CN219921096U

CN219921096U - Marker capturing device

Info

Publication number: CN219921096U
Application number: CN202320112750.2U
Authority: CN
Inventors: 蒋霆辉; 梁晓飞; 张慧欣; 沈天皓; 陆珺; 刘艳
Original assignee: Shanghai Xinguang Layer Biomedical Technology Co ltd
Current assignee: Shanghai Xinguang Layer Biomedical Technology Co ltd
Priority date: 2022-01-27
Filing date: 2023-01-18
Publication date: 2023-10-31
Anticipated expiration: 2033-01-18

Abstract

The utility model discloses a marker capture device, which comprises a sleeve component and a magnetic component; the sleeve assembly comprises an outer sleeve and an attaching sleeve arranged in the outer sleeve, and a groove is formed in the outer surface of the attaching sleeve; the outer sleeve and the attaching sleeve can slide relatively, so that at least part of the groove is exposed out of the outer sleeve, and one end of the attaching sleeve exposed out of the outer sleeve is a closed end; the magnetic assembly is disposed within the attachment sleeve to capture magnetically labeled markers into the grooves. The capture device has wide application range, can capture all substances which can be magnetically marked by the utility model, can be expanded to adsorption of viruses, fluids or gas suspended matters and the like, and has extremely high prospect in the fields of medicine, biology, industry or environmental protection.

Description

Marker capturing device

Technical Field

The utility model belongs to the field of medical instruments, and particularly relates to a marker capturing device.

Background

Cancer metastasis is largely due to metastasis of cancer cells from the primary tumor foci to other organs, forming new metastatic tumors. Blood flow transfer is the widest and fastest transfer range and is called final transfer. One current focus of research on cancer is based on such abnormal cells with metastatic potential: circulating tumor cells (Circulating Tumor Cell, CTCs), i.e. cancer cells cruising in the blood. On the other hand, many defects of traditional pathological biopsies of tumors are not overcome all the time, which makes CTCs one of the main diagnostic methods of liquid biopsies of tumors. In addition, after CTCs are captured, various detection can be performed to obtain more transfer related information, and meanwhile, the cancer metastasis direction can be tracked in real time and the treatment prognosis can be estimated.

However, enrichment is a problem because CTCs are extremely rare in blood. At present, the detection of CTCs at home and abroad is basically limited to a blood sampling test mode of traditional test medicine, the enrichment efficiency is low, and the whole body condition and the tumor heterogeneity of tumor patients are hardly reflected. A common bottleneck in this mode is that the blood collection sample size is very small. The method breaks through the bottleneck of small sample quantity, can enrich more CTCs, and has important significance for the dynamic monitoring of tumor blood metastasis and the development of liquid biopsy technology.

Disclosure of Invention

The utility model aims to design an instrument for introducing into a human body, which can collect CTCs from a large amount of flowing blood and greatly improve the enrichment efficiency of the CTCs.

In order to achieve the above object, the present utility model provides a marker capture device comprising a cannula assembly and a magnetic assembly;

the sleeve assembly comprises an outer sleeve and an attaching sleeve arranged in the outer sleeve, and a groove is formed in the outer surface of the attaching sleeve;

the outer sleeve and the attaching sleeve can slide relatively, so that at least part of the groove is exposed out of the outer sleeve, and one end of the attaching sleeve exposed out of the outer sleeve is a closed end;

the magnetic assembly is disposed within the attachment sleeve to capture magnetically labeled markers into the grooves.

Optionally, the closed end is an arc end face.

Optionally, an 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.

Optionally, the depth of the groove is 1/2-3/4 of the thickness of the wall of the attached casing.

Optionally, the grooves are screw grooves, linear grooves or grid grooves.

Optionally, the magnetic component comprises a magnetic bead chain formed by a plurality of magnetic beads which are sequentially arranged, and a metal wire connected with the magnetic bead chain in series; the polarities of the adjacent magnetic poles of the two adjacent magnetic beads are the same, so that a gap exists between the two adjacent magnetic beads.

Optionally, a limiting structure is arranged on the metal wire and positioned at the outer side of the magnetic beads at the two ends of the magnetic bead chain.

Optionally, the end face of the magnetic bead is an arc end face.

Optionally, an intermediate is arranged between two adjacent magnetic beads, and the end face of the intermediate, facing the magnetic beads, is an arc-shaped end face.

Optionally, one or more sets of magnetic components are disposed within the attachment sleeve.

