CN103642684B - A kind of magnetic probe search type cell sorting device - Google Patents

A kind of magnetic probe search type cell sorting device Download PDF

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CN103642684B
CN103642684B CN201310688961.1A CN201310688961A CN103642684B CN 103642684 B CN103642684 B CN 103642684B CN 201310688961 A CN201310688961 A CN 201310688961A CN 103642684 B CN103642684 B CN 103642684B
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probe
magnetic probe
outer cover
axis
target cell
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CN103642684A (en
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黎子民
张�杰
田放
张丽
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YUNNAN HUIBO TECHNOLOGY Co Ltd
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YUNNAN HUIBO TECHNOLOGY Co Ltd
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04Cell isolation or sorting

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Abstract

The present invention relates to a kind of magnetic probe search type cell sorting device.Sorting unit is by planer-type XYZ three axle robert device, mechanical manipulator digitial controller, support, body, magnetic probe, probe jig, test board, testing cassete and release magnet are formed, magnetic probe is connected on probe jig, probe jig is placed on planer-type XYZ three axle robert device, mechanical manipulator digitial controller connects planer-type XYZ three axle robert device, planer-type XYZ three axle robert device is placed in above testing cassete, testing cassete is placed on the table top of test board, test board is placed on body, body is placed in above support, release magnet to be placed in body and to be positioned at the below of testing cassete, in testing cassete, sample liquid is housed, magnetic probe is installed on probe jig, the movement of probe card prodigiosin in planer-type XYZ three axle robert device, after magnetic probe completes and catches the suction of target cell in testing cassete, by release magnet to the suction effect of target cell, complete and the recovery of the target cell on magnetic probe is collected.

Description

A kind of magnetic probe search type cell sorting device
Technical field
The present invention relates to a kind of magnetic probe search type cell sorting device, particularly relate to the highly sensitive automatic biological cell sorting techniques in biological ceils field, belong to biological ceils equipment.
Background technology
In medical diagnosis on disease, the fields such as drug test, researchist needs from the sample mixing various tissue of biological cells, extract specific cells technology and equipment, to obtain pure cell sample to do various experimental analysis and diagnosis.Obtain higher sensitivity, higher separation velocity and purity, better sample type adaptive faculty, more efficient cell sorting techniques and equipment are automatically the targets of cell sorting field effort.
Existing cell sorting equipment mainly contains:
One, centrifugal classification technology, for the cell that sorting is greatly different in size, is more used for sorting cells device.Can by preliminary for organoid sorting by differential centrifugation, often need further by density level bands centrifugal row again sorting purifying.Velocity sedimentation technology is the one in centrifugal classification technology, the cell differed in size for separating density is close or organoid.This to fall the Media density that method adopts lower, and the maximum density Should of medium is less than the minimum density being sorted biological particles.It utilizes biological particles, comprises cell or thin device reaches sorting by respective settling ratio with different velocity sedimentations in very mild density gradient medium.This method can the cell of sorting very limited, and huge centrifugal force and process is all unfavorable to cell for a long time.Maxicell is more subject to the damage of high centrifugal force than minicell, and the cell rested in isodensity medium is subject to larger damage than being in the cell in moving.Therefore, this method is suitable for sorting cells device, and is not too suitable for sorting and purifying cells.
Two, fluidic cell sorting technology art is a special kind of skill of individual cells being carried out to fast quantitative analysis and sorting.In analysis or assorting room, wrap in the nozzle that the cell in sheath fluid is controlled by HF oscillation, form the drop comprising individual cells, under the irradiation of laser beam, these cells send scattered light and fluorescence, detect Turn be changed to electrical signal through detector, send into computer disposal, export statistics, and highly purified cell subsets can be sub-elected according to these character.Though this method purity and the rate of recovery high, apparatus expensive, technical sophistication, needs professional and technical personnel to operate, during operational cost.Because what have that sample must contact reuses parts, sample cross contamination can not be avoided completely.In addition, this method requires that the treated sample number of cells that hits can not be less than hundreds of.The sample separation results few to target cell content is not good.In addition, it is also not suitable for requiring higher application to cytoactive.
