CN101548172A - Fluidic cell manipulator - Google Patents
Fluidic cell manipulator Download PDFInfo
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- CN101548172A CN101548172A CNA2007800444693A CN200780044469A CN101548172A CN 101548172 A CN101548172 A CN 101548172A CN A2007800444693 A CNA2007800444693 A CN A2007800444693A CN 200780044469 A CN200780044469 A CN 200780044469A CN 101548172 A CN101548172 A CN 101548172A
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/1404—Handling flow, e.g. hydrodynamic focusing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C1/00—Magnetic separation
- B03C1/02—Magnetic separation acting directly on the substance being separated
- B03C1/28—Magnetic plugs and dipsticks
- B03C1/282—Magnetic plugs and dipsticks with associated accumulation indicator, e.g. Hall sensor
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C5/00—Separating dispersed particles from liquids by electrostatic effect
- B03C5/02—Separators
- B03C5/022—Non-uniform field separators
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/1404—Handling flow, e.g. hydrodynamic focusing
- G01N2015/1415—Control of particle position
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Abstract
The present invention discloses a system (100) for individually manipulating, e.g. orienting, a particle (104) in a fluid (106). The manipulating system (100) comprises a particle trapping system (111) allowing trapping of the particle (111) in a fluid channel (102) and a controller for controlling shear force gradients on the particle. Shear force gradients on the particle are 5 controlled by positioning a particle off center in the fluid channel (102) in a laminar flow or by controlling the laminar flow itself. The laminar flow thereby is generated using a flow generator (108). The system (100) for manipulating may be used in a particle characterization system or may be used for performing actions on the particle (104) under predetermined orientations.
Description
Technical field
The present invention relates to particle characterization and manipulation field.More specifically, the present invention relates to handle object or,, also relate to the software of implementing this method so that they are checked or characterize such as the method and system of particles such as biological cell.
Background technology
The sign of analyte is in being usually used in chemistry, biochemistry or biologic test, with existing of the analyte that detects some type.For example, by detecting and/or describing cellularity, can detect malignant cell in principle, precancerous cell for example detects and/or the possibility of monitoring of diseases progress thereby provide, for example from before invading to the progress of invasion.The detection of single particle and/or sign because be generally used in the application of biology sensor, thereby allow to obtain qualitative and quantitative result.A kind of selection that detects the single particle characteristic be optionally with bind particles of interest in the surface and its special characteristic of sensing.The another kind of detection single particle characteristic selects to be to use the single particle in the capture system seizure fluid.
Many different capturing technologies are known, as using the optics capture system, for example based on laser instrument, are called tweezer (tweezer) again, use dielectrophoresis, use sound field, use contraction of flow channel or the like.Great majority in these technology do not allow to determine or control the orientation of cell.Yet, can bring into play significant role in the sign that is oriented in cell of cell, for example when particle hinders detection to the particle characteristics that exists at the particle back side, or when the predetermined orientation of particle was favourable for this particle of manipulation, detection may make a mistake.In other words, can make wait to characterize with pending particle orientation may be highly significant to the influence of research and unicellular application.
In International Patent Application WO 2006/059109, the single cell analysis instrument has been described, wherein use ligh trap to carry out the seizure and the manipulation of cell.Ligh trap uses laser instrument and condenser lens to handle the cell in the ligh trap.By along three-dimensional mobile focussed laser beam, can change the position of cell, by adjusting the interval between a plurality of hot spots, cell can be stretched or compress, and, cell can be rotated by the polarization of rotary beam or the pattern of beam spot.
Summary of the invention
The purpose of this invention is to provide a kind of better systems and the method for the particle in the fluid and software of implementing this method handled.The advantage of present embodiment is, can select the orientation of particle, for example single particle at sign, detection and/or processing intent in the described system and method.Can realize above-mentioned purpose by method and apparatus of the present invention.
The present invention relates to the system of the particle in a kind of individual operation fluid, described system comprises mobile generator, be used for producing the laminar fluid flow of described fluid in the fluid passage, and particle manipulator, be used for catching the described particle of described fluid passage and making its orientation by control the clean shearing force that described laminar fluid flow causes on described particle.Described particle manipulator can be used for controlling the orientation and/or the rotation of described particle by changing described particle in the position in the flow field of the laminar flow of described fluid and/or by changing velocity distribution in the flow field at the laminar flow of described fluid.Can provide clean shearing force by in having the shearing force field of shear force gradient, introducing particle.Thereby because the shearing force of a side is greater than the shearing force of opposite side, particle can rotate, and causes clean shearing force on particle.The advantage of embodiments of the invention is that described system allows to change the orientation of particle.Being also advantageous in that of embodiments of the invention can obtain the accurate orientation and the location of particle.Being also advantageous in that of embodiments of the invention can obtain the single particle control system.Being also advantageous in that of embodiments of the invention can obtain each required orientation of particle.Particle manipulator can directly act on the particle that will be captured or can act on the described particle by acting on the label that is bound by on the particle.
Described particle manipulator can comprise the particle position controller that is used for being substantially perpendicular to the described particle position of control on the flow direction of described laminar fluid flow.The advantage of this embodiment is that described capture system and particle position controller can be same parts, promptly can be by same parts performance location and seizure effect.This embodiment is also advantageous in that, can control orientation by described particle position, thereby allows the described system of operation in continuous flow.
Described particle position controller can be used for described particle is moved to the precalculated position of described fluid passage, and described there laminar flow causes predetermined clean shearing force on described particle.This embodiment is also advantageous in that, described particle position controller allows accurately to move described particle.The advantage of this embodiment is, can select the rotation direction of described particle.This embodiment is also advantageous in that, can be provided with at an easy rate and can obtain required amount of spin exactly.The advantage of this embodiment is, can obtain required orientation effectively.
The shape of described fluid passage can be arranged to described fluid passage and comprise that in the capture region of described particle at least one does not wherein have clean shearing force to act on position on the described particle when having laminar flow.The advantage of this embodiment is that described system can be used for continuous laminar flow zone.Described particle position controller can be used for described particle moved to does not wherein have shear force gradient to act on position on the described particle when having laminar flow.
