CN207751770U - A kind of blood-taking device of screening circulating tumor cell - Google Patents

A kind of blood-taking device of screening circulating tumor cell Download PDF

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Publication number
CN207751770U
CN207751770U CN201721928557.7U CN201721928557U CN207751770U CN 207751770 U CN207751770 U CN 207751770U CN 201721928557 U CN201721928557 U CN 201721928557U CN 207751770 U CN207751770 U CN 207751770U
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ctc
blood
enrichers
outer tube
plasma
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CN201721928557.7U
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王思娜
李思韵
韩建红
陈俊雅
曹肖文
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Yangpu Medical Technology Co ltd
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Guangzhou Improve Medical Technology Co ltd
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Abstract

The utility model discloses a kind of blood-taking device of screening circulating tumor cell, including outer tube, plasma cure unit, CTC enrichers and safety cap, the plasma cure unit is removable installed in CTC enrichers bottom end, the plasma cure unit is connected to the CTC enrichers, CTC enrichers top is detachably connected with the safety cap, the plasma cure unit is in the outer tube, the safety cap is connected in the outer tube top, and the CTC enrichers are built-in with the filter membrane in default aperture, the outer tube bore is preset with negative pressure of vacuum.Blood-taking device provided by the utility model, the other compositions in CTC and blood are efficiently separated by filter membrane and using gravity and suction function, CTC is isolated from filter membrane upper surface, compared with prior art, the present apparatus solves the enrichment of CTC and the separation of blood plasma simultaneously in a branch pipe, need not be by other large scale equipments such as CTC separate apparatus, centrifuge, at low cost, whole process takes extremely short.

Description

A kind of blood-taking device of screening circulating tumor cell
Technical field
The utility model is related to medical instruments field, more particularly to a kind of blood-taking device of screening circulating tumor cell.
Background technology
The illness rate of tumour increases year by year in recent years, and the relevant test in laboratory of tumour and imageological examination have obtained considerable Development, in order to improve tumor cure rate, new treatment means and drug continuously emerge, it is early find, early diagnosis becomes to closing weight It wants.Histopathologic slide is diagnosing tumor and the highest method of histological type accuracy, is cut in either performing the operation or fine needle is worn Piercing and sucking takes, and is all invasive detection, there is the risk for causing metastases.The liquid of relevant disease information is obtained using human body fluid Body Biopsy, with its Small side effects, easy to operate, repeatable sampling, it is at low cost, successfully manage the advantages that Tumor Heterogeneity times Favored.Wherein, blood is most traditional, and is endowed the desired body fluid sample of at most innovation.
Circulating tumor cell (CTC, Circulating Tumor Cell) is that the various tumours that are present in peripheral blood are thin The general designation of born of the same parents, because spontaneous or operation of diagnosis and treatment falls off from entity tumor lesion (primary tumor, transfer stove), most of CTC is outside entering Apoptosis occurs after all blood or is removed by phagocytosis, minority can escape and develop into transfer stove, increase malignant tumor patient death Risk.Dissociative DNA in blood, refer to the extracellular body endogenous dna degraded is free in circulating, and wherein with tumour Cell has the part of identical gene mutation to be referred to as Circulating tumor DNA (ctDNA, Circulating Tumor DNA).In blood Existing CTC and ctDNA is capable of providing the hereditary information in all tumour sources, can track genome evolution chance comprehensively, but Be that these substances are very rare in peripheral blood, huge difficulty brought to detection, thus in peripheral blood sample CTC and The enrichment of ctDNA is very significant.
