量的10000倍。
步骤五，捕获结束后，向前推动外套管1，将附着套管2的附着段完全收入外套管1内，再将捕获装置整体取出。
步骤六，将附着套管2的附着段从外套管1的前端推出，并置于装有试剂的试管中，从附着套管2的后端抽出磁性组件，剪断附着套管2的附着段，置于装有试剂的试管中，得到CTCs。
上述步骤三至步骤六可循环进行若干次，以使CTCs均能够被捕获并脱离血液。
综上所述，本实用新型提供的标记物捕获装置，其附着套管外设有凹槽，为标记物提供了容纳空间，有助于保持标记物的原有状态和活性，陷入凹槽中的标记物能够避免因触碰外套管、血管壁或皮下组织造成刮蹭而脱落，外套管也能对凹槽中的标记物起到保护作用。其磁性装置包括由依次排列的磁珠组成的磁珠链，相邻磁珠的相邻端极性相同，相互排斥，使磁场能够均匀分布于磁珠链全长，且周围360°磁场分布均匀无盲区，增强了磁珠链的吸附效果，金属丝又确保了磁珠链的柔顺和牢固。
尽管本实用新型的内容已经通过上述优选实施例作了详细介绍，但应当认识到上述的描述不应被认为是对本实用新型的限制。在本领域技术人员阅读了上述内容后，对于本实用新型的多种修改和替代都将是显而易见的。因此，本实用新型的保护范围应由所附的权利要求来限定

Claims (10)

  1. 一种标记物捕获装置，其特征在于，包括套管组件和磁性组件；
    所述套管组件包括外套管和设于所述外套管内的附着套管，所述附着套管的外表面设有凹槽；
    所述外套管与所述附着套管能够相对滑动，使至少部分所述凹槽暴露于所述外套管之外，所述附着套管暴露于所述外套管外的一端为封闭端；
    所述磁性组件设于所述附着套管内，以将被磁性标记的标记物捕获至所述凹槽中。
  2. 如权利要求1所述的标记物捕获装置，其特征在于，所述封闭端为弧形端面。
  3. 如权利要求1所述的标记物捕获装置，其特征在于，所述附着套管位于所述外套管内的一端为开口端，所述磁性组件通过所述开口端置于所述附着套管内。
  4. 如权利要求1所述的标记物捕获装置，其特征在于，所述凹槽的深度为所述附着套管管壁厚度的1/2-3/4。
  5. 如权利要求1所述的标记物捕获装置，其特征在于，所述凹槽为螺纹凹槽、直线型凹槽或网格状凹槽。
  6. 如权利要求1-5任意一项所述的标记物捕获装置，其特征在于，所述磁性组件包括由若干依次排列的磁珠组成的磁珠链，以及串联所述磁珠链的金属丝；相邻两个所述磁珠的相邻磁极的极性相同，使相邻两个所述磁珠间因磁力排斥而存在间隙。
  7. 如权利要求6所述的标记物捕获装置，其特征在于，所述金属丝上，位于所述磁珠链两端的磁珠外侧的位置，设有限位结构。
  8. 如权利要求6所述的标记物捕获装置，其特征在于，所述磁珠的端面为弧形端面。
  9. 如权利要求6所述的标记物捕获装置，其特征在于，相邻两个所述磁珠间设有中间体，所述中间体朝向所述磁珠的端面为弧形端面。
  10. 如权利要求6所述的标记物捕获装置，其特征在于，所述附着套管内，设有一组或多组磁性组件。
PCT/CN2023/073588 2022-01-27 2023-01-28 一种标记物捕获装置 WO2023143526A1 (zh)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
CN202220225700.0 2022-01-27
CN202220225700 2022-01-27
CN202220603759.9 2022-03-20
CN202220603759 2022-03-20
CN202320112750.2U CN219921096U (zh) 2022-01-27 2023-01-18 一种标记物捕获装置
CN202320112750.2 2023-01-18

Publications (1)

Publication Number Publication Date
WO2023143526A1 true WO2023143526A1 (zh) 2023-08-03