The utility model has the technical effects that:

(1) The external sleeve is provided with the groove, so that an accommodating space is provided for the markers such as CTCs and the like, the original state and activity of the markers are maintained, the markers trapped in the groove can be prevented from falling off due to scraping caused by touching the external sleeve, the vessel wall or subcutaneous tissue, and the external sleeve can also protect the markers in the groove.

(2) The magnetic device comprises the magnetic bead chains composed of the magnetic beads which are sequentially arranged, the adjacent ends of the adjacent magnetic beads have the same polarity and repel each other, so that the magnetic field can be uniformly distributed on the whole length of the magnetic bead chains, and the surrounding 360-degree magnetic field is uniformly distributed without blind areas, thereby enhancing the adsorption effect of the magnetic bead chains.

(3) Mutual exclusion between adjacent magnetic beads can generate a tiny gap, and is favorable for flexible bending of the magnetic bead chains.

(4) The magnetic bead chains connected in series can ensure firm connection of the magnetic bead chains through the morphological plastic metal wires, such as nickel-titanium alloy wires, and the metal wires can be pre-bent into different shapes according to requirements.

(5) The safety design of the utility model has the advantages that the outer sleeve and the attaching sleeve completely use the catheter materials used in the current vascular intervention, thereby being safe and reliable; the magnetic component is not contacted with blood and human body, so that the magnetic component is safe and reliable; the closed end of the attached sleeve is round and smooth, and the operation is guided by the ultra-smooth guide wire, so that the operation is safer than the operation of the existing venous stent and the like; CTCs capture is only an interventional secondary operation, i.e. the resident can independently complete, and the academy will make special safety procedures to ensure safety; aiming at thrombus problems possibly occurring in vascular operation, the interventional medical community has a fully mature heparinized operation procedure; the nanometer magnetic preparation is currently an FDA approved preparation for a magnetic resonance contrast agent, and is safe and reliable.

(6) The capture device has wide application range, can capture all substances which can be magnetically marked by the utility model, can be expanded to adsorption of viruses, fluids or gas suspended matters and the like, and has extremely high prospect in the fields of medicine, biology, industry or environmental protection.

Drawings

FIG. 1 is a schematic diagram of the structure of a marker capture device of the present utility model.

FIG. 2 is a schematic diagram showing the internal structure of the label capturing device according to the present utility model.

Fig. 3 is a schematic structural view of the magnetic device of the present utility model.

FIG. 4 is a schematic diagram of an arrangement of magnetic beads.

FIG. 5 is a schematic diagram of another bead arrangement.

Fig. 6 is a schematic diagram of the magnetic field of the magnetic bead cross section shown in fig. 5.

FIG. 7 is a schematic diagram of the magnetic field of a cross section of a magnetic bead chain of the present utility model.

FIG. 8 is a schematic diagram of the magnetic field on the side of the magnetic bead chain of the present utility model.

Fig. 9 is a schematic diagram of another structure of the magnetic device of the present utility model.

In the figure, the outer sleeve is 1-, the attaching sleeve is 2-, the groove is 20-, the closed end is 21-, the magnetic beads are 3-, the metal wires are 4-, the gaps are 5-, the limiting structure is 6-and the intermediate is 7-.

Detailed Description

The following description of the embodiments of the present utility model will be made apparent and fully in view of the accompanying drawings, in which some, but not all embodiments of the utility model are shown. All other embodiments, which can be made by those skilled in the art based on the embodiments of the utility model without making any inventive effort, are intended to be within the scope of the utility model.

In the description of the present utility model, it should be noted that the positional or positional relationship indicated by the terms "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. are based on the positional or positional relationship shown in the drawings, are merely for convenience of describing the present utility model and simplifying the description, and do not indicate or imply that the apparatus or elements referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as limiting the present utility model. Furthermore, the terms "first," "second," "third," and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

In the description of the present utility model, it should be noted that, unless explicitly specified and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; may be a mechanical connection; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present utility model will be understood in specific cases by those of ordinary skill in the art.

The utility model provides a marker capture device comprising a cannula assembly and a magnetic assembly.

As shown in fig. 1, the sleeve assembly comprises an outer sleeve 1 and an attaching sleeve 2 arranged in the outer sleeve 1, wherein the outer surface of the attaching sleeve 2 is provided with a groove 20. The outer sleeve 1 and the attaching sleeve 2 can slide relatively, so that at least part of the groove 20 is exposed out of the outer sleeve 1, and one end of the attaching sleeve 2 exposed out of the outer sleeve 1 is a closed end 21. The magnetic assembly is arranged in the attachment sleeve 2. The end of the attachment sleeve 2 located inside the outer sleeve 1 is an open end (rear end) through which the magnetic assembly is placed in the attachment sleeve 2.