Currently, circulating tumor cell detection technique bottleneck has three:First, sensitivity is low.Peripheral bloods of the CTC in tumor patient In be with a calculating, it is considered that only have 1-10 CTC in patient's 10ml blood, and there are 50,000,000,000 red blood cells in 10ml blood the inside With more than one hundred million a leucocytes, therefore it is very big that the CTC in peripheral blood in patients screened difficulty completely.Second, cumbersome. With more and more hospitals and doctor by CTC detections as diagnosing tumor, rapid evaluation curative effect and monitoring tumor drug resistance with it is multiple The effective means of hair, easy operating process or the high-throughput a large amount of clinical samples of processing of automation have become most urgent need, But current circulating tumor cell acquisition is highly difficult.Third, screening goes out the feasibility of the Molecular Detection after CTC.With people Continuous intensification that CTC is understood, domestic and international numerous medical personnels and scientific research personnel have not only been satisfied with the meter to CTC Number, but sight is locked in for the CTC subtype of cells with different clinical meanings (such as susceptibility, drug resistance, transfer, recurrence) It carries out in comprehensive genetic analysis, to which various understandings such as generation, growth, transfer to tumour can be deepened, and finds Go out new tumor markers (including albumen and nucleic acid), to provide better objective basis for the prevention of tumour.
Therefore, it is high how to provide a kind of circulating tumor cell bioaccumulation efficiency, while circulating tumor cell easy to operate is adopted Acquisition means are those skilled in the art's technical problems urgently to be resolved hurrily.
Utility model content
The purpose of this utility model is to provide a kind of blood-taking device of screening circulating tumor cell, circulating tumor cell enrichment It is efficient while easy to operate, it is provided a convenient for the enrichment of circulating tumor cell, work accuracy rate is high, substantially increases doctor It works the efficiency of work, reduces working procedure and time, further bring glad tidings for tumor patient.
In order to solve the above technical problems, the utility model provides a kind of blood-taking device of screening circulating tumor cell, including Outer tube, plasma cure unit, CTC enrichers and safety cap, the plasma cure unit are removable installed in the CTC Enricher bottom end, the plasma cure unit are connected to the CTC enrichers, CTC enrichers top and the safety Cap is detachably connected, and for the plasma cure unit in the outer tube, the safety cap is connected in the outer tube top, and The CTC enrichers are built-in with the filter membrane in default aperture, and the outer tube bore is preset with negative pressure of vacuum.
Preferably, the aperture of the filter membrane is 8um~10um.
Preferably, the filter membrane is distributed in laminated multi-layer.
Preferably, several hollow fiber conduits built in the plasma cure unit, and set on the tube wall of the fibre pipe The filter opening of preset diameters is set, the fiber bottom of the tube is connected to the outer tube bore.
Preferably, a diameter of 1um~5um of the filter opening.
Preferably, the plasma cure unit top is connect with the CTC enrichers bottom thread.
Preferably, it is provided with anti-coagulants on the CTC enrichers inner wall.
Preferably, it is provided with nucleic acid inhibitor on the outer tube wall
The blood-taking device of screening circulating tumor cell provided by the utility model includes mainly outer tube, membranous type blood plasma point From device, CTC enrichers and safety cap, plasma cure unit is removable installed in CTC enrichers bottom end, the separation of membranous type blood plasma Device is connected to CTC enrichers, and CTC enrichers top is detachably connected with safety cap, and plasma cure unit is in outer tube, peace Full cap is connected in outer tube top, and CTC enrichers are built-in with the filter membrane in default aperture, and outer tube bore is preset with negative pressure of vacuum.This The blood-taking device for the circulating tumor cell that utility model provides, is provided with outer tube, CTC enrichers and filter membrane, simultaneously by filter membrane The other compositions in CTC and blood are efficiently separated using gravity and suction function, CTC is isolated from filter membrane upper surface, blood Other compositions are isolated from region between the pipe of filter membrane lower surface and outer tube, and compared with prior art, the present apparatus is same in a branch pipe When solve the enrichment of CTC and the separation of blood plasma, need not be by other large scale equipments such as CTC separate apparatus, centrifuge, cost It is low, save space and manpower;Whole process takes extremely short, after blood sampling, heparin tube is vertically put on rack for test tube and is hung on i.e. The separation of CTC and blood plasma can be achieved;A variety of detections such as immunofluorescence, FISH, the Molecular Detection in the compatible downstreams CTC of enrichment, With higher cell activity, cell culture and drug sensitive experiment can be carried out;The blood plasma isolated can be transported and be preserved for a long time, - 20 DEG C or -80 DEG C can be directly stored in, solves the problems, such as haemolysis during existing product preservation, meets ctDNA detection needs.
