CN109107621A - Cancer cell separator and control system based on cells deformation amount and dielectrophoretic force - Google Patents
Cancer cell separator and control system based on cells deformation amount and dielectrophoretic force Download PDFInfo
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Abstract
The invention discloses a kind of cancer cell separator and control system based on cells deformation amount and dielectrophoretic force, the device include cell liquid storage device, injection Micropump；One end of injection Micropump is protruded into cell liquid storage device, and the other end is connected with the arrival end of cells deformation amount detection chip；The outlet end of cells deformation amount detection chip is connected with the ameboid cell arrival end of cancer cell separating chips；CMOS high-speed camera, which is arranged under cells deformation amount detection chip, captures ameboid cell image；Processor determines the deformation quantity of ameboid cell according to the ameboid cell image of acquisition, and determine whether the ameboid cell is cancer cell according to this deformation quantity, if then processor output drive signal driving electrodes generate the cancer cell outlet end that dielectrophoretic force makes ameboid cell flow to cancer cell separating chips.With the application of the invention, the deformation quantity of cell can be detected quickly, and cancer cell is separated from patient blood sample according to cancer cell is different from normal cell deformation quantity.
Description
Technical field
It is the present invention relates to cell sorting separation technology field, in particular to a kind of based on cells deformation amount and dielectrophoretic force
Cancer cell separator and control system.
Background technique
Cancer is a kind of major disease for seriously endangering human health, and morbidity and mortality become in what is risen year by year
Gesture.For the cell of identical source, the cell that canceration occurs is softer than normal cell, it is easier to be deformed, it is easier to cancer
It shifts.For a long time, mechanical phenotype have always been considered as be the changes of function of physiology and pathological origin in quantization cell nothing
Labeling method.This method is verified under cell differentiation and the background of pernicious transfer, and has been expedited the emergence of many bases and ground
Study carefully the development of method.Wherein, the change of single celled morphotropism can be used as a kind of important indicator of biological study.Relative to
Biomolecular labeling object, the index of this unmarked deformability do not need some pre-treatment steps such as dyeing, antibody processing,
More operating costs can be saved.
For cell during canceration, the deformation properties of cell just have occurred that variation.In the different canceration stages
Cell, deformability are different.This shows the rigidity by measuring cell, however, it would be possible to distinguish and be in different canceration journeys
The cell of degree, this provides a kind of possibility for occurrence and development of the monitoring cancer before invasion to invasion.The morphotropism of cell can be with
As the sensitive labels of cell carcinogenesis, therefore cell rigidity is measured with important clinical meaning.Current detecting cell morphotropism
Method mainly have Atomic Force Microscopy, means of micropipette aspiration technique, cell impression, laser diffractometry, fluid shearing method etc..This
A little measurement methods respectively have advantage and disadvantage, if micropipette aspiration method is one of current research common method of cyto-mechanics, but this side
Method can only once reflect individual cells morphotropism, and detection rates are low (10-100 cell/h), be not suitable for clinical application；And atom
Force microscope method is complicated for operation, and equipment is expensive, and detection rates are equally very low.Therefore a kind of cancer cell deformation of high throughput is designed
The method of amount be very it is necessary to.The rigidity of high throughput detection diseased region cell, not only may determine that patient is in cancer
Stage, and cell can be separated according to the difference of cell rigidity.
Although detect cells deformation amount method it is very much, these methods only detect the rigidity of cell, do not consider by
The foundation that this unmarked feature of cell is separated as cancer cell.Deformability signature based on cell is as separation mark pair
Have great potential significance in the research and diagnosis of cancer, can be used for cancer by stages, recurrence detection, cancer drug resistance molecule
Analysis etc..