The described particle manipulator that is used to control the clean shearing force that described laminar fluid flow causes on described particle can be used to control the intensity of the laminar fluid flow that described mobile generator produces.
Described particle manipulator can comprise the flow controller of the intensity that is used to control the laminar fluid flow that described mobile generator produces.Described flow strength is for example determined by Peak Flow Rate, can change between predetermined Peak Flow Rate 0 for Peak Flow Rate.Control described clean shearing force and can comprise the ON/OFF state of controlling described mobile generator and/or the flow velocity of described laminar fluid flow.The advantage of this embodiment is that described system can be used for various types of fluid passages, for example the fluid passage of different shape.This embodiment is also advantageous in that, can select the rotating speed of described particle.
Described particle manipulator can comprise at least one light tweezer.Described particle manipulator can comprise two crossed optical tweezers.Described smooth tweezer can comprise and can be provided with and adjustable focus, thereby allow in two non-parallel direction position particles perpendicular to flow direction.
Described particle manipulator can comprise at least one dielectrophoretic trap.
Described system can also comprise the feedback system that is used to measure particle position and orientation and is used for providing to described particle manipulator feedback control signal.Advantage according to the system of present embodiment is, mode and/or automated manner that can robotization be handled.
Described system can also comprise and is used for when the predetermined orientation of described particle material injected described particle and/or from the disposal system of described particle extraction of substance.The advantage of this embodiment is, can realize the more accurate processing of particle, and not need particle is orientated biochemically.
It is 0m/s～10 that described mobile generator can be used to provide Peak Flow Rate
-3The laminar fluid flow of m/s.Selectively or in addition, it is 0m/s～10 that described flow controller can be used to provide Peak Flow Rate
-3The laminar fluid flow of m/s.Peak Flow Rate can be the speed in described fluid passage central authorities, can be 0mm/s～10 at least
-3M/s.Selectively or in addition, Peak Flow Rate can be at least 10
-5Mm/s, for example at least 10
-4Mm/s, for example at least 10
-3Mm/s.
Described system can be used for the individual operation biological cell.
The invention still further relates to a kind of characterization system that characterizes particle, described particle characterization system comprises the system of the particle in the above-mentioned individual operation fluid, for example this system comprises mobile generator, be used for producing the laminar fluid flow of described fluid in the fluid passage, and particle manipulator, be used for catching the described particle of described fluid passage and making its orientation by control the clean shearing force that described laminar fluid flow causes on described particle, described characterization system also is used to measure the characteristic performance of particle.
Described characterization system can comprise and be used to detect described particle or be bound by the magnetic property of the label on the described particle or the pick-up unit of optical property.Advantage is according to an embodiment of the invention, can carry out more accurate and/or effective sign to particle.
The invention still further relates to the method for the particle in a kind of individual operation fluid, described method is included in the laminar fluid flow that produces described fluid in the fluid passage, catch separately the described particle in the described fluid passage and make described particle orientation by control the clean shearing force that described laminar fluid flow causes on described particle.Can control clean shearing force by in having the shearing force field of shear force gradient, introducing particle.Make described particle orientation can comprise by change described particle in the flow field of the laminar flow of described fluid the position and/or control the orientation and/or the rotation of described particle by changing velocity distribution in the flow field of the laminar flow of described fluid.Thereby because the shearing force of a side is greater than the shearing force of opposite side, particle can rotate, and causes clean shearing force on particle.Described control can comprise is in the laminar flow field that produces clean shear force gradient on the described particle described particle.Described control can comprise by opening the laminar flow field cause shear force gradient on described particle.Handle described particle and can make described particle orientation.Handling described particle can be to handle biological cell.
The invention still further relates to a kind of method that characterizes the particle in the fluid, comprise the described particle of method individual operation, thereby obtain the predetermined orientation of described particle according to the particle in the above-mentioned manipulation fluid, and the performance of under described predetermined orientation, measuring described particle.
The invention still further relates to the controller that uses in a kind of system of the particle (biological example cell) in above-mentioned individual operation fluid.
The invention still further relates to a kind of computer program, be used for when on calculation element, carrying out, carry out the method for the particle (biological example cell) in the individual operation fluid, described method is included in the laminar fluid flow that produces described fluid in the fluid passage, catch separately the described particle in the described fluid passage and make described particle orientation by control the clean shearing force that described laminar fluid flow causes on described particle.
The invention still further relates to a kind of machine readable data storage device and/or the transmission of described computer program on local or wide-area communication network that is used to store above-mentioned computer program.
Being also advantageous in that of embodiments of the invention obtains effective system and method that object or particle (for example single particle) are orientated.The advantage of embodiments of the invention is, do not need complicated capture system, for example has a plurality of spots or has the laser system of rotating laser beam.The advantage of embodiments of the invention is that mode makes particle orientation accurately.Being also advantageous in that of embodiments of the invention can controllable mode make particle orientation.The advantage of embodiments of the invention is, the initial orientation of the particle that is captured (for example cell), and for example random orientation can change, and can Be Controlled.In other words, specific embodiment of the present invention provides the controlling mechanism that allows with the controlled manner rotating particle.Being also advantageous in that of embodiments of the invention, the disturbance that the particle that uses described method and system to be orientated is subjected to, change and/or damage are minimum, for example, because do not need Mechanical Contact.
In appended independent claims and dependent claims, illustrated of the present invention specific and preferred aspect.The feature of dependent claims can be with the characteristics combination of independent claims, make up aptly with the feature of other dependent claims, and is not only clear and definite those of record in claims.
Instruction of the present invention allows design to characterize and/or handles improving one's methods and installing of particle, for example optical characterisation particle.From below in conjunction with will very clear above-mentioned and other characteristics of the present invention the detailed description of accompanying drawing, feature and advantage, wherein accompanying drawing is used to illustrate principle of the present invention.Instructions only is as an example, and does not limit the scope of the invention.The reference drawing number of quoting from below refers to accompanying drawing.
Description of drawings
Fig. 1 is the synoptic diagram according to the system of the manipulation of particles of first aspect present invention embodiment.