Description of the drawings
In order to illustrate the embodiment of the utility model or the technical proposal in the existing technology more clearly, below will be to embodiment Or attached drawing needed to be used in the description of the prior art is briefly described, it should be apparent that, the accompanying drawings in the following description is only It is the embodiments of the present invention, for those of ordinary skill in the art, without creative efforts, also Other attached drawings can be obtained according to the attached drawing of offer.
Fig. 1 is a kind of overall structure diagram of specific implementation mode provided by the utility model;
Fig. 2 is the exploded perspective view of structure shown in Fig. 1.
Wherein, in Fig. 1-Fig. 2:
Outer tube -1, plasma cure unit -2, CTC enricher -3, safety cap -4, filter membrane -5, a-CTC, b-blood Slurry.
Specific implementation mode
The following will be combined with the drawings in the embodiments of the present invention, carries out the technical scheme in the embodiment of the utility model Clearly and completely describe, it is clear that the described embodiments are only a part of the embodiments of the utility model, rather than whole Embodiment.Based on the embodiments of the present invention, those of ordinary skill in the art are without making creative work The every other embodiment obtained, shall fall within the protection scope of the present invention.
Referring to FIG. 1, Fig. 1 is a kind of overall structure diagram of specific implementation mode provided by the utility model.
In a kind of specific implementation mode provided by the utility model, the blood-taking device for screening circulating tumor cell is main Including outer tube 1, plasma cure unit 2, CTC enrichers 3 and safety cap 4, plasma cure unit 2 is removable installed in 3 bottom end of CTC enrichers, plasma cure unit 2 are connected to CTC enrichers 3, and 3 top of CTC enrichers is detachable with safety cap 4 Connection, for plasma cure unit 2 in the outer tube 1, safety cap 4 is connected in 1 top of outer tube, and CTC enrichers 3 be built-in with it is default The filter membrane 5 in aperture, 1 inner cavity of outer tube are preset with negative pressure of vacuum.
Wherein, filter membrane 5 is put into 3 bottom surface of CTC enrichers, and sprays into anti-coagulants in 3 inner wall of CTC enrichers, such as: EDTA.K2, EDTA.K3, EDTA.Na2 or sodium citrate etc., between CTC enrichers 3 and the rubber plug of outer tube 1 in a snap-fit manner Fastening, plasma cure unit 2 screw in the lower end of CTC enrichers 3, and CTC enrichers 3 are set to the top of plasma cure unit 2 End, forms key function component, and 1 inside of outer tube can spray into the nuclease protections agent such as nucleic acid inhibitor, key function component is set In outer tube 1, carry out tamponade is vacuumized to outer tube 1, then assembles safety cap 4 in 1 top edge of outer tube, you can complete the device Installation, it should be noted that be provided with anti-coagulants on 3 inner wall of CTC enrichers.