Three, cell electrophoresis technology.Under certain pH value, cell surface is with clean plus or minus electric charge, and under the effect of extra electric field, swimming can occur, this phenomenon is called cell electrophoresis.Various cell or to be in the allogenic cell carrying capacity of different physiological status different, therefore mobility speed in certain electric field is different.Under constant current field condition, homocellular electrophoretic velocity quite stable, thus coming some cell types position of sorting by measuring electrophoretic velocity, therefore on diagnosing the illness, having certain values.The shortcoming of this sorting technology has damage to cytoactive, is difficult to the cell that sorting kind is close
Four, immunological magnetic bead sorting technology.Immunomagnetic beads method sorting cells can combine with the specific monoclonal antibody being connected with magnetic bead based on cell-surface antigens, in externally-applied magnetic field, the cell be connected with magnetic bead by antibody is trapped in by adsorbing in magnetic field, cell without this kind of surface antigen does not have magnetic owing to can not be combined with the specific monoclonal antibody being connected to magnetic bead, do not stop in magnetic field, thus make cell be able to sorting.This technology is strong to the resolving power of target cell, and without the need to the large-scale instrument of costliness, equipment is relatively cheap, and method is simple, is the very potential method of one.But existing size separation equipment efficiency is low, and consumptive material is more expensive, very responsive to the impurity be sorted in sample.Greatly limit its practical function.
The equipment of this technology of current employing mainly contains following several:
1, magnetic cell sorting instrument, comes from German Mei Tian Ni biotech company (MiltenyiBiotec), and it adopts the design of magnetic pipeline streaming, the less magnetic bead of general use.Very effective on this theoretical method, but be difficult to avoid oarse-grained biological tissue because be sorted in sample in actual use, the stifled match of pipeline or target cell (10) is caused to lose, so the index that the cell sorting reliability that can reach in practicality and sensitivity and producer declare has suitable distance.
2, magnetic bead catches instrument (BeadRetriever), comes from Dynal company of the U.S., and it adopts the design of magnetic post test tube type, the larger magnetic bead of general use.This method can avoid the problem of line clogging, but sensitivity is not enough, cell capture rate and purity lower, practical effect is also undesirable.
3, cell searching instrument (CallSearch), be subsidiary corporation of Johnson Co. Veridex, LLC develops recently, also adopts immunological magnetic bead sorting primary reason.Now by U.S. FDA access, being applied to prediction has the progresson free survival rate of metastatic mammary cancer, colorectal cancer or prostate cancer and total survival rate.This equipment has certain effect to cancer diagnosis.But the cell sub-elected loses activity, which has limited its range of application.
Summary of the invention
The object of the invention is to solve above-mentioned existing technological deficiency, provides a kind of better target cell capture rate high, adaptable to sample, easy and simple to handle, the magnetic probe search type cell sorting device (also known as CI cell searching instrument) that level of automation is high.
Technical solution of the present invention is: magnetic probe search type cell sorting device is made up of planer-type XYZ three axle robert device (1), mechanical manipulator digitial controller (2), support (3), body (4), magnetic probe (5), probe jig (51), test board (6), testing cassete (7) and release magnet (8)
Described magnetic probe (5) is connected on probe jig (51), probe jig (51) is placed on planer-type XYZ three axle robert device (1), mechanical manipulator digitial controller (2) connects planer-type XYZ three axle robert device (1), planer-type XYZ three axle robert device (1) is placed in testing cassete (7) top, testing cassete (7) is placed on the table top of test board (6), test board (6) is placed on body (4), body (4) is placed in support (3) top, and release magnet (8) to be placed in body (4) and to be positioned at the below of testing cassete (7);
Wherein: testing cassete is equipped with sample liquid in (7), magnetic probe (5) is installed on probe jig (51), probe jig (51) can movement in planer-type XYZ three axle robert device (1), magnetic probe (5) testing cassete (7) inner complete the suction of target cell (10) is caught after, by release magnet (8) to the suction effect of target cell (10), complete and the recovery of the target cell (10) on magnetic probe (5) is collected.
