CN109136081A - Cancer cell separator and control system based on cells deformation amount and surface acoustic wave - Google Patents
Cancer cell separator and control system based on cells deformation amount and surface acoustic wave Download PDFInfo
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- CN109136081A CN109136081A CN201810853141.6A CN201810853141A CN109136081A CN 109136081 A CN109136081 A CN 109136081A CN 201810853141 A CN201810853141 A CN 201810853141A CN 109136081 A CN109136081 A CN 109136081A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/04—Cell isolation or sorting
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/84—Systems specially adapted for particular applications
Abstract
The invention discloses a kind of cancer cell separator and control system based on cells deformation amount and surface acoustic wave, 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 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 interdigital transducer generates the cancer cell outlet end that surface acoustic wave 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 surface acoustic wave
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 after canceration is softer than normal cell, it is easier to be deformed, it is easier to cancer hair
Raw transfer.For a long time, mechanical phenotype have always been considered as be in quantization cell the changes of function of physiology and pathological origin without mark
Note method.This method is verified under cell differentiation and the background of pernicious transfer, and has expedited the emergence of many basic research sides
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 biology
Molecular marked compound, the index of this unmarked deformability do not need some pre-treatment steps such as dyeing, antibody processing, can save
Save more operating costs.
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 shape of high throughput is designed
The method of variable be very it is necessary to.
The rigidity of high throughput detection diseased region cell, the stage that not only potential can be judged patient and be in cancer, and
It can be classified according to the difference of cell rigidity to cell.Technology of today is only limited to the rigidity of detection cell, does not consider
The foundation that this unmarked feature of cell is separated as cell.Deformability signature based on cell as separation mark for
The research and diagnosis of cancer have great potential significance, can carry out cancer by stages, recurrence detection, cancer drug resistance molecule point
Analysis etc..
Currently, traditional cell separation technology such as centrifugal process and filtration method time-consuming, low yield, the sample size of needs are big, no
It is suitble to the analysis of micro precious sample.Nowadays, the microchannel of micro-fluidic chip narrows down to micron order, can accurately manipulate minute yardstick
Fluid, the consumption of sample and reagent is greatly lowered, and the reaction time is fast, is very suitable to cell separation.With micro-
The development of fluidics, surface acoustic wave start to be introduced on micro-fluidic chip, the separation and manipulation for particle, drop, cell.
Particle will receive acoustic radiation force and viscous force in the micro-fluidic chip of surface acoustic wave, for being greater than the particle of critical dimension, sound
Radiant force plays a leading role, and particle is mobile to node location；For being less than the particle of critical dimension, viscous force counteracts major part
Acoustic radiation force, result in the lateral movement of very little, thus realize particle is efficiently separated.In micro-fluidic sound field,
It is closely related to act on the size of the acoustic radiation force of particle and the size of particle, density, compressible three, and passes through
Adjust the driving frequency of interdigital transducer, thus it is possible to vary separate the critical dimension of particle, therefore the miniflow based on surface acoustic wave
Control chip separates relatively flexibly cell.
Nowadays the separation method based on surface acoustic wave is carried out according to cell size size and density, this allows for separating
Cancer cell be that ensure that consistency in size, and specificity cannot be guaranteed.
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 surface acoustic wave 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 surface acoustic wave, 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 arrival end of cell separation chip is connected；The cancer cell separating chips are equipped with 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
Interdigital transducer 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；It is described micro- logical
The two sides in road are correspondingly arranged the interdigital transducer；The surface acoustic wave that the interdigital transducer generates acts on described micro-
Ameboid cell in channel.
Optionally, a height of 50 μm of the microchannel；The width of the microchannel is 800 μm.
Optionally, the interdigital transducer includes 50 pairs interdigital, and the interdigital width is 100 μm, described interdigital
Spacing is 100 μm, and the interdigital period is 400 μm, and the interdigital intersection length is 11mm.
Optionally, the material of the piezoelectric substrate of the interdigital transducer is lithium niobate (LiNbO3) material；The piezoelectricity
The size of substrate is 25mm*25mm*500 μm.