Specifically, in the actual use process, 3 upper surface of CTC enrichers is provided with filter membrane 5, when blood passes through this ,, can be easily by the filter opening on film such as red blood cell and blood platelet due to there is type ingredient in haemocyte when region, and leucocyte It is under the action of negative pressure, most of to pass through filter membrane 5 with preferable morphotropism, only stay volume larger and also deformability compared with The CTC and a small amount of leucocyte of difference are on film;In plasma cure unit 2, include several hollow fiber materials (such as:It is poly- Vinyl alcohol, PS membrane, cellulose acetate film), gather on this fibrous material micropore, and above-mentioned micropore only allows the blood plasma in blood B passes through, and other have type ingredient that cannot pass through, and stays in region between pipe, and blood plasma b imported into quilt in outer tube 1 by hollow fiber conduit It collects;In blood collection procedure, blood enters CTC enrichers 3 under the action of negative pressure, passes through filter membrane 5, CTCa after being contacted with anti-coagulants It is trapped on filter membrane 5, other blood constituents enter the fiber ligament of plasma cure unit 2.Blood plasma b is passed through on fibre pipe Micropore enter in fibre pipe, import outer tube plasma collection area, remaining blood constituent is left in fiber ligament, and enrichment is completed Blood have the characteristics that well arranged, CTCa, blood plasma b and blood other costs are separately separated, after the completion, can will be acquired The pipe lid of device is opened, and 2 part of plasma cure unit is discarded, by the blood plasma being collected into and CTC carry out next step transport and Detect work.Compared with prior art, the present apparatus solves the enrichment of CTC and the separation of blood plasma simultaneously in a branch pipe, is not required to It will be by other large scale equipments such as CTC separate apparatus, centrifuge, at low cost, saving space and manpower;Whole process takes pole It is short, after blood sampling, blood-taking device is vertically put in hang on rack for test tube the separation of CTC and blood plasma can be realized;The CTC of enrichment A variety of detections such as immunofluorescence, FISH, the Molecular Detection in compatible downstream have higher cell activity, can carry out cell training Foster and drug sensitive experiment.
Referring to FIG. 2, Fig. 2 is the exploded perspective view of structure shown in Fig. 1.
It is 8um by the aperture design of filter membrane 5 to optimize the effect of blood-taking device separation and concentration CTCa in above-described embodiment ~10um.Clinical experiments have proved that the average diameter 8um of CTCa, and the design of 5 aperture concrete numerical value of filter membrane, CTCa is complete It is isolated from 5 upper surface of filter membrane so that the enrichment of CTCa is more efficient.
Further, filter membrane 5 is distributed in laminated multi-layer, the form of such laminated multi-layer can make CTCa more efficient Ground is enriched to 5 upper surface of filter membrane, can be with the filtering screening effect of enhanced CT Ca.
Based on this, several hollow fiber conduits built in plasma cure unit 2, and be arranged on the tube wall of fibre pipe default straight The filter opening of diameter, fiber bottom of the tube are connected to 1 inner cavity of outer tube, a diameter of 1um~5um of filter opening of fibre pipe.In addition in peripheral blood CTC, the ingredient in blood plasma also have great diagnostic significance.Several hollow fiber conduits built in plasma cure unit 2, and it is fine Tie up the filter opening that a diameter of 1um~5um is provided on the tube wall of pipe, the especially filter opening of 1um.By clinical experiments have proved that human body Blood has in type ingredient, and only blood plasma can be by the filter opening of diameter 1um, therefore, and plasma cure unit 2 is provided with diameter The filter opening of 1um~5um can be such that the blood plasma in blood is more efficiently separated, and blood platelet etc. is collected in the separation of membranous type blood plasma In device 2, blood plasma then imported into outer tube 1 and is collected.Above-mentioned design can make blood separation more have levels, in addition to CTC is detached Except effect, the separation of blood plasma can also be carried out, is conducive to carry out blood analysis to patient.
In addition, 2 top of plasma cure unit is threadedly coupled mode with 3 bottom of CTC enrichers coordinates installation, it is easy to raw Production assembling, while storing and being provided with nucleic acid inhibitor on 1 inner wall of outer tube of blood plasma.Plasma cure unit 2 and CTC enrichers The design of nucleic acid inhibitor, can make the blood plasma of collection more on 1 inner wall of outer tube of 3 thread connecting modes and storage blood plasma Next step experiment purpose is easily carried out, the blood plasma isolated can be transported and be preserved for a long time, also can directly be stored in -20 DEG C Or -80 DEG C, it solves the problems, such as haemolysis during existing product preservation, meets ctDNA detection needs.
Tracking mode experimental record is done for CTC separating effects, and enumerates the data such as experimental result.