Before capturing, CTCs in bloodBy Fe ₃ O ₄ The nanoparticles are magnetically labeled with antibodies (the magnetic label of the utility model is a paramagnetic label). In the initial state, the attachment sleeve 2 is completely located within the outer sleeve 1. After the capturing device is placed at the capturing position, the outer sleeve 1 is retracted, the outer sleeve 1 and the attaching sleeve 2 slide relatively, so that the groove of the attaching sleeve 2 is exposed outside the outer sleeve 1, and one end of the attaching sleeve 2 exposed outside the outer sleeve 1 is used as the front end of the attaching sleeve 2. The magnetic force of the magnetic assembly provided in the attachment sleeve 2 may penetrate the attachment sleeve 2 to radiate outward, attracting magnetically labeled CTCs to the outer circumference of the attachment sleeve 2. CTCs have a tendency to approach the magnetic assembly, the outer surface of the attachment sleeve 2 is provided with grooves 20, the bottoms of the grooves 20 are closer to the magnetic assembly 2, so the magnetic force at the bottoms of the grooves 20 is stronger, and thus, CTCs can be captured and stored in the grooves 20. The grooves 20 provide accommodation space for CTCs, which is beneficial to maintaining the original state of CTCs and protecting cell activity.

After the capturing is finished, the outer sleeve 1 is pushed forward, and the outer sleeve 1 and the attaching sleeve 2 slide relatively, so that the attaching sleeve 2 is completely positioned in the outer sleeve 1. Because CTCs can be attracted in the groove 20 all the time under the magnetic force of the magnetic component, the edge of the outer sleeve 1 can not scratch the CTCs and can not cause the CTCs to fall off in the process that the outer sleeve 1 and the attached sleeve 2 slide relatively.

Finally, the capturing device as a whole is removed from the capturing position. When the CTCs are removed, the attaching sleeve 2 is completely positioned in the outer sleeve 1, CTCs stored in the groove 20 cannot be scraped and fallen off by the vascular wall or subcutaneous tissue under the coating protection of the outer sleeve 1, and all CTCs attracted and captured by the magnetic component can be stored in the groove 20 through the capturing device provided by the utility model and can be completely taken out of the capturing position.

In some embodiments, the closed end 21 is an arc end surface, and the edge of the arc end surface is smooth, so that when the closed end 21 of the attaching sleeve 2 is positioned outside the outer sleeve 1, the arc end surface does not damage human tissues or blood vessel walls. In other embodiments, the closed end 21 comprises a closed end cap 210, the closed end cap 210 also having an arcuate end surface, preferably the closed end cap 210 is of hemispherical configuration.

In some embodiments, the depth of the groove 20 is 1/2-3/4 of the wall thickness of the attachment sleeve 2. The grooves 20 are screw grooves, linear grooves or grid grooves. The number of the grooves is 8-12.

As shown in fig. 2 and 3, the magnetic assembly comprises a magnetic bead chain composed of a plurality of magnetic beads 3 which are sequentially arranged, and a metal wire 4 connected in series with the magnetic bead chain, wherein the polarities of adjacent magnetic poles of two adjacent magnetic beads 3 are the same, so that a gap 5 exists between the two adjacent magnetic beads 3. The magnetic beads 3 are made of permanent magnetic materials such as neodymium iron boron and the like.

The magnetic beads 3 comprise an N-pole and an S-pole. The magnetic beads 3 may be arranged in the following ways:

(1) As shown in fig. 4, two adjacent magnetic beads are longitudinally arranged (i.e., 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 polarities of the adjacent magnetic poles of the adjacent magnetic beads are opposite, i.e., the adjacent magnetic beads attract each other. The arrangement mode makes the magnetic field only present at two ends of the whole magnetic bead chain, the magnetic field formed by the magnetic beads in the middle is all vanished due to mutual coupling, and the magnetism of the whole magnetic bead chain is very low.

(2) As shown in fig. 5 and 6, two adjacent magnetic beads are arranged transversely (i.e., the arrangement direction of the magnetic beads is perpendicular to the connection line direction from the N pole to the S pole in each magnetic bead), and the adjacent magnetic beads are arranged upside down. The magnetic field distribution of this arrangement mode is shown in fig. 6, although the whole length of the magnetic bead chain has magnetic field distribution, the magnetic field on the cross section of the magnetic bead chain is uneven and takes a dumbbell shape, two symmetrical magnetic blind areas are arranged between the waists of the N pole and the S pole, and the position adsorption effect of the magnetic blind areas is greatly reduced.