Fig. 2 is the synoptic diagram of the influence of the particle in the fluid stream fluid flow, and this may occur in the system according to the manipulation of particles of first aspect present invention embodiment.
Fig. 3 is at the xsect medium velocity of the axial symmetric fluid passage figure to the position, and this can be used in the system according to the manipulation of particles of first aspect present invention embodiment.
Fig. 4 is the figure of shear force versus position in the xsect of axial symmetric fluid passage, and this can be used in the system according to the manipulation of particles of first aspect present invention embodiment.
Fig. 5 and Fig. 6 are according to two light tweezers of use of first specific embodiment of first aspect present invention synoptic diagram (part) as the example system of the manipulation of particles of the vertical and horizontal positioning device of particle.
Fig. 7 is by being used in the synoptic diagram according to the beam position cell in the system of the manipulation of particles of first aspect present invention embodiment.
Fig. 8 is according to light tweezer of use of second specific embodiment of first aspect present invention synoptic diagram as the system of the manipulation of particles of the locating device of particle.
Fig. 9 is the synoptic diagram according to the sign of the sign particle of second aspect present invention embodiment.
Figure 10 is the synoptic diagram that can be used for implementing according to the computing system of the method for the manipulation of particles of fourth aspect present invention embodiment.
In different accompanying drawings, identical Reference numeral is used in reference to identical or similar elements.
Embodiment
Describe the present invention below with reference to specific embodiment with reference to some accompanying drawing, but the invention is not restricted to this, but limit by claims.Any Reference numeral in claims should not be interpreted as limited field.Shown in accompanying drawing just schematically, be not restrictive.In the accompanying drawings, for the purpose of illustration, some size of component may be exaggerated, rather than draw in proportion.
If use term " to comprise " in instructions and claims, then it does not get rid of other elements or step.If used a kind ofly when referring to singular noun, unless then specify in addition, it comprises the plural number of this noun.In addition, the term in instructions and claims first, second etc. be used to distinguish similar elements, and not necessarily time or spatial order are described with rank or in any other mode.In addition, the term top in instructions and claims, bottom etc. are used for illustration purpose, not necessarily describe relative position.Be appreciated that used term suitably can exchange under the situation, and the embodiment of the invention as herein described can be with sequence outside described herein or the explanation and/or orientation operation.
In this manual, when mentioning " embodiment ", be meant that this embodiment described special characteristic, structure or a characteristic comprise at least one embodiment of the present invention.Therefore, in this manual, when occurring in the phrase " in one embodiment ", not necessarily all mention same embodiment, but also may be like this various.In addition, can any suitable mode make up special characteristic, structure or characteristic in one or more embodiments, this will be obvious for those skilled in the art.
Equally, should recognize that when describing exemplary embodiment of the present invention, various features of the present invention are combined in together sometimes in an embodiment, accompanying drawing or its explanation, to simplify disclosure and to help to understand one or more inventive aspects.Yet, this disclosure method should not be interpreted as having reflected invention required for protection than in each claim clearly the feature needs of statement more many purpose of feature.On the contrary, reflect that inventive aspect is to be less than all features of an above-mentioned disclosure embodiment as claims.Therefore, appended claims is incorporated in the detail specifications clearly, and each claim itself is as independent embodiment of the present invention.
In addition, though embodiment more described herein comprise some features, rather than other features that comprise among other embodiment, the combination of features of different embodiment is also within the scope of the invention, and constitute different embodiment, this is understandable for those skilled in the art.For example, in appended claims, any embodiment required for protection all can be used in any combination.
In addition, this paper describes processor that work can be by computer system with some embodiment or the method implemented by other modes that realize this function or the combination of method key element.Therefore, have be used to implement described method or method key element must instruction processor constitute the device of implementing described method or method key element.In addition, the described key element of device embodiment is the example for the mode of the function that key element realizes that realizes the object of the invention.
In the explanation that is provided, many details have been described.Yet, be appreciated that embodiments of the invention can implement under the situation of these details not having.In other cases, well-known method, structure and technology do not go out out in detail, in order to avoid overslaugh is to the understanding of instructions.
Following term or definition are provided, only are used for the auxiliary invention of understanding.
If use term " particle " in the present invention, then can refer to chemistry, biochemistry or biomone, for example need detected particle, such as but not limited to cell, organelle, film, bacterium, virus, chromosome, DNA, RNA, organic molecule, metabolin, protein (comprising enzyme, polypeptide, nucleic acid fragment, spore, microbial body and its fragment or product), polymkeric substance, metallic ion, toxin, illegal medicine, explosive etc.The preferred diameter of particle is greater than 0.1 μ m, more preferably greater than 0.5 μ m, for example greater than 1 μ m, because these particles can be subjected to extra intrinsic diffusion motion still less usually.Particle, especially less particle, for example some DNA, RNA, nucleic acid fragment etc. also can be connected with bigger particle, so that their are orientated or locate them.Particle can be a biological cell.
If use term " laminar flow " in the present invention, then refer to mobile flow region take place in such as parallel layers or concentric layer according to the shape of flow channel.Flow and also can be described as non-turbulent flow or streamline flow.For example, can measure flow by Reynolds number, Reynolds number represent this product ratio for density, fluid velocity with on average by the product of diameter and the ratio of viscosity.In the present embodiment, flowing to have 0～10 Reynolds number, and for example Reynolds number is 0～1, and for example Reynolds number is 0～0.5.
In first aspect, the present invention relates to a kind of system that handles the particle in the fluid.This system allows particle to be orientated in fluid thus, and for example fruit will detect particle characteristics, but be hidden in the particle back side with respect to detection system, if perhaps the detection of predetermined orientation or processing are preferred, this is favourable so.This system can be used for handling single particle, i.e. individual operation particle, biological example particle.This system comprises the particle manipulator that is used for catching at the mobile generator and being used for that the fluid passage produces the laminar fluid flow of the fluid comprise particle the shearing force that is caused by laminar fluid flow on the particle of fluid passage and the control particle.Therefore, this particle manipulator can comprise the particle capture system, as the optics capture system, uses sound field, uses dielectrophoresis, uses the distortion of passage, and for some particles, uses electric field and/or magnetic field.In addition, it can comprise particle position controller and/or the flow controller that is used to control mobile generator.