Described planer-type XYZ three axle robert device (1) comprising: X-axis servomotor (11) connects X-axis beam guideway (12), and Y-axis servomotor (13) connects the two guide rail (14) of Y-axis planer-type, and Z axis servomotor (15) connects Z axis slide block (16),
Wherein: magnetic probe (5) connects Z axis slide block (16), Z axis slide block (16) is fixed on probe jig (51), and Z axis servomotor (15) control magnetic probe (5) prolongs Z axis and slides up and down on Z axis slide block (16);
Described probe jig (51) is placed on X-axis beam guideway (12), and under the effect of X-axis servomotor (11), probe jig (51) moves horizontally on X-axis beam guideway (12);
Described X-axis beam guideway (12) is fixed on the two guide rail (14) of Y-axis planer-type, and X-axis beam guideway (12) moves horizontally under the effect of Y-axis servomotor (13) on the two guide rail (14) of Y-axis planer-type;
Described mechanical manipulator digitial controller (2) connects X-axis servomotor (11), Y-axis servomotor (13) and Z axis servomotor (15), for controlling the movement of magnetic probe (5) in body (4) inside.
Described testing cassete (7) is provided with three containers, be respectively sampling receptacle (71), clean container (72) and target cell (10) and collect container (73), sample liquid is housed in sampling receptacle (71), clean container is equipped with scavenging solution in (72), magnetic probe (5) stretches into collection adsorption target cell (10) in sampling receptacle (71) and regains afterwards, move to again and extend into cleaning DC thing (101) in clean container (72), finally collect in container (73) in target cell (10) and target cell (10) is discharged.
It is inner that described release magnet (8) is placed in body (4), is positioned at target cell (10) and collects immediately below container (73).
5. according to a kind of magnetic probe search type cell sorting device in the claims described in any one, it is characterized in that described magnetic probe (5) end also comprises an isolation outer cover (52) be removably set with, the cover mouth edge of described isolation outer cover (52) has that a circle is outward extending prolongs limit (53).
Also comprise isolation outer cover (52) handling frame, described isolation outer cover (52) handling are placed on testing cassete (7) side or are installed on the edge of body (4), isolation outer cover (52) handling mount and comprise encapsulation parts and dismounting parts, encapsulation parts and dismounting parts all have the probe draw-in groove (91) that is held magnetic probe (5), the upper end place of probe draw-in groove (91) has a spacing and is greater than isolation outer cover (52) internal diameter, is less than the baffle plate (92) prolonging limit (53) internal diameter of isolation outer cover (52)
Isolation outer cover (52) can be positioned in the draw-in groove of encapsulation parts, and that isolates outer cover (52) prolongs limit (53) card shelves on baffle plate (92);
Stretch into the magnetic probe of isolating outer cover (52) after in the draw-in groove dismantling parts, up move, the limit (53) of prolonging of isolation outer cover (52) stops by baffle plate (92), completes the dismounting isolating outer cover (52).
Also comprise discarded isolation outer cover disposable box (54), described discarded isolation outer cover disposable box (54) is placed in immediately below isolation outer cover handling frame (9).
Described magnetic probe (5) is changeable type probe, and magnetic probe (5) is permanent magnetism probe or electromagnetic probe.
Described testing cassete (7) three containers: container (73) collected by sampling receptacle (71), clean container (72) and target cell (10), has at least two groups to form side by side, meanwhile, the quantity of magnetic probe (5) and the quantity of groups of containers consistent.
Described sample liquid is blood, marrow, body fluid or the liquid containing viable cell.