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 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 surface acoustic wave, 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 interdigital transducer, for judge the ameboid cell deformation quantity whether
Greater than the given threshold for being stored in advance in the processor, and when the deformation quantity of the ameboid cell is greater than the given threshold
The driving signal is transmitted to the interdigital transducer to drive the interdigital transducer generation sound by output drive signal
Surface wave makes the ameboid cell flow to the cancer cell outlet ends of cancer cell separating chips；When the deformation quantity of the ameboid cell is small
Output drive signal, the ameboid cell are not flowing to the cancer cell separating chips just when the given threshold
Normal cell outlet end；The given threshold 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 surface acoustic wave, 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 arrival end of chip is connected；Cancer cell separating chips are equipped with normal cell outlet end and cancer cell outlet end；LED light is arranged thin
In born of the same parents' deformation quantity detection chip；CMOS high-speed camera, which is arranged under cells deformation amount detection chip, captures the detection of cells deformation amount
Ameboid cell image in chip；The input terminal of processor is connect with CMOS high-speed camera, and the processor is according to the change of acquisition
Shape cell image determines the deformation quantity of ameboid cell, and determines whether the ameboid cell is that cancer is thin according to the deformation quantity of ameboid cell
Born of the same parents, if then processor output drive signal driving interdigital transducer generates surface acoustic wave and makes ameboid cell flow to cancer cell to go out
Mouth end.With the application of the invention, the deformation quantity of cell can be detected quickly, and incited somebody to action according to cancer cell is different from normal cell deformation quantity
Cancer cell is separated from patient blood sample.
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 surface acoustic wave
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.
The present invention provides a kind of quickly detection cancer cell deformation quantity and the devices separated based on surface acoustic wave to it
And control system, it is according to the difference of cancer cell and normal cell deformation quantity while detecting sample deformability deformability of cells, cancer is thin
Born of the same parents separate from sample.Up to now, there are no sort on the basis of detecting cancer cell morphotropism to cancer cell
The research of this aspect.
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 surface acoustic wave
Figure, as shown in Figure 1, the cancer cell separator provided in an embodiment of the present invention based on cells deformation amount and surface acoustic wave includes note
Penetrate Micropump 1, polymer pipe 2, LED light 3, cells deformation amount detection chip 4, cancer cell separating chips 5, cell liquid storage device 7, CMOS
High-speed camera 8, interface channel 9 and processor 10；The cancer cell separating chips 5 are equipped with cancer cell outlet end 6 and normally
Cell outlet end 11.
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 4；The cells deformation amount detection chip 4 goes out
Mouth end is connected by interface channel 9 with the arrival end of the cancer cell separating chips 5.
The LED light 3 is arranged in the cells deformation amount detection chip 4 and to the cells deformation amount detection chip 4
Interior ameboid cell is irradiated, and the CMOS high-speed camera 8 is arranged under the cells deformation amount detection chip 4 and to institute
The ameboid cell stated in cells deformation amount detection chip 4 is shot.
The input terminal of the processor 10 is connect with the CMOS high-speed camera 8, the output end of the processor 10 with
Interdigital transducer 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 4
End outside, is connected by polymer pipe 2 with the arrival end of cells deformation amount detection chip 4, guarantees leakproofness, by cell liquid storage device
Configured cell suspending liquid is entered in cells deformation amount detection chip 4 by pressure-driven in 7, and cell suspending liquid is driven to exist
It is flowed in the miniature channel of cells deformation amount detection chip 4.
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 4 includes that the first substrate of glass and the cover plate containing miniature channel, the two pass through
Plasma bonding；The miniature channel successively includes first passage, shrinks channel and second channel；It is described to shrink the transversal of channel
Face is square, and the size of the cross section for shrinking channel is 25 μm * 25 μm, primarily to it is micro- to guarantee that the size of cell accounts for
The 50%-90% of contracting channel size guarantees that the same time allows to pass through individual cells.The first passage and the second channel
Diameter be 1.5mm.The length in the miniature channel is 5mm.Miniature channel uses dimethyl silicone polymer (PDMS) material,
Miniature channel is prepared using standard photolithography process.
Cell suspending liquid enters miniature channel by the arrival end of cells deformation amount detection chip 4, is shrinking Air conduct measurement
Cells deformation amount is finally flowed out from the outlet end of cells deformation amount detection chip 4.When cell flows through contraction channel, pass through shearing
Stress and barometric gradient and deform.