In Fig. 1 example of passing the imperial examinations at the provincial level different standards and selectable unit (SU) are shown, but the invention is not restricted to this.Discuss the different parts of the example system 100 of manipulation of particles 104 in more detail below with reference to Fig. 1～Fig. 8.
The system 100 that handles the particle 104 in the fluid 106 comprises the generator 108 that flows.The generator 108 that flows can for example be (part or all of) active Flow generator, comprise the aspirator that for example aspirates fluids 106 by fluid passage 102, control by controlling this aspirator thus, and/or mobile generator 108 can be (part or all of) passive mobile generator, wherein flows and uses valve or valve group to carry out FLOW CONTROL thus by producing such as natural forces such as gravitative pressure or capillary forces.The generator 108 that flows is fit to generate the fluid passage 102 of laminar flow, and wherein, 104 in the manipulation of particles fluid will carry out 106.The generator 108 that flows can for example be used to produce fluid velocity, makes for given fluid viscosity and density and given fluid channel dimensions, obtains laminar flow.When fluid generation laminar flow, there is different shear stresses at the diverse location of flow channel.For example, this mobile Reynolds number that is characterised in that is 0～4000, and preferred Reynolds number is 0～3000, and more preferably Reynolds number is 0～2000 again.The generator 108 that flows for example can be used to provide 0m/s～10
-3The fluid velocity of m/s, for example 0m/s～10
-4M/s, for example 0m/s～1 10
-5M/s, for example 0m/s～1 10
-6M/s.The size and dimension of the fluid passage 102 in the system 100 also can be the OK range that is used to be easy to obtain laminar flow condition.Fluid passage 102 can be a tubular in shape, axisymmetric shape for example, thus produce concentric laminar flow, promptly fluid velocity has radial distribution and the particle 104 in the fluid flow of the center of fluid passage 102 does not have flowing of clean shearing force basically.Fluid passage 102 also can be a rectangular shape roughly, and promptly fluid stream for example can be the fluid stream between two plates.For ease of understanding, each embodiment and example will describe at the tubular fluid passage with axisymmetric shape, but the invention is not restricted to this.For example, also can use other shapes of fluid passage 102, thereby have their own specific laminar fluid flow velocity distribution.Though preferably have at least one point in the xsect of fluid passage 102, roughly the same at this both sides flow velocity, making does not roughly have clean shearing force on particle 104, the invention is not restricted to this.Such as will be described, for example also can control rotation by such fluid stream of controlling.
By producing laminar flow, different fluid velocities will take place in general diverse location in fluid passage 102.For the example of axial symmetric fluid path 10 2, the latter will illustrate in Fig. 2 to Fig. 4, but the invention is not restricted to this.Fig. 2 shows, if there are not 102 the central authorities in the fluid passage of fluid stream and particle, then will cause rotating on particle 104.To occur rotating along direction shown in the arrow r.The rotating speed of particle may depend on the position of cell in flow velocity and the passage.This rotation by two of particle 104 in the fluid 106 not the current difference of ipsilateral caused.Speed is presented among Fig. 3 along the distribution of axial symmetric fluid path 10 2 diameters, has shown current difference.Such velocity distribution causes shear stress on particle, as shown in Figure 4.The shear stress gradient is caused by the laminar flow of all positions in pipe, except the position on the tube hub axle, and perhaps for the more general shape of fluid passage, the central authorities in the fluid passage.From showing as can be seen as Fig. 4 of the shear stress of function of position, i.e. 102 the middle position in the fluid passage, shear stress is zero, do not rotate thereby cause, and the closer to the fluid passage 102 wall, shear stress is big more, thereby causes rotation.In other words, if produce laminar flow, then will not rotate along a direction in the central authorities of fluid passage or the particle of central shaft.According to particle position, can cause that bear or positive shear stress, thereby particle 104 is rotated along different directions.
As mentioned above, system 100 also comprises particle manipulator 110.Particle manipulator 110 is used for catching the particle of fluid passage 102.Therefore, particle manipulator 110 preferably includes particle capture system 111.Particle capture system 111 can be used for catching relevant particle 104 at the xsect that is substantially perpendicular to direction of fluid flow.Particle capture system 111 can be based on any suitable seizure mechanism, catch mechanism such as but not limited to optics, for example make and use the light tweezer, use the mechanism of dielectrophoresis, use the mechanism of sound field, make fluid passage 102 produce the mechanism of distortion, for example make fluid passage 102 produce the system of shrinking, under situation about using, use the mechanism of magnetic field and/or electric field to the particle of magnetic field or electric field-sensitive, or the like.If insensitive to power used in the mechanism of catching by the particle handled, so for example they can also be tied on the label to power sensitivity used in the mechanism of catching.For example, when using magnetic force to catch mechanism, can be the non magnetic particle that is bound by on magnetic or the magnetisable label with the particle that is captured.Particle capture system 111 is preferred for catching particle 104 with the fluid stream further dilatory power in fluid passage 102 that is enough to stop particle 104 to be applied in.For instance, show the example that allow to stop the capture system that particle 104 is stowed under the power effect that flow velocity causes.For example, the light tweezer can apply the power of slight Newton range.In steady state (SS), streaming flow is applied to power on the sphaerocyst by 3 π η VD, and wherein V is a rate of flow of fluid, and η is a fluid viscosity, and D is a cell dia.Utilize η=110
-3Pas, D=1 10
-5M, and resistance is set is 1 10
-12N as can be seen, can compensate 1 10 at an easy rate
-5The flow velocity of m/s.
