CN103604679B - A kind of circulating tumor cell is caught instrument and catches colouring method - Google Patents
A kind of circulating tumor cell is caught instrument and catches colouring method Download PDFInfo
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- CN103604679B CN103604679B CN201310600744.2A CN201310600744A CN103604679B CN 103604679 B CN103604679 B CN 103604679B CN 201310600744 A CN201310600744 A CN 201310600744A CN 103604679 B CN103604679 B CN 103604679B
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Abstract
The invention discloses a kind of circulating tumor cell and catch instrument, comprising: Multi-way valve device, Wheel disc device, loading needle device and injection device, wherein, described Multi-way valve device is connected with pack, selects different types of reagent by described Multi-way valve device; Described Wheel disc device is equipped with filter, and described loading needle device can insert the described filter of described Wheel disc device to connect gas circuit and fluid path; Described reagent injector is entered described filter after drawing required reagent by described Multi-way valve device by described injection device.The present invention's method of also openly utilizing circulating tumor cell of the present invention to catch instrument to carry out catching and dyeing in addition.Circulating tumor cell according to the present invention is caught instrument and the rejection that tumour cell is caught is higher than to the rejection of manually catching; The Color that circulating tumor cell according to the present invention catches instrument in addition has homogeneity and the consistance of height compared with manually, and clean background.
Description
Technical field
The present invention relates to a kind of biological detection instrument, particularly relate to a kind of circulating tumor cell and catch instrument and catch colouring method.
Background technology
Tumor micrometastasis stove originates from the tumour cell invaded in circulation, and therefore, circulating tumor cell (circulatingtumorcells, CTCs) may be the one mark of tumour DISTANT METASTASES IN.In recent years, along with the development of sensitive molecule technology, make to be separated, counting peripheral blood CTCs becomes possibility.At disease commitment, CTCs may contribute to discriminating that is good, malignant tumour, the prediction shifted risk and judgement; In the progression of disease phase, CTCs perhaps can provide important prognosis information, and helps doctor's monitoring therapeuticing effect; And CTCs may reflect tumoral character, can the formulation of guiding treatment scheme, and can as the target of targeted therapy.Existing CTCs is separated, detection technique method is more, cuts both ways.Enrichment method normally based on physical property (density and size) or the immune magnetic of CTCs, comprises gradient centrifugation, filtration method, immune magnetic separating method.Detection method comprises immunological technique, based on RT-PCR technology, ELISpot (ELISPOT) technology and CTCs chip technology.Wherein immune magnetic separating method is CTCs enrichment method the most frequently used at present. and the proprietary technology CellSearchTMSystem of Veridex company of U.S. research and development has become a standard protocols.Gradient centrifugation and filtration method are also important means and the method for CTCs cell capture, the people such as FrankA.W.Coumans have made good effect with filtration method in laboratory, CTCs cell capture method is carried out about employing membrane filtration, scientist and scholar conduct extensive research, but everybody adopts laboratory techniques to carry out, adopt and manually operate, it is single that second phase implements flux, manually operated process one brings huge problem to industrialization, two is that During manual operation can introduce corresponding operate miss, affect experimental result, human factor impact is larger, up to the present, also do not utilize the commercially produced product that the method realizes on the market.
Summary of the invention
For this reason, the present invention proposes a kind of circulating tumor cell that is that can solve the problem or that at least can partly solve the problem and catch instrument.
According to an aspect of the present invention, provide a kind of circulating tumor cell and catch instrument, comprising: Multi-way valve device, Wheel disc device, loading needle device and injection device, wherein,
Described Multi-way valve device is connected with pack, selects different types of reagent by described Multi-way valve device;
Described Wheel disc device is equipped with filter, and described loading needle device can insert the filter of described Wheel disc device, connects gas circuit and fluid path;
Described reagent injector is entered described filter after drawing required reagent by described Multi-way valve device by described injection device.
Circulating tumor cell according to the present invention is caught instrument and the rejection that tumour cell is caught is higher than to the rejection of manually catching; The Color that circulating tumor cell according to the present invention catches instrument in addition has homogeneity and the consistance of height compared with manually, and clean background.Utilize and carry out cell capture and dyeing according to the instrument of catching of circulating tumor cell of the present invention, be fixed to rinsed with deionized water from cell and achieve full-automation, improve accuracy, repeatability and consistance; Flux is many, can enter multiple sample simultaneously, shorten the running time; In addition, have also been devised man-machine interaction, adjustablely to catch and dyeing course parameter, easy to operate.