In addition, the magnetic bead chains in the above (1) and (2) are mutually attracted by magnetic force, so that the connection between the adjacent magnetic beads is stiff, when the magnetic bead chain is bent, larger external force is needed to overcome the attractive force between the adjacent magnetic beads, and after the attractive force is overcome to separate and bend the adjacent magnetic beads, the magnetic bead chain is easy to break. The magnetic beads are connected into strings only by magnetic force, so that the risk of chain breakage is further increased.

In the present utility model, as shown in fig. 3 and 9, adjacent magnetic poles of adjacent magnetic beads 3 have the same polarity, that is, adjacent magnetic beads 3 repel each other. Therefore, the magnetic field of the utility model can be uniformly distributed on the whole length of the magnetic bead chain, and the magnetic field distribution of 360 degrees around the magnetic bead chain is free from magnetic dead zones, thereby enhancing the attraction effect of the magnetic bead chain on the marker. The adjacent magnetic beads 3 repel each other to form a tiny gap 5, so that the magnetic bead chain can be flexibly bent. The arrangement mode of the utility model can not lead adjacent magnetic beads 3 to naturally attract into strings, so the magnetic bead chains are connected in series through the metal wires 4, the metal wires 4 can be made of nickel-titanium alloy materials so as to firmly connect a plurality of magnetic beads 3, the chains are not easy to break, and the nickel-titanium alloy is a memory alloy and can be bent into different shapes in advance so as to adapt to the requirements of different bending degrees.

The magnetic beads 3 are provided with through holes, and the metal wires 4 sequentially penetrate through the through holes of the magnetic beads 3 to connect a plurality of magnetic beads 3 in series to form a magnetic bead chain. And the metal wire 4 is provided with a limiting structure 6 at the outer side of the magnetic beads at the two ends of the magnetic bead chain. The size of the limiting structure is larger than that of the through hole of the magnetic bead 3, so that the magnetic beads 3 which are connected in sequence are locked between the limiting structures 6 at the two ends. Therefore, even if the adjacent magnetic beads 3 are mutually exclusive, the plurality of magnetic beads 3 can still be kept in the attaching sleeve 2 all the time after being connected in series by the metal wires 4.

In some embodiments, as shown in fig. 3, 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 larger bending space, and the flexibility degree between the adjacent magnetic beads 3 can be further increased.

In some embodiments, as shown in fig. 9, an intermediate 7 is disposed between two adjacent magnetic beads 3, and after the intermediate 7 is spaced, a repulsive force still exists between the adjacent magnetic beads 3. The end face of the intermediate body 7 facing the magnetic beads is an arc end face, and optionally, the intermediate body 7 is a spherical iron bead or steel ball. The presence of the intermediate body 7 causes the gaps between adjacent magnetic beads 3 to release the magnetic field of the magnetic beads more sufficiently, and the irradiation range of such magnetic field is wider. The smooth intermediate 7 can further increase the flexibility between the adjacent magnetic beads 3, and the end faces of the magnetic beads 3 can be arc-shaped or plane.

In some embodiments, the wires 4 may be single strands, bent into a spiral-spindle basket, or may be double strands or multiple strands in parallel, naturally forming a basket shape. Within the attachment sleeve 2, the magnetic assembly is provided with one or more groups. Both the magnetic field radiation attraction and the basket configuration can expand the capture range in the section of the blood vessel to achieve the aim of 'three-dimensional capture'.

After the whole capturing device is moved out of the capturing position, the magnetic component in the attaching sleeve 2 is taken out from the opening at the rear end of the attaching sleeve 2, and the CTCs in the groove 20 naturally fall off or are eluted due to the loss of attraction, so that further detection, identification and collection culture of the adsorbed CTCs can be realized.

According to the capturing device disclosed by the utility model, the magnetic component is inserted into the attaching sleeve 2, and the attaching sleeve 2 isolates the CTCs from the magnetic component, so that the CTCs are not in direct contact with the magnetic component, and the CTCs are prevented from being directly adsorbed on the magnetic component, so that cells cannot be eluted after capturing. The magnetic component is drawn out from the attachment sleeve 2, so that the attraction between CTCs and the magnetic component can be eliminated, and the method of forced demagnetization such as high-temperature demagnetization is not needed, thereby avoiding damage to cells. The magnetic component is always in the package of the sleeve component and is not contacted with blood or tissues, so that the magnetic component can be reused.

The capture device of the present utility model is capable of capturing magnetically labeled markers into the grooves of the attachment sleeve using a magnetic assembly disposed within the attachment sleeve. The capture device can be used not only for enrichment of Circulating Tumor Cells (CTCs), but also for any substance that can be magnetically labeled, such as viruses, suspensions in fluids, etc., the capture device can be used to capture and isolate the label.