Selectively or in addition, if for example in fluid passage 102 not point do not have clean shearing force basically, but be not limited thereto, by controlling the laminar flow that the generator 108 that flows is produced, can realize control so to the clean shearing force that is caused.In other words, selectively or or except particle position controller 112, particle manipulator 110 can comprise and is used to control the flow activation of generator 108 or the flow controller 113 of inactivation.Control activates and can also comprise and be controlled at the fluid flow velocity that is produced in the fluid passage 102.In other words, flow controller 113 can be used for opening or closing the flow field, and randomly also is used to change flow field intensity when opening the flow field.The latter allows to use the rotation speed change of this system's acquisition.Flow controller 113 can directly be connected with mobile generator 108, or can be connected with mobile generator via system controller.Flow controller and/or mobile generator can be used for control and flow, and make that the Peak Flow Rate in the passage is 0m/s～10
-3M/s.Selectively or or in addition, it is 0m/s～10 that flow controller can be used to provide Peak Flow Rate
-3The laminar fluid flow of m/s, for example 0m/s～10
-4M/s, for example 0m/s～1 10
-5M/s, for example 0m/s～1 10
-6M/s.Peak Flow Rate can be the speed of fluid passage central authorities, can be 0m/s～10
-3M/s.Selectively or in addition, Peak Flow Rate can be at least 10
-5Mm/s, for example at least 10
-4Mm/s, for example at least 10
-3Mm/s.
Therefore, by changing particle 104 in the position of clean shearing force field or by opening or closing clean shearing force field, for example by opening or closing laminar flow, particle manipulator 112 can be controlled the shearing force on the particle.
The system 100 that handles the particle 104 in the fluid 106 can also comprise the system controller 116 that is used to control particle manipulator 110 and mobile generator 108.System controller 116 can comprise the synchronizer 118 that makes particle manipulator 110 and mobile generator 108 simultaneous actions, i.e. for example action between any in particle capture system 111, flow generator 108 and particle position controller 112 or flow controller 113.Therefore, these parts can be provided with the input media that is used to receive synchronizing signal.Synchronously can be randomly based on the input of feedback system 114.System controller 116 can also comprise and is used to bring into play the not processor 120 of same-action.System controller 116 can be based on predetermined algorithm, use look-up table, based on neural network or operate in any other suitable manner.Control system can robotization mode and/or automated manner operation.
In a preferred embodiment, the system 100 of manipulation of particles 104 can comprise feedback system 114.Feedback system 114 can help further systems stabilisation 100.A kind of mode that feedback system 114 is provided is that combination is used for determining the position of particle 104 and/or the position and/or the orientation detector 115 of orientation.From the position and/or the directional detectors position and/or the orientation information that obtain can output to controller 116 by feedback system 114, or directly output to particle manipulator 110, thereby for example allow desired location position particles 104 and/or in required angle rotating particle 104.Position and/or orientation detector can be the optical detection systems, for example based on fluorescence detector.By unique label is provided for particle 104, particle surface for example, and, can help the optical detection of position and orientation by detecting the unique position of label on particle 104.This label can be energized, and also corresponding exciting bank can be set, for example exciting irradiation driving source, for example electricity and/or the magnetic field generator of fluorescence labels, excitation electricity and/or magnetic label.Selectively, Du Te label also can just be present in the shape or structure of particle originally.Thereby the time that particle rotates is suitable for obtaining relevant feedback from feedback mechanism.For the example of top definite maximum fluid velocity, diameter is that its rotation time of particle of 0.1 micron is 1 second.
For instance, but the invention is not restricted to this, the specific embodiment according to first aspect present invention is discussed in more detail below.
In first specific embodiment, the present invention relates to handle the system 200 of the particle 104 in the fluid 106, as mentioned above, wherein carry out the seizure of particle 104 and the clean shearing force on the control particle 104 by same parts.For example, controlling under the situation of the clean shearing force on the particle 104, can use the mechanism identical to carry out position control with capture system by the position of control particle 104.In the present embodiment, therefore capture system 111 can be used on the direction with at least one component that flows perpendicular to fluid improved.This can be used at the xsect that is substantially perpendicular to fluid stream improved, and wherein particle is captured.In a preferred embodiment, can be in two non-parallel direction position particles perpendicular to fluid stream.An example that allows the system component of seizure and location sample for example can be a cover crossed optical tweezers 202,204, as being shown among Fig. 5 and Fig. 6 with way of example.This crossed optical tweezers 202,204 allows to catch particle and improved in the xsect of fluid passage 102.Thereby xsect can be perpendicular to the cross section of the flow direction of fluid 106.The advantage of present embodiment is that particle is caught and located required number of components is limited.
For instance, but the present invention and embodiment be not limited thereto, and the system 200 that has tubular fluid path 10 2 has been shown among Fig. 5 and Fig. 6.The light tweezer 202,204 of catching and moving can allow to catch basically particle 104 in perpendicular to the plane of flow direction.Can change the orientation of particle 104 by position particles in the fluid stream that is to cause on the particle 104 clean shearing force.Therefore, particle can be reorientated the central authorities away from fluid passage 102.If particle 104 has left the central authorities of fluid passage 102, then this reorientating there is no need.Fluid stream can be continuous or can with the reorientating synchronously of particle 104, for example begin fluid after outside and flow, and stop fluid obtaining suitable orientation by moved on to central authorities at particle 104.Depend on the fluid velocity in the xsect of fluid passage 102 and/or position or its combination of particle 104, particle 104 will be more, degree or do not rotate still less.Thereby, because the asymmetric stress that is applied on the particle 104 causes rotation.Can change the speed that causes change in orientation by changing fluid velocity.When obtaining suitable orientation, can be by 102 centrally-located or reorientate particle 104 and stop operating in the fluid passage.As mentioned above, selectively, fluid stream can be closed, and therefore, fluid velocity can be 0m/s.It must be noted that,, can consider the inertia of particle 104 with respect to rotational motion for obtaining suitable orientation.
By change the focus of the light tweezer 202,204 of using (for example laser instrument), can change the particle 104 that is captured position in x and/or y direction.The latter can for example utilize controlled and adjustable lens is realized, as fluid lens, for example based on the wetting principle of electricity or by the mechanical alteration focus, for example by changing lens.Use the generator 108 that flows to change fluid stream.Advantage is that the suitable location positioning cell by in the fluid passage can obtain the rotation to any required orientation.By utilizing two crossed optical tweezers 202,204, can avoid being used to cover along the mechanical component that direction is improved.The advantage of this embodiment is, obtains symmetric force at x-and y-direction.For instance, two illumination beams 206,208 of use shown in Figure 7 position particles 104 in the xsect of fluid passage 102.