Alternatively, circulating tumor cell according to the present invention catches instrument, and wherein said Multi-way valve device comprises: banked direction control valves, the first Multipath valve rack, the second Multipath valve rack, banked direction control valves web joint, banked direction control valves absolute value encoder and banked direction control valves stepper motor, wherein,
Described Multi-way valve device comprises: banked direction control valves, the first Multipath valve rack, the second Multipath valve rack, banked direction control valves web joint, banked direction control valves absolute value encoder and banked direction control valves stepper motor, wherein,
Described banked direction control valves stepper motor first end is connected with described banked direction control valves, and the second end is connected with described banked direction control valves absolute value encoder;
Described first Multipath valve rack carries out coaxial support with described second Multipath valve rack to described banked direction control valves, described banked direction control valves stepper motor and described banked direction control valves absolute value encoder and is connected;
Described banked direction control valves web joint is connected to the top of described first Multipath valve rack and described second Multipath valve rack.
Circulating cells according to the present invention catches the Multi-way valve device in instrument, is by selecting different reagent to the switching of passage.Wherein said banked direction control valves motor, banked direction control valves stepper motor and banked direction control valves absolute value encoder are fixed on on an axis by the first Multipath valve rack and the second Multipath valve rack and banked direction control valves web joint.When certain reagent of needs, judge which position banked direction control valves is in regulate and exports correct reagent by banked direction control valves absolute value encoder feedback signal.Described Multi-way valve device is connected with pack, banked direction control valves is provided with multiple passage and connects from different reagent, and the banked direction control valves other end then arranges a passage, and this channel selecting and the expanding channels being wherein connected reagent needed for certain, can draw required reagent.
Alternatively, circulating tumor cell according to the present invention catches instrument, and wherein said Wheel disc device comprises: filter, filter pallet, wheel disc, synchronizing wheel, wheel disc stepper motor, synchronous belt, absolute value encoder and wheel disc axle, wherein,
Described filter is arranged on described filter pallet;
Described filter pallet is arranged on described wheel disc;
Described synchronizing wheel is arranged on describedly takes turns tray bottom;
Described synchronous belt is arranged on described synchronizing wheel;
Described wheel disc stepper motor drives described synchronizing wheel to rotate by described synchronous belt, thus drives described wheel disc to rotate;
Described wheel disc axle passes described wheel disc and is fixed together with described wheel disc;
Described absolute value encoder is arranged on described wheel disc axle.
Alternatively, circulating tumor cell according to the present invention catches instrument, comprising filter described at least one.
Circulating tumor cell according to the present invention catches instrument, wherein said Wheel disc device, is used to rotate filter that user puts into machine system and carries out loading in turn.Wherein filter is arranged on pallet, can install 10 filters, use for you to choose simultaneously, and the position being judged wheel disc by the feedback signal of absolute value encoder, thus select suitable filter to test.
Alternatively, circulating tumor cell according to the present invention catches instrument, and wherein said loading needle device comprises: loading needle rack, cylinder, the first briquetting, the second briquetting and loading pin, wherein,
Described loading pin is arranged on described loading needle rack front end, and described loading pin is successively through described first briquetting and described second briquetting;
Described cylinder drives described loading needle rack to move up and down.
Circulating tumor cell according to the present invention catches the loading needle device of instrument, is used for reagent to inject filter, controls the upper-lower position of loading needle rack with stroke cylinder.When needs sample introduction, under the drive of cylinder, the first briquetting is first pressed onto filter, ensures that filter is not crooked, then the second briquetting is pressed onto filter, now loading needle-penetration filter.And reaching upper extreme position and lower limit position needing the long period by interior details structure keeps motionless situation without the need to providing source of the gas.
Alternatively, circulating tumor cell according to the present invention catches instrument, and wherein said injection device comprises: syringe, injector plate, syringe holder, ball screw, shaft coupling, syringe rack, syringe stepper motor, wherein,
Described syringe stepper motor is arranged in described injector plate by described syringe rack;
Described syringe stepper motor is connected with described ball screw by described shaft coupling;
Described ball screw drives described syringe to move by described syringe holder.
Circulating tumor cell according to the present invention catches the injection device of instrument, be used for extracting quantitative reagent, ball screw motion is driven by injection stepper motor, described ball screw drives described syringe to move, thus syringe is moved, reagent needed for quantitative by described Multi-way valve device extraction, and required reagent injector is entered in described filter.