Currently, consuming time is long, the sample size of low yield, needs for existing cell separation technology such as centrifugal process and filtration method
Greatly, be not suitable for the analysis of micro precious sample；Method based on antibody can obtain certain types of cell and but need complexity
Treatment process.Nowadays, the microchannel of micro-fluidic chip narrows down to micron order, can accurately manipulate the fluid of minute yardstick, sample with
And the consumption of reagent is substantially reduced, the reaction time greatly shortens, and is very suitable to cell separation.With microflow control technique
Development, dielectrophoretic force technology are introduced on micro-fluidic chip, the separation and manipulation for particle, drop and cell.For
For dielectrophoretic force technology, by making particle generate polarization phenomena in inhomogeneous field, driven under the action of dielectrophoretic force
Make cell movement.The size of dielectrophoretic force is proportional to the size for the particle being manipulated, according to different cells in micro-fluidic chip
In suffered dielectrophoretic force difference, to realize separation to cell.Micro-fluidic chip based on dielectrophoretic force is for cell
Separation has many advantages, such as, firstly, not needing dyeing or antibody processing；Secondly, good biocompatibility, will not generate damage to cell
Wound；Finally, the voltage of electric field and the suffered dielectrophoretic force of frequency shift cell can be applied by adjusting convenient for control, because
This separates relatively flexibly cell.
Although the separation method based on dielectrophoretic force has many advantages, such as, but cannot separate specific objective according to marker
Cell.
Summary of the invention
The object of the present invention is to provide a kind of cancer cell separator based on cells deformation amount and dielectrophoretic force and controls
System, can quickly detect the deformation quantity of cell, and according to cancer cell it is different from normal cell deformation quantity by cancer cell from disease
It is separated in human blood sample.
To achieve the above object, the present invention provides following schemes:
A kind of cancer cell separator based on cells deformation amount and dielectrophoretic force, the cancer cell separator include thin
Born of the same parents' liquid storage device, injection Micropump, LED light, cells deformation amount detection chip, cancer cell separating chips, CMOS high-speed camera and
Processor；
Cell suspending liquid is placed in the cell liquid storage device；The cell suspending liquid is cell to be detected；
One end of the injection Micropump is protruded into the cell liquid storage device, and the other end of the injection Micropump passes through polymer
Pipe is connected with the arrival end of the cells deformation amount detection chip；The outlet end of the cells deformation amount detection chip and the cancer
The ameboid cell arrival end of cell separation chip is connected；The cancer cell separating chips are additionally provided with sheath stream arrival end, normal cell
Outlet end and cancer cell outlet end；
The LED light is arranged in the cells deformation amount detection chip and in the cells deformation amount detection chip
Ameboid cell is irradiated, and the CMOS high-speed camera is arranged under the cells deformation amount detection chip and to the cell
Ameboid cell in deformation quantity detection chip is shot；
The input terminal of the processor is connect with the CMOS high-speed camera, the output end of the processor and the cancer
Electrode connection in cell separation chip.
Optionally, the cells deformation amount detection chip includes the first substrate of glass and the cover plate containing miniature channel；Institute
Miniature channel is stated successively to include first passage, shrink channel and second channel；The cross section for shrinking channel is square；Institute
The size for stating the cross section in contraction channel is 25 μm * 25 μm；The diameter of the first passage and the second channel is
1.5mm。
Optionally, the length in the miniature channel is 5mm.
Optionally, the cancer cell separating chips include the second substrate of glass and the cover plate containing microchannel；Described micro-
The electrode of multiple dentalations is inlayed in the inner wall side in channel, and the polarity of adjacent electrode is opposite；The dielectric that the electrode generates
Swimming power acts on the ameboid cell in the microchannel.
Optionally, a height of 60 μm of the microchannel, the width of the microchannel are 3mm；Second substrate of glass
With a thickness of 500 μm.
Optionally, the electrode is then led to by sputtering at the platinum electrode of 200nm thickness on the titanium adhesive layer of 20nm thickness
It is formed after crossing removing patterning.
Optionally, one layer of electrode upper berth porous hydrogel glue-line.
Optionally, the cancer cell separator further includes interface channel；The outlet of the cells deformation amount detection chip
End is connected by the interface channel with the ameboid cell arrival end of the cancer cell separating chips.
Optionally, the injection Micropump is for providing driving force.
The present invention also provides a kind of the cancer cell separation control system based on cells deformation amount and dielectrophoretic force, the cancer
Cell separation control system includes:
The CMOS high-speed camera is used to capture the ameboid cell image in cells deformation amount detection chip；
The processor includes processing module and judgment module；
The processing module is connect with the CMOS high-speed camera, for obtaining the ameboid cell image, and to institute
It states ameboid cell image to be handled, determines the deformation quantity of ameboid cell；
The judgment module is connect with the electrode, for judging whether the deformation quantity of the ameboid cell is greater than in advance
It is stored in the given threshold of the processor, and the output driving when the deformation quantity of the ameboid cell is greater than the given threshold
The driving signal is transmitted to the electrode to drive the electrode to generate dielectrophoretic force and flow to the ameboid cell by signal
The cancer cell outlet end of cancer cell separating chips；When the deformation quantity of the ameboid cell is less than or equal to the given threshold
Not output drive signal, the ameboid cell flow to the normal cell outlet end of the cancer cell separating chips；The setting threshold
Value is the cut off value of normal cells deformation amount and cancer cell deformation quantity.