At second specific embodiment, the present invention relates to aforesaid system 250, for example described in first specific embodiment, but wherein particle manipulator 110 is based on the single smooth tweezer 252 that can machinery moves.In other words, only use an optical illumination source for assigned direction, laser instrument for example, thus if desired, carry out the location of particle in second direction by mobile optical irradiation source on slide block 254.This move can be mechanically, electric means, magnetic mode wait and carry out, but the invention is not restricted to this.Illustrate in Fig. 8 example of passing the imperial examinations at the provincial level according to the example system 250 of second specific embodiment.
In another embodiment, the present invention relates to the system 100 of manipulation of particles 104, system 100 also comprises the disposal system 130 of operation or processing particle 104 thus.Disposal system 130 can be an extracorporeal treatment, and wherein the orientation of particle may be significant.This disposal system 130 can be material to be injected particle or from the system of particle extraction of substance.This disposal system 130 can for example be the microinjection system, thus microinjection in particle 104 under the controlled orientation of particle.Selectively or in addition, this disposal system 130 also can provide the system of the electroporation of particle or bombardment or the like.Can use some example technique of carrying out according to system of the present invention is transfectional cell and in vitro fertilization, but the invention is not restricted to this.Operation or disposal system 130 schematically are shown among Fig. 1.
Advantage according to the embodiment of this aspect is, can control the orientation of single particle.
In second aspect, the present invention relates to a kind of characterization system that characterizes particle, comprising system as the described individual operation particle of first aspect.This system is shown among Fig. 9 for example.Therefore, characterization system 600 comprises the system of above-mentioned individual operation particle 104, can also comprise the detection system 602 that is used to measure particle 104 characteristics.This detection system 602 can comprise excitation system and be used to encourage the particle 104 and the detecting device that is used to detect its response that is captured and chooses orientation wantonly.Selectively or except detecting device and/or exciting bank, characterization system 600 can also allow the details of optical detection particle, as visual examination.This detecting device can for example be a fluorescence detector, for example is used to detect the fluorescence detector of the fluorescence reaction of particle, is used to detect the magnetic detector of magnetic property, as hall detector or magnetoresistance detector.Characterization system 600 can also utilize the detection based on label, and wherein label is bound by on the particle with predetermined characteristics by selectivity, and label detects the particle that allows quantification and sign to have this predetermined characteristics.In other words, characterization system 600 is used in label detection at particles, for example at the cell membrane place, and/or the performance characterization of particle 104.Characterization system 600 can be used for the detection of particles particle performance to a plurality of different orientations, for example by many predetermined orientations being provided for particle and characterizing or detect performance for each predetermined orientation.Control system 100 can for example be used for checking the back side that whether has label or other correlated performances not to be hidden in particle 104, thereby stashes for characterizing or detecting.In this way, use can obtain better characterizing qualitatively according to characterization system of the present invention.Except detection system 602, characterization system 600 comprises also that preferably being used for accepting detection information and processing and optional analysis from detection system 602 detects information processing device 604.Result is exportable to the user.This treating apparatus 604 is process information in any suitable manner, for example based on predetermined algorithm, neural network etc., and the mode of robotization and/or automated manner operation.
In the third aspect, the present invention relates to be used for controlling the system controller 116 of the individual operation of particles in system 100, for example first aspect is described like that.System controller 116 can be controlled the overall operation of the system 100 of individual operation particle 104.The generator 108 that flows can be connected with system controller 116 usually with particle manipulator 110.In addition, system controller 116 can obtain input from feedback system.According to the system controller 116 of this aspect be used for control system be used for produce fluid 106 laminar flow mobile generator 108 and be used to control the particle manipulator 110 that is used for catching the particle 104 of fluid passage 102 and is used to control the shearing force that laminar fluid flow causes on particle.The latter can be undertaken by control signal predetermined or that calculate is provided to flow generator 108 and particle manipulator 110.By the flow controller 113 of control particle position controller 112 and/or the mobile generator 108 of control, can control shearing force.If exist, system controller 116 can also comprise flow controller 113, thereby brings into play its effect.System controller 116 can also comprise the storer that is used to store the controlled variable of controlling flow generator and particle manipulator.This controller can comprise computing equipment, microprocessor for example, and for example it can be a microcontroller.Especially, it can comprise Programmable Logic Controller, and programmable digital logic device for example is as programmable logic array (PAL), programmable logic array, programmable gate array, especially field programmable gate array (FPGA).Utilize FPGA to allow subsequently to control system 100 programmings, for example by downloading required FPGA setting.System controller 116 can be according to set parameter running.
In fourth aspect, the present invention relates to the method for the particle 104 in a kind of individual operation fluid 106.According to this aspect, fluid stream is produced becomes to make the laminar flow that obtains fluid 106 in fluid passage 102.The latter can be undertaken by the fluid stream that comprises particle 104 is provided passively and/or on one's own initiative.Initiatively providing for example can be by obtaining via fluid passage 102 suction fluids 106.If cause under such as natural forces such as capillary action or actions of gravity flowing and by by-pass valve control make fluid by or obstructedly come to carry out FLOW CONTROL, the passive fluid stream that provides can be provided like this.This method also comprises the particle 104 of catching in the fluid passage 102.Can catch particle 104 by optics, for example utilize the light tweezer,,,, carry out the latter by applying magnetic field and/or electric field etc. by applying sound field by the distortion of fluid passage 102.This method also comprises the clean shearing force that the control laminar flow causes on particle 104.This control can cause shear force gradient to be carried out on particle 104 by particle 104 is in the flow field that produces clean shearing force on the particle 104 or by opening the flow field.The latter allows particle 104 orientations, for example according to predetermined direction.In one embodiment, the method for this aspect can also be included in operation or processing particle 104 under the predetermined orientation according to the present invention.Such operation or processing can for example be the microinjections with particle 104.This method can be particularly suitable for using carries out according to the described system 100 of first aspect present invention, and wherein different functions of components are corresponding to the possible method step of this aspect of the present invention.
Aspect the 5th, the present invention relates to a kind of method that characterizes particle 104, wherein this method comprises the method step of the described individual operation particle 104 of fourth aspect, this method also comprises the step of the characteristic performance of measuring particle 104.The latter can comprise excitation particle 104 and detect the physical reactions of particle 104, as fluorescence signal, magnetic response, electricity reaction etc.The characteristic performance of measuring particle 104 can also comprise to be differentiated particle 104 or checks whether particle 104 belongs to a certain kind.The characteristic performance of measuring particle 104 can also comprise the particle mechanics of measuring particle 104, because the latter can allow understanding or detect some disease.Characterizing method can also comprise the particle 104 of characteristic performance measure to(for) the different orientation of particle.The latter can be orientated whether some performance is hidden by particle 104 as some that help to detect for particle, or more generally is the characterization result reliability that improves gained.Similarly step and feature can be further provided, and be described as fourth aspect, and for example represented by the functions of components of the present invention first and second aspects.
Said method embodiment of the present invention can implement in disposal system 700, as shown in figure 10.A kind of configuration of Figure 10 display processing system 700, it comprises at least one programmable processor 703 that is connected with memory sub-system 705, this memory sub-system comprises the storer of at least a form, for example, RAM, ROM or the like.It must be noted that processor 703 or a plurality of processor can be the processors of general purpose or specific use, and can be incorporated in the equipment for example, have the chip of the miscellaneous part of carrying out other functions.Therefore, one or more aspect of the present invention can be implemented in Fundamental Digital Circuit or in computer hardware, firmware, software or in their combination.This disposal system can comprise storage subsystem 707, and it has at least one disc driver and/or CD-ROM drive and/or DVD driver.In some embodiments, display system, keyboard and pointing device may be comprised, as the part of user interface subsystem 709, so that the manual input information of user.Also can comprise the input and output FPDP.Can comprise more element, as network connect, with interface of various device or the like, but be not shown among Figure 10.Each element of disposal system 700 can connect in every way, comprises via bus sub 713, and Figure 10 is for simply showing a bus, but it will be understood by those skilled in the art that the system that comprises at least one bus.The storer of memory sub-system 705 some the time can carry part or all of (under any situation, all being shown as 711) of a cover instruction, when carrying out on disposal system 700, the step of method embodiment as herein described is carried out in described instruction.Therefore, although disposal system as shown in figure 10 700 is prior aries, comprise that the system of the instruction of the method each side of carrying out manipulation of particles or characterizing particle is not a prior art, so Figure 10 is not labeled as prior art.
The present invention also comprises a kind of computer program, and when carrying out on calculation element, this product provides the function of any method according to the present invention.This computer program can visibly embody in the mounting medium of the machine readable code that carrying is carried out by programmable processor.Therefore, the present invention relates to a kind of mounting medium that carries computer program, when on calculation element, carrying out, provide the instruction of carrying out above-mentioned any method.Term " mounting medium " refers to participate in provide any medium of instruction to carrying out processor.This medium can be taked various ways, includes but not limited to non-volatile media and transmission medium.Non-volatile media comprises for example CD or disk, as the memory device as the part of high capacity storage.The common type of computer-reader form medium comprises any other medium that CD-ROM, DVD, floppy disk, tape, storage chip or disk or computing machine can read.Various forms of computer-readable mediums can be for carrying out one or more sequences that processor carries one or more instructions.Computer program also can be by the carrier-wave transmission in the network, as LAN (Local Area Network), wide area network or internet.Transmission medium can be the form of sound wave or light wave, those as producing in radiowave and infrared data communication.Transmission medium comprises concentric cable, copper cash and optical fiber, is included in the electric wire that has bus in the computing machine.
The advantage of specific embodiment of the present invention is that these can be advantageously used in the research particle, for example studies cell.Being also advantageous in that of specific embodiment of the present invention, described method can be used for medical science and cell science field.
The advantage of specific embodiment of the present invention is, can determine the orientation of single cell.
Though be appreciated that at device according to the present invention preferred embodiment, concrete structure and configuration and material be discussed, under situation about not departing from the scope of the present invention with spirit, can make various variations or modification from form and details.
Claims (21)
1. the system (100) of the particle (104) in the individual operation fluid (106), described system (100) comprising:
-the generator (108) that flows, be used for (102) the described fluids of generation (106) in the fluid passage laminar fluid flow and
-particle manipulator (110) is used for catching the described particle (104) of described fluid passage (102) and making described particle (104) orientation in the described fluid passage (102) by control clean shearing force that described laminar fluid flow causes on described particle (104).
2. the system as claimed in claim 1 (100), wherein said particle manipulator (110) comprise the particle position controller (112) that is used for being substantially perpendicular to the position of the described particle of control (104) on the flow direction of described laminar fluid flow.
3. system as claimed in claim 2 (100), wherein said particle position controller (112) is used for described particle (104) is moved to the precalculated position of described fluid passage (102), and described there laminar flow causes predetermined clean shearing force on described particle.
4. as each described system (100) in the claim 1～3, the shape of wherein said fluid passage (102) is arranged to make described fluid passage (102) to comprise the position that at least one is such in the capture region of described particle, does not wherein have clean shearing force to act on the described particle (104) when having laminar flow.
5. as each described system (100) in the claim 1～4, the described particle manipulator (110) that wherein is used to control the clean shearing force that described laminar fluid flow causes on described particle (104) is used to control the intensity of the laminar fluid flow that described mobile generator (108) produced.
6. as each described system (100) in the claim 1～5, wherein said particle manipulator (110) comprises the flow controller (113) of the intensity that is used to control the laminar fluid flow that described mobile generator (108) produced.
7. as each described system (100) in the claim 1～6, wherein said particle manipulator (110) comprises at least one light tweezer (202,204,252).
8. as each described system (100) in the claim 1～7, wherein said particle manipulator (110) comprises at least one dielectrophoretic trap.