The present invention is based on immune antibody magnetic cell separation principle, adopt floating magnetic field probe and the cell harvesting access panel of unique design, complete by the search of immunomagnetic beads labeled cell and acquisition procedure under the operation of computer controller efficiently fast automaticly, successfully realize the cell separation apparatus with highly sensitive height and high reliability.
Principle of work: in the liquid sample adopting planer-type XYZ three axle robert device (1) operating magnetic probe (5) to be inserted into containing target cell (10) as searching movement to realize target cell (10) sorting.The liquid sample be sorted first does immunomagnetic beads mark, then inject in the sampling receptacle (71) of testing cassete (7), when the probe with strong magnetic near target cell (10) that are labeled time, target cell (10) can be adsorbed to detecting head surface, the three coordinate robotic manipulation that magnetic probe (5) is controlled by mechanical manipulator digitial controller (2), by the whole sample of desired guiding trajectory mobile search, after having searched for, magnetic probe (5) moves in clean container (72) to wash is infected with dirt outside target cell (10), move to again in target cell (10) collection container (73) and collect being released into target cell (10) by the target cell (10) adsorbed from magnetic probe (5) in container (73) by the release magnet (8) of reverse magnetic force.Magnetic probe (5) appearance cover have the non magnetic single use can isolating sample and probe body isolate outer cover (52) with avoid magnetic probe (5) and sample contaminated.
The present invention realizes automated cell sorting by following steps:
One, the sampling receptacle (71) of testing cassete (7) will be put into by the sample liquids that immunomagnetic beads marks, cell scavenging solution is put in clean container (72), in collection container, put into cell-preservation liquid, then testing cassete (7) is put into the test board (6) of apparatus of the present invention.
Two, magnetic probe (5) moves to isolation outer cover (52) handling frame under the operation of planer-type XYZ three axle robert device (1), above encapsulation parts, aim at the isolation outer cover (52) being in probe draw-in groove (91) decline afterwards, stretch into in isolation outer cover (52), stretch back after suit, complete automatic sleeving isolation outer cover (52).
Three, magnetic probe (5) inserts in sampling receptacle (71) under the operation of planer-type XYZ three axle robert device (1), and presses along circular arc, spiral and straight path with the search target cell (10) in the XX speed sampling receptacle (71) of setting.
Four, after having searched, under the operation of planer-type XYZ three axle robert device (1), magnetic probe (5) inserts clean container (72), washing motion is made, to remove other contaminants (101) outside the target cell (10) being attached to isolation outer cover (52) outside surface along desired guiding trajectory and speed.
Five, after having cleaned, under the operation of planer-type XYZ three axle robert device (1), isolation outer cover (52) and magnetic probe (5) make suitable part lock out operation, increase the spacing of magnetic probe (5) to isolation outer cover (52) surface targets cell (10), to reduce magnetic probe (5) to the suction of target cell (10); Inserted in target cell (10) collection container (73) by magnetic probe (5) and move along desired guiding trajectory and speed, release magnet (8) effect of collecting container (73) below by being arranged on target cell (10) is released into collection container by being attached to target cell (10) absorption isolating outer cover (52) outside surface.
Six, after having discharged, under the operation of planer-type XYZ three axle robert device (1), magnetic probe (5) enters the dismounting parts place in isolation outer cover (52) handling frame, stretch into the magnetic probe (5) of isolating outer cover (52) after in the draw-in groove dismantling parts, up move, the limit (53) of prolonging of isolation outer cover (52) stops by baffle plate (92), completes the dismounting of isolation outer cover (52), isolation outer cover (52) and magnetic probe (5) sorting completely.
Above step realizes the assorting room of target cell (10).Actual measurement shows, the present invention can obtain high cell sorting purity, and has high cellular resolution, can sub-elect a unique target cell (10) from billions of cell fast.Therefore the present invention has great using value.
Apparatus of the present invention achieve the multinomial advantage that existing cell separation technology equipment does not possess, and comprise easy and simple to handle, and be separated fast, use cost is cheap.