Alternatively, circulating tumor cell according to the present invention catches instrument, and the wherein said course of work of catching each device of instrument comprises:
First described Wheel disc device turns to specific filter position;
Then described loading needle device inserts in described specific filter;
Described Multi-way valve device selects particular agent from pack afterwards;
Be injected in described specific filter after last described injection device draws quantitative reagent from described Multi-way valve device.
According to a further aspect in the invention, what provide a kind of circulating tumor cell catches colouring method,
There is provided a kind of circulating tumor cell to catch instrument, it comprises: Multi-way valve device, Wheel disc device, loading needle device and injection device, wherein,
Described Multi-way valve device is connected with pack, selects different types of reagent by described Multi-way valve device;
Described Wheel disc device is equipped with filter, and described loading needle device can insert the filter of described Wheel disc device to connect gas circuit and fluid path;
Described reagent injector is entered described filter after drawing required reagent by described Multi-way valve device by described injection device;
Further, the method comprising the steps of:
Described Wheel disc device turns to specific filter position, and described filter carries out filtration to circulating tumor cell sample and catches;
Described loading needle device inserts in described specific filter, connects gas circuit and fluid path;
Described Multi-way valve device selects different reagent from pack;
Described injection device is injected into draw quantitative particular agent from described Multi-way valve device after in described specific filter, dyes to circulating tumor cell.
Catch colouring method according to circulating tumor cell of the present invention, the rejection of manually catching is higher than to the rejection that tumour cell is caught; Color has homogeneity and the consistance of height compared with manually, and clean background.
Accompanying drawing explanation
By reading hereafter detailed description of the preferred embodiment, various other advantage and benefit will become cheer and bright for those of ordinary skill in the art.Accompanying drawing only for illustrating the object of preferred implementation, and does not think limitation of the present invention.And in whole accompanying drawing, represent identical parts by identical reference symbol.Wherein in the accompanying drawings, the multiple identical parts of alphabetic flag instruction after reference number, when making a general reference these parts, by its last alphabetic flag of omission.In the accompanying drawings:
Fig. 1 shows and catches instrument according to the circulating tumor of one embodiment of the present invention;
Fig. 2 shows the Multi-way valve device according to one embodiment of the present invention;
Fig. 3 shows the Wheel disc device according to one embodiment of the present invention;
Fig. 4 shows the loading needle device according to one embodiment of the present invention;
Fig. 5 shows the injection device according to one embodiment of the present invention;
Fig. 6 shows and utilizes circulating tumor cell of the present invention to catch instrument to carry out dyeing and the contrast effect figure of hand dyeing;
Fig. 7 shows the operating process schematic diagram of catching instrument according to circulating tumor cell of the present invention;
Wherein Reference numeral is:
Circulating tumor cell catches instrument 1000
Multi-way valve device 1100, banked direction control valves 1110, first Multipath valve rack 1120, second Multipath valve rack 1130, banked direction control valves web joint 1140, banked direction control valves absolute value encoder 1150, Wheel disc device 1200, filter 1210, filter pallet 1220, wheel disc 1230, synchronizing wheel 1240, wheel disc stepper motor 1250, synchronous belt 1260, absolute value encoder 1270, wheel disc axle 1280, loading needle device 1300, loading needle rack 1310, cylinder 1320, first briquetting 1330, second briquetting 1340, loading pin 1350, injection device 1400, syringe 1410, injector plate 1420, syringe holder 1430, ball screw 1440, shaft coupling 1450, syringe rack 1460, syringe stepper motor 1470, pack 1500.
Embodiment
The invention provides many applicable creative concepts, this creative concept can be reflected in a large number of in concrete context.The specific embodiment described in following embodiments of the present invention only as the exemplary illustration of specific implementation of the present invention, and does not form limitation of the scope of the invention.
Circulating tumor cell of the present invention catches instrument 1000, comprise: Multi-way valve device 1100, Wheel disc device 1200, loading needle device 1300 and injection device 1400, wherein, Multi-way valve device 1100 is connected with pack 1500, selects different types of reagent by Multi-way valve device 1100; Wheel disc device 1200 is equipped with filter 1210, loading needle device 1300 can insert the filter 1210 of Wheel disc device 1200, connects gas circuit and fluid path; Reagent injector is entered filter 1210 after drawing required reagent by Multi-way valve device 1100 by injection device 1400.