9. as each described system (100) in the claim 1～8, described system (100) also comprises the feedback system (114) that is used to measure particle position and orientation and is used for providing to described particle manipulator (110) feedback control signal.
10. as each described system (100) in the claim 1～9, described system (100) also comprises and is used for when the predetermined orientation of described particle (104) material injected described particle (104) and/or from the disposal system (130) of described particle (104) extraction of substance.
11. as each described system (100) in the claim 1～10, it is 0m/s～10 that wherein said mobile generator (108) is used to provide Peak Flow Rate
-3The laminar fluid flow of m/s.
12. as each described system (100) in the claim 1～11, wherein said system is used for the individual operation biological cell.
13. characterization system (600) that characterizes particle, described particle characterization system (600) comprises the system (100) as the particle (104) in each described individual operation fluid (106) in the claim 1～12, and characterization system (600) also is used to measure the characteristic performance of particle (104).
Be used to detect described particle or be bound by the magnetic property of the label on the described particle or the pick-up unit of optical property 14. characterization system as claimed in claim 13, described characterization system comprise.
15. the method for the particle (104) in the individual operation fluid (106), described method comprises
-the laminar fluid flow of the described fluid of generation (106) in fluid passage (102),
-catch separately in the described fluid passage (102) described particle (104) and
-make described particle orientation by the clean shearing force that on described particle (104), causes of the described laminar fluid flow of control.
16. the method for individual operation particle as claimed in claim 15 (104), wherein make described particle orientation comprise by change described particle in the flow field of the laminar flow of described fluid (106) the position and/or control the orientation or the rotation of described particle by changing velocity distribution in the flow field of the laminar flow of described fluid (106).
17. method that characterizes the particle (104) in the fluid (106), comprise according to each described particle of described method individual operation (104) in the claim 15～16, thereby obtain the predetermined orientation of described particle, and the performance of under described predetermined orientation, measuring described particle.
18. controller that in system, uses as the particle (104) in each described individual operation fluid (106) in the claim 1～12.
19. a computer program is used for when carrying out on calculation element, carries out the method for the particle (104) in the individual operation fluid (106), described method comprises:
-the laminar fluid flow of the described fluid of generation (106) in fluid passage (102),
-catch separately in the described fluid passage (102) described particle (104) and
-make described particle orientation by the clean shearing force that on described particle (104), causes of the described laminar fluid flow of control.
20. machine readable data storage device that is used to store the described computer program of claim 19.
21. the transmission of computer program as claimed in claim 19 on local or wide-area communication network.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06125224 | 2006-12-01 | ||
| EP06125224.3 | 2006-12-01 |
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|---|---|
| CN101548172A true CN101548172A (en) | 2009-09-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800444693A Pending CN101548172A (en) | 2006-12-01 | 2007-11-29 | Fluidic cell manipulator |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2010510803A (en) |
| CN (1) | CN101548172A (en) |
| BR (1) | BRPI0719508A2 (en) |
| WO (1) | WO2008068680A2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104765165A (en) * | 2015-04-20 | 2015-07-08 | 三峡大学 | Method and device for micro ball to rapidly achieve optical suspension |
| CN105068237A (en) * | 2015-07-21 | 2015-11-18 | 大连理工大学 | Method in which oblique incident light generates tunable non-gradient optical force on surface of chalcogenide metal multilayer core-shell |
| CN105116536A (en) * | 2015-07-21 | 2015-12-02 | 大连理工大学 | Method for producing tunable non-gradient optical force on surface of liquid crystal material/metal multilayer nuclear-shell based on linearly-polarized non-planar light |
| CN113647904A (en) * | 2021-07-12 | 2021-11-16 | 中国科学院深圳先进技术研究院 | Rotation control module, method and system |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI127992B (en) * | 2014-08-29 | 2019-07-15 | Svanbaeck Sami | Method and system for determining dissolution properties of matter |
| US10416065B2 (en) * | 2014-12-16 | 2019-09-17 | Celldynamics I.S.R.L. | Device for real time analysis of particles suspended in a fluid and method for the analysis of said particles |
| CN111965050B (en) * | 2020-08-19 | 2022-06-07 | 天津大学 | Method for testing shearing force of colloidal particle microfluid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002519176A (en) * | 1998-06-26 | 2002-07-02 | エボテック バイオシステムズ アクチェン ゲゼルシャフト | Electrode structure for generating functional electric field barrier in microsystem |
| EP1620203A2 (en) * | 2003-04-10 | 2006-02-01 | U.S. Genomics, Inc. | Manipulation of polymers in a microchannel |
-
2007
- 2007-11-29 CN CNA2007800444693A patent/CN101548172A/en active Pending
- 2007-11-29 JP JP2009538840A patent/JP2010510803A/en active Pending
- 2007-11-29 WO PCT/IB2007/054841 patent/WO2008068680A2/en active Application Filing
- 2007-11-29 BR BRPI0719508-7A patent/BRPI0719508A2/en not_active Application Discontinuation
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104765165A (en) * | 2015-04-20 | 2015-07-08 | 三峡大学 | Method and device for micro ball to rapidly achieve optical suspension |
| CN105068237A (en) * | 2015-07-21 | 2015-11-18 | 大连理工大学 | Method in which oblique incident light generates tunable non-gradient optical force on surface of chalcogenide metal multilayer core-shell |
| CN105116536A (en) * | 2015-07-21 | 2015-12-02 | 大连理工大学 | Method for producing tunable non-gradient optical force on surface of liquid crystal material/metal multilayer nuclear-shell based on linearly-polarized non-planar light |
| CN105068237B (en) * | 2015-07-21 | 2022-11-18 | 大连理工大学 | Method for generating tunable non-gradient optical force on chalcogenide metal multilayer core-shell surface by oblique incident light |
| CN113647904A (en) * | 2021-07-12 | 2021-11-16 | 中国科学院深圳先进技术研究院 | Rotation control module, method and system |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008068680A3 (en) | 2008-08-14 |
| JP2010510803A (en) | 2010-04-08 |
| WO2008068680A2 (en) | 2008-06-12 |
| BRPI0719508A2 (en) | 2013-12-31 |
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