The specific embodiment provided according to the present invention, the invention discloses following technical effects:
The present invention provides a kind of cancer cell separator and control system based on cells deformation amount and dielectrophoretic force, should
Device includes the interior cell liquid storage device for placing cell suspending liquid, injection Micropump；One end of injection Micropump is protruded into cell liquid storage device,
The other end is connected with the arrival end of cells deformation amount detection chip；The outlet end of cells deformation amount detection chip is separated with cancer cell
The ameboid cell arrival end of chip is connected；It is thin that cancer cell separating chips are additionally provided with sheath stream arrival end, normal cell outlet end and cancer
Born of the same parents outlet end；LED light is arranged in cells deformation amount detection chip；The setting of CMOS high-speed camera detects core in cells deformation amount
Piece gets off to capture the ameboid cell image in cells deformation amount detection chip；The input terminal and CMOS high-speed camera of processor connect
It connects, the output end of processor is connect with the electrode of cancer cell separating chips；The processor is true according to the ameboid cell image of acquisition
Determine the deformation quantity of ameboid cell, and determine whether the ameboid cell is cancer cell according to the deformation quantity of ameboid cell, if then locating
Reason device output drive signal driving electrodes, which generate dielectrophoretic force, makes ameboid cell flow to cancer cell outlet end.With the application of the invention, energy
The deformation quantity of enough quickly detection cells, and according to cancer cell it is different from normal cell deformation quantity by cancer cell from patient blood sample
It is separated in this.
Detailed description of the invention
It in order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, below will be to institute in embodiment
Attached drawing to be used is needed to be briefly described, it should be apparent that, the accompanying drawings in the following description is only some implementations of the invention
Example, for those of ordinary skill in the art, without creative efforts, can also obtain according to these attached drawings
Obtain other attached drawings.
Fig. 1 is the structural representation of cancer cell separator of the embodiment of the present invention based on cells deformation amount and dielectrophoretic force
Figure；
Fig. 2 is the structural schematic diagram of cells deformation amount detection chip of the present invention and the partial enlarged view for shrinking channel；
Fig. 3 is the structural schematic diagram of cancer cell shape separating chips of the present invention.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
Since the morphotropism of cell can be used as the identification that a kind of unmarked method is used for cancer cell, the present invention is provided
A kind of cancer cell separator and control system based on cells deformation amount and dielectrophoretic force, in detection sample deformability deformability of cells
While according to the difference of cancer cell and the deformation quantity of normal cell, cancer cell is separated from sample.
To keep above-mentioned purpose of the invention, feature and advantage more obvious and easy to understand, with reference to the accompanying drawing and have
The present invention is described in further detail for body embodiment.
Fig. 1 is the structural representation of cancer cell separator of the embodiment of the present invention based on cells deformation amount and dielectrophoretic force
Figure.
As shown in Figure 1, the cancer cell separator provided in an embodiment of the present invention based on cells deformation amount and dielectrophoretic force
Including injecting Micropump 1, polymer pipe 2, LED light 3, cancer cell separating chips 5, cell liquid storage device 7, cells deformation amount detection chip
8, CMOS high-speed camera 9, interface channel 10 and processor 11；The cancer cell separating chips 5 are equipped with ameboid cell entrance
End 13, sheath stream arrival end 4, cancer cell outlet end 6 and normal cell outlet end 12.
Cell suspending liquid is placed in the cell liquid storage device 7；The cell suspending liquid is cell to be detected.
One end of the injection Micropump 1 is protruded into the cell liquid storage device 7, and the other end of the injection Micropump 1 passes through institute
Polymer pipe 2 is stated to be connected with the arrival end of the cells deformation amount detection chip 8；The cells deformation amount detection chip 8 goes out
Mouth end passes through the ameboid cell arrival end 13 of interface channel 10 and the cancer cell separating chips 5.