The Multi-way valve device 1100 that circulating tumor cell of the present invention catches instrument (1000) comprises: banked direction control valves 1110, first Multipath valve rack 1120, second Multipath valve rack 1130, banked direction control valves web joint 1140, banked direction control valves absolute value encoder 1150 and banked direction control valves stepper motor, wherein, Multi-way valve device 1100 comprises: banked direction control valves 1110, first Multipath valve rack 1120, second Multipath valve rack 1130, banked direction control valves web joint 1140, banked direction control valves absolute value encoder 1150 and banked direction control valves stepper motor, wherein, banked direction control valves stepper motor first end is connected with banked direction control valves 1110, second end is connected with banked direction control valves absolute value encoder 1150, first Multipath valve rack 1120 and the second Multipath valve rack 1120 pairs of banked direction control valves 1110, banked direction control valves stepper motor and banked direction control valves absolute value encoder 1150 carry out coaxial support and are connected, banked direction control valves web joint 1140 is connected to the top of the first Multipath valve rack 1120 and the second Multipath valve rack 1130.
Multi-way valve device is by selecting different reagent to the switching of passage.Wherein banked direction control valves, banked direction control valves stepper motor and banked direction control valves absolute value encoder are fixed on an axis by the first Multipath valve rack and the second Multipath valve rack and banked direction control valves web joint.When certain reagent of needs, judge which position banked direction control valves is in regulate and exports correct reagent by banked direction control valves absolute value encoder feedback signal.Multi-way valve device is connected with pack, banked direction control valves is provided with multiple passage and connects from different reagent, and the banked direction control valves other end then arranges a passage, and this channel selecting and the expanding channels being wherein connected reagent needed for certain, can draw required reagent.
Circulating tumor cell according to the present invention catches the Wheel disc device of instrument 1000, wherein Wheel disc device 1200 comprises: filter 1210, filter pallet 1220, wheel disc 1230, synchronizing wheel 1240, wheel disc stepper motor 1250, synchronous belt 1260, absolute value encoder 1270 and wheel disc axle 1280, wherein, filter 1210 is arranged on filter pallet 1220; Filter pallet 1220 is arranged on wheel disc 1230; Synchronizing wheel 1240 is arranged on bottom wheel disc 1230; Synchronous belt 1260 is arranged on synchronizing wheel 1240; Wheel disc stepper motor 1250 drives synchronizing wheel 1240 to rotate by synchronous belt 1260, thus drives wheel disc 1230 to rotate; Wheel disc axle 1280 passes wheel disc 1230 and is fixed together with wheel disc 1230; Absolute value encoder 1270 is arranged on wheel disc axle 1280.Comprising at least one filter 1210.
Wheel disc device is used to rotate filter that user puts into machine system and carries out loading in turn, wherein filter is arranged on pallet, 10 filters can be installed simultaneously, use for you to choose, and judged the position of wheel disc by the feedback signal of absolute value encoder, thus select suitable filter to test.
Tumour cell according to the present invention catches the loading needle device of instrument 1000, wherein loading needle device 1300 comprises: loading needle rack 1310, cylinder (the 320, first briquetting 1330, second briquetting 1340 and loading pin 1350, wherein, loading pin 1350 is arranged on loading needle rack 1310 front end, and loading pin 1350 is successively through the first briquetting 1330 and the second briquetting 1340; Cylinder 1320 drives loading needle rack 1310 to move up and down.
Loading needle device is used for reagent to inject filter, controls the upper-lower position of loading needle rack with stroke cylinder.When needs sample introduction, under the drive of cylinder, the first briquetting is first pressed onto filter, ensures that filter is not crooked, then the second briquetting is pressed onto filter, now loading needle-penetration filter.And reaching upper extreme position and lower limit position needing the long period by interior details structure keeps motionless situation without the need to providing source of the gas.
Injection device 1400 according to cell capture instrument 1000 of the present invention comprises: syringe 1410, injector plate 1420, syringe holder 1430, ball screw 1440, shaft coupling 1450, syringe rack 1460, syringe stepper motor 1470, wherein, syringe stepper motor 1470 is arranged in injector plate 1420 by syringe rack 1460; Syringe stepper motor 1470 is connected with ball screw 1440 by shaft coupling 1450; Ball screw 1440 drives syringe 1410 to move by syringe holder 1430.
Injection device is used for extracting quantitative reagent, drive ball screw motion by injection stepper motor, ball screw drives syringe motion, thus syringe is moved, by Multi-way valve device extract quantitative needed for reagent, and required reagent injector to be entered in filter.