Family

ID=87470640

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2023/073588 WO2023143526A1 (zh) 2022-01-27 2023-01-28 一种标记物捕获装置

Country Status (1)

Country Link
WO (1) WO2023143526A1 (zh)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5714063A (en) * 1996-05-28 1998-02-03 Brunsting; William J. Apparatus for the removal of ferrous particles from liquids
US6558541B1 (en) * 2000-10-12 2003-05-06 Av Lubricants, Inc. Contaminant capture device and method for use
JP2011020078A (ja) * 2009-07-17 2011-02-03 Sanyo Electric Co Ltd 磁性不純物分離装置
CN214387535U (zh) * 2020-12-18 2021-10-15 上海杰灵磁性器材有限公司 一种内磁式颗粒选别装置
CN114279763A (zh) * 2022-01-27 2022-04-05 蒋霆辉 一种可吸附、容纳和保护微小吸附物的套管装置
CN114624092A (zh) * 2022-03-20 2022-06-14 蒋霆辉 一种均场磁链

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5714063A (en) * 1996-05-28 1998-02-03 Brunsting; William J. Apparatus for the removal of ferrous particles from liquids
US6558541B1 (en) * 2000-10-12 2003-05-06 Av Lubricants, Inc. Contaminant capture device and method for use
JP2011020078A (ja) * 2009-07-17 2011-02-03 Sanyo Electric Co Ltd 磁性不純物分離装置
CN214387535U (zh) * 2020-12-18 2021-10-15 上海杰灵磁性器材有限公司 一种内磁式颗粒选别装置
CN114279763A (zh) * 2022-01-27 2022-04-05 蒋霆辉 一种可吸附、容纳和保护微小吸附物的套管装置
CN114624092A (zh) * 2022-03-20 2022-06-14 蒋霆辉 一种均场磁链

Similar Documents

Publication Publication Date Title
Theise Macroregenerative (dysplastic) nodules and hepatocarcinogenesis: theoretical and clinical considerations
WO2023143526A1 (zh) 一种标记物捕获装置
CN102703597B (zh) 血液白细胞分离液及其制作方法、真空采血管
LU500008B1 (en) Animal tissue clearing method
Takayasu et al. HGMS studies of blood cell behavior in plasma
CN219921096U (zh) 一种标记物捕获装置
CN214387535U (zh) 一种内磁式颗粒选别装置
JP2016526688A (ja) ルテリアルの形態学的特性を用いた疾病の診断方法
CN111903606A (zh) 一种经皮穿刺接种的肺癌原位pdx模型的构建方法
CN114624092A (zh) 一种均场磁链
CN109342720A (zh) 在体肿瘤细胞富集检测装置及方法
CN114279763A (zh) 一种可吸附、容纳和保护微小吸附物的套管装置
CN214761225U (zh) 一种超低温冷冻隧道穿刺型负压引流器
CN210765257U (zh) 一种动静脉血管循环肿瘤细胞捕获网篮
CN112569425A (zh) 一种方便使用的医疗输液设备
CN212522079U (zh) 采用免疫磁吸附原理捕获目标物的捕获装置和捕获导管
CN215606025U (zh) 一次性门静脉阻断装置
KR20240055804A (ko) 누공성 항문회음 병변의 치료를 위한 나노입자의 용도
CN111849697A (zh) 一种动静脉血管循环肿瘤细胞捕获网篮
CN107374778A (zh) 腔静脉滤器及其回收装置
CN111419315A (zh) 一种用于内镜下消化道吻合的可变形自组装磁吻合环
Cho et al. Clinical significance of lymph node dissection in patients with muscle-invasive upper urinary tract transitional cell carcinoma treated with nephroureterectomy
CN208212242U (zh) 一种膀胱冲洗连接管
CN116492525A (zh) 一种血液打捞系统、其使用方法及用途
CN206594041U (zh) 一种磁性物质捕获分析装置

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23746403

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
NENP Non-entry into the national phase

Ref country code: DE