The LED light 3 is arranged in the cells deformation amount detection chip 8 and to the cells deformation amount detection chip 8
Interior ameboid cell is irradiated, and the CMOS high-speed camera 9 is arranged under the cells deformation amount detection chip 8 and to institute
The ameboid cell stated in cells deformation amount detection chip 8 is shot.
The input terminal of the processor 11 is connect with the CMOS high-speed camera 9, the output end of the processor 11 with
Electrode connection in the cancer cell separating chips 5.
The injection Micropump 1 provides driving force: the injection Micropump 1 is mounted on the entrance of cells deformation amount detection chip 8
End outside, is connected by polymer pipe 2 with the arrival end of cells deformation amount detection chip 8, guarantees leakproofness and biocompatibility.
Cell suspending liquid configured in cell liquid storage device 7 is entered in cells deformation amount detection chip 8 by pressure-driven, and is driven
Cell suspending liquid flows in the miniature channel of cells deformation amount detection chip 8.
Fig. 2 be cells deformation amount detection chip of the present invention structural schematic diagram and contraction channel partial enlarged view, such as
Shown in Fig. 2, the cells deformation amount detection chip 8 includes that the first substrate of glass and the cover plate containing miniature channel, the two pass through
Plasma treatment is bonded after five minutes；The miniature channel successively includes first passage, shrinks channel and second channel；The receipts
The cross section in contracting channel is square, it is described shrink channel cross section size be 25 μm * 25 μm, this design primarily to
Guarantee that the size of cell accounts for the 50%-90% of miniature channel size, guarantees that the same time only allows to pass through individual cells.Described
The diameter of one channel and the second channel is 1.5mm.The length in the miniature channel is 5mm.Miniature channel uses poly- two
Methylsiloxane (PDMS) material, and standard photolithography process is prepared.
Cell suspending liquid enters miniature channel by the arrival end of cells deformation amount detection chip 8, is shrinking Air conduct measurement
Cells deformation amount is finally flowed out from the outlet end of cells deformation amount detection chip 8.When cell flows through contraction channel, pass through shearing
Stress and barometric gradient and deform.
9 real-time capture ameboid cell image of CMOS high-speed camera, and ameboid cell image is sent to processor 11.It is logical
Contour area and perimeter that the algorithm write in advance in processor 11 obtains cell when cell flows through miniature channel are crossed, calculates and becomes
The deformation quantity of shape cell.The critical value of deformation quantity is stored in advance in processor 11, as the foundation of next step cancer cell separation, such as
Detect that the deformation quantity of cell is greater than critical dimension in fruit sample, otherwise 11 output drive signal of processor does not have.
Fig. 3 is the structural schematic diagram of cancer cell shape separating chips of the present invention, as shown in figure 3, the cancer cell separating chips 5
Including the second substrate of glass and contain the cover plate of microchannel.A height of 60 μm of microchannel, width 3mm.Second substrate of glass
With a thickness of 500 μm.The material of the microchannel of cancer cell separating chips 5 still uses dimethyl silicone polymer (PDMS).
The preparation process of microchannel are as follows: standard photolithography process is used, by constructing the SU-8 layer of 20 μ m-thicks, in top of electrodes
Generate microchannel.
It is inlaid with the electrode of multiple dentalations, and positive and negative electrode arranged crosswise in microchannel interior walls side, for micro-
Dielectrophoretic force is generated in channel；The dielectrophoretic force that the electrode generates acts on the ameboid cell in the microchannel.
Electrode in the microchannel wall of cancer cell separating chips 5 is platinum, and platinum is a kind of inert metal, when doing electrode
Itself is simultaneously not involved in electrode reaction.
It, in this way can be to avoid ameboid cell and electricity in one layer of platinum electrode upper berth porous hydrogel glue-line in order not to damaging cells
It is contacted between pole.
The preparation process of electrode are as follows: the platinum electrode of 200nm thickness is sputtered on the titanium adhesive layer of 20nm thickness, and pass through removing
Further patterning, ultimately forms electrode.
There are two entrances and two outlets respectively for cancer cell separating chips 5, wherein ameboid cell arrival end 13 and cell shape
The outlet end of variable detection chip 8 is connected, and sheath stream arrival end 4 is then passed through the suspension (sheath stream) without containing cell, in fluid force
Guarantee that cell suspending liquid remains at the side of the microchannel wall containing electrode under effect, is easy the work by dielectrophoretic force
With.Two outlets are respectively cancer cell outlet end 6 and normal cell outlet end 12.