7. circulating tumor cell according to claim 1 catches instrument (1000), and the wherein said course of work of catching each device of instrument comprises:
First described Wheel disc device (1400) turns to specific filter position;
Then described loading needle device (1300) is inserted in described specific filter;
Described Multi-way valve device (1100) selects particular agent from pack (1500) afterwards;
Last described injection device (1400) is injected in described specific filter draw quantitative reagent from described Multi-way valve device (1100) after.
In addition, additionally provide and utilize circulating tumor cell of the present invention to catch instrument catching and colouring method circulating tumor cell, the method comprising the steps of: described Wheel disc device 1200 turns to specific filter position, and described filter carries out filtration to circulating tumor cell sample and catches; Described loading needle device 1300 inserts in described specific filter, connects gas circuit and fluid path; Described Multi-way valve device 1100 selects different reagent from pack 1500; Described injection device 1400 is injected in described specific filter draw quantitative particular agent from described Multi-way valve device 1100 after, dyes to circulating tumor cell.
Catch instrument optional element according to tumour cell of the present invention more, different embodiments can be designed according to the claims in the present invention, instrument will be caught for embodiment with circulating tumor cell below and carry out exemplary illustration to of the present invention.
Embodiment
The circulating tumor cell of the one embodiment of the present invention according to Fig. 1 catches instrument 1000, comprise: Multi-way valve device 1100, Wheel disc device 1200, loading needle device 1300 and injection device 1400, wherein, Multi-way valve device 1100 is connected with pack 1500, selects different types of reagent by Multi-way valve device 1100; Wheel disc device 1200 is equipped with filter 1210, loading needle device 1300 can insert the filter 1210 of Wheel disc device 1200, connects gas circuit and fluid path; Reagent is injected into filter 1210 by loading needle device 1300 after drawing required reagent by Multi-way valve device 1100 by injection device 1400.
Multi-way valve device 1100 according to Fig. 2 comprises: banked direction control valves 1110, first Multipath valve rack 1120, second Multipath valve rack 1130, banked direction control valves web joint 1140, banked direction control valves absolute value encoder 1150 and banked direction control valves stepper motor, wherein, banked direction control valves stepper motor first end is connected with banked direction control valves 1110, and the second end is connected with banked direction control valves absolute value encoder 1150; First Multipath valve rack 1120 and the second Multipath valve rack 1120 pairs of banked direction control valves 1110, banked direction control valves stepper motor and banked direction control valves absolute value encoder 1150 carry out coaxial support and are connected; Banked direction control valves web joint 1140 is connected to the top of the first Multipath valve rack 1120 and the second Multipath valve rack 1130.
Wheel disc device 1200 according to Fig. 3 comprises: filter 1210, filter pallet 1220, wheel disc 1230, synchronizing wheel 1240, wheel disc stepper motor 1250, synchronous belt 1260, absolute value encoder 1270 and wheel disc axle 1280, wherein, filter 1210 is arranged on filter pallet 1220; Filter pallet 1220 is arranged on wheel disc 1230; Synchronizing wheel 1240 is arranged on bottom wheel disc 1230; Synchronous belt 1260 is arranged on synchronizing wheel 1240; Wheel disc stepper motor 1250 drives synchronizing wheel 1240 to rotate by synchronous belt 1260, thus drives wheel disc 1230 to rotate; Wheel disc axle 1280 passes wheel disc 1230 and is fixed together with wheel disc 1230; Absolute value encoder 1270 is arranged on wheel disc axle 1280.Comprising at least one filter 1210.
Loading needle device 1300 according to Fig. 4 comprises: loading needle rack 1310, cylinder (the 320, first briquetting 1330, second briquetting 1340 and loading pin 1350, wherein, loading pin 1350 is arranged on loading needle rack 1310 front end, and loading pin 1350 is successively through the first briquetting 1330 and the second briquetting 1340; Cylinder 1320 drives loading needle rack 1310 to move up and down.
Injection device 1400 according to Fig. 5 comprises: syringe 1410, injector plate 1420, syringe holder 1430, ball screw 1440, shaft coupling 1450, syringe rack 1460, syringe stepper motor 1470, wherein, syringe stepper motor 1470 is arranged in injector plate 1420 by syringe rack 1460; Syringe stepper motor 1470 is connected with ball screw 1440 by shaft coupling 1450; Ball screw 1440 drives syringe 1410 to move by syringe holder 1430.