In clinical application, the people with green fluorescent protein (Green Fluorescent Protein, GFP) is non-small Representatives of the cell lung carcinoma lines A549 as CTC, is counted after cell suspension is made, and is added to the healthy will of fresh acquisition Fully reverse mixing in hope person's peripheric venous blood.One end of vein blood taking needle is inserted into the blood sample, the other end is inserted into this No. 1 pipe of utility model product, concrete operation step are as previously described.
Filter membrane is taken out from CTC enrichment regions with tweezers, fluorescence microscopy is placed under the microscope, counts A549 cells on whole film Quantity.As shown in table 1CTC bioaccumulation efficiencies, the CTC bioaccumulation efficiencies of the utility model are distributed in 70%-96%, and average value is 88%.Illustrate that the utility model effectively can easily be enriched with CTC in peripheral blood.
Table 1
Tracking mode experimental record is done for blood plasma separating effect, and enumerates the data such as experimental result.
In clinical application, No. 1 pipe of EDTA vacuum blood collection tubes and the utility model acquisition venous blood 3ml is used respectively.Point 3rd day separated plasma not on the day of blood sampling and after blood sampling.EDTA vacuum blood collection tubes use centrifuge separated plasma, and this reality The operation of blood plasma separation is carried out according to aforementioned operation step with novel product.Collected Plasma volumes are measured respectively and are surveyed Measure content of hemoglobin in blood plasma.
EDTA vacuum blood collection tube blood plasma separating steps:1, EDTA vacuum blood collection tubes are placed in 1600g centrifugations 10 in centrifuge Minute, in Biohazard Safety Equipment, upper plasma is carefully sucked out with pipettor and is moved into 2ml centrifuge tubes;2, centrifuge tube is put into 16000g centrifugations after ten minutes, upper plasma are transferred in new centrifuge tube in centrifuge, and record the Plasma volumes being collected into, The free hemoglobin content of blood plasma collected by each experimental group is measured, and is recorded in the following table 2 Plasma volumes and the trip of 3 blood plasma of table From content of hemoglobin.
Table 2
Table 3
Based in table 2 and table 3 the experimental results showed that, EDTA vacuum blood collection tubes with collected by the utility model product For blood plasma on the day of blood sampling, volume and free hemoglobin content do not have notable difference.Illustrate that the utility model product is separated to arrive Blood plasma in quality and quantity, with EDTA vacuum blood collection tube indifferences, high-quality blood plasma can be detached.EDTA vacuum blood collection tubes exist The 3rd day Plasma volumes being separated to have a declining tendency after blood sampling, and content of hemoglobin increases, and also explanation has generation haemolysis.This The Plasma volumes and content of hemoglobin of utility model product separation do not occur significantly to change the 3rd day after blood sampling.Explanation The utility model product is more advantageous to the long term storage of blood sample.
In conclusion the blood-taking device for the screening circulating tumor cell that the present embodiment is provided includes mainly outer tube, membranous type Plasma separator, CTC enrichers and safety cap, plasma cure unit are removable installed in CTC enrichers bottom end, membranous type blood Slurry separator is connected to CTC enrichers, and CTC enrichers top is detachably connected with safety cap, and plasma cure unit is embedded in outer In pipe, safety cap is connected in outer tube top, and CTC enrichers are built-in with the filter membrane in default aperture, and outer tube bore is preset with vacuum Negative pressure.The blood-taking device of circulating tumor cell provided by the utility model is provided with outer tube, CTC enrichers and filter membrane, passes through Filter membrane is simultaneously efficiently separated the other compositions in CTC and blood using gravity and suction function, and CTC is isolated from filter membrane upper table Face, blood other compositions are isolated from region between the pipe of filter membrane lower surface and outer tube, and compared with prior art, the present apparatus is at one It solves the enrichment of CTC and the separation of blood plasma simultaneously in pipe, other large sizes need not be set by CTC separate apparatus, centrifuge etc. It is standby, it is at low cost, save space and manpower;Whole process takes extremely short, after blood sampling, heparin tube is vertically put on rack for test tube and is waited for The separation of CTC and blood plasma can be realized in a moment;Immunofluorescence, FISH, the Molecular Detection in the compatible downstreams CTC of enrichment etc. are a variety of Detection has higher cell activity, can carry out cell culture and drug sensitive experiment;The blood plasma isolated can be transported and be protected for a long time It deposits, also can directly be stored in -20 DEG C or -80 DEG C, solve the problems, such as haemolysis during existing product preservation, meet ctDNA detections It needs.