After above-mentioned cancer cell deformation quantity detection, a specific deformation quantity data can be obtained to each cell；According to
The deformation quantity of the critical value of the deformation quantity of setting, cancer cell can be more than critical value, and at this moment processor 11 will generate a pulse
Signal (driving signal) is sent to electrode, so that it is generated dielectrophoretic force driving cancer cell and shifts to cancer cell outlet end 6；Normal cell
Deformation quantity be less than critical value, processor 11 will not generate pumping signal, and normal cell flows to normal cell along flow velocity direction
Outlet end 12.
The use process of device provided in an embodiment of the present invention are as follows:
Cell liquid storage device 7 places cell suspending liquid first, and injection Micropump 1 is connected to cells deformation amount by polymer pipe 2
In detection chip 8；Cell enters cells deformation amount detection chip 8, CMOS high-speed camera under the pressure effect of injection Micropump 1
9 obtain the strain image of cell in real time, and processor 11 carries out image analysis at the same time, and the deformation quantity of cell is calculated；Carefully
After the detection of born of the same parents' deformation quantity, cell suspending liquid enters cancer cell separating chips 5 by interface channel 10；The cancer that deformation quantity is met the requirements
Cell meeting trigger electrode work, cancer cell shifts to cancer cell outlet end 6 under the action of dielectrophoretic force, and normal cell is in nature
Normal cell outlet end 12 is flowed under state.
Embodiment two
The embodiment of the invention provides a kind of cancer cell separation control system based on cells deformation amount, the separation of this cancer cell
For control system on the device that embodiment one provides, the cancer cell separation control system includes: that the CMOS high speed is taken the photograph
Camera 9 is used to capture the ameboid cell image in cells deformation amount detection chip 8.
The processor 11 includes processing module and judgment module.
The processing module is connect with the CMOS high-speed camera 9, for obtaining the ameboid cell image, and it is right
The ameboid cell image is handled, and determines the deformation quantity of ameboid cell.
The judgment module is connect with the electrode, for judging whether the deformation quantity of the ameboid cell is greater than in advance
It is stored in the given threshold of the processor, and the output driving when the deformation quantity of the ameboid cell is greater than the given threshold
The driving signal is transmitted to the electrode to drive the electrode to generate dielectrophoretic force and flow to the ameboid cell by signal
The cancer cell outlet end 6 of cancer cell separating chips 5；When the deformation quantity of the ameboid cell is less than or equal to the given threshold
When output drive signal, the ameboid cell do not flow to the normal cell outlet end 12 of the cancer cell separating chips 5；It is described to set
Determine the cut off value that threshold value is normal cells deformation amount and cancer cell deformation quantity.
Embodiment three
Separation method is carried out to it the embodiment of the invention provides measurement cancer cell deformation quantity and based on dielectrophoretic force technology,
The specific implementation steps are as follows:
A, the preparation of cell: getting out the blood sample for needing to detect in advance, and sample is centrifuged 5min at 115g, then weighs
It is newly suspended in phosphate buffer (PBS), so that the final concentration of cell is 106Cells/mL, detection only needs 100 μ L every time
Cell suspending liquid is just met the requirements.Isotonic solution is configured, the conductivity 0.55S/m of cell suspending liquid when making to test.It is inciting somebody to action
For cell suspending liquid before the injection Micropump 1 that cell liquid storage device 7 sucks 1mL, cell suspending liquid, which will be placed at 37 DEG C, keeps thin
Cytoactive.
B, experimental provision prepares: by being rinsed with ethyl alcohol (70%) and deionized water come thorough clean injectors Micropump 1, being gathered
Close the channel of property management 2 and cells deformation amount detection chip 8, cell separation chip 5.Before the start of the measurement, flow is constant
Stablize 2min under flow velocity.All data acquisitions are all to reach the contraction position of 300 μm long of stable state in cell shape
What rear portion carried out.9 running parameter of CMOS high-speed camera be set as the time for exposure be 1 μ s, work frame number be 4000f.p.s, sense
Interest region is 250*80pixels.