According to the circulating tumor cell capture systems of the present embodiment, devise human-computer interaction interface, be used for operating machines and show relevant visual information to user, human-computer interaction interface includes display system and by key control, the display system display operation information of user, system information, running status and warning message, by key control can be touch-screen button also G be mechanical key, user operates with it; Machine body is used as transmission and control subject; Also comprise source of the gas in the entire system, for providing source of the gas to machine; In addition, be also provided with other overage, comprising filter, filter is used for putting into machine system, carries out the Bioexperiment of being correlated with, also comprises pack, and for providing relevant reagent, outside consumptive material, for carrying out pre-service to sample.
In addition, additionally provide and utilize circulating tumor cell of the present invention to catch instrument to catch colouring method to circulating tumor cell, a kind of circulating tumor cell is provided to catch instrument 1000, it comprises: Multi-way valve device 1100, Wheel disc device 1200, loading needle device 1300 and injection device 1400, wherein, described Multi-way valve device 1100 is connected with pack 1500, selects different types of reagent by described Multi-way valve device 1100; Described Wheel disc device 1200 is equipped with filter 1210, and described loading needle device 1300 can insert the filter 1210 of described Wheel disc device 1200 to connect gas circuit and fluid path; Described reagent injector is entered described filter 1210 after drawing required reagent by described Multi-way valve device 1100 by described injection device 1400; Further, the method comprising the steps of: described Wheel disc device 1200 turns to specific filter position, and described filter carries out filtration to circulating tumor cell sample and catches; Described loading needle device 1300 inserts in described specific filter, connects gas circuit and fluid path; Described Multi-way valve device 1100 selects different reagent from pack 1500; Described injection device 1400 is injected in described specific filter draw quantitative particular agent from described Multi-way valve device 1100 after, dyes to circulating tumor cell.
Fig. 7 show according to circulating tumor cell of the present invention catch instrument catch dying operation schematic flow sheet, this flow process comprises the following steps:
701: user opens source of the gas after the power is turned, this is the basic condition that machine runs;
702: machine carries out opening initialization, and check each functional device, whether the content of inspection comprises pack and puts into, and whether the amount of reagent of pack is enough, and whether filter the factor affecting duty such as puts into;
703: when judging in good condition, wheel disc rotates;
704: find specific filter position;
705: loading pin inserts in filter, and gas circuit is connected with filter with fluid path;
706: banked direction control valves rotates, and selects different reagent passage;
707: the reagent that syringe suction from banked direction control valves is quantitative;
708: reagent injector is entered in filter;
Through said process, catch dyeing to sample, this process repeatedly repeats the function of Multi-way valve device and injection device; After having operated, dial rotation, selected another one filter, carries out above-mentioned repetitive process.
Utilize the circulating tumor cell of the present embodiment to catch instrument catch circulating tumor cell and dye, and the result of catching and dye and the result of manually catching and dye are compared.
The CTCs separation principle that this detection system adopts mainly carries out enrichment based on the difference of tumour cell and the cell size of haemocyte and the deformability of cell.Wherein clinical data display, in normal blood, red blood cell diameter is greatly about 5-9 micron, and granulocyte diameter is at 10-15 micron, and lymphocyte diameter is at 7-18 micron, monocyte diameter is at 12-20 micron, and typical circulating tumor cell diameter is greater than 20 microns (depending on tumor type slightly differences).In addition tumour cell caryoplasm is than relatively large, and cell is comparatively hard is not easy distortion, and haemocyte has very strong retractility, if normocyte deformable is by the capillary of 3.3 microns.According to these physical characteristics difference, great many of experiments basis is optimized filter membrane technological parameter and sample preprocessing method, both ensure that and the rejection that native system is very high to tumour cell effectively reduced again haemocyte background.
Wherein, carried out three times to circulating tumor cell and retained contrast, the rejection wherein manually retained is followed successively by: 78%, 70% and 65%; Rejection that instrument carries out automatic-diversion closure is followed successively by utilize circulating tumor cell of the present invention to catch: 73%, 75% and 74%.As can be seen here, the capture rate consistance utilizing circulating tumor cell of the present invention to catch instrument is better than manual effect.
In addition, utilize circulating tumor cell of the present invention to catch instrument catch circulating tumor cell and carried out dyeing process to tumour cell.The ultimate principle of dyeing adopts Romanowsky staining technique: dissimilar cell and intracellular different component are due to the difference of chemical property, different with the affinity of basic-dyeable fibre (methylenum careuleum) to acid dyes in dyeing liquor (eosin).By this complex staining technology, cell presents different dyeing characteristics, thus reaches the object distinguishing its morphological feature.Carry out three dyeing, and coloration result and manual coloration result are compared, comparative result as shown in Figure 6,3 figure are the results manually dyeed above in figure 6,3 figure are utilize circulating tumor cell of the present invention to catch results that instrument carries out automatic staining below, utilize circulating tumor cell of the present invention to catch effect that instrument carries out dyeing is compared with the effect manually dyeed: homogeneity and consistance good, and clean background.