Accompanying drawing explanation
Fig. 1: magnetic probe search type cell sorting device schematic diagram.
Fig. 2: testing cassete structural representation.
Fig. 3: magnetic probe structural representation.
Fig. 4 and isolation outer cover scheme of installation.
Fig. 5: load isolation outer cover schematic diagram.
Fig. 6: be separated isolation outer cover schematic diagram.
Fig. 7: acquisition target cell schematic diagram in sampling receptacle.
Fig. 8: clean target cell schematic diagram in clean container.
Fig. 9: target cell is collected in container and discharges target cell schematic diagram.
Figure 10: target cell capture rate statistics figure.
Figure 11: captured target cell Photomicrograph.
Figure 12: magnetic probe search type cell sorting device for carrying out said structure front view.
Figure 13: magnetic probe search type cell sorting device for carrying out said structure side view.
Wherein: 1-planer-type XYZ three axle robert device, 11-X-axis servomotor, 12-X-axis beam guideway, 13-Y-axis servomotor, the two guide rail of 14-Y-axis planer-type, 15-Z axis servomotor, 16-Z axis slide block,
2-mechanical manipulator digitial controller, 3-support, 4-body,
5-magnetic probe, 51-probe jig, 52-isolation outer cover, 53-prolong limit, 54-discarded isolation outer cover disposable box,
6-test board,
7-testing cassete, 71-sampling receptacle, 72-clean container, 73-target cell collects container,
8-release magnet,
9-isolation outer cover handling frame, 91-probe draw-in groove, 92-baffle plate,
10-target cell, 101-contaminant.
Embodiment
Sorting unit of the present invention is shown in Fig. 1, Figure 11 and Figure 12.Comprise and being made up of planer-type XYZ three axle robert device 1, mechanical manipulator digitial controller 2, support 3, body 4, magnetic probe 5, probe jig 51, test board 6, testing cassete 7 and release magnet 8,
Magnetic probe 5 is connected on probe jig 51, probe jig 51 is placed on planer-type XYZ three axle robert device 1, mechanical manipulator digitial controller 2 connects planer-type XYZ three axle robert device 1, planer-type XYZ three axle robert device 1 is placed in above testing cassete 7, testing cassete 7 is placed on the table top of test board 6, test board 6 is placed on body 4, and body 4 is placed in above support 3, and release magnet 8 to be placed in body 4 and to be positioned at the below of testing cassete 7;
X-axis servomotor 11 connects X-axis beam guideway 12, and Y-axis servomotor 13 connects the two guide rail 14 of Y-axis planer-type, and Z axis servomotor 15 connects Z axis slide block 16,
Wherein: magnetic probe 5 connects Z axis slide block 16, Z axis slide block 16 is fixed on probe jig 51, and Z axis servomotor 15 controls magnetic probe 5 and on Z axis slide block 16, prolongs Z axis slide up and down;
Described probe jig 51 is placed on X-axis beam guideway 12, and under the effect of X-axis servomotor 11, probe jig 51 moves horizontally on X-axis beam guideway 12;
Described X-axis beam guideway 12 is fixed on the two guide rail 14 of Y-axis planer-type, and X-axis beam guideway 12 moves horizontally under the effect of Y-axis servomotor 13 on the two guide rail 14 of Y-axis planer-type;
Described mechanical manipulator digitial controller 2 connects X-axis servomotor 11, Y-axis servomotor 13 and Z axis servomotor 15, for controlling the movement of magnetic probe 5 in body 4 inside.
Testing cassete 7 is provided with two groups of three containers, be respectively two sampling receptacles, 71, two clean containers 72 and target cell 10 collects container 73, be equipped with in two sampling receptacles 71 in sample liquid, clean container 72 and scavenging solution is housed, slide block is equipped with probe jig 51, two magnetic probes 5 are installed.Concrete implementation and operation step is as follows: 1, operator will be placed with 2 ~ 10 milliliters of human peripheral blood cell's sample liquid to be measured of cultivating through magnetic bead, after the testing cassete 7 of cell scavenging solution and cell culture fluid is positioned over test board 6 fixed position, start automatic target cell 10 assorting room by controlling computer command mechanical manipulator digitial controller 2.
Automatic sorting process is by loading isolation outer cover 52, magnetic probe 5 is moved to the cleaning being placed in isolation outer cover handling frame 9 and isolates directly over outer cover 52 by mechanical manipulator, accurately magnetic probe 5 is inserted isolation outer cover 52, isolation outer cover 52 endoporus and magnetic probe 5 closely fit, magnetic probe 5 moves up and isolation outer cover 52 is pulled away in the lump isolation outer cover handling frame 9, and it is complete that isolation outer cover 52 loads step.See Fig. 5.
The magnetic probe 5 that isolation outer cover 52 is housed moves to above sampling receptacle 71 by mechanical manipulator, slow insertion is equipped with in the sampling receptacle 71 of sample solution, then move magnetic probe 5 in the horizontal direction with 2 mm/second, magnetic probe 5 motion track covers whole sampling receptacle 71 surface-area.Magnetic probe 5 translational speed is by amendment mechanical manipulator digitial controller 2 parameter change.In slow moving process, neighbouring target cell 10 is adsorbed onto isolation outer cover 52 surface by the powerful magnetic field of magnetic probe 5 end.To be sought complete, magnetic probe 5 slowly moves up and leaves sample solution.Now isolate outer cover 52 surface and have captured target cell 10 and a small amount of contaminant 101.See Fig. 6.
In order to improve the purity of sorting cells, next needing to carry out cleaning step: probe moves to above clean container 72 by mechanical manipulator, slowly inserts cleaning solution, then making washing motion in the horizontal direction with the speed of 4 ~ 10 mm/second.Magnetic probe 5 translational speed is slightly faster than catching step, to reach the effect of the contaminant 101 of cleaning non-target cell 10.Cleaning translational speed is also by amendment mechanical manipulator digitial controller 2 parameter change.In moving process, target cell 10 is firmly adsorbed by the powerful magnetic field of magnetic probe 5 end, is not subject to washing away of scavenging solution by the contaminant 101 of marked by magnetic bead and departs from isolation outer cover 52 surface.Cleaning process terminated after two minutes, and magnetic probe 5 again slowly moves up and leaves cleaning solution.A small amount of contaminant 101 of now isolating outer cover 52 surface is removed.See Fig. 7.
Next just can discharge captured target cell 10 collects container 73 to target cell 10.In order to the target cell 10 being adsorbed on isolation outer cover 52 surface being discharged, in this device, magnetic probe 5 will be moved to isolation outer cover 52 and to load and unload on frame and in a probe draw-in groove 91, isolation outer cover 52 is made part and be separated, to reduce the magnetic attracting force of popping one's head in target cell 10 by mechanical manipulator.Then, magnetic probe 5 is moved to target cell 10 and collects above container 73 by mechanical manipulator, inserts target cell 10 and collects in the cell culture fluid in container 73.Immediately below target cell 10 collection container, be provided with powerful magnet release magnet 8, release magnet 8 has stronger magnetism to the target cell 10 being adsorbed on isolation outer cover 52 surface.Target cell 10, under the effect of the magnetic force of release magnet 8, departs from isolation outer cover 52, sinks to collection container bottom.Dispose procedure terminated after one minute, and magnetic probe 5 moves up and leaves collection container, sees Fig. 8.
For avoiding sample cross contamination, isolation outer cover 52 only makes a one-time use only, after target cell 10 in a sample is discharged, in the probe draw-in groove 91 that in this device, magnetic probe 5 will move on dismounting parts that isolation outer cover 52 loads and unloads on frame by mechanical manipulator, isolation outer cover 52 is separated completely, stretch into the magnetic probe 5 of isolating outer cover 52 after in the draw-in groove dismantling parts, up move, the limit 53 of prolonging of isolation outer cover 52 stops by baffle plate 92, completes the dismounting of isolation outer cover 52.Isolation outer cover 52 after separation falls into isolation outer cover 52 and collects box wait regularly removing.See Fig. 5.
