CN1221309C - Apparatus for corpuscle field and flow separation by sound field force and other active force - Google Patents
Apparatus for corpuscle field and flow separation by sound field force and other active force Download PDFInfo
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Abstract
The present invention relates to the field of field flow separation, and particularly to discloses a device and a method thereof of a sound field force recognizing material which uses a sound field or is added with electrophoretic force or dielectrophoresis force as auxiliary during the field flow separation.
Description
Technical field
This invention is relevant with the field flow separation field.Especially, this invention has disclosed flow point on the scene from middle use sound field power or be aided with electrophoretic force or the apparatus and method of the sound field power recognition material of dielectrophoresis force.
Background technology
Field of engineering technology is very familiar to electricity-field flow separation (E-FFF) separates (DEP-FFF) with dielectric-field flow method.For example, United States Patent (USP) disclosed for No. 5240618 a kind of electric field flow point from method, United States Patent (USP) No. 5888370, No. 5993630 uses tradition to carry out the method and apparatus that field flow separates with the dielectrophoresis method of expanding with having disclosed for No. 5993632.In electricity-field flow separated, electrophoretic force was used for balance settling capacity (apply to big particulate, particle size reaches several microns or bigger) and/or diffusive force (applying to small particle), and the equilibrium position (or balanced distribution) of control particulate in fluid velocity distributes.Particle Distribution with different charge numbers, size, density is in different equilibrium positions (or different zonations), and with different speed by reaction tank, thereby can be separated into different parts.(Biophys is Aug:73 (2) J.1997: 1118-29 for Huang et al for example, Introducing dielelectrophoresis as a new force field for field-flow fractionation at dielectric-field flow separation method; Markx et al, applications of dielectrophoresis inbiotechnology, Trends Biotechnol, 1997 Oct, 15 (10): 426-32 and Wang et al, Separation of polystyrene mircrobeads using dielectrophoretic/gravitationalfield-flow-fractionation, Biophys J, 1998 May:74 (5): 2689-701), the vertical component of dielectrophoresis force is used for the balance settling capacity and controls the equilibrium position of particulate at fluid.Particle Distribution with different dielectric character is at the differing heights place of fluid and with different speed motions.Be directed to that electricity-field flow separates or dielectric-field flow separating reaction pond in particle mixture can isolate several subclass according to the time that particulate leaves reaction tank.The principle of electricity-field flow separation method has obtained confirmation on separation colloid adsorption complex.The principle of dielectric-field flow separation method has obtained confirmation when separating artificial synthetic polystyrene pearl body and biological cell.
But there is following limitation in the existing method and apparatus that is used for the field flow separation.Separate for electricity-field flow, galvanic polarization is a very significant problem, because added most voltage has all lost by electrode/medium interface the time.And electric charge only could be as the parameter of separating in some special case.Similar, to separate for dielectric-field flow, the dielectric properties of particulate also only could be as the parameter of separating in some special case.And in the dielectric-field flow of particulate separated, the forward dielectrophoresis force never was used.The separation efficiency of existing field flow separation method is still unsatisfactory in many application.The method that like this, just requires further improvement the field flow separation is to improve the separation efficiency of this method.The present invention just is in this purpose, and relates to the others of this technology.
List of references involved in the present invention is:
Barmatz?MB?et?al.，US?patent?4523682，June?1985
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Summary of the invention
The present invention discloses and use sound field radiant force (or sound field power), electrophoresis (E) power, dielectrophoresis (DEP) power, gravity, fluid force and fluid distribution carrying out particulate to identify, handle and method of separating and required device.Separate (E-FFF) and separate (DEP-FFF) field with dielectric-field flow because new power (as the sound field radiant force) is introduced into field flow separation (FFF), electrophoresis-field flow, the method that this new invention separates with traditional field flow, electricity-field flow separation separates with dielectric-field flow is compared, and has had many advantages:
Particulate, cell for example can be according to they character itself, separates as size, density, dielectric parameter, institute are electrically charged etc.Equally, acoustic impedance also is a kind of like this character of particulate itself, can be used as particulate identification and the parameter of separating.
The forward dielectrophoresis force also can be used for separation of particles---and widened and can only use the dielectric field flow point of negative sense dielectrophoresis force originally from the field.
Can obtain better separation of particles efficient.
Owing to increased sound field radiant force (perhaps simply being called sound field power) as a kind of additional power, so flow point on the scene can influence the position of particulate in the operation that, electricity-field flow separates, dielectric-field flow separates, comprise the equilibrium position that changes particulate, or the zonation of particulate comprises the balanced distribution band of particulate, and sound field-field flow separates so these methods are called as, sound field-electrophoresis-field flow separates and separates with sound field-dielectric-field flow.Here, particulate can be the material of various kinds, as dissolved substances in particle matter, the solution, or the assembly of these materials.Sound field power is caused by sound wave (as standing wave), and the direction of sound field power is vertical with fluid flow direction in reaction tank, and is parallel with active dielectrophoresis force or electrophoretic force direction.Standing wave can be generated by several different methods, as using piezoelectric sensor.
The present invention discloses the method and the required device that are used to discern all kinds particulate and material and dissolved substance.Here, identification comprises multiple implication, for example to separation, evaluation, differentiation and the manipulation of particulate.The present invention requires particulate before introducing device, floats on a liquid earlier.Identifying occurs in the device, and this device is the thin type reaction tank of a sealing.Particulate can as density, size, dielectric permittivity, conductivity, surface charge, surface structure or the difference of acoustic impedance, obtain separating in reaction tank according to the difference of character own.Apparatus and method of the present invention can be used for discerning simultaneously different types of particulate.
The present invention can apply to separation, evaluation and the manipulation to various particulates, and these particulates can be solid particle such as beaded glass, emulsion particle, liquid particulate such as drop or gaseous state particulate such as bubble or the like; Particulate also can be an organism, as mammalian cell, bacterium, virus or other microorganism, can be inorganics also, as metal particle; The shape of particulate also can have nothing in common with each other, as sphere, ellipse, cube, cheese and needle-like etc.; The size of particulate also can be different, and as the gold size group of nanometer scale, to the cell of micron dimension, extremely the particulate polymer of millimeter magnitude all is suitable for.Analyzable particulate can be, but be not limited only to biomolecule such as DNA, RNA, chromosome, protein molecular (as antibody), cell and colloidal particles (as the polystyrene bead body).
This invention can apply to every separation of particles problem, is particularly useful for the cell separation operation of biomedical sector.The example of separation of particles comprises, but be not limited to, with cancer cell separate with normal cell, with the transfevent cancer cell from haemocyte, separate, from pregnant woman's red blood cell/karyoblast the isolating fetal karyoblast, isolate in the allogenic cell by the cell of virus infections, distinguish red blood cell and white blood cell and separation of bacterial or the like from human body liquid metabolins such as blood, urine.When this invention is used for the biological study field, when active somatic cell was analyzed, the modification of carrying out aglucon, coloring agent, antibody or alternate manner without pair cell just can separate by pair cell.In the abiology research field, same, particulate to be analyzed also be need not to do any modification.Certainly, for the biological agents of modified, the method that provides with this invention is analyzed also and is well suited for.Almost influence or influence are very not little for the particulate of need being analyzed based on the separation of particles process of this invention.Active somatic cell can be unaffected in whole detachment process, do not modified, and keeps active.We can say that perhaps enough little of the influence of this separation method pair cell separated the back cell and still can be continued to apply to further check, analysis, evaluation or growth.
A. use the device of sound field power
The device that flow point on the scene carries out material identification from middle use sound field power has been described in this invention, the comprising of this device:
A) reaction tank that contains an ingress port and one outlet port at least, and the structural design of this reaction tank will satisfy following requirement, promptly is introduced in the reaction tank when mounting medium, and the flow velocity of mounting medium that is arranged in the reaction tank diverse location is different;
B) have at least a piezoelectric sensor to form the part of reaction tank, wherein said piezoelectric sensor can excite and produce sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
Device can comprise single ingress port and single outlet port.Perhaps, also can comprise a plurality of ingress ports and outlet port.Preferably will export port directly receives on a gathering-device or the identification apparatus.The outlet port of the reaction tank that this invention is designed can have various ways.Can have single outlet port, also can have a plurality of outlet ports, even can be the array of a multiple exit port.The width of outlet port can consistent with reaction tank or only account for the part of reaction tank width.Can collect the particulate of difformity and size from the outlet port.The size of outlet port can be from the twice of particle size to consistent with the width of reaction tank.In the entity example, the outlet port is made of one or more tubular structure (as polyfluortetraethylene pipe).These tubular structures can be combined into a compound sample outlet end mouth.Further, outlet can directly be received on fraction collector or the collection hole to collect the sample that separates.Except gathering-device, other device also can be received the end of tripping device, as measuring and diagnostic device, for example hemacytometer, batch particle-counting system and spectrophotometer.Other is used for separate substance is further checked and the device analyzed also can be connected to device of the present invention.
The project organization in device reaction pond wants to make that the fluid (liquid or gas) of introducing reaction tank has different flow rates in different positions, and fluid (liquid or gas) is followed the rule of velocity distribution in by reaction tank.For example, reaction tank can be a square shape, comprises a top cover, a bottom surface and two sidewalls.Top cover should be parallel fully or substantially parallel with the bottom surface, and the distance between top cover and the bottom surface is exactly the height of reaction tank.If reaction tank only comprises an entrance and exit, the distance between the export and import is exactly the length of reaction tank so.Two sidewalls should be parallel fully or substantially parallel.Distance between these two parallel side walls just is called the width of reaction tank.Two sidewalls can be the parts of packing ring between top cover and the bottom surface.Packing ring can cut out the structure of flat sexangle, ellipse, circle or other shape at the middle part.In the entity example of determining, reaction tank be the flat structure of a centre with rectangular channel (be length and the width that the height of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).The advantage of the reaction tank of this structure is when mounting medium is flowed through rectangular channel (or flowing through reaction tank), can form para-curve or approximate parabolical velocity distribution.Near the mounting medium flow velocity of top cover and bottom surface is zero, and flow velocity leaves the increase of top cover and bottom surface distance along with mounting medium and increases, top cover and basal spacing from half place reach maximal value.In other entity examples, reaction tank be a thin-and-long structure (be height and the length that the width of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).Reaction tank can also be circle, ellipse, triangle, rectangle, hexagon an or the like structure.Reaction tank can be made up of a top cover, bottom surface and the packing ring between top cover and bottom surface.Packing ring can cut out flat hex hole, the hole that also can be cut into ellipse, circle or other shape at the middle part.In some entity examples, reaction tank be a flat structure (be length and the width that the height of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).The advantage of the reaction tank of such flat structure is when mounting medium is flowed through reaction tank, can form para-curve or approximate parabolical velocity distribution.Near the mounting medium flow velocity of top cover and bottom surface is zero, and flow velocity leaves the increase of top cover and bottom surface distance along with mounting medium and increases, top cover and basal spacing from half place reach maximal value.Generally speaking, for rectangular channel, width can be from 1mm to 20cm, and height is from 20 μ m to 10mm, and length is from 1cm to 200cm, and suitable length is that 10cm is to 50cm.Though provided above-mentioned data, and do not meant that requirement reaction tank of the present invention all is the geometric configuration of rule.Reaction tank can be made by various materials, and as metal of glass, polymer, plastics, quartz, coating or the like, but its design feature need satisfy following requirement: when mounting medium was flowed through reaction tank, the velocity of medium at diverse location place was different in the reaction tank.
Device comprises one or more piezoelectric sensors.A plurality of piezoelectric sensors can pass to identical electric signal or different electric signal excites.These piezoelectric sensors can be positioned at the inside surface or the outside surface of reaction tank, also can be positioned at mounting medium to flow through on the fully parallel plane of reaction tank direction.
Usually by electric signal generator output be used to excite the amplitude and the frequency of electric signal of piezoelectric sensor to regulate.
In a first-selected entity example, reaction tank is a tubular structure.One or more piezoelectric sensors are to be positioned on the inside surface or outside surface of tubular structure.
In another first-selected entity example, reaction tank is made of a top cover, a bottom surface and two sidewalls.One or more piezoelectric sensors can be positioned on the top cover of reaction tank, perhaps are positioned at the bottom surface of reaction tank, also can be at the reverse side of reaction tank.The height of reaction tank (distance between top cover and the bottom surface) half-wavelength best and standing wave is approaching.
Flow point on the scene comprises in essence from the device of middle use sound field power recognition material: a) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank; B) have at least a piezoelectric sensor to be positioned at certain part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
B. use the device of electrophoresis harmony field force
On the other hand, this invention is pointed out, flow point on the scene comprises from the device of middle use electrophoresis harmony field force recognition material: a) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank; B) have at least two electrodes to form the part of described reaction tank, described electrode can excite the generation electric field by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the electrophoretic force on the material in the described mounting medium, this electrophoretic force has the component perpendicular to the mounting medium moving direction.C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
Device comprises an ingress port and an outlet port, also can comprise a plurality of ingress ports and a plurality of outlet port.Preferably exporting port and gathering-device or identification apparatus directly joins.The outlet port of the reaction tank that the present invention is designed can have various ways, as being single outlet port, also can be the multiple exit port, even can be an outlet array of ports.The width of outlet port can consistent with reaction tank or only account for the part of reaction tank width.Can collect the particulate of difformity and size from the outlet port.The range of size of outlet port can be from the twice of particle size to consistent with the width of reaction tank.In an entity example, the outlet port is to be made of one or more tubular structure (as polyfluortetraethylene pipe).These tubular structures can be combined into a compound sample outlet end mouth.For example, the outlet port can directly be received on fraction collector or the collection hole to collect the sample that separates.Except gathering-device, other device also can be received the end of tripping device, as measuring and diagnostic device, for example hemacytometer, batch particle-counting system and spectrophotometer.Other is used for separate substance is further checked and the device analyzed also can be connected to tripping device.
The reaction tank project organization of device wants to make that the fluid (liquid or gas) of introducing reaction tank has different flow rates in different positions, and fluid (liquid or gas) is followed the rule of velocity distribution in by reaction tank.For example, this reaction tank can be a square shape, comprises a top cover, a bottom surface and two sidewalls.Top cover should be parallel fully or substantially parallel with the bottom surface, and the distance between top cover and the bottom surface is exactly the height of reaction tank.If reaction tank only comprises an ingress port and outlet port, the distance that exports so between port and the ingress port is exactly the length of reaction tank.Two sidewalls should be parallel fully or substantially parallel.Distance between these two parallel side walls just is called the width of reaction tank.Two sidewalls can be the parts of the packing ring between top cover and the bottom surface.Packing ring can cut out the flattened hexagon structure at the middle part, also can be oval, circular or other shape.In the entity example, reaction tank be the flat structure of a centre with rectangular channel (be length and the width that the height of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).The advantage of the reaction tank of this structure is when mounting medium is flowed through rectangular channel (or flowing through reaction tank), can form para-curve or approximate parabolical velocity distribution.Near the mounting medium flow velocity of top cover and bottom surface is zero, and flow velocity leaves the increase of top cover and bottom surface distance along with mounting medium and increases, top cover and basal spacing from half place reach maximal value.In other entity examples, reaction tank be a thin-and-long structure (be height and the length that the width of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).Reaction tank can also be cast, ellipse, triangle, rectangle, hexagon an or the like structure.Reaction tank can be made up of a top cover, bottom surface and the packing ring between top cover and bottom surface.Packing ring can cut out the structure of rectangle at the middle part, also can cut out ellipse, circle or other shape.In some entity example, reaction tank be a flat structure (be length and the width that the height of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).The advantage of the reaction tank of such flat structure is when mounting medium is flowed through reaction tank, can form para-curve or approximate parabolical velocity distribution.Near the mounting medium flow velocity of top cover and bottom surface is zero, and flow velocity leaves the increase of top cover and bottom surface distance along with mounting medium and increases, top cover and basal spacing from half place reach maximal value.Generally speaking, for rectangular channel, width can be from 1mm to 20cm, and height is from 20 μ m to 10mm, and length is from 1cm to 200cm, preferably from 10cm to 50cm.Though provided above-mentioned data, and do not meant that requirement reaction tank of the present invention all is the geometric configuration of rule.Reaction tank can be made by various materials, and as metal of glass, polymer, plastics, quartz, bag quilt or the like, but its design feature need satisfy following requirement: when mounting medium was flowed through reaction tank, the velocity of medium at diverse location place was different in the reaction tank.
Device comprises two or a plurality of electrode.Each electrode all is connected on the electrical lead in the electrical lead bus that is electrically connected with electric signal generator individually.Electrode can be arranged on the reaction tank in mode laterally or longitudinally.Electrode can be lined up a plane substantially parallel with mounting medium direction of motion, preferably lines up the electrod-array on a plane.Electrod-array can be interlaced formula electrod-array, interlaced formula castle electrod-array, have the alternating expression electrod-array of outstanding cambered top end.Preferably these electrodes are the metal levels that are coated in the reaction tank surface, as gold layer electrode.Also can use other metal, as platinum, aluminium, chromium, titanium, copper and silver etc.
The electric signal generator that is used for exciting electrode generation electrophoretic force can be the dc signal source of energy regulation voltage amplitude, also can be the ac signal which that can regulate amplitude and frequency.Be used for electric signal that exciting electrode produces electrophoretic force preferably direct current signal or low-frequency ac signal.
Have one or a plurality of piezoelectric sensor in the device.If a plurality of piezoelectric sensors, they can pass to identical electric signal, also can pass to different electric signal and excite.A plurality of piezoelectric sensors can be positioned at the inside surface or the outside surface of reaction tank, also can be positioned at mounting medium to flow through on the fully parallel plane of reaction tank direction.
Usually by electric signal generator output be used to excite piezoelectric sensor can regulate with the amplitude and the frequency of the electric signal that produces sound field power.
The common electrical conductor bus is used to connect a plurality of electrodes and signal generator.The common electrical conductor bus can be taked the method for making the same with installing top electrode, or is one or more conducting parts, as with tape conductor, metal tape or plated the plastics of metal.For the formula electrod-array that interlaces alternately, staggered electrode can link together and obtain electric signal from signal generator.Signal generator can be the direct supply that adjustable voltage can be provided.It is 0 to 15 volt that method and apparatus of the present invention requires the scope of voltage, and optimum value is 0 to 2 volt.Signal generator also can be the power supply that adjustable voltage and frequency can be provided, as the multifunctional signal generator of this class of No.8116A type signal generator of Hewlett-Packard.It is 0 to 15 volt that the used method and apparatus of this invention requires the scope of voltage, and frequency range is 0.1Hz to 100KHz, and optimum value is 0 to 2 volt of a voltage, and frequency 0.1 is to 1KHz.
In a first-selected entity example, the reaction tank in the device is a tubular structure.Electrode and/or piezoelectric sensor, perhaps the major part in them can be positioned at the inside surface or the outside surface of tubular structure.
In another first-selected entity example, reaction tank is made of a top cover, a bottom surface and two sidewalls.Electrode and/or piezoelectric sensor, perhaps the major part in them can be distributed on the top cover of reaction tank, or is positioned at the bottom surface of reaction tank, in another structure, electrode and/or piezoelectric sensor, perhaps the major part in them also can be distributed in the reverse side of reaction tank.The height of reaction tank (distance between top cover and the bottom surface) half-wavelength best and standing wave is approaching.
In another first-selected entity example, device comprises: a) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank; B) have at least two electrodes to form the part of described reaction tank, wherein said electrode can excite the generation electric field by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the electrophoretic force on the material in the described mounting medium, this electrophoretic force has the component perpendicular to the mounting medium moving direction; C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
C. use the device of dielectrophoresis harmony field force
On the other hand, the invention provides the device of a flow point on the scene from middle use dielectrophoresis harmony field force recognition material, this device comprises: a) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank; B) have at least two electrodes to form the part of described reaction tank, wherein said electrode can excite by at least one road electric signal that is produced by electric signal generator and produce a non-uniform electric field, thereby cause at least one to put on the dielectrophoresis force on the material in the described mounting medium, this dielectrophoresis force has the component perpendicular to the mounting medium moving direction; C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
Device comprises an ingress port and an outlet port, also can comprise a plurality of ingress ports and a plurality of outlet port.Preferably exporting port and gathering-device or identification apparatus directly joins.The outlet port of the reaction tank that the present invention is designed can have various ways, as being single outlet port, also can be the multiple exit port, even can be an outlet array of ports.The width of outlet port can consistent with reaction tank or only account for the part of reaction tank width.Can collect the particulate of difformity and size from the outlet port.The range of size of outlet port can be from the twice of particle size to consistent with the width of reaction tank.In an entity example, the outlet port is to be made of one or more tubular structure (as polyfluortetraethylene pipe).These tubular structures can be combined into a compound sample outlet end mouth.For example, the outlet port can directly be received on fraction collector or the collection hole to collect the sample that separates.Except gathering-device, other device also can be received the end of tripping device, as measuring and diagnostic device, for example hemacytometer, batch particle-counting system and spectrophotometer.Other is used for separate substance is further checked and the device analyzed also can be connected to tripping device.
The reaction tank project organization of device wants to make that the fluid (liquid or gas) of introducing reaction tank has different flow rates in different positions, and fluid (liquid or gas) is followed the rule of velocity distribution in by reaction tank.For example, this reaction tank can be a square shape, comprises a top cover, a bottom surface and two sidewalls.Top cover should be parallel fully or substantially parallel with the bottom surface, and the distance between top cover and the bottom surface is exactly the height of reaction tank.If reaction tank only comprises an ingress port and outlet port, the distance that exports so between port and the ingress port is exactly the length of reaction tank.Two sidewalls should be parallel fully or substantially parallel.Distance between these two parallel side walls just is called the width of reaction tank.Two sidewalls can be the parts of the packing ring between top cover and the bottom surface.Packing ring can cut out the flattened hexagon structure at the middle part, also can be oval, circular or other shape.In the entity example, reaction tank be the flat structure of a centre with rectangular channel (be length and the width that the height of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).The advantage of the reaction tank of this structure is when mounting medium is flowed through rectangular channel (or flowing through reaction tank), can form para-curve or approximate parabolical velocity distribution.Near the mounting medium flow velocity of top cover and bottom surface is zero, and flow velocity leaves the increase of top cover and bottom surface distance along with mounting medium and increases, top cover and basal spacing from half place reach maximal value.In other entity examples, reaction tank be a thin-and-long structure (be height and the length that the width of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).Reaction tank can also be circle, ellipse, triangle, rectangle, hexagon an or the like structure.Reaction tank can be made up of a top cover, bottom surface and the packing ring between top cover and bottom surface.Packing ring can cut out rectangular configuration at the middle part, also can be cut into ellipse, circle or other shape.In some entity example, reaction tank be a flat structure (be length and the width that the height of reaction tank is significantly less than reaction tank, and reaction tank be shaped as rectangle).The advantage of the reaction tank of such flat structure is when mounting medium is flowed through reaction tank, can form para-curve or approximate parabolical velocity distribution.Near the mounting medium flow velocity of top cover and bottom surface is zero, and flow velocity leaves the increase of top cover and bottom surface distance along with mounting medium and increases, top cover and basal spacing from half place reach maximal value.Generally speaking, for rectangular channel, width can be from 1mm to 20cm, and height is from 20 μ m to 10mm, and length is from 1cm to 200cm, preferably from 10cm to 50cm.Though provided above-mentioned data, and do not meant that requirement reaction tank of the present invention all is the geometric configuration of rule.Reaction tank can be made by various materials, and as metal of glass, polymer, plastics, quartz, bag quilt or the like, but its design feature need satisfy following requirement: when mounting medium was flowed through reaction tank, the velocity of medium at diverse location place was different in the reaction tank.
Device comprises two or a plurality of electrode.Each electrode all is connected on the electrical lead in the electrical lead bus that is electrically connected with electric signal generator individually.Electrode can be arranged on the reaction tank in mode laterally or longitudinally.Electrode also can be distributed in a plane substantially parallel with mounting medium direction of motion, preferably lines up the electrod-array on a plane.Electrod-array can be interlaced formula electrod-array, interlaced formula castle electrod-array, have the alternating expression electrod-array of outstanding cambered top end.Preferably these electrodes are the metal levels that are coated in the reaction tank surface, as gold layer electrode.Also can use other metal, as platinum, aluminium, chromium, titanium, copper and silver etc.
The electric signal generator that is used for exciting electrode generation electrophoretic force can be the dc signal source of energy regulation voltage amplitude, also can be the ac signal which that can regulate amplitude and frequency.
Have one or a plurality of piezoelectric sensor in the device.If outstanding a plurality of piezoelectric sensors, they can pass to identical electric signal, also can pass to different electric signal and excite.A plurality of piezoelectric sensors can be positioned at the inside surface or the outside surface of reaction tank, also can be positioned at mounting medium to flow through on the fully parallel plane of reaction tank direction.
Usually by electric signal generator output be used to excite piezoelectric sensor can regulate with the amplitude and the frequency of the electric signal that produces sound field power.
The common electrical conductor bus is used to connect a plurality of electrodes and signal generator.The common electrical conductor bus can be taked the method for making the same with installing top electrode, or is one or more conducting parts, as with tape conductor, metal tape or plated the plastics of metal.For the formula electrod-array that interlaces alternately, staggered electrode can link together and obtain electric signal from signal generator.Signal generator can be the direct supply that adjustable voltage can be provided.It is 0 to 15 volt that method and apparatus of the present invention requires the scope of voltage, and optimum value is 0 to 10 volt.Signal generator also can be the power supply that adjustable voltage and frequency can be provided, as the multifunctional signal generator of this class of No.8116A type signal generator of Hewlett-Packard.It is 0 to 15 volt that the used method and apparatus of this invention requires the scope of voltage, and frequency range is 0.1Hz to 500MHz, and optimum value is 0 to 10 volt of a voltage, and frequency 0.1 is to 10MHz.Because the characteristic of utilizing the required frequency of dielectrophoresis force recognition material to depend on to be identified material and the conductivity of medium (as cell suspending liquid), so frequency described herein is just as an example.The identification of material is also depended on shape, the size of electrode and arranges.In an entity example, used signal is sinusoidal wave, can certainly use other periodicity or acyclic waveforms.Electric signal can have the amplitude of regulating the output electric signal and the electric signal generator of frequency capabilities produces by one or more.
In a first-selected entity example, the reaction tank in the device is a tubular structure.Electrode and/or piezoelectric sensor, perhaps the major part in them can be positioned at the inside surface or the outside surface of tubular structure.
In another first-selected entity example, reaction tank is made of a top cover, a bottom surface and two sidewalls.Electrode and/or piezoelectric sensor, perhaps the major part in them can be distributed on the top cover of reaction tank, or is positioned at the bottom surface of reaction tank, in another structure, electrode and/or piezoelectric sensor, perhaps the major part in them also can be distributed in the reverse side of reaction tank.The height of reaction tank (distance between top cover and the bottom surface) half-wavelength best and standing wave is approaching.
In another first-selected entity example, device comprises: a) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank; B) have at least two electrodes to form the part of described reaction tank, wherein said electrode can excite the generation electric field by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the electrophoretic force on the material in the described mounting medium, this electrophoretic force has the component perpendicular to the mounting medium moving direction; C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
D. use sound field power or use the method for sound field power recognition material simultaneously with electrophoresis or dielectrophoresis force
From other aspect, the invention provides " continuous mode " method that a kind of flow point on the scene comes recognition material from middle use sound field power, this method comprises: a) obtain a device of describing in the A joint; B) mounting medium that will contain material to be identified of the ingress port by described device imports in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; C) excite the generation sound wave by piezoelectric sensor being applied other at least one road electric signal that produces by electric signal generator, thereby cause having at least one to put on that the sound field power on the material has a component that moves through the reaction tank direction perpendicular to mounting medium in the described mounting medium, and be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.Sound field that Here it is-field flow is separated the (continuous mode of sound field-FFF).It can use any device of describing in the A joint.
On the other hand, the invention provides a kind of flow point on the scene from " batch mode " method of using sound field power recognition material.This method comprises: a) obtain a device of describing in the A joint; B) ingress port by described device imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium; C) mounting medium of the sample delivery (as inject) that will contain material to be identified in the reaction tank; D) piezoelectric sensor is applied at least one road electric signal that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power to be applied on the described material; E) ingress port by device imports to mounting medium in the reaction tank of device, wherein said importing makes mounting medium pass through reaction tank according to velocity distribution, be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction." batch mode " that this sound field-field flow separates can use any device of describing in the A joint.
In " batch mode " method that above-mentioned sound field-field flow separates, the best way is, it makes mounting medium pass through reaction tank (step e) according to a velocity distribution before the guiding mounting medium enters reaction tank, make it produce sound field masterpiece to be used on above-mentioned substance applying electric signal on the piezoelectric sensor, this sound field power cause species distribution along perpendicular to medium by the equilibrium position on the flow direction of reaction tank.
On the other hand, the invention provides a kind of flow point on the scene from " continuous mode " method of using electrophoretic force harmony field force recognition material simultaneously.This method comprises: a) obtain a device of describing in the B joint; B) mounting medium that will contain material to be identified of the ingress port by described device imports in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; C) excite the generation electric field by electrode being applied at least one road electric signal that produces by electric signal generator, thereby cause having at least one to put on that the electrophoretic force on the material has a component that moves through the reaction tank direction perpendicular to mounting medium in the described mounting medium; D) excite the generation sound wave by piezoelectric sensor being applied other at least one road electric signal that produces by electric signal generator, thereby cause having at least one to put on that the sound field power on the material has a component that moves through the reaction tank direction perpendicular to mounting medium in the described mounting medium, be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.Any device of describing in the B joint can be used for the continuation mode that this sound field-electrophoresis-field flow separates (sound field-electrophoresis-field flow separates).
On the other hand, the invention provides a kind of flow point on the scene from use " batch mode " method of electrophoretic force harmony field force recognition material simultaneously.This method comprises: a) obtain a device of describing in the B joint; B) ingress port by described device imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium; C) mounting medium of the sample delivery (as inject) that will contain material to be identified in the reaction tank; D) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an electric field, thereby causes having at least an electrophoretic force to be applied on the described material; E) piezoelectric sensor is applied another road electric signal at least that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power to be applied on the described material; F) ingress port by device imports to mounting medium in the reaction tank of device, wherein said importing makes mounting medium pass through reaction tank according to velocity distribution, be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.Any device of describing in the B joint can be at " batch mode " that use this sound field-electrophoresis-field flow to separate.
In " batch mode " method that above-mentioned sound field-electrophoresis-field flow separates, the best way is, it makes mounting medium pass through reaction tank (step f) according to a velocity distribution before the guiding mounting medium enters reaction tank, apply electric signal generation sound field masterpiece and be used at above-mentioned substance on piezoelectric sensor, this sound field power causes material moving to an equilibrium position on perpendicular to the flow direction of medium by reaction tank.
On the other hand, the invention provides a kind of flow point on the scene from use " continuous mode " method of dielectrophoresis force harmony field force recognition material simultaneously, this method comprises: a) obtain a device of describing in the C joint; B) ingress port by described device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; C) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an inhomogeneous field, thereby causes having at least a dielectrophoresis force that is applied on the described material to have a component that moves through the reaction tank direction perpendicular to mounting medium; D) piezoelectric sensor is applied another road electric signal at least that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power that is applied on the described material to have a component that moves through the reaction tank direction perpendicular to mounting medium; Be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.Any device of describing in the C joint may be used to the continuation mode that this sound field-dielectrophoresis-field flow separates (sound field-dielectric-field flow separates).
On the other hand, the invention provides a kind of flow point on the scene from use " batch mode " method of dielectrophoresis force harmony field force recognition material simultaneously, this method comprises: a) obtain a device of describing in the C joint; B) ingress port by described device imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium; C) mounting medium of the sample delivery (as inject) that will contain material to be identified in the reaction tank; D) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an electric field, thereby causes having at least a dielectrophoresis force to be applied on the described material; E) piezoelectric sensor is applied another road electric signal at least that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power to be applied on the described material; F) ingress port by device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; Be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.Any device of describing in the B joint can be at " batch mode " that use this sound field-dielectric-field flow to separate.
In " batch mode " method that above-mentioned sound field-dielectric-field flow separates, the best way is, before entering reaction tank, the guiding mounting medium make mounting medium pass through reaction tank (step f) according to a velocity distribution, produce the sound field rent paid in labour and be used on the above-mentioned substance applying electric signal on the piezoelectric sensor, this sound field power cause species distribution along perpendicular to medium by the equilibrium position on the flow direction of reaction tank.
In above-mentioned sound field-electrophoresis-field flow separation or sound field-dielectric-field flow separation method, similar, but preferably use different electric signal to produce sound field power, electrophoresis or dielectrophoresis force.
In above-mentioned sound field-electrophoresis-field flow separation or sound field-dielectric-field flow separation method, sound field power, electrophoretic force or dielectrophoresis force can produce simultaneously or sequentially.
Above-mentioned sound field-electrophoresis-field flow separates, sound field-electrophoresis-field flow separates and sound field-dielectric-field flow separation method can further comprise one according to mounting medium by the velocity distribution of reaction tank and in reaction tank the speed of the determining positions of material in velocity distribution move the step of recognition material.
Above-mentioned sound field-electrophoresis-field flow separates, sound field-electrophoresis-field flow separates and sound field-dielectric-field flow separation method can further comprise a step material and the device of identification are separated, and also is separated from each other between the material that preferably causes being identified.By after separating in the mounting medium of reaction tank of the present invention, separated material left from the single or multiple outlet ports of reaction tank according to the position of material in the velocity distribution of mounting medium during by reaction tank different time that do not coexist.Especially, the material that is distributed in differing heights in velocity distribution flows with different speed, so can discern different materials by the speed of positions different in velocity distribution and motion.Single or multiple outlet ports from reaction tank leave the material of diverse location with different speed motions and in the different time in velocity distribution.
Velocity distribution can be that dynamic fluid distributes as the mobile distribution of para-curve.For the reaction tank of rectangle, the architectural feature of reaction tank can be defined by the length of reaction tank, the width of reaction tank and the height of reaction tank.Velocity distribution can be by known fluid-flow rate and reaction tank the length decision of width, thickness and reaction tank.For example, be far longer than the rectangle reaction tank of the height of reaction tank, in reaction tank, can set up a thin layer and distribute for reaction tank length and width.Mainly be similar to the para-curve fluid in the speed of diverse location mounting medium and distribute (or being similar to parabolic distribution), provide by following formula by the distance decision of its wall at the bottom of the reaction tank and velocity distribution
Wherein＜V
mBe the average velocity of mounting medium, H is the height of reaction tank, V
mBe that the mounting medium position is the speed of z apart from reaction tank bottom surface distance.It is to be noted that it only is to be far longer than the approximate of velocity distribution under the reaction tank height condition at reaction tank length and width that top parabolic velocity distributes.Therefore we have used this speech of approximate parabolic distribution in this patent text.Along the reaction tank Width, above formula parabolic distribution at the medium position of reaction tank Width than more accurate at end position.Similar, along the reaction tank length direction, above formula parabolic distribution at the medium position of reaction tank length direction than more accurate at end position.Average velocity can calculate according to following formula:
Average velocity＜V
m〉=(flowing velocity)/(reaction tank width * reaction tank height or thickness)
Like this, the architectural feature that influences the mobile velocity distribution of fluid of reaction tank comprises: reaction tank width, reaction tank height (or reaction tank thickness) and reaction tank length.When fluid passes through reaction tank, the reaction tank of different size and geometric configuration will cause different velocity distribution.The parameter of velocity distribution included, but are not limited to the reaction tank physical dimension when decision fluid flowed; The compression of fluid flow path and expansion, for example, those are in the relative reaction pool wall of not parallel position, or suitably place the barrier or the wing; The surfaceness of reaction pool wall; The architectural feature of reaction pool wall causes fluid thickness cycle or aperiodic correction, comprises electrode unit and other surface structures structure, and the geometric configuration of reaction tank can be, for example, and rectangle, circle, wedge shape etc.
In the above methods, the material of separation can be according to the discharge of the position in velocity distribution from a plurality of outlet ports of reaction tank.In a first-selected entity example, act on its action direction of gravity on the material perpendicular to the flow direction of mounting medium in the reaction tank.
Sound field described herein-field flow separates, sound field-electrophoresis-field flow separates and sound field-dielectric-field flow separation method can be used to discern any material.In the specific entity example, needing the material of identification is cell, organelle, virus, molecule or their aggregate or complex.But recognizing cells is including, but not limited to zooblast, vegetable cell, mushroom cell, bacterium, cultured cell or recombinant cell.Discernible organelle is including, but not limited to nucleus, mitochondria, chloroplast, ribosomes, rough surfaced endoplasmic reticulum (RER), golgiosome, lysosome, proteasome, excretion vesicles, vacuole or microsome.Discernible molecule comprises inorganic for example ion, organic molecule or their compound.Discernible ion is including, but not limited to sodium, potassium, magnesium, calcium, aluminium, chlorine, iron, copper, zinc, manganese, cobalt, iodine, molybdenum, vanadium, nickel, chromium, fluorine, silicon, tin, boron, arsenic ion.Discernible organic molecule is including, but not limited to amino acid, peptide, protein, nucleosides, nucleotide, oligonucleotide, nucleic acid, vitamin, monose, oligosaccharides, carbohydrates, lipid or their compound.Material to be identified can be a size arbitrarily.Yet the size of best material to be identified is between 0.01 micron to 1000 microns.
Description of drawings
Fig. 1 is the synoptic diagram that has the rectangular channel sound field-field flow separating reaction pond of severing in the centre.Illustrated the principle of sound field-field flow mask work simultaneously.
Fig. 2 is the synoptic diagram that has the oval-shaped passageway sound field-field flow separating reaction pond of severing in the centre.
Fig. 3 is the synoptic diagram that has the oval sound field-field flow separating reaction pond of severing passage in the centre.
Fig. 4 is the synoptic diagram that has the sound field-field flow separating reaction pond of a plurality of outlets at the endpiece of reaction tank.
Fig. 5 is the synoptic diagram that has the rectangular channel sound field-electrophoresis-field flow separating reaction pond of severing in the centre.Illustrated the principle of sound field-electrophoresis-field flow mask work simultaneously.
Fig. 6 is the electrod-array that can be used for sound field-electrophoresis-field flow tripping device.(A) mutual dislocation formula electrod-array.(B) mutual dislocation formula castle electrod-array.
Fig. 7 is the sound field-dielectric-field flow separating reaction pond synoptic diagram that has the rectangular channel of severing in the centre, has illustrated the principle of sound field-dielectric-field flow mask work simultaneously.
Fig. 8 is the electrod-array that can be used for sound field-dielectric-field flow tripping device.(A) have the mutual dislocation formula electrod-array of triangle shaped ends.(B) have the periodically mutual dislocation formula electrod-array of curved end.
Fig. 9 has illustrated that use sound field-field flow separates, sound field-electrophoresis-field flow separates and " the batch mode principle of work " of sound field-dielectric-field flow tripping device.(A) apply the effect of power in " relaxing " process, dissimilar Particle Distribution is in different balance heights position.(B) be distributed under the influence that the fluid of dissimilar particulates in reaction tank of different balance heights position flow and move along reaction tank with different speed.
Figure 10 has illustrated that use sound field-field flow separates, sound field-electrophoresis-field flow separates and " the batch mode principle of work " of sound field-dielectric-field flow tripping device.At the continuous injection reaction tank of the particulate of mounting medium, and be distributed in different height and positions continuously in mounting medium, and then different outlet ports is discharged.
Implement pattern of the present invention
A. definition
Unless other definition is arranged, all technology used herein and scientific terminology and general same meaning can be understood by any one people who has at field of the present invention common skill.So sequence in the application of patent, application, announcement and other publications and the gene pool and should all being incorporated in this patent with the database that middle any part is quoted with the form of list of references.
Here, " material " refers to particle matter, solable matter or their bond.
What here, " electrode unit (or electrode) " referred to the structure that is made of the high conductivity material can apply voltage constant or approximately constant.The approximately constant meaning is that the value of the voltage drop on such conductivity structure is very little so that electric signal can produce an enough strong electric field when being applied on ellipse, triangle, rectangle, hexagon or other geometrical layout around electrode unit.Typical high conductivity material such as metallic film (as gold, platinum, titanium, chromium etc.), semiconductor material such as silicon mix up (doping phosphorus, arsenic, antimony, aluminium, gallium or indium as silicon), and the high material of other conductances.For the present invention, the high conductivity material refer to conductivity fully greater than be used for the isolated vectors medium (as the conductance of conductive material be the twice of mounting medium or more than the twice).It must be understood that for the term of describing in current explanation and the claim that comprises all electrode structures.
Said here " electrod-array " refers to the set of a plurality of electrodes.In electrod-array, the relative position of the electrode that each is independent can be arranged by certain geometric relationship of specifying.For example, mutual dislocation formula electrod-array, mutual dislocation formula castle electrod-array, has the mutual dislocation formula electrod-array of cycle apex (or circular arc top, rectangle top) or similar electrod-array at the polynomial expression electrod-array.Electrod-array can comprise the electrode of a plurality of identical or different geometric configuratioies.
Here the said mounting medium " perpendicular to transmission direction " that flows through reaction tank refers to relative or not parallel with a flow direction basically direction.For example, when the length direction that is prolonging a rectangle reaction tank when a mounting medium flows through, the direction of " perpendicular to transmission direction " can be the direction of passing the reaction tank width, pass the direction of reaction tank height, perhaps such direction, its be arranged in by the reaction tank width and the parallel plane a certain plane of decision highly, perhaps any one direction, the flow direction with mounting medium is not relative to need only it.Usually, the angle of transmission direction and " perpendicular to transmission direction " is spent to 135 degree between 45, and preferably this angle is to spend to 100 degree between 80, better spends to 95 degree between 85.
" separated and collected device (perhaps collecting pit, gathering-device) " comprises storage and gathering-device, is used to preserve material separation or that distinguished or that be identified.
" identification apparatus " refers to that those can be used in those materials separated or that be identified or that distinguished of evaluation.Identification apparatus can be one and be used to write down the batch particle-counting system that particulate number or particulate leave the time of reaction tank.Identification apparatus can also be to be used to more analyse in depth and the calibrating installation that separates.
" piezoelectric sensor " refers to the piezoelectric member, can produce electric field when it causes dimensional variation owing to the mechanical force of being forced.Mechanical pressure can obtain by applying electric signal.In this invention, we apply ac signal to produce the alternation mechanical pressure to piezoelectric sensor, are coupled into sound wave and enter separation and the identification that mounting medium is used for material.
" architectural feature of reaction tank " refers to the architectural feature of reaction tank, including, but not limited to geometric configuration, size, structure and the reaction tank position (for example top cover, bottom surface, sidewall) each other of reaction tank.
The design feature that " speed of its motion of mounting medium of diverse location is different in reaction tank " refers to reaction tank be designed or be chosen as mounting medium in reaction tank at least two positions its movement velocity be different.Generally do not need mounting medium its movement velocity of all positions in reaction tank all different.In a lot of examples, as long as the height (or width) that mounting medium is being determined, or be identical a speed that allocates really on the face perpendicular to direction of motion, but with other height (or width), or the movement velocity of the mounting medium on other parallel plane is different just passable.
" material is transferred to certain position along specific direction " refers to material and moves to a definite position owing to be subjected to applying the effect of power thereon along an interested direction.The position here is confirmed as place or the site on this direction.For example in a rectangle reaction tank, this reaction tank constitutes by top cover and bottom surface and with the thin packing ring that they separate, and is carved with shallow rectangular channel in the middle of the thin packing ring, and the mounting medium that comprises material to be distinguished just moves along the length direction of this passage.Electrode and piezoelectric sensor are assembled in the top of reaction tank or/and the bottom.When electric signal is applied on electrode and the piezoelectric sensor, the material that sound field power and dielectric masterpiece are used for mounting medium will be produced.These power have component vertically, with the direction of motion quadrature.These components can make material arrive different positions along movement in vertical direction.For example, when apply electric signal with exciting electrode and piezoelectric sensor after, originally be positioned at material near reaction tank bottom and can move to position apart from a certain height in bottom.The power that is used to change the material position in the present invention comprises sound field power, electrophoretic force, dielectric power, gravity, fluid lift force, thermal diffusion power.Be heated " material " of diffusive force influence for the position, the position of " material " is meant along the distribution of a certain direction or CONCENTRATION DISTRIBUTION.For the be not heated material of diffusive force influence of position, " material " just refers to " material " particular location on this direction in the position on a certain direction.
" velocity distribution in displacement " refers to the material displacement in the velocity distribution curve of the mounting medium that moves in reaction tank.The displacement here is meant the displacement on the velocity distribution curve direction.Be arranged in velocity distribution fast moving part material will than be arranged in velocity distribution at a slow speed the motion of matter of movable part get soon.For the be heated material of diffusive force effect of position, " material " displacement in the velocity distribution refers to the CONCENTRATION DISTRIBUTION of the material in the velocity distribution reference framework.Be not heated " material " of diffusive force effect for the position, the material displacement in the velocity distribution refers to the material displacement in the velocity distribution reference framework.
" material is shifted onto the equilibrium position on a certain direction " refers to material in the next interested equilibrium position that moves on on a certain direction of the influence of the power that is applied to it.The equilibrium position refers to place or the site on this direction.The clean power that the equilibrium position refers on this place's material is zero or is approximately zero that material just can remain on this position like this.For the material that the position is heated and extends influence, " material " refers to material on this direction in the equilibrium position on certain direction equilibrium position distributes.For the material that the position is not heated and extends influence, " material " refers to when the material stress balance in the equilibrium position on certain direction, and " material " be residing position on this direction.
" length of reaction tank is with respect to width and highly be fully big " refers in the shape of not considering the real reaction pond, and the typical length of reaction tank is reaction tank representative width and twice highly at least.Preferably typical length is representative width and highly three times at least, and situation preferably is that the typical length of reaction tank is representative width and height five times at least.Though the width of reaction tank with highly can be identical or approximate identical, preferably one longer than another, fully greater than height, for example, the representative width of reaction tank can be the twice at least, three times or five times big of exemplary height as width.
For the clarity of describing, be not subjected to the limitation of mode, the detailed description of invention is divided into following two parts.
B. exemplary device
B.1. sound field-field flow separating reaction pond
Fig. 1 has shown the entity example in a sound field-field flow separating reaction pond and the operation principles that sound field-field flow separates.Reaction tank has a top cover 10 and bottom surface 20.Top cover and bottom surface separate with packing ring that is carved with rectangular channel 40 or dividing plate 30.Passage 40 ends are taper.For clarity, separately show top cover 10, packing ring 30 and bottom surface 20.During use, these parts are joined together to form sound field-field flow separating reaction pond.Inlet 50 and outlet 60 lay respectively at top cover and bottom surface, the ingress port of reaction tank and outlet port.Inlet 50 links to each other with an injection device 70, mounting medium can be amassed material to be distinguished and be incorporated in the reaction tank.Injection device can be a syringe pump (Wang, et al., 1998) of being furnished with fillup valve.Outlet 60 links to each other with collection or calibrating installation 80, can be used for the calibrating that sound field-field flow separates the material of the separated and differentiation in back.Collection or calibrating installation can be batch particle-counting system, liquid blood cell counter or separated and collected device.
In the figure of entity example, whole bottom surface 20 is piezoelectric sensors.The upper surface 90 of bottom surface 20 and lower surface 100 are coated metallic film or other conductive materials.Be added to the upper surface 90 and the lower surface 100 of piezoelectric sensor 20 from the ac signal of signal generator 110 output, produce the sound wave of direction and surface 90 and 100 quadratures.The sound wave that piezoelectric sensor sends is reflected on the top cover 10.Sound wave that piezoelectric sensor sends and top cover sound wave stack reflectingly form the interior synthetic sound field of reaction tank.Synthetic sound field can have two components, standing wave component and traveling-wave component.The ratio of standing wave component and traveling-wave component is decided by the height (distance between top cover and bottom surface) of reaction tank, the wavelength of sound wave, the acoustic properties of top cover 10 and bottom surface 20, the attenuation coefficient of sound wave in mounting medium.An entity example is that the reaction tank height is half of standing wave wavelength, can form standing wave in reaction tank.The central plane of reaction tank exists the acoustic pressure node.The another one example is that the reaction tank height is greater than or less than half of standing wave wavelength.
In the example of Fig. 1, bottom surface 20 is corresponding to piezoelectric sensor.Assemble one or more piezoelectric sensor along the various piece of reaction tank multiple variation can be arranged.Can be contained in top cover or bottom surface.For the situation that piezoelectric sensor is contained in the bottom surface, sensor can be combined on the lower surface of a solid plate, like this should flat board just can form the bottom surface of reaction tank.Piezoelectric sensor produces sound wave and is coupled to mounting medium in the reaction tank by solid plate.Similarly for situation about piezoelectric sensor being contained on the top cover, sensor can be combined on the upper surface of a solid plate, and this flat board just can form the top cover of reaction tank.Piezoelectric sensor produces sound wave and is coupled to mounting medium in the reaction tank by solid plate.Field flow separating reaction pond among Fig. 1 comprises a piezoelectric sensor.Can use a plurality of piezoelectric sensors in the reaction tank.These sensors can be connected in the top cover or the bottom of reaction tank, and perhaps top cover and bottom have, and form piezoelectric sensor array.Can on these piezoelectric sensors, apply same or different electric signal, thereby in reaction tank, produce sound wave.
Be introduced in the effect that material in the reaction tank can be subjected to different power in the reaction tank.We consider such situation: the material of introducing is tiny particulate, and reaction tank keeps flat.These power are:
Vertical direction
The sound field radiant forceF
Acoustic120, point to or leave top cover (bottom surface), be decided by and particulate and suspending carrier density, factor that acoustic impedance is relevant.This sound field radiant force F
Acoustic120 may just act on the one-component of the whole sound field power on the particulate.
Lifting or precipitation particulate
GravityF
G130, be decided by the relative density of particulate and suspending carrier.
Fluid lift forceF
Lift140, trend is released the reaction tank pond with particulate.Though convection cell lift has carried out different theories and experimental study, its essence remains problem (Williams et al., 1992; 1994; 1996; 1997).Howsoever, generally accepted viewpoint is when particulate during very near reaction pool wall (for example in the thick reaction tank of 200um with the distance of wall less than 5um), this power performance great role.Recently separate (Huang et al., 1997 for dielectric-field flow; Wang et al., 1998) studies show that this power is limited for dielectric-field flow centrifugation.
These three masterpieces are used for particulate, and it is moved to the equilibrium position, locate the mutual balance of each power in the equilibrium position, and the clean power that acts on the single particulate is zero in vertical direction, is exactly:
F
acoustic(z)+F
Lift(z)-F
G＝0
The height difference of the particulate equilibrium position of heterogeneity (as: size, geometric configuration, density, acoustic impedance).For example, particulate 150 and 160 is transferred to differing heights from the reaction tank bottom surface.When flowing by inlet 50 introducing mounting mediums generations, velocity distribution 170 appears.Direction of motion in this example is parallel to top cover and bottom surface, points to endpiece from the reaction tank inlet end.Mounting medium has friction speed at diverse location.For the example among Fig. 1, when reaction tank length (being etched passage length) and width (being width of channel) during much larger than height (being the distance of top cover and bottom surface), obeying approximate parabolic velocity in vertical direction from the speed of the conduit wall of packing ring formation mounting medium far away distributes
Here V
mBe the speed of carrier when the height z of distance reaction tank bottom surface,＜V
mBe the average velocity of carrier, H is the reaction tank height.Mounting medium in the reaction tank forms approximate parabolic velocity distribution in vertical direction like this.Particulate 150 can be distinguished according to height h1 of living in and h2 on the direction vertical with mounting medium direction of motion with 160.In addition, can further be distinguished according to the upright position particulate 150 on the velocity distribution and 160.Further again, particulate 150 and 160 passes reaction tank with friction speed.If particulate 150 and 160 is almost introduced reaction tank simultaneously with friction speed, because delivery speed difference, particulate 150 and 160 will stop different time in reaction tank.Particulate of different nature (for example size, density, geometric configuration, acoustic impedance) can be transferred to the diverse location on the vertical direction, can or be distinguished according to the transferring position on the vertical direction or in the velocity distribution, can be passed the speed or the residence time differentiation of reaction tank according to particulate.Particulate of different nature can be divided into sub-group.In addition, if export in the terminal vertical distribution of reaction tank, when particulate left reaction tank by the difference outlet, the particulate of differing heights can be divided into sub-group.
In the superincumbent discussion, consideration be the situation that reaction tank keeps flat.Yet reaction tank can be put to become any angle along any direction or with surface level.In these cases, we still consider to act on the particulate to be distinguished advocate will be along the direction vertical with mounting medium direction of motion.The difference of these situations and above-mentioned reaction tank horizontal positioned is gravity.In the superincumbent situation, the angle of the action direction of gravity and the direction of motion of carrier is 90 degree.At reaction tank is not under the situation about keeping flat, and the angle of the action direction of gravity and the direction of motion of carrier may not be 90 degree.Like this, when analysis when to be applied to material upper edge to be distinguished and mounting medium direction of motion angle be power on the 90 degree directions, need only consider the one-component of gravity.
The velocity distribution of reaction tank is decided by the architectural feature of reaction tank among Fig. 1.When reaction tank length and width during, exist para-curve or approximate parabolical velocity distribution along the vertical direction of reaction tank much larger than height.Approximate parabolical reason is or not " parabolic distribution " near the velocity distribution that gasket wall goes out.When the reaction tank width with highly near the time, the speed of mounting medium can be followed other velocity distribution, rather than above-mentioned " parabolic distribution ".In addition, top cover and bottom surface are considered to smooth and are parallel to each other in the above-mentioned discussion.When top cover and/or bottom surface out-of-flatness or be not parallel to each other mutually, when perhaps top cover or bottom surface were changed by the structural element of different-thickness, the velocity distribution of mounting medium can be different with above-mentioned " being similar to parabolic distribution ".
In order to produce different mounting medium velocity distribution, can be on the packing ring 30 between top cover 10 and the bottom surface 20 the difform passage of etching.For example, the passage 40 of Fig. 2 midfield flow point in reaction tank is oval.When mounting medium during through such reaction tank, different among velocity distribution and Fig. 1.Similarly, when the passage in mounting medium process Fig. 3 reaction tank, can produce unique velocity distribution.
We mainly concentrate on the differentiation of particulate and have ignored the influence of thermal diffusion effect in discussing about field flow separating reaction pond above-mentioned.Trickle material for to be distinguished in the field flow separating reaction pond is necessary to consider thermal diffusion power.In this case, stressed effect is shifted or material position in velocity distribution is meant species distribution under the stressed function influence along certain direction.Along certain direction or the species distribution in velocity distribution be meant material along certain direction or in velocity distribution CONCENTRATION DISTRIBUTION.
Field flow separating reaction pond can have one or more to enter the mouth to introduce material to be distinguished and mounting medium.Field flow separating reaction pond can have one or more to export the material and the mounting medium of deriving after the differentiation.Entrance and exit can be positioned at top cover and/or bottom surface.Entrance and exit can be the hole (diameter is from several microns to several millimeters) of boring on top cover and/or bottom surface.PEEK, plastics or metal catheter can insert in the hole coupled reaction pond and external fluid passage are as injecting or gathering-device.Entrance and exit also can be the passage (width is from several microns to several millimeters) that drills through at the reaction tank end.Line up banded multitube road system can with passage to connecing.In Fig. 4 reaction tank, the bottom surface of reaction tank, single inlet-hole-be positioned at.Two output ports 180 and 190 that are positioned at top cover and bottom simultaneously are the passages that cut on wall.Great majority are lined up banded piping system as the outlet that is used for interface channel.Two outlets that are arranged in top cover and bottom are corresponding to being used for tripping device (Springston et al, 1987 that field flow separates; Lee et al, 1989; Levin and Giddings, 1991).
B.2. sound field-electrophoresis-flow point is from reaction tank
Specific implementation that Fig. 5 has showed that sound field-electrophoresis-field flow separates and principle of operation.Reaction tank has top cover 210 and bottom surface 220.Top cover and bottom surface are separated by a packing ring or a dividing plate 230 that is carved with rectangular channel 240.Passage 240 has the end of taper.For clarity, top cover 210, bottom surface 220, packing ring 230 and passage 240 separately show.During use, these parts are joined together to form a sound field-electrophoresis-field flow separating reaction pond.Inlet 250 and outlet 260 lay respectively at top cover and bottom surface, the inlet end of reaction tank and endpiece.Enter the mouth 250 and one and be used for mounting medium and material to be distinguished are introduced the injection device 270 of reaction tank.Injection device can be a syringe pump (Wang et al., 1998, Huang et al., 1999, Yang et al., 1999) that combines fillup valve.Outlet 260 is used for one that the verification field flow point separates and the collection or the calibrating of the material distinguished after effect.Collection or calibrating installation can be a batch particle-counting system, liquid blood cell counter or separated and collected device.
In Fig. 5 example, whole bottom surface is a piezoelectric sensor.The end face 290 of bottom surface 220 and bottom surface 300 have applied layer of metal film or other conductive material.Be added to the upper surface 290 and the lower surface 300 of piezoelectric sensor 220 from the ac signal of signal generator 310 output, produce the sound wave of direction and surface 290 and 300 quadratures.The sound wave that piezoelectric sensor sends is reflected on the top cover 210.Sound wave that piezoelectric sensor sends and top cover sound wave stack reflectingly form the interior synthetic sound field of reaction tank.Synthetic sound field can have two components, standing wave component and traveling-wave component.The ratio of standing wave component and traveling-wave component is decided by the height (distance between top cover and bottom surface) of reaction tank, the wavelength of sound wave, the acoustic properties of top cover 210 and bottom surface 220, the attenuation coefficient of sound wave in mounting medium.An entity example is that the reaction tank height is half of standing wave wavelength, wherein can form standing wave.The central plane of reaction tank exists the acoustic pressure node.The another one example is that the reaction tank height is greater than or less than half of standing wave wavelength.
In the example of Fig. 5, bottom surface 220 is corresponding to piezoelectric sensor.Assemble one or more piezoelectric sensor along the various piece of reaction tank multiple variation can be arranged.Can be contained in top cover or bottom surface.For the situation that piezoelectric sensor is contained in the bottom surface, sensor can be combined on the lower surface of a solid plate, like this should flat board just can form the bottom surface of reaction tank.Piezoelectric sensor produces sound wave and is coupled to mounting medium in the reaction tank by solid plate.Similarly for situation about piezoelectric sensor being contained on the top cover, sensor can be combined on the upper surface of a solid plate, and this flat board just can form the top cover of reaction tank.Piezoelectric sensor produces sound wave and is coupled to mounting medium in the reaction tank by solid plate.Field flow separating reaction pond among Fig. 5 comprises a piezoelectric sensor.Can use a plurality of piezoelectric sensors in the reaction tank.These sensors can be connected in the top cover or the bottom of reaction tank, and perhaps top cover and bottom have, and form piezoelectric sensor array.Can on these piezoelectric sensors, apply same or different electric signal, thereby in reaction tank, produce sound wave.
In the illustration 5, be used to produce the electrode of electric field in the reaction tank corresponding to the upper surface 290 of bottom surface 220 and the lower surface 295 of top cover 210.The upper surface 290 of bottom surface 220 and the lower surface 295 of top cover 210 have applied layer of metal film or other conductive material.The dc signal of signal generator 315 generations or low-frequency ac signal are applied between the surface 290 and 295 like this, and generation one is orthogonal to the electric field of top cover and bottom surface.The material that is incorporated into this electric field can be subjected to being decided by the effect of the electrophoretic force of field strength and material effective charge.
In the example of Fig. 5, the upper surface 290 of bottom surface 220 also is used to encourage simultaneously piezoelectric sensor as an electrode that produces electric field.Usually, the electrode that is used to produce electric field encourages the electrode of piezoelectric sensor different with being used to.In addition, the electrode that is used to produce electric field only part cover the lower surface of top cover or the upper surface of bottom surface.Can use different electrod-arrays on these surfaces (being the lower surface of top cover or the upper surface of bottom surface).Fig. 6 has shown an interlaced formula electrod-array 400 and an interlaced formula castle type electrod-array 410.Electrode can be vertically along reaction tank (as Fig. 6 A or Fig. 6 B) or laterally (be electrode among Fig. 6 A revolve turn 90 degrees) distribute.In single electrode in the electrod-array and the two-way electrical lead bus 405 and 408 a road links to each other.When the signal that sends when signal source was linked the electrical lead bus, exciting electrode produced electric field.Utilize electrod-array to produce in the situation of electric field at these, produce electric field and can use different electric signal connection modes with the excitation piezoelectric sensor.For example, the lower surface that is used for top cover when reaction tank produces electric field when an electrode forms conductive plane, the lower surface plating film of bottom surface, and upper surface covers the chiasma type electrod-array, forms piezoelectric sensor.The electric signal that produces electric field in reaction tank can apply in the lower surface that passes top cover and the crossed array arbitrary or two electrical lead buses (among Fig. 6 A 405 and 408).The electric signal that produces electric field in reaction tank can apply in the lower surface that passes the bottom surface and the crossed array arbitrary or two electrical lead buses (among Fig. 6 A 405 and 408).
Be introduced in the effect that material in sound field-electrophoresis-field flow separating reaction pond can be subjected to different power in the reaction tank.We consider such situation: the material of introducing is tiny particulate, and reaction tank keeps flat.With reference to figure 5, these power are:
Vertical direction
The sound field radiant forceF
Acoustic320, point to or leave top cover (bottom surface), be decided by and particulate and suspending carrier density, factor that acoustic impedance is relevant.This sound field radiant force F
Acoustic320 may just act on the one-component of whole sound field power on the particulate.
Vertically act on the electrophoretic force F on the charged corpuscle
E325.Be decided by that the particulate positively charged still is the direction of negative electricity, DC electric field.The reaction tank bottom surface is pointed to or left to this power.This electrophoretic force F
E325 may just act on the one-component of whole electrophoretic forces on the particulate.
Lifting or precipitation particulate
GravityF
G130, be decided by the relative density of particulate and suspending carrier.
Fluid lift forceF
Lift340, trend is released the reaction tank pond with particulate.Though convection cell lift has carried out different theories and experimental study, its essence remains problem (Williams et al., 1992; 1994; 1996; 1997).Howsoever, generally accepted viewpoint is when particulate during very near reaction pool wall (for example in the thick reaction tank of 200um with the distance of wall less than 5um), this power performance great role.Recently separate (Huang et al., 1997 for dielectric-field flow; Wang et al., 1998) studies show that this power is limited for dielectric-field flow centrifugation.
These several masterpieces are used for particulate, and it is moved to the equilibrium position, locate the mutual balance of each power in the equilibrium position, and the clean power that acts on the single particulate is zero in vertical direction, is exactly:
F
acoustic(z)+F
Lift(z)+F
E(z)-F
G＝0
The height difference of the particulate equilibrium position of heterogeneity (as size, geometric configuration, density, acoustic impedance).For example, particulate 350 and 360 is transferred to differing heights from the reaction tank bottom surface.When flowing by inlet 250 introducing mounting mediums generations, velocity distribution 270 appears.Direction of motion in this example is parallel to top cover and bottom surface, points to endpiece from the reaction tank inlet end.Mounting medium has friction speed at diverse location.For the example among Fig. 5, when reaction tank length (being etched passage length) and width (being width of channel) during much larger than height (being the distance of top cover and bottom surface), obeying approximate parabolic velocity in vertical direction from the speed of the conduit wall of packing ring formation mounting medium far away distributes
Here V
mBe the speed of carrier when the height z of distance reaction tank bottom surface,＜V
mBe the average velocity of carrier, H is the reaction tank height.Mounting medium in the reaction tank forms approximate parabolical velocity distribution in vertical direction like this.Particulate 350 can be distinguished according to height h1 of living in and h2 on the direction vertical with mounting medium direction of motion with 360.In addition, can further be distinguished according to the upright position particulate 350 on the velocity distribution and 360.Further again, particulate 350 and 360 passes reaction tank with friction speed.If particulate 350 and 360 is almost introduced reaction tank simultaneously with friction speed, because delivery speed difference, particulate 350 and 360 will stop different time in reaction tank.Particulate of different nature (for example size, density, geometric configuration, acoustic impedance) can be transferred to the diverse location on the vertical direction, can or be distinguished according to the transferring position on the vertical direction or in the velocity distribution, can be passed the speed or the residence time differentiation of reaction tank according to particulate.Particulate of different nature can be divided into sub-group.In addition, if export in the terminal vertical distribution of reaction tank, when particulate left reaction tank by the difference outlet, the particulate of differing heights can be divided into sub-group.
In above discussion, reaction tank is considered to horizontal positioned, but in fact reaction tank can be to place along any direction, or becomes arbitrarily angled placement with surface level.In these cases, we also need consider those act on the object to be separated, with mounting medium direction of motion angle be the power of 90 degree.This compares with reaction tank horizontal positioned situation discussed above, and difference is the difference of action of gravity.In the situation of Tao Luning, the direction of motion angle of the action direction of gravity and mounting medium is 90 degree in front.When reaction tank was not horizontal positioned, the angle of the action direction of gravity and the direction of motion of mounting medium may not be 90 degree.Like this, when analysis when to be applied to material upper edge to be distinguished and mounting medium direction of motion angle be power on the 90 degree directions, need only consider the one-component of gravity.
Velocity distribution in the rectangle reaction tank shown in Figure 5 depends on the architectural characteristic of this reaction tank.When height that the length and the width of reaction tank is far longer than reaction tank, a parabolic type vertically and approximate parabola shaped velocity distribution can appear in this reaction tank.The velocity distribution that the approximate parabola shaped reason of formation is close gasket wall place is not parabola shaped distribution.When the width of reaction tank and its are highly onesize, the speed of mounting medium will be different with above-mentioned distribution in the reaction tank.In addition, top cover and bottom surface are considered to flat and parallel to each other in above-mentioned discussion.When top cover and/or bottom surface when not being flat, perhaps mutual when not parallel when top cover and bottom surface, perhaps when top cover and bottom surface change with the structural detail of different-thickness, the velocity distribution of mounting medium will be different from nearly parabolic velocity discussed above and distribute.
For the friction speed that produces mounting medium distributes, the packing ring 230 between top cover 210 and bottom surface 220 can cut the passage that forms other shape from the centre.For example, the passage in sound field-dielectric-field flow separating reaction pond can be one oval-shaped, similar in appearance to the passage in sound field shown in Fig. 2-field flow separating reaction pond.When mounting medium during by such reaction tank, what the velocity distribution of mounting medium will be with shown in Fig. 5 is different.Same, the passage in the sound field shown in Fig. 3-field flow separating reaction pond can be used as a sound field-dielectric-field flow separating reaction pond.When mounting medium passed through this passage, such reaction tank will make mounting medium form a unique velocity distribution.
More than the discussion in relevant sound field-dielectric-field flow separating reaction pond mainly concentrate on separation of particles, ignored the influence of thermal diffusion effect.For those small-size objects to be separated in sound field-dielectric-field flow separating reaction pond, should count thermal diffusion effect.Like this, along the position of a direction or the material in velocity distribution, arranged, refer to the distribution of material under external force under external force.This object along certain direction or certain velocity distribution distributes and promptly refers in the direction or the CONCENTRATION DISTRIBUTION or the position distribution of the object of velocity distribution.
Can there be one or more inlet in sound field-dielectric-field flow separating reaction pond, to import object to be separated and mounting medium.Reaction tank also can have one or more outlets, to export object and the mounting medium that has separated.Entrance and exit can be placed on the top cover of reaction tank or/and the bottom surface.Entrance and exit can be to be drilled in the reaction tank top cover or/and the aperture of bottom surface (diameter little to several microns or arrive several millimeters greatly).PEEK or plastics perhaps insert in the hole metal tube, as the fluid connection of reaction tank and external fluid loop (for example disperser or gathering-device).On the other hand, entrance and exit also can be a passage at the reaction tank endpiece (width by micron to millimeter).Complex pipe is arranged with band shape, can connect with above-mentioned passage.Example sound field shown in Fig. 4-field flow separating reaction pond can be used as the example in a sound field-dielectric-field flow separating reaction pond.At this moment, a single input port (hole) is positioned at the bottom surface of reaction tank.Two outlets 180 and 190 are positioned at the top cover and the bottom surface of reaction tank, are the thin thin passages that cutting obtains on wall.Many pipes of arranging with band shape are used for linking to each other with the outlet of these passages.Two outlets that are arranged in top cover and bottom are corresponding to being used for tripping device (Springston et al, 1987 that field flow separates; Lee et al, 1989; Levin and Giddings, 1991).
B3. sound field-dielectric-field flow separating reaction pond
Shown in Figure 7 is the principle of work in a sound dielectric-field flow separating reaction pool structure harmony dielectric-field flow separating reaction pond.Reaction tank has top cover 510 and bottom surface 520, and both are separated by pad 530, is carved with a rectangular channel 540 on 530.540 two ends are tapers.A piezoelectric sensor 525 is arranged in the bottom surface.For the purpose of clear, top cover 510, pad 530, bottom surface 520, piezoelectric sensor 525 illustrate respectively.In use, these elements are bonded on and constitute a sound dielectric-field flow separating reaction pond together.Inlet 550 and outlet 560 lay respectively at top cover and bottom surface, promptly respectively at the inlet end and the endpiece of reaction tank.Inlet 550 links to each other with injection device 570, and 570 can import mounting medium and object to be separated.Injection device can be syringe pump (Wang et al., 1998 that introduction valve is arranged; Huang et al., 1999; Yang et al., 1999).Outlet 560 links to each other with a collecting device 580, and 580 can identify by the object of sound dielectric-field flow separating reaction pond separation.Collecting device can be a batch particle-counting system, a flow cytometer or a separated and collected device.
In example 7, piezoelectric sensor 525 is corresponding to entire reaction pond base surface area, and its upper surface 590 and lower surface 600 have been coated with metal film and other conductive material.The ac signal that signal generator produces is applied to the upper surface 590 and the lower surface 600 of piezoelectric sensor 525, produces sound wave on the direction vertical with 590,600 with the excitation piezoelectric sensor in reaction tank.Sound wave that piezoelectric sensor sends and bottom surface 520 are coupled in the reaction tank, are reflected by top cover 510.The stack of piezoelectric sensor propagation wave and top cover reflection wave constitutes the whole sound fields in the reaction tank.There are two components, i.e. standing wave component and traveling-wave component in the full acoustic wave field.The ratio of the size of two components depends on reaction tank height (being the distance between reaction tank top cover, the bottom surface), wave length of sound, and the acoustic characteristic of top cover 510, bottom surface 520 and piezoelectric sensor 525, and the decay factor of mounting medium and sound wave.In one implementation, the reaction tank height between top cover, the bottom surface is the half-wavelength of standing wave, therefore constitutes standing wave in reaction tank.There is the acoustic pressure node in the reaction tank mid-plane.In another implementation, the reaction tank height is greater than the half-wavelength of (or less than) standing wave.
In Fig. 7, piezoelectric sensor 525 and reaction tank bottom surface 520 bondings.One or more piezoelectric sensors can there be multiple mode along the placement of reaction tank each several part.525 can be placed on top cover and (or) bottom surface.When piezoelectric sensor was placed on top cover, it can be from top cover and a solid piece bonding, and solid piece constitutes the top cover of reaction tank like this.Sound wave can be produced and is coupled in the mounting medium in the reaction tank by solid piece by piezoelectric sensor.In addition, piezoelectric sensor also can directly be used as the reaction tank top cover.When the bottom surface that piezoelectric sensor is placed on reaction tank is, sensor can directly be used as the reaction tank bottom surface, and microelectrode element or array can directly be made at the upper surface of this piezoelectric sensor.Sound shown in Figure 7 dielectric-field flow separating reaction pond comprises a piezoelectric sensor in the reaction tank.A plurality of piezoelectric sensors can be placed in the same reaction tank.They can in series be placed on top cover or bottom surface or place simultaneously and constitute piezoelectric sensor array.A plurality of piezoelectric sensors can be encouraged the sound wave that produces in the reaction tank by identical or different electric signal.
In the example of Fig. 7, be used for producing the electrode member of electric field corresponding to the electrod-array 545 on 520 upper surfaces of bottom surface at reaction tank.Signal generator 615 can be applied on the electrod-array 545 and produce AC signal, in reaction tank, to form a non-uniform electric field.Be subjected to the object of this non-uniform electric field effect will be subjected to the effect of dielectrophoresis force, this power and object and the specific inductive capacity of media is relevant, also relevant with the uneven distribution of electric field on every side.
In the example of Fig. 7, electrod-array 545 is placed on the upper surface of bottom surface 520 and produces non-uniform electric field.Usually, the electrode member that is used to produce electric field can partly cover the upper surface of the lower surface of top cover and bottom surface or two kinds.On these surfaces, can adopt the electrod-array (being the lower surface of top cover and the upper surface of bottom surface) of different structure.Can adopt Fig. 6 A, the interlaced formula electrod-array 400 of 6B and interlaced formula castle electrod-array 410.Electrode is along vertically (array 545 among Fig. 7 for Fig. 6 A, 6B) or laterally (electrode member of array 545 revolves and turn 90 degrees among Fig. 7 for Fig. 6 A, 6B) distribution of reaction tank.Similarly, the also available interlaced formula electrod-array that cycle triangle (700) or arcuation electrode (710) are arranged shown in Figure 8, vertically (Fig. 8 A, 8B) or laterally (Fig. 8 A's electrode, the electrode member among the 8B revolves and turn 90 degrees) distributes along reaction tank.Fig. 8 A, one of the single electrode member among the 8B in the electrod-array and two common electrical conductor bus 705,708 link to each other.It is that electrode member just is energized and produces electric field that the electric signal that sends when signal source is added to the electrical lead bus.
The structure of example shown in Figure 7 is that electrod-array 545 is placed on the reaction tank bottom surface 520, and piezoelectric sensor 525 is bonded on the bottom surface 520.In other implementation, difference also can directly be made on piezoelectric sensor in conjunction with the electrod-array of shape.For example, PZT is a kind of piezoelectric, can be used for piezoelectric sensor.When its surface is ground to when enough smooth, just can adopt micro-processing method on its Piezoelectric Substrates, to make microelectrode.In the operation in structure sound dielectric-field flow separating reaction pond, upper surface has microelectrode, lower surface to have the piezoelectric sensor of plate electrode can be with the bottom surface in the dielectric of uttering a word-field flow separating reaction pond.Can apply electric signal to microelectrode array from upper surface and produce dielectrophoresis force.Simultaneously, electric signal can be applied to upper electrode array (by electrical lead bus 705 and 708) and the lower electrode array produces sound field and power.The advantage of this method is that the electrod-array that is used for producing dielectrophoresis force is integrated on the surface of piezoelectric sensor.This method that electrod-array and piezoelectric sensor is integrated and sound field flow point shown in Figure 5 are similar from the method for reaction tank.Be used for producing the electrode of electrophoretic force among Fig. 5 on the upper surface of piezoelectric sensor.
Be introduced into the sound field-dielectric-object in field flow separating reaction pond and in reaction tank, will be subjected to the effect of multiple power.We consider that the object of introducing is a molecule, and reaction tank is the situation of horizontal positioned.With reference to Fig. 7, these power are
Sound field radiant force F
Acoustic620: vertically pointing to or away from top cover (bottom surface), depend on one with particulate and suspension media density, the relevant coefficient of acoustic impedance.This sound field radiant force F
Acoustic620 may just act on the one-component of whole sound field power on the particulate.
Dielectrophoresis force F
DEP625: vertically acting on the polarization particle.According to particulate around the easier or more difficult polarization of media, this power is pointed to or away from electrode member.This dielectrophoresis force F
DEP625 may just act on the one-component of whole dielectrophoresis forces on the particulate.
Gravity F
G630: make the power of particle suspension or deposition, with particulate with the density relative size of media is relevant on every side.
Fluid lift force F
Lift640: attempt to order about particulate away from the reaction pool wall.Existing various theory and experimental studies about fluid lift force, but its essence is still unknown.Present received viewpoint is only when particulate is in close proximity to reaction pool wall (for example in the thick distance that reaches in 200 microns the reaction tank less than 5 microns), and this power just plays an important role.Recently some are about work (Huang et al., 1997 of dielectric-field flow separation; Wang etal., 1998) show that this power role in dielectric-field flow separation is handled is very little.
More than these masterpieces be used on the particulate, order about particulate towards the motion of the position of total dynamic balance, the clean power that therefore acts on single particulate in the vertical is 0, promptly
F
acoustic(z)+F
Lift(z)+F
DEP(z)-F
G＝0
Particulate of different nature (as size, geometric configuration, density, specific inductive capacity, acoustic impedance) reaches balance at various height.For example (h1 h2) locates balance to particulate 650 and 660 at distance reaction tank bottom surface differing heights.When mounting medium from entering the mouth 550 when injecting reaction tanks and forming fluids, can produce a fluid velocity and distribute 670.At this moment direction of motion is parallel with the bottom surface with the reaction tank top cover, and points to endpiece from inlet end.The mounting medium at diverse location place has different speed in the reaction tank.As the example in 7, when the reaction tank length passage length of middle part cutting (promptly) and reaction tank width (being channel width) during much larger than reaction tank height (being the distance of top cover and bottom surface), mounting medium is obeyed approximate parabolic velocity distribution longitudinally in the speed away from the position of reaction pool wall.
V wherein
mBe that media is the speed at Z place at distance reaction tank bottom surface height,＜V
mBe the average velocity of media, H is the reaction tank height.So just the mounting medium in the reaction tank longitudinally having been set up an approximate parabolic velocity distributes.Particulate 550,560 just can be separated according to residing diverse location in velocity distribution thus.Further, particulate 550,560 passes through reaction tank with different speed.If particulate 550,560 is simultaneously by reaction tank, then owing to their movement velocity differences in reaction tank, they leave reaction tank simultaneously with portion.The particulate of tool position of different nature (as size, geometric configuration, density, specific inductive capacity, acoustic impedance) can longitudinally be placed on different positions, can be separated according to the difference of placement location in the vertical, can pass through the difference of reaction tank speed according to particulate, or leave the difference of reaction tank time according to particulate and separate.
In above discussion, reaction tank is considered to horizontal positioned, but in fact reaction tank can be to place along any direction, or becomes arbitrarily angled placement with surface level.In these cases, we also need consider those act on the object to be separated, with mounting medium direction of motion angle be the power of 90 degree.This compares with reaction tank horizontal positioned situation discussed above, and difference is the difference of action of gravity.In the situation of Tao Luning, the direction of motion angle of the action direction of gravity and mounting medium is 90 degree in front.When reaction tank was not horizontal positioned, the angle of the action direction of gravity and the direction of motion of mounting medium may not be 90 degree.Like this, when analysis when to be applied to material upper edge to be distinguished and mounting medium direction of motion angle be power on the 90 degree directions, need only consider the one-component of gravity.
Velocity distribution in the rectangle reaction tank shown in Figure 7 depends on the architectural characteristic of this reaction tank.When height that the length and the width of reaction tank is far longer than reaction tank, a parabolic type vertically and approximate parabola shaped velocity distribution can appear in this reaction tank.The velocity distribution that the approximate parabola shaped reason of formation is close gasket wall place is not parabola shaped distribution.When the width of reaction tank and its are highly onesize, the speed of mounting medium will be different with above-mentioned distribution in the reaction tank.In addition, top cover and bottom surface are considered to flat and parallel to each other in above-mentioned discussion.When top cover and/or bottom surface when not being flat, perhaps mutual when not parallel when top cover and bottom surface, perhaps when top cover and bottom surface change with the structural detail of different-thickness, the velocity distribution of mounting medium will be different from nearly parabolic velocity discussed above and distribute.
For the friction speed that produces mounting medium distributes, the packing ring 530 between top cover 510 and bottom surface 520 can cut the passage that forms other shape from the centre.For example, the passage in sound field-dielectric-field flow separating reaction pond can be one oval-shaped, similar in appearance to the passage in sound field shown in Fig. 2-field flow separating reaction pond.When mounting medium during by such reaction tank, what the velocity distribution of mounting medium will be with shown in Fig. 7 is different.Same, the passage in the sound field shown in Fig. 3-field flow separating reaction pond can be used as a sound field-dielectric-field flow separating reaction pond.When mounting medium passed through this passage, such reaction tank will make mounting medium form a unique velocity distribution.
More than the discussion in relevant sound field-dielectric-field flow separating reaction pond mainly concentrate on separation of particles, ignored the influence of thermal diffusion effect.For those small-size objects to be separated in sound field-dielectric-field flow separating reaction pond, should count thermal diffusion effect.Like this, along the position of a direction or the material in velocity distribution, arranged, refer to the distribution of material under external force under external force.This object along certain direction or certain velocity distribution distributes and promptly refers in the direction or the CONCENTRATION DISTRIBUTION or the position distribution of the object of velocity distribution.
Can there be one or more inlet in sound field-dielectric-field flow separating reaction pond, to import object to be separated and mounting medium.Reaction tank also can have one or more outlets, to export object and the mounting medium that has separated.Entrance and exit can be placed on the top cover of reaction tank or/and the bottom surface.Entrance and exit can be to be drilled in the reaction tank top cover or/and the aperture of bottom surface (diameter little to several microns or arrive several millimeters greatly).PEEK or plastics perhaