CN109946217B - Sound-driven flow cytometry detection device - Google Patents
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- CN109946217B CN109946217B CN201711396348.7A CN201711396348A CN109946217B CN 109946217 B CN109946217 B CN 109946217B CN 201711396348 A CN201711396348 A CN 201711396348A CN 109946217 B CN109946217 B CN 109946217B
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Abstract
The application discloses acoustic drive's flow cytometry detection device, including cell control module, imaging module and image processing module, the cell control module includes that flow chamber and ultrasonic radiation force take place the system, and ultrasonic radiation force takes place the system and is used for producing the acoustic radiation force to the cell granule, controls the cell granule and arranges into parallel lines, realizes the multirow focus, makes the cell granule suspension, and the directional transport of drive cell granule simultaneously realizes multichannel parallel detection to the detection area. Since the cell particles are controlled by the acoustic radiation force to realize transportation and focusing, a complex pump system is not needed to drive and control the fluid, and sheath fluid is not needed to be introduced; the cell is arranged by using the virtual channel formed by the acoustic radiation force, so that the problem of cavity channel blockage is avoided; because the acoustic radiation force can arrange a plurality of lines of cells, multi-channel parallel processing of a plurality of lines of focusing is realized; because the flow chamber has low cost and can be replaced every time, the problem that the residue in the flow channel pollutes a new sample is avoided.
Description
Technical Field
The present invention relates to a flow cytometer detection device, and more particularly, to an acoustically driven flow cytometer detection device.
Background
A Flow cytometer (Flow cytometer) is a device that automatically analyzes and sorts cells. The flow cell and the fluid drive system are key components of the flow cytometer. The flow chamber is composed of a sample tube, a sheath liquid tube, a nozzle and the like, is made of transparent and stable materials such as optical glass, quartz and the like, is fine in design and manufacture, and is the core of a liquid flow system. The sample tube stores a sample, and the single cell suspension is ejected from the sample tube under the action of liquid flow pressure; the sheath liquid flows from the sheath liquid pipe to the spray hole from the periphery, surrounds the sample 1, and is sprayed from the spray nozzle. The cells to be detected are confined to the axis of the flow due to the action of the sheath fluid.
Therefore, the current flow cytometry mainly utilizes water flow power to realize the transportation and flow focusing of cell particles in a microfluidic cavity, and the technical scheme mainly has the following problems: the suspended particles easily block the micro-cavity channel, and the cost for replacing the cavity channel is high; flow-focused experiments require expensive sheath fluid to constrain the cells to be aligned in a single column; the need to utilize complex and expensive microfluidic pump systems to drive fluid flow; the current flow cytometer is mainly a single-channel processing mode, but not a multi-channel parallel processing mode; is not easy to clean, and the residual sample in the flow channel can pollute the new sample.
The current flow cytometry mainly utilizes water flow dynamics to realize the transportation and flow focusing of cells waiting for detection particles in a micro-fluid cavity. In order to make the fluid flow, an air compression pump is usually used to compress air to provide the necessary pressure for the fluid flow, and the pressure regulator is used to stabilize the liquid flow pressure, so as to form a steady flow, so that the sample particles can flow into the flow chamber at a constant speed. However, the air passages and control methods involved in such pump systems are complex, require many parts, and are bulky in system assembly.
Flow focusing is a key module of a flow cytometer, and generally, a sheath fluid flow focusing mode is utilized to form a wrapping extrusion effect on a sample flow, so that the sample flow is focused at the center of a channel, and cell particles in the sample flow are wrapped and clamped into linear arrangement, thereby realizing that the cell particles pass through a detection area one by one. The introduction of the sheath fluid by this method increases the amount of liquid introduced as a whole, increases the complexity of the entire fluid flow control system, and the sheath fluid is an expensive consumable.
In another method, a sheath liquid is not needed, and a focusing effect is generated on cells through an externally applied field force or a fluid acting force in a channel, so that the cells pass through a detection area one by one. In the patent of a microfluidic chip and a preparation method and application thereof (application No. 201611146452.6) and in the patent of a particle sorting method and a device and application thereof (application No. 201710016125.7), cell particles are arranged into one or more lines by using an external standing wave sound field, so that single-row or multi-row focusing is realized, and cells pass through a detection area one by one. The literature also reports that cell particles are focused by fluid forces such as reflux force, fluid inertial lift force, eddy effect force, inertial dean flow lift force and the like after fluid separation. Although this method does not require the introduction of an external force field, it requires precise control of the liquid, increasing the complexity of the system. In patent publication No. US2009/0042241A1, a convergent type unsheathed fluid flow cell particle focusing method is adopted, but the fluid channel is easily blocked by large particles. In addition, these methods still require complex pumping systems to power the liquid handling cells.
Most of the current flow cytometers are single-channel focusing processing systems, and flow cytometers of multi-channel parallel processing systems have been reported in patent documents in order to improve throughput. The patent of microfluidic chip, its preparation method and application (application No. 201611146452.6) uses standing wave field generated by multiple transducers to arrange cells into multiple lines, so as to realize multi-line focusing and parallel processing. The patent system and method for measuring multiple emissions from multiple parallel flow channels in a flow cytometer system (application No. 201080027480.0) discloses a multiple parallel flow channel flow cytometer system to increase the number of cells detected by the system per second.
The common defects of the prior art mainly comprise the following three points:
complex pump systems are used for driving fluid, and the cost of a liquid flow driving system is high;
the transportation, focusing and detection of the particles are carried out in a single or a plurality of micro-flow channels, and the suspended cell particles in the channels are easy to block the channels, so that the system is invalid and the replacement cost is high;
not easy to clean, residual sample in the flow chamber and the liquid path system can contaminate new sample.
Disclosure of Invention
The technical problem that this application will be solved is to providing a flow cytometry detection device of acoustic drive to the not enough of prior art.
The technical problem to be solved by the application is solved by the following technical scheme:
an acoustically-driven flow cytometry detection device comprises a cell manipulation module, an imaging module and an image processing module, wherein the cell manipulation module is used for manipulating cell particles in a sample solution, the imaging module is used for carrying out fluorescence imaging on stained cell particles, the image processing module is used for processing and analyzing fluorescence images, counting the cell particles and estimating the size of the cell particles, the cell manipulation module comprises a flow chamber and an ultrasonic radiation force generation system, and the flow chamber is used for containing the sample solution containing the cell particles; the ultrasonic radiation force generation system is used for generating acoustic radiation force on cell particles, controlling the cell particles to be arranged into parallel lines, realizing multi-line focusing, suspending the cell particles, and simultaneously driving the cell particles to be directionally conveyed to a detection area to realize multi-channel parallel detection.
The ultrasonic radiation force generation system comprises a radiation force generation mechanism, a signal generator and a power amplifier, wherein an electric signal generated by the signal generator is amplified by the power amplifier, and then the radiation force generation mechanism is excited to generate ultrasonic waves and further generate radiation force on particles so as to realize the transportation and control of cells.
The flow chamber comprises a substrate, a PDMS side wall and a glass top cover, wherein the PDMS side wall is respectively bonded with the substrate and the glass top cover, and the substrate is made of quartz glass, organic glass or silicon.
The radiation force generating mechanism comprises an ultrasonic transducer and an artificial structure arranged in the flow chamber, and the ultrasonic transducer is excited to generate ultrasonic waves and further generate radiation force on particles by electric signals amplified by the power amplifier.
The artificial structure comprises an artificial periodic structure or an artificial aperiodic structure.
Artifical periodic structure includes the base plate and sets up a plurality of sand grips of base plate lower surface, sand grip parallel arrangement and interval equal.
The ultrasonic transducer is disposed outside the flow chamber and is not coincident with a geometric center of the artificial periodic structure.
The radiation force generating mechanism includes a plurality of transducers disposed outside the flow chamber for synthesizing an acoustic field.
The multiple transducers comprise at least one ultrasonic transducer and interdigital transducers which are arranged in pairs and are arranged in parallel, the interdigital transducers are used for synthesizing a standing wave field and arranging cells for focusing, and the ultrasonic transducer is used for generating an offset Gaussian beam to convey the cells.
Due to the adoption of the technical scheme, the beneficial effects of the application are as follows:
in a specific embodiment of the present application, the cell manipulation module comprises a flow chamber and an ultrasonic radiation force generation system, and the flow chamber is used for containing a sample solution containing cell particles; the ultrasonic radiation force generation system is used for generating acoustic radiation force on cell particles, controlling the cell particles to be arranged into parallel lines, realizing multi-line focusing, suspending the cell particles, and simultaneously driving the cell particles to be directionally conveyed to a detection area to realize multi-channel parallel detection. Since the cell particles are controlled by the acoustic radiation force to realize transportation and focusing, a complex pump system is not needed to drive and control the fluid, and sheath fluid is not needed to be introduced; since the cells are arranged by using the virtual channel formed by the acoustic radiation force, a micro-channel used in the prior art is not needed, so that the problem of cavity channel blockage is avoided; because the acoustic radiation force can arrange a plurality of lines of cells, multi-channel parallel processing of a plurality of lines of focusing is realized; because parts such as the flow chamber in the cell control module in the application have low cost and simple process, and can be replaced by a new device when measuring a new sample every time, the problem that residues in a flow channel pollute the new sample in the prior art is avoided. In conclusion, the flow cytometry detection scheme is free of micro-flow channels, micro-flow pumps, sheath fluid, disposability, parallel processing and low in cost.
Drawings
FIG. 1 is a functional block diagram of an apparatus of the present application in one embodiment;
FIG. 2 is a schematic diagram of an artificial periodic structure of the present application in one embodiment;
FIG. 3 is a transmission spectrum of the artificial periodic structure shown in FIG. 2;
FIG. 4 is a distribution of an artificial periodic structure modulated sound field along the x direction;
FIG. 5 shows that the cell is subjected to x, y and z directions of acoustic radiation force in an acoustic field of an artificial structure;
FIG. 6 is the acoustic pressure field distribution and the directions of the radiation force components Fy and Fz at the time of the resonance of the artificial periodic structure in the yz plane;
FIG. 7 is a graph of the distribution of the radiation force components Fy and Fz along the y-direction at resonance of an artificial periodic structure in the yz plane;
FIG. 8 is the acoustic pressure field distribution and the directions of the radiation force components Fy and Fz when the artificial periodic structure is not resonant in the yz plane;
FIG. 9 is the acoustic pressure field distribution and the distribution of the radiation force components Fy and Fz in the y-direction when the artificial periodic structure is not resonant in the yz plane;
FIG. 10 is a distribution of acoustic radiation force components Fx and Fz along a transport direction x;
FIG. 11 is an image acquired using the acoustically-driven flow cytometry detection apparatus of the present application;
fig. 12 is a schematic structural view of a radiation force generating mechanism of the present application in one embodiment.
Detailed Description
The present application will be described in further detail below with reference to the accompanying drawings by way of specific embodiments.
The first embodiment is as follows:
as shown in fig. 1, the acoustically-driven flow cytometry apparatus of the present application, in one embodiment, includes a cell manipulation module 10, an imaging module 20, and an image processing module 30. The cell manipulation module 10 is used for manipulating cell particles in a sample solution, the imaging module 20 is used for performing fluorescence imaging on the stained cell particles, and the image processing module 30 is used for processing and analyzing the fluorescence image, counting the cell particles and estimating the size of the cell particles. The cell manipulation module 10 can include a flow cell, which can be a microcavity, for holding a sample solution containing cell particles, and an ultrasonic radiation force generation system. The ultrasonic radiation force generation system is used for generating acoustic radiation force on cell particles, controlling the cell particles to be arranged into parallel lines, realizing multi-line focusing, suspending the cell particles and simultaneously driving the cell particles to be directionally conveyed to a detection area to realize multi-channel parallel detection.
The imaging module 20 may include a fluorescence excitation source, optical lenses, a high-sensitivity fluorescence camera. The image processing module 30 may include a computer, a high-speed data acquisition card, hardware control software, and image acquisition analysis processing software for processing and analyzing the fluorescence image, counting cells, and estimating cell size. The radiation force generated by the ultrasonic radiation force generation system is mainly utilized to realize the focusing and the transportation of the cells.
In one embodiment, an ultrasonic radiation force generating system includes a radiation force generating mechanism, a signal generator, and a power amplifier. After the electric signal generated by the signal generator is amplified by the power amplifier, the radiation force generating mechanism is excited to generate ultrasonic waves, and then radiation force is generated on particles so as to realize the transportation and control of cells.
The flow chamber of this application can include base, PDMS lateral wall and glass top cap, and the PDMS lateral wall bonds with the base, and the PDMS lateral wall also bonds with the glass top cap simultaneously. In one embodiment, the substrate may be made of quartz glass, plexiglass or silicon.
In one embodiment, the radiation force generating mechanism may include an ultrasound transducer and an artificial structure. The ultrasonic transducer is arranged outside the flowing chamber, the artificial structure is arranged inside the flowing chamber, and the ultrasonic transducer is excited to generate ultrasonic waves through electric signals amplified by the power amplifier so as to generate radiation force on particles. The artificial structure may be an artificial periodic structure or an artificial non-periodic structure. As shown in fig. 2, the artificial periodic structure includes a substrate 11 and a plurality of convex strips 12 disposed on the lower surface of the substrate 11, wherein the convex strips 12 are disposed in parallel and at equal intervals. FIG. 2 is a schematic diagram of an artificial periodic structure employed in an acoustic radiation force generation system. t is the thickness of the plate, p is the period of the structure, w is the width of the grid, and h is the height of the grid. The material is stainless steel, and the parameters are t-20-100 μm, h-10-50 μm, w-20-100 μm and p-50-300 μm. FIG. 3 is a transmission spectrum of the artificial periodic structure shown in FIG. 2, with a resonant frequency of 5.94 MHz.
The ultrasonic radiation force generation system of the application, wherein, ultrasonic transducer sets up outside the flow cell, and ultrasonic transducer and artificial periodic structure's geometric center do not coincide. In one embodiment, the ultrasonic transducer may be affixed to the exterior of the flow chamber, and in particular may be affixed to the lower surface of the substrate. The ultrasonic transducer may be a biased gaussian beam sound source. The artificial structure modulates the ultrasonic transducer to emit a sound field to generate a sound field with control functions of transportation, arrangement and the like, so that the focusing and transportation of cells are realized.
The numerical simulation researches the acoustic radiation force of the cells in a sound field obtained by modulating Gaussian sound beams in an artificial periodic structure, and discloses a mechanism for directionally transporting micro-nano particles in the artificial periodic structure sound field. Fig. 4 is a distribution of an artificial periodic structure modulated sound field in the x direction, and it can be seen that the sound pressure distribution follows a gaussian distribution in which a theoretical calculation value is represented by a dotted line portion and an experimental measurement value is represented by a solid line portion. As shown in fig. 5, the cells are subjected to acoustic radiation forces in three directions of x, y and z in an artificial structure sound field, wherein the x-direction acoustic radiation force Fx causes directional movement of the micro-nano particles towards the strongest direction of the sound field, so as to realize transportation; the arrangement of the micro-nano particles is caused by the acoustic radiation force Fy in the y direction, so that focusing is realized, the confinement effect on the particles is realized, the lateral movement interval of the micro-nano particles is limited, and a virtual micro-cavity channel is formed; and the z-direction acoustic radiation force Fz is responsible for suspension and capture of the micro-nano particles. The combined action of these three directional acoustic radiation forces ultimately results in transport and focusing of the cell.
Fig. 6 shows the distribution of the acoustic pressure field and the directions of the radiation force components Fy and Fz at resonance of the artificial periodic structure in the yz plane (resonance frequency of 5.94 MHz). Fig. 7 shows the distribution of the radiation force components Fy and Fz in the y-direction at the resonance of the artificial periodic structure in the yz plane (resonance frequency of 5.94 MHz). It can be seen that in the equilibrium position shown by the circle, the radiation force component Fz is negative, i.e. vertically downwards, and therefore will stably capture the cells on the surface of the structure.
Fig. 8 shows the directions of the acoustic pressure field (driving frequency 5.92MHz) and the radiation force components Fy and Fz at non-resonance obtained by numerical simulation calculation. Fig. 9 shows the spatial distribution of the acoustic pressure field (driving frequency 5.92MHz) and the radiation force components Fy and Fz in the y direction at non-resonance calculated by numerical simulation. Fig. 8 is a schematic diagram of sound field distribution and stress in the yz plane, and it can be seen that the sound field form at non-resonance is greatly different from the sound pressure field distribution at resonance in fig. 6. The position shown by the circle is the equilibrium position of the particle in the sound field. In this position, the vertical upward radiation force component Fz just counteracts the gravity action in the z direction, causing the particles to be suspended; the y-direction, where the y-direction acoustic radiation force component Fy is 0 and the deviation from this position Fy is not zero, is directed towards this position, which is thus the equilibrium position of the particles in the y-direction and is arranged one after the other in the transport direction, so that focusing is achieved.
Fig. 10 shows the spatial distribution of the radiation force components Fx and Fz in the transport direction x at off-resonance (drive frequency 5.92MHz) calculated by numerical simulation. The position where x is 0 is the center position of the sound source where the sound pressure is maximum. It can be seen that the radiation force component Fz is always positive, meaning that the direction of the force is opposite to the direction of gravity, and thus the particles can be suspended. The radiation force component Fx is zero at the sound source center (x ═ 0), and is always positive at a position deviated from the sound source center. This means that the direction of the radiation force component Fx is directed towards the centre of the sound source, and therefore the radiation force component Fx will drive the particles to be transported directionally towards the sound source.
Since the cell particles are controlled by the acoustic radiation force to realize transportation and focusing, a complex pump system is not needed to drive and control the fluid, and sheath fluid is not needed to be introduced; since the cells are arranged by using the virtual channel formed by the acoustic radiation force, a micro-channel used in the prior art is not needed, so that the problem of cavity channel blockage is avoided; because the acoustic radiation force can arrange a plurality of lines of cells, multi-channel parallel processing of a plurality of lines of focusing is realized; because parts such as the flow chamber in the cell control module in the application have low cost and simple process, and can be replaced by a new device when measuring a new sample every time, the problem that residues in a flow channel pollute the new sample in the prior art is avoided. In conclusion, the flow cytometry detection scheme is free of micro-flow channels, micro-flow pumps, sheath fluid, disposability, parallel processing and low in cost.
Example two:
the second embodiment is a specific application example of the acoustic-driven flow cytometer detection apparatus of the present application. The artificial periodic structure shown in fig. 2 was prepared using C304 stainless steel based on a standard chemical etching process with parameters t-30 μm, h-20 μm, w-50 μm, and p-200 μm. The flow cell is composed of a quartz glass substrate, PDMS (polydimethylsiloxane) walls, and a glass top cap. The PDMS walls may be bonded to the base and cap. The ultrasonic transducer is a PZT4 piezoelectric ceramic plate with the center frequency of 6MHz, and is bonded with the glass substrate through epoxy resin. The geometric center of the ultrasonic transducer is not coincident with that of the artificial periodic structure, namely the ultrasonic transducer needs to be placed in an offset mode, the purpose of the ultrasonic transducer is to generate an offset sound source, so that cell particles which are deviated from the center of the sound source are subjected to the action of radiation force Fx shown in figure 10, and therefore directional transportation is conducted on the sound source. The control software controls a signal generator (AFG 3102, Tektronix, Beaverton, OR, USA) to generate a Chirp signal with a frequency of 5.90-5.94MHz, and the Chirp signal is amplified by a power Amplifier (150A100B, Amplifier Research, Souderton, PA, USA) to excite the piezoelectric ceramic plate PZT4 to generate ultrasonic waves. The ultrasonic excitation of the artificial periodic structure produces a local field on its surface as shown in figure 8 and an acoustic radiation force on the cell particles as shown in figures 9-10. When the cells are transported to a detection area, a high-pressure mercury lamp with a fluorescence excitation light source of 100W excites the stained cells to emit fluorescence, and a high-sensitivity fluorescence camera (QIMAGING optiMOS) records fluorescence images and transmits data to a computer. The image analysis processing software extracts the fluorescence intensity distribution of the image and further calculates the size and number of the cells.
Fig. 11 is an image acquired using an acoustically-driven flow cytometry detection system. The cells used in the experiment were MCF-7 tumor cells with a diameter of 15 μm. Cells were stained with calcein fluorochrome and injected into the flow cell. The radiation force generated by the ultrasonic radiation force generating system aligns the cells and transports the cells to the detection area. When the cells reach the detection area, the fluorescence excitation light source excites the stained cells to emit green fluorescence, and a fluorescence image is recorded by a high-sensitivity fluorescence camera and is transmitted into a computer through a high-speed acquisition card. The image analysis processing software of the computer automatically extracts the fluorescence intensity curve, and respectively calculates the size of the cells and the number of the cells according to the size of the peak value and the number of the peaks. FIG. 11 extracts the fluorescence intensity curves of a single column of cells in a dashed box.
Example three:
the third embodiment is different from the first embodiment in the structure of the radiation force generating mechanism. As shown in fig. 12, the radiation force generating mechanism may include a plurality of transducers disposed outside the flow chamber and used to synthesize the sound field.
In one embodiment, the plurality of transducers includes at least one ultrasonic transducer and interdigital transducers arranged in pairs and in parallel, the interdigital transducers are used for synthesizing standing wave fields to arrange the cells for focusing, and the ultrasonic transducer is used for generating bias Gaussian beams to transport the cells. The interdigital transducers can be a pair or a plurality of pairs, and fig. 12 includes a pair of interdigital transducers, namely a first interdigital transducer 13 and a second interdigital transducer 14, wherein the ultrasonic transducer 15 is a piezoelectric transducer PZT, and 40 is a cell. The interdigital transducer 1 and the interdigital transducer 2 are used for synthesizing a standing wave field to arrange cells for focusing, and the piezoelectric transducer PZT is used for generating a bias Gaussian beam to convey the cells.
The ultrasonic radiation force generating system may include a plurality of ultrasonic transducers, a signal generator, and a power amplifier. A part of the ultrasonic transducer is used for controlling the cell arrangement to focus; the other part of the transducers is used as a biased gaussian beam source to drive the particle transport. The sound field synthesized by the sound waves emitted by the ultrasonic transducers generates a sound field with operation and control functions of transportation, arrangement and the like, so that the focusing and transportation of cells are realized.
The foregoing is a more detailed description of the present application in connection with specific embodiments thereof, and it is not intended that the present application be limited to the specific embodiments thereof. It will be apparent to those skilled in the art from this disclosure that many more simple derivations or substitutions can be made without departing from the spirit of the disclosure.