C, when working, injection Micropump 1 maintains cell diluent flow velocity in 0.04 μ L/s.Cell suspending liquid is in injection Micropump 1
Driving under pass through polymer pipe 2 enter cells deformation amount detection chip 8.The miniature channel of cells deformation amount detection chip 8
The LED light 3 for shrinking the ameboid cell high power pulsed ion beams in channel is irradiated, and with CMOS high-speed camera 9 to becoming in miniature channel
Cell is imaged.It is obscured to reduce cell by image when miniature passages shrink hole, controls LED using pulse current
Lamp 3 illuminates sample, and the shutter trigger pulse of CMOS high-speed camera 9 is to ensure synchronous image exposure.
D, each frame image for obtaining CMOS high-speed camera 9 is converted to grayscale image.Then processor 11 is according to cell
Threshold process is carried out with the degree of background, Canny marginalisation extraction is carried out, obtains the profile of ameboid cell, finally calculate deformation
The contour area and perimeter of cell, determine the deformation quantity of ameboid cell.
E, corresponding deformation quantity is obtained from each cell that cells deformation amount detection chip 8 flows out.According to different thin
The difference of born of the same parents system cancerous tumor cell deformation quantity sets the critical value of normal cell and cancerous tumor cell deformation quantity, thin as next step cancer
The judgment basis of born of the same parents' separation.
F, when detecting that the deformation quantity of cell in sample is greater than isolated critical value at cells deformation amount detection chip 8,
The cell is assert to need cancer cell to be separated.The flow velocity of sheath stream arrival end 4 is slightly larger than the flow velocity of ameboid cell arrival end 13, protects
Ameboid cell is demonstrate,proved close to electrode side, ameboid cell is made to be easy the influence by dielectrophoretic force.The electrode of cancer cell separating chips 5
A driving signal is obtained, electrode will obtain voltage 10Vpp, driving frequency 15KHz at this time.Work of the cancer cell in dielectrophoretic force
Under, cancer cell outlet end 6 is flowed to.
G, when detecting that the deformation quantity of cell in sample is less than isolated critical value at cells deformation amount detection chip 8,
Assert that the cell is normal cell, electrode will not obtain any signal.Normal cell proper flow in microchannel, flow direction are normal
Cell outlet end 12.
H, the cell for taking out separator well from cancer cell outlet end 6 and normal cell outlet end 12 respectively, can obtain from sample
The cancer cell and normal cell of separator well in this.
The present invention compared with prior art, has following obvious prominent substantive distinguishing features and remarkable advantage:
1) present invention can sort cancer cell on the basis of measuring the morphotropism of cell, realize cancer cell deformation
Two kinds of functions of the detection of amount and cancer cell separation.
2) high throughput may be implemented in the deformation quantity of present invention detection cell, meets the needs of clinical great amount of samples analysis.
3) carrying out sorting to cancer cell is using the mechanical property of its own as foundation, is a kind of unmarked separation side
Method, this unmarked characteristic make separation cell higher using dielectrophoretic force progress cancer cell separation specificity than simple.
4) equipment needed for method of the invention is simple and reliable, easy to operate.
A specific example illustrates the principle and implementation of the invention, and the explanation of above example is only intended to sides
Assistant solves method and its core concept of the invention；At the same time, for those skilled in the art, think of according to the present invention
Think, there will be changes in the specific implementation manner and application range.In conclusion the content of the present specification should not be construed as pair
Limitation of the invention.
Claims (10)
1. a kind of cancer cell separator based on cells deformation amount and dielectrophoretic force, which is characterized in that the cancer cell separation
Device includes cell liquid storage device, injection Micropump, LED light, cells deformation amount detection chip, cancer cell separating chips, CMOS high speed
Video camera and processor；
Cell suspending liquid is placed in the cell liquid storage device；The cell suspending liquid is cell to be detected；
It is described injection Micropump one end protrude into the cell liquid storage device, it is described injection Micropump the other end by polymer pipe with
The arrival end of the cells deformation amount detection chip is connected；The outlet end of the cells deformation amount detection chip and the cancer cell
The ameboid cell arrival end of separating chips is connected；The cancer cell separating chips are additionally provided with sheath stream arrival end, normal cell outlet
End and cancer cell outlet end；
The LED light is arranged in the cells deformation amount detection chip and to the deformation in the cells deformation amount detection chip
Cell is irradiated, and the CMOS high-speed camera is arranged under the cells deformation amount detection chip and to the cells deformation
Ameboid cell in amount detection chip is shot；
The input terminal of the processor is connect with the CMOS high-speed camera, the output end of the processor and the cancer cell
Electrode connection in separating chips.
2. cancer cell separator according to claim 1, which is characterized in that the cells deformation amount detection chip includes
First substrate of glass and cover plate containing miniature channel；The miniature channel successively includes first passage, shrinks channel and second
Channel；The cross section for shrinking channel is square；The size of the cross section for shrinking channel is 25 μm * 25 μm；It is described
The diameter of first passage and the second channel is 1.5mm.
3. cancer cell separator according to claim 2, which is characterized in that the length in the miniature channel is 5mm.
4. cancer cell separator according to claim 1, which is characterized in that the cancer cell separating chips include second
Substrate of glass and cover plate containing microchannel；The electrode of multiple dentalations, and phase are inlayed in the inner wall side of the microchannel
The polarity of adjacent electrode is opposite；The dielectrophoretic force that the electrode generates acts on the ameboid cell in the microchannel.
5. cancer cell separator according to claim 4, which is characterized in that a height of 60 μm of the microchannel, it is described
The width of microchannel is 3mm；Second substrate of glass with a thickness of 500 μm.
6. cancer cell separator according to claim 4, which is characterized in that the electrode is by the way that 200nm is thick
Platinum electrode sputters on the titanium adhesive layer of 20nm thickness, then by being formed after removing patterning.
7. cancer cell separator according to claim 4, which is characterized in that one layer of electrode upper berth porous aquagel
Layer.
8. cancer cell separator according to claim 1, which is characterized in that the cancer cell separator further includes connecting
Connect road；The change that the outlet end of the cells deformation amount detection chip passes through the interface channel and the cancer cell separating chips
Shape cell entry end is connected.
9. cancer cell separator according to claim 1, which is characterized in that the injection Micropump is for providing driving
Power.
10. a kind of cancer cell separation control system based on cells deformation amount and dielectrophoretic force, which is characterized in that the cancer cell
Separation control system includes:
The CMOS high-speed camera is used to capture the ameboid cell image in cells deformation amount detection chip；
The processor includes processing module and judgment module；
The processing module is connect with the CMOS high-speed camera, for obtaining the ameboid cell image, and to the change
Shape cell image is handled, and determines the deformation quantity of ameboid cell；
The judgment module is connect with the electrode, is stored in advance for judging whether the deformation quantity of the ameboid cell is greater than
In the given threshold of the processor, and when the deformation quantity of the ameboid cell is greater than the given threshold, output driving is believed
Number, the driving signal is transmitted to the electrode to drive the electrode to generate dielectrophoretic force and the ameboid cell is made to flow to cancer
The cancer cell outlet end of cell separation chip；Not when the deformation quantity of the ameboid cell is less than or equal to the given threshold
Output drive signal, the ameboid cell flow to the normal cell outlet end of the cancer cell separating chips；The given threshold
For the cut off value of normal cells deformation amount and cancer cell deformation quantity.
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| CN110241018A (en) * | 2019-06-21 | 2019-09-17 | 上海大学 | A kind of cancer cell separation system and method |
| CN111494089A (en) * | 2020-04-22 | 2020-08-07 | 西安交通大学 | Abdominal cavity thermal perfusion chemotherapy treatment system |
| CN111744565A (en) * | 2020-05-26 | 2020-10-09 | 东南大学 | Microfluidic device and system for multi-channel parallel detection of cell deformability |
| CN112683756A (en) * | 2020-12-01 | 2021-04-20 | 山东交通学院 | Portable mobile equipment with cell detection function and use method thereof |
| CN112946091A (en) * | 2019-12-10 | 2021-06-11 | 中国科学院大连化学物理研究所 | System for quantitatively detecting target protein in single cell |
| EP3858484A1 (en) * | 2020-02-03 | 2021-08-04 | Vrije Universiteit Brussel | On-chip structured silicon-on-insulator vortex inducer |
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| CN110241018A (en) * | 2019-06-21 | 2019-09-17 | 上海大学 | A kind of cancer cell separation system and method |
| CN112946091A (en) * | 2019-12-10 | 2021-06-11 | 中国科学院大连化学物理研究所 | System for quantitatively detecting target protein in single cell |
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