Robot actions has been popped one's head in after above step and has been automatically reset, and completes with sound prompt operator cell sorting process, can take out testing cassete 7 pairs of target cell 10 process for further analysis.
By showing the actual test that the former blood containing human circulation tumour cell CTC does on this device, the inventive method can reach the capture rate of more than 90%, sees Fig. 9.Whole point of selection operation required time is less than 30 minutes.Further experiment also shows, this contrive equipment has and mixing the sensitivity of catching a unique circulating tumor cell in the former blood of cell containing billions of, and not by the interference of the impurity such as macrobead.Captured cytoactive is good, still has division and proliferation ability, sees Figure 10.
This device contrasts with existing cell sorting method described in background technology, has target cell 10 capture rate high, adaptable to sample, easy and simple to handle, the remarkable advantage that level of automation is high, to cancer diagnosis, drug test and biomass cells correlative study have obvious practical value.

Claims (1)

1. a magnetic probe search type cell sorting device, it is characterized in that being made up of planer-type XYZ three axle robert device (1), mechanical manipulator digitial controller (2), support (3), body (4), magnetic probe (5), probe jig (51), test board (6), testing cassete (7) and release magnet (8)
Described magnetic probe (5) is connected on probe jig (51), probe jig (51) is placed on planer-type XYZ three axle robert device (1), mechanical manipulator digitial controller (2) connects planer-type XYZ three axle robert device (1), planer-type XYZ three axle robert device (1) is placed in testing cassete (7) top, testing cassete (7) is placed on the table top of test board (6), test board (6) is placed on body (4), body (4) is placed in support (3) top, and release magnet (8) to be placed in body (4) and to be positioned at the below of testing cassete (7);
Wherein: testing cassete is equipped with sample liquid in (7), magnetic probe (5) is installed on probe jig (51), probe jig (51) can movement in planer-type XYZ three axle robert device (1), magnetic probe (5) testing cassete (7) inner complete the suction of target cell (10) is caught after, by release magnet (8) to the suction effect of target cell (10), complete and the recovery of the target cell (10) on magnetic probe (5) is collected;
Described planer-type XYZ three axle robert device (1) comprising: X-axis servomotor (11) connects X-axis beam guideway (12), and Y-axis servomotor (13) connects the two guide rail (14) of Y-axis planer-type, and Z axis servomotor (15) connects Z axis slide block (16),
Wherein: magnetic probe (5) connects Z axis slide block (16), Z axis slide block (16) is fixed on probe jig (51), and Z axis servomotor (15) control magnetic probe (5) prolongs Z axis and slides up and down on Z axis slide block (16);
Described X-axis beam guideway (12) is fixed on the two guide rail (14) of Y-axis planer-type, and X-axis beam guideway (12) moves horizontally under the effect of Y-axis servomotor (13) on the two guide rail (14) of Y-axis planer-type;
Described mechanical manipulator digitial controller (2) connects X-axis servomotor (11), Y-axis servomotor (13) and Z axis servomotor (15), for controlling the movement of magnetic probe (5) in body (4) inside;
Described testing cassete (7) is provided with three containers, be respectively sampling receptacle (71), clean container (72) and target cell (10) and collect container (73), sample liquid is housed in sampling receptacle (71), clean container is equipped with scavenging solution in (72), magnetic probe (5) stretches into collection adsorption target cell (10) in sampling receptacle (71) and regains afterwards, move to again and extend into cleaning DC thing (101) in clean container (72), finally collect in container (73) in target cell (10) and target cell (10) is discharged;
Described magnetic probe (5) end also comprises an isolation outer cover (52) be removably set with, and the cover mouth edge of described isolation outer cover (52) has that a circle is outward extending prolongs limit (53);
Described probe jig (51) is placed on X-axis beam guideway (12), and under the effect of X-axis servomotor (11), probe jig (51) moves horizontally on X-axis beam guideway (12).