Claims (6)
1. An acoustically-driven flow cytometry device comprises a cell manipulation module, an imaging module and an image processing module, wherein the cell manipulation module is used for manipulating cell particles in a sample solution, the imaging module is used for carrying out fluorescence imaging on stained cell particles, the image processing module is used for processing and analyzing fluorescence images, counting the cell particles and estimating the size of the cell particles, and the acoustically-driven flow cytometry device is characterized in that the cell manipulation module comprises a flow chamber and an ultrasonic radiation force generation system, and the flow chamber is used for containing the sample solution containing the cell particles; the ultrasonic radiation force generation system is used for generating an acoustic radiation force on cell particles, controlling the cell particles to be arranged into parallel lines, realizing multi-line focusing, suspending the cell particles, and simultaneously driving the cell particles to be directionally conveyed to a detection area to realize multi-channel parallel detection;
the ultrasonic radiation force generation system comprises a radiation force generation mechanism, a signal generator and a power amplifier, wherein an electric signal generated by the signal generator is amplified by the power amplifier, and then the radiation force generation mechanism is excited to generate ultrasonic waves and further generate radiation force on particles so as to realize the transportation and control of cells; the radiation force generating mechanism comprises an ultrasonic transducer and an artificial structure arranged in the flow chamber, and the ultrasonic transducer is excited to generate ultrasonic waves and further generate radiation force on particles by electric signals amplified by the power amplifier; the artificial structure comprises an artificial periodic structure;
the ultrasonic transducer is disposed outside the flow chamber and is not coincident with a geometric center of the artificial periodic structure.
2. The acoustically-driven flow cytometer detection device of claim 1, wherein the flow cell comprises a substrate, PDMS sidewalls, and a glass cap, the PDMS sidewalls bonded to the substrate and the glass cap, respectively, the substrate being made of quartz glass, plexiglass, or silicon.
3. The acoustically driven flow cytometer detection device of claim 1, wherein the artificial periodic structure comprises a substrate and a plurality of ribs disposed on a lower surface of the substrate, the ribs being disposed in parallel and at equal intervals.
4. The acoustically driven flow cytometer detection device of claim 1, wherein the artificial structure is fabricated from a stainless steel material.
5. The acoustically-driven flow cytometry apparatus of claim 1 wherein said radiation force generating mechanism comprises a plurality of transducers positioned outside the flow chamber for synthesizing an acoustic field.
6. The acoustically-driven flow cytometer detection device of claim 5, wherein the plurality of transducers comprises at least one ultrasonic transducer and a pair of interdigital transducers arranged in parallel, the interdigital transducers configured to synthesize a standing wave field to align the cells for focusing, the ultrasonic transducer configured to generate an offset gaussian beam to transport the cells.
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| CN111530513B (en) * | 2020-04-24 | 2021-06-25 | 南京师范大学 | Acoustic tweezers based on artificial structure is dull and stereotyped |
| CN112899158B (en) * | 2021-01-15 | 2022-08-05 | 深圳康沃先进制造科技有限公司 | Micro-processing gas matching layer modulation body ultrasonic cell assembling and arranging device, preparation method and application |
| WO2023283752A1 (en) * | 2021-07-12 | 2023-01-19 | 中国科学院深圳先进技术研究院 | Rotation control module, method, and system |
| CN114088606B (en) * | 2021-10-23 | 2023-05-09 | 广州市艾贝泰生物科技有限公司 | Cell analysis device |
| CN114146890B (en) * | 2021-12-03 | 2022-09-13 | 深圳先进技术研究院 | Ultrasonic sound control method and sound tweezers device |
| WO2023108473A1 (en) * | 2021-12-15 | 2023-06-22 | 中国科学院深圳先进技术研究院 | Acoustic artificial structure-based particle sorting method |
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| CN105395215A (en) * | 2015-12-30 | 2016-03-16 | 中国科学院声学研究所东海研究站 | Ultrasonic imaging device and method |
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