Utilize and carry out cell capture and dyeing according to the instrument of catching of circulating tumor cell of the present invention, be fixed to rinsed with deionized water from cell and achieve full-automation, repeatability is high, improves accuracy and consistance (also can be realize full-automation from entering blood to rinsed with deionized water); Multiple sample can be entered simultaneously, shorten the running time; In addition, have also been devised man-machine interaction, adjustablely catch the parameter with dyeing course, easy to operate.
It should be noted, the present invention will be described instead of limit the invention for above-described embodiment, and those skilled in the art can design alternative embodiment when not departing from claims scope.In the claims, any reference symbol between bracket should be configured to limitations on claims.Word " comprises " not to be got rid of existence and does not arrange element in the claims or step.
Claims (5)
1. a circulating tumor cell catches instrument (1000), comprising: Multi-way valve device (1100), Wheel disc device (1200), loading needle device (1300) and injection device (1400), wherein,
Described Multi-way valve device (1100) is connected with pack (1500), selects different types of reagent by described Multi-way valve device (1100);
Described Wheel disc device (1200) is equipped with filter (1210), described loading needle device (1300) can insert the filter (1210) of described Wheel disc device (1200) to connect gas circuit and fluid path;
Described reagent injector is entered described filter (1210) after drawing required reagent by described Multi-way valve device (1100) by described injection device (1400);
Wherein said Multi-way valve device (1100) comprising: banked direction control valves (1110), the first Multipath valve rack (1120), the second Multipath valve rack (1130), banked direction control valves web joint (1140), banked direction control valves absolute value encoder (1150) and banked direction control valves stepper motor, wherein
Described banked direction control valves stepper motor first end is connected with described banked direction control valves (1110), and the second end is connected with described banked direction control valves absolute value encoder (1150);
Described first Multipath valve rack (1120) is carried out coaxial support with described second Multipath valve rack (1130) to described banked direction control valves (1110), described banked direction control valves stepper motor and described banked direction control valves absolute value encoder (1150) and is connected;
Described banked direction control valves web joint (1140) is connected to described first Multipath valve rack (1120) and described second Multipath valve rack (1130) top;
Wherein said loading needle device (1300) comprising: loading needle rack (1310), cylinder (1320), the first briquetting (1330), the second briquetting (1340) and loading pin (1350), wherein
Described loading pin (1350) is arranged on described loading needle rack (1310) front end, and the needle tip of described loading pin (1350) is successively through described first briquetting (1330) and described second briquetting (1340);
Described cylinder (1320) drives described loading needle rack (1310) to move up and down;
Wherein said injection device (1400) comprising: syringe (1410), injector plate (1420), syringe holder (1430), ball screw (1440), shaft coupling (1450), syringe rack (1460), syringe stepper motor (1470)
Wherein, described syringe stepper motor (1470) is arranged in described injector plate (1420) by described syringe rack (1460);
Described syringe stepper motor (1470) is connected with described ball screw (1440) by described shaft coupling (1450);
Described ball screw (1440) drives described syringe (1410) to move by described syringe holder (1430).
2. circulating tumor cell according to claim 1 catches instrument (1000), wherein said Wheel disc device (1200) comprising: filter (1210), filter pallet (1220), wheel disc (1230), synchronizing wheel (1240), wheel disc stepper motor (1250), synchronous belt (1260), absolute value encoder (1270) and wheel disc axle (1280), wherein
Described filter (1210) is arranged on described filter pallet (1220);
Described filter pallet (1220) is arranged on described wheel disc (1230);
Described synchronizing wheel (1240) is arranged on described wheel disc (1230) bottom;
Described synchronous belt (1260) is arranged on described synchronizing wheel (1240);
Described wheel disc stepper motor (1250) drives described synchronizing wheel (1240) to rotate by described synchronous belt (1260), thus drives described wheel disc (1230) to rotate;
Described wheel disc axle (1280) is through described wheel disc (1230) and be fixed together with described wheel disc (1230);
Described absolute value encoder (1270) is arranged on described wheel disc axle (1280).