The foregoing description of the disclosed embodiments enables professional and technical personnel in the field to realize or use this practicality new Type.Various modifications to these embodiments will be apparent to those skilled in the art, and determine herein The General Principle of justice can be realized in other embodiments without departing from the spirit or scope of the present utility model.Cause This, the utility model is not intended to be limited to the embodiments shown herein, and is to fit to and principles disclosed herein The widest range consistent with features of novelty.

Claims (8)

1. a kind of blood-taking device of screening circulating tumor cell, which is characterized in that including outer tube (1), plasma cure unit (2), CTC enrichers (3) and safety cap (4), the plasma cure unit (2) are removable installed in the CTC enrichers (3) bottom end, the plasma cure unit (2) are connected to the CTC enrichers (3), CTC enrichers (3) top and institute It states safety cap (4) to be detachably connected, the plasma cure unit (2) is in the outer tube (1), safety cap (4) card It is connected to the outer tube (1) top, and the CTC enrichers (3) are built-in with the filter membrane (5) in default aperture, outer tube (1) inner cavity It is preset with negative pressure of vacuum.
2. blood-taking device according to claim 1, which is characterized in that the aperture of the filter membrane (5) is 8um~10um.
3. blood-taking device according to claim 2, which is characterized in that the filter membrane (5) is distributed in laminated multi-layer.
4. blood-taking device according to claim 3, which is characterized in that several built in the plasma cure unit (2) Hollow fiber conduit, and the filter opening of preset diameters, the fiber bottom of the tube and the outer tube (1) are set on the tube wall of the fibre pipe Inner cavity is connected to.
5. blood-taking device according to claim 4, which is characterized in that a diameter of 1um~5um of the filter opening.
6. blood-taking device according to claim 5, which is characterized in that plasma cure unit (2) top with it is described CTC enrichers (3) bottom thread connects.
7. blood-taking device according to claim 6, which is characterized in that be provided with anti-freezing on CTC enrichers (3) inner wall Agent.
8. blood-taking device according to claim 6, which is characterized in that be provided with nuclease suppression on outer tube (1) inner wall Preparation.
CN201721928557.7U 2017-12-30 2017-12-30 A kind of blood-taking device of screening circulating tumor cell Active CN207751770U (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107917835A (en) * 2017-12-30 2018-04-17 广州阳普医疗科技股份有限公司 A kind of blood-taking device for screening circulating tumor cell
RU2731909C1 (en) * 2019-11-20 2020-09-09 Гаррий Дмитриевич Иващенко Device for blood collection during operation
EP4016085A1 (en) 2020-12-21 2022-06-22 Tecan Trading AG Iterative liquid aspiration

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107917835A (en) * 2017-12-30 2018-04-17 广州阳普医疗科技股份有限公司 A kind of blood-taking device for screening circulating tumor cell
RU2731909C1 (en) * 2019-11-20 2020-09-09 Гаррий Дмитриевич Иващенко Device for blood collection during operation
EP4016085A1 (en) 2020-12-21 2022-06-22 Tecan Trading AG Iterative liquid aspiration
EP4521120A1 (en) 2020-12-21 2025-03-12 Tecan Trading AG Iterative liquid aspiration
US12455293B2 (en) 2020-12-21 2025-10-28 Tecan Trading Ag Iterative liquid aspiration

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