2. a kind of magnetic probe search type cell sorting device according to claim 1, is characterized in that described release magnet (8) is placed in body (4) inner, is positioned at target cell (10) and collects immediately below container (73).
3. a kind of magnetic probe search type cell sorting device according to claim 1, characterized by further comprising isolation outer cover (52) handling frame, described isolation outer cover (52) handling are placed on testing cassete (7) side or are installed on the edge of body (4), isolation outer cover (52) handling mount and comprise encapsulation parts and dismounting parts, encapsulation parts and dismounting parts all have the probe draw-in groove (91) that is held magnetic probe (5), the upper end place of probe draw-in groove (91) has a spacing and is greater than isolation outer cover (52) internal diameter, be less than the baffle plate (92) prolonging limit (53) internal diameter of isolation outer cover (52),
Isolation outer cover (52) can be positioned in the draw-in groove of encapsulation parts, and that isolates outer cover (52) prolongs limit (53) card shelves on baffle plate (92);
Stretch into the magnetic probe of isolating outer cover (52) after in the draw-in groove dismantling parts, up move, the limit (53) of prolonging of isolation outer cover (52) stops by baffle plate (92), completes the dismounting isolating outer cover (52).
4. a kind of magnetic probe search type cell sorting device according to claim 1, characterized by further comprising discarded isolation outer cover disposable box (54), described discarded isolation outer cover disposable box (54) is placed in immediately below isolation outer cover handling frame (9).
5. a kind of magnetic probe search type cell sorting device according to claim 1, it is characterized in that described magnetic probe (5) is for changeable type probe, magnetic probe (5) is permanent magnetism probe or electromagnetic probe.
6. a kind of magnetic probe search type cell sorting device according to claim 1, it is characterized in that described testing cassete (7) three containers: sampling receptacle (71), clean container (72) and target cell (10) collect container (73), two groups are had at least to form side by side, meanwhile, the quantity of magnetic probe (5) and the quantity of groups of containers consistent.
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CN106092174A (en) * 2016-08-24 2016-11-09 北京主导时代科技有限公司 A kind of carrier localization method based on sensor technology and positioner
CN106841037A (en) * 2017-03-14 2017-06-13 骏实生物科技(上海)有限公司 A kind of magnetisable material captures analytical equipment and its application
CN109971615B (en) * 2019-04-24 2022-06-03 重庆工商大学 Device for assembling cell microcarrier through magnetic guidance
CN110919634B (en) * 2019-12-12 2023-02-07 重庆工商大学 Device for enhancing magnetic induction intensity by arranging permanent magnets in tree root-shaped multi-layer manner

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN202011883U (en) * 2007-12-12 2011-10-19 里兰斯坦福初级大学理事会 Device for capturing and separating target cell
CN102435726A (en) * 2010-09-23 2012-05-02 财团法人工业技术研究院 Chemical or biochemical analysis device and chemical or biochemical analysis method
CN102564920A (en) * 2010-10-29 2012-07-11 索尼公司 Cell sorter and cell sorting method
CN102690786A (en) * 2012-06-05 2012-09-26 武汉格蓝丽富科技有限公司 Cell enriching, separating and extracting method and instrument and single cell analysis method

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN202011883U (en) * 2007-12-12 2011-10-19 里兰斯坦福初级大学理事会 Device for capturing and separating target cell
CN102435726A (en) * 2010-09-23 2012-05-02 财团法人工业技术研究院 Chemical or biochemical analysis device and chemical or biochemical analysis method
CN102564920A (en) * 2010-10-29 2012-07-11 索尼公司 Cell sorter and cell sorting method
CN102690786A (en) * 2012-06-05 2012-09-26 武汉格蓝丽富科技有限公司 Cell enriching, separating and extracting method and instrument and single cell analysis method

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