3. circulating tumor cell according to claim 2 catches instrument (1000), comprising filter described at least one (1210).
4. circulating tumor cell according to claim 1 catches instrument (1000), and the wherein said course of work of catching each device of instrument comprises:
Described Wheel disc device (1400) turns to specific filter position;
Described loading needle device (1300) is inserted in described specific filter;
Described Multi-way valve device (1100) selects particular agent from pack (1500);
Described injection device (1400) is injected in described specific filter draw quantitative reagent from described Multi-way valve device (1100) after.
5. circulating tumor cell catch a colouring method,
A kind of circulating tumor cell is provided to catch instrument (1000), it comprises: Multi-way valve device (1100), Wheel disc device (1200), loading needle device (1300) and injection device (1400), wherein said Multi-way valve device (1100) is connected with pack (1500), selects different types of reagent by described Multi-way valve device (1100); Described Wheel disc device (1200) is equipped with filter (1210), described loading needle device (1300) can insert the filter (1210) of described Wheel disc device (1200) to connect gas circuit and fluid path; Described reagent injector is entered described filter (1210) after drawing required reagent by described Multi-way valve device (1100) by described injection device (1400);
Further, the method comprising the steps of:
Described Wheel disc device (1200) turns to specific filter position, and described filter carries out filtration to circulating tumor cell sample and catches;
Described loading needle device (1300) is inserted in described specific filter, connects gas circuit and fluid path;
Described Multi-way valve device (1100) selects different reagent from pack (1500);
Described injection device (1400) is injected in described specific filter draw quantitative particular agent from described Multi-way valve device (1100) after, dyes to circulating tumor cell;
Wherein said Multi-way valve device (1100) comprising: banked direction control valves (1110), the first Multipath valve rack (1120), the second Multipath valve rack (1130), banked direction control valves web joint (1140), banked direction control valves absolute value encoder (1150) and banked direction control valves stepper motor
Wherein, described banked direction control valves stepper motor first end is connected with described banked direction control valves (1110), and the second end is connected with described banked direction control valves absolute value encoder (1150);
Described first Multipath valve rack (1120) is carried out coaxial support with described second Multipath valve rack (1130) to described banked direction control valves (1110), described banked direction control valves stepper motor and described banked direction control valves absolute value encoder (1150) and is connected;
Described banked direction control valves web joint (1140) is connected to described first Multipath valve rack (1120) and described second Multipath valve rack (1130) top;
Wherein said loading needle device (1300) comprising: loading needle rack (1310), cylinder (1320), the first briquetting (1330), the second briquetting (1340) and loading pin (1350),
Wherein, described loading pin (1350) is arranged on described loading needle rack (1310) front end, and the needle tip of described loading pin (1350) is successively through described first briquetting (1330) and described second briquetting (1340);
Described cylinder (1320) drives described loading needle rack (1310) to move up and down;
Wherein said injection device (1400) comprising: syringe (1410), injector plate (1420), syringe holder (1430), ball screw (1440), shaft coupling (1450), syringe rack (1460), syringe stepper motor (1470)
Wherein, described syringe stepper motor (1470) is arranged in described injector plate (1420) by described syringe rack (1460);
Described syringe stepper motor (1470) is connected with described ball screw (1440) by described shaft coupling (1450);
Described ball screw (1440) drives described syringe (1410) to move by described syringe holder (1430).
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| CN108220152B (en) * | 2016-12-21 | 2021-05-14 | 益善生物技术股份有限公司 | Circulating tumor cell capturing system |
| CN107988042B (en) * | 2017-11-27 | 2021-03-09 | 长春理工大学 | Circulating tumor cell separation device and detection method thereof |
| CN108359639B (en) * | 2018-01-24 | 2020-10-23 | 杭州安弼晟生物科技有限公司 | Circulating tumor cell capturing system |
| CN108804878B (en) * | 2018-06-16 | 2020-08-11 | 志诺维思（北京）基因科技有限公司 | Dyeing simulation method and device |
| CN109827806A (en) * | 2019-03-18 | 2019-05-31 | 中国科学院重庆绿色智能技术研究院 | A kind of acquisition device and method of circulating tumor cell |
| CN111537423A (en) * | 2020-04-21 | 2020-08-14 | 山东第一医科大学(山东省医学科学院) | Detection and identification method for circulating tumor cells CTCs |
| CN112625877B (en) * | 2021-01-27 | 2022-09-13 | 杨苗苗 | Sorting and filtering device for tumor cell mass for oncology department |
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