The use method of the capturing device comprises the following steps:

step one, 5-8mg of magnetic enhancer (superparamagnetic particles) was intravenously injected 20-30 minutes before surgery to label CTCs.

Step two, puncturing femoral veins in groin under local anesthesia, introducing a catheter sheath, and establishing a vein channel; inferior vena cava contrast is performed to determine the capture device and capture location based on inferior vena cava morphology. The aorta, the superior vena cava, or the blood vessels downstream of the tumor can also be selected as the capturing position according to the requirements.

Step three, guiding the capturing device to enter a capturing position of a inferior vena cava through a catheter sheath by a guide wire, backing the outer sleeve 1, exposing the groove 20 of the attaching sleeve 2, starting to absorb and capture CTCs, and capturing the CTCs as an attaching section of the attaching sleeve 2; preferably, the attachment sleeve 2 containing the whole length of the bead chain has grooves 20 on the outer surface thereof, and the grooves 20 are completely exposed to the blood flow and serve as attachment sections.

Step four, the capture time is designed to be half an hour. The average human blood circulation time of 3min is 10 cycles, the half hour is calculated by 5000ml of total blood volume of the human body, the half hour is equivalent to 50000ml of filtered blood, and 10000 times of the blood sampling volume of the traditional test medicine.

And fifthly, after the capturing is finished, pushing the outer sleeve 1 forwards, fully taking the attaching section of the attaching sleeve 2 into the outer sleeve 1, and taking out the capturing device integrally.

Step six, pushing out the attachment section of the attachment sleeve 2 from the front end of the outer sleeve 1, placing the attachment section into a test tube filled with a reagent, extracting the magnetic component from the rear end of the attachment sleeve 2, cutting off the attachment section of the attachment sleeve 2, and placing the attachment section into the test tube filled with the reagent to obtain CTCs.

The above steps three to six can be cycled several times to enable CTCs to be captured and shed from the blood.

In summary, the label capturing device provided by the utility model has the advantages that the groove is arranged outside the attaching sleeve, so that an accommodating space is provided for the label, the original state and activity of the label can be maintained, the label trapped in the groove can be prevented from falling off due to scraping caused by touching the outer sleeve, the blood vessel wall or subcutaneous tissue, and the outer sleeve can also protect the label in the groove. The magnetic device comprises a magnetic bead chain composed of magnetic beads which are sequentially arranged, the adjacent ends of adjacent magnetic beads have the same polarity and repel each other, so that the magnetic field can be uniformly distributed on the whole length of the magnetic bead chain, and the surrounding 360-degree magnetic field is uniformly distributed without blind areas, thereby enhancing the adsorption effect of the magnetic bead chain, and ensuring the softness and firmness of the magnetic bead chain by the metal wires.

While the present utility model has been described in detail through the foregoing description of the preferred embodiment, it should be understood that the foregoing description is not to be considered as limiting the utility model. Many modifications and substitutions of the present utility model will become apparent to those of ordinary skill in the art upon reading the foregoing. Accordingly, the scope of the utility model should be limited only by the attached claims.

Claims

1. A marker capture device comprising a cannula assembly and a magnetic assembly;

2. The marker capture device of claim 1, wherein the closed end is an arcuate end surface.

3. The marker capture device of claim 1, wherein the end of the attachment sleeve within the outer sleeve is an open end through which the magnetic assembly is disposed within the attachment sleeve.

4. The marker capture device of claim 1, wherein the depth of the groove is 1/2-3/4 of the wall thickness of the attached cannula.

5. The marker capture device of claim 1, wherein the grooves are threaded grooves, linear grooves, or grid grooves.

6. A tag capture device according to any one of claims 1 to 5, wherein the magnetic assembly comprises a magnetic bead chain comprising a plurality of magnetic beads arranged in sequence, and a wire connecting the magnetic beads in series; the polarities of the adjacent magnetic poles of the two adjacent magnetic beads are the same, so that a gap exists between the two adjacent magnetic beads due to magnetic repulsion.

7. The marker capture device of claim 6, wherein the wire is provided with a limit structure at a location outside the magnetic beads at both ends of the magnetic bead chain.

8. The marker capture device of claim 6, wherein the end face of the magnetic bead is an arcuate end face.

9. The marker capture device of claim 6, wherein an intermediate is disposed between two adjacent magnetic beads, and an end surface of the intermediate facing the magnetic beads is an arcuate end surface.

10. The marker capture device of claim 6, wherein one or more sets of magnetic elements are disposed within the attachment sleeve.