8 real-time capture ameboid cell image of CMOS high-speed camera, and ameboid cell image is sent to processor 10.It is logical
Contour area and perimeter that the algorithm write in advance in processor 10 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 10, 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 10 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；The two sides of the microchannel are correspondingly arranged the interdigital transducing
Device；The surface acoustic wave that the interdigital transducer generates acts on the ameboid cell in the microchannel.The height of the microchannel
It is 50 μm；The width of the microchannel is 800 μm.
The interdigital of the interdigital transducer is prepared by Ti/Au (20nm/100nm) film deposition, interdigital transducing
Device includes 50 pairs interdigital, and the interdigital width is 100 μm, and the interdigital spacing is 100 μm, and the interdigital period is
400 μm, the interdigital intersection length is 11mm.The material of the piezoelectric substrate of the interdigital transducer is lithium niobate
(LiNbO3) material；The size of the piezoelectric substrate is 25mm*25mm, with a thickness of 500 μm, in the driving of sinusoidal voltage 22Vpp
Under can piezoelectric substrate surface generate surface acoustic wave；The size and density of every kind of cancerous cell line are all different, sound surfaces
The driving frequency of wave is determined by the type of cancer cell to be separated；In general, the size of cell to be separated is bigger, same frequency
The bigger therefore required frequency of lower suffered acoustic radiation force will be smaller.
The surface acoustic wave that interdigital transducer T is generated acts on the cancer cell in microchannel.Cancer cell separating chips 5 have one
A arrival end, two outlet ends, respectively cancer cell outlet end and normal cell outlet end.The material of microchannel is still using poly-
Dimethyl siloxane (PDMS).
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 10 will generate a pulse
Signal (driving signal) is sent to interdigital transducer, so that it is generated surface acoustic wave driving cancer cell and shifts to cancer cell outlet end；
The deformation quantity of normal cell is less than critical value, and processor 10 will not generate pumping signal, and normal cell is flowed to along flow velocity direction
Normal cell outlet end.
In cancer cell separating chips 5, interdigital transducer (IDT) is nuclear structure therein.Interdigital transducer
(IDT) it is a kind of periodic structure, is deposited in piezoelectric substrate, electricity and the conversion function between sound, sound and electricity may be implemented,
Directly determine the working characteristics of cancer cell separating chips 5, the preparation method of interdigital transducer, including the following steps:
1) lithium niobate base bottom (LiNbO is cleaned using deionized water3)。
2) Ti/Au (20nm/100nm) bilayer is plated in substrate using RF sputtering technology.
3) layer photoresist is smeared on Ti/Au bilayer.
4) interdigital shape is formed on the substrate under ultraviolet light irradiation in mold.
5) substrate is cleaned using golden etchant, removes extra Au layer.
6) photoresist is removed, is finally formed on lithium niobate base bottom interdigital.
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 4；Cell enters cells deformation amount detection chip 4 under the pressure of injection Micropump 1, and CMOS high-speed camera 8 is real
When obtain cell strain image, at the same time processor 10 carry out image analysis, the deformation quantity of cell is calculated；Cell shape
After variable detection, cell suspending liquid enters cancer cell separating chips 5 by interface channel 9；The cancer cell that deformation quantity is met the requirements
Interdigital transducer work can be triggered, cancer cell shifts to cancer cell outlet end 6 under the action of surface acoustic wave, and normal cell exists
Normal cell outlet end 11 is flowed under natural conditions.
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 8 is used to capture the ameboid cell image in cells deformation amount detection chip 4.
The processor 10 includes processing module and judgment module.
The processing module is connect with the CMOS high-speed camera 8, 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 interdigital transducer, for judge the ameboid cell deformation quantity whether
Greater than the given threshold for being stored in advance in the processor, and when the deformation quantity of the ameboid cell is greater than the given threshold
The driving signal is transmitted to the interdigital transducer to drive the interdigital transducer generation sound by output drive signal
Surface wave makes the ameboid cell flow to the cancer cell outlet ends 6 of cancer cell separating chips 5；When the deformation quantity of the ameboid cell
Output drive signal, the ameboid cell do not flow to the cancer cell separating chips 5 when less than or equal to the given threshold
Normal cell outlet end 11；The given threshold is the cut off value of normal cells deformation amount and cancer cell deformation quantity.
Embodiment three
The embodiment of the invention provides the method for measuring cancer cell deformation quantity and being separated based on surface acoustic wave to it, tools
Body realizes that 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.By cell suspending liquid from cell liquid storage device 7 suck 1mL injection Micropump 1 before, cell
Suspension will be placed at 37 DEG C and keep cell activity.
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 4, cancer cell separating chips 5.Before the start of the measurement, flow is in perseverance
Stablize 2min under constant current speed.All data acquisitions are all to reach 300 μm long of contraction position of stable state in cell shape
Rear portion carry out.8 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,
Area-of-interest 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 4.The miniature channel of cells deformation amount detection chip 4
The LED light 3 for shrinking the ameboid cell high power pulsed ion beams in channel is irradiated, and with CMOS high-speed camera 8 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 8 is to ensure synchronous image exposure.
D, each frame image for obtaining CMOS high-speed camera 8 is converted to grayscale image.Then processor 10 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 4 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 4,
The cell is assert to need cancer cell to be separated.Interdigital transducer (IDTs) obtains the driving signal of a processor 10 output
Interdigital transducer IDTs will obtain voltage 22Vpp, driving frequency 19.6MHz.Cancer cell is under the action of acoustic radiation force, stream
To cancer cell outlet end 6.
G, when detecting that the deformation quantity of cell in sample is less than isolated critical value at cells deformation amount detection chip 4,
Assert that the cell is normal cell, interdigital transducer will not obtain any signal.Normal cell proper flow in microchannel,
Flow to normal cell outlet end 11.
H, the cell for taking out separator well from cancer cell outlet end 6 and normal cell outlet end 11 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；It is right
Cancer cell, which carries out sorting, to be a kind of unmarked separation method, is compounded with sound using the mechanical property of its own as foundation
The specific advantage of the cellifugal high pass flow characteristic of surface wave point and similar molecular marked compound separation.
3) 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 surface acoustic wave, 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 arrival end of separating chips is connected；The cancer cell separating chips are equipped with 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
Interdigital transducer 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 two sides of the microchannel are correspondingly arranged the interdigital transducer；The fork
The surface acoustic wave that finger formula energy converter 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 50 μm of the microchannel；It is described
The width of microchannel is 800 μm.
6. cancer cell separator according to claim 4, which is characterized in that the interdigital transducer includes 50 pairs of forks
Refer to, the interdigital width is 100 μm, and the interdigital spacing is 100 μm, and the interdigital period is 400 μm, described interdigital
Intersection length be 11mm.
7. cancer cell separator according to claim 4, which is characterized in that the piezoelectric substrate of the interdigital transducer
Material be lithium niobate (LiNbO3) material；The size of the piezoelectric substrate is 25mm*25mm*500 μm.
8. cancer cell separator according to claim 1, which is characterized in that the cancer cell separator further includes connecting
Connect road；The outlet end of the cells deformation amount detection chip is entered by the interface channel and the cancer cell separating chips
Mouth 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 surface acoustic wave, 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 interdigital transducer, for judging whether the deformation quantity of the ameboid cell is greater than
It is stored in advance in the given threshold of the processor, and is exported when the deformation quantity of the ameboid cell is greater than the given threshold
The driving signal is transmitted to the interdigital transducer to drive the interdigital transducer generation sound surface by driving signal
Wave makes the ameboid cell flow to the cancer cell outlet ends of cancer cell separating chips；Be less than when the deformation quantity of the ameboid cell or
Output drive signal, the ameboid cell do not flow to the normal thin of the cancer cell separating chips when person is equal to the given threshold
Born of the same parents outlet end；The given threshold is the cut off value of normal cells deformation amount and cancer cell deformation quantity.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810853141.6A CN109136081A (en) | 2018-07-30 | 2018-07-30 | Cancer cell separator and control system based on cells deformation amount and surface acoustic wave |
Applications Claiming Priority (1)
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| CN115417585B (en) * | 2022-09-22 | 2023-08-29 | 重庆理工大学 | Processing device and processing method for glass capillary tube with multiple shrinkage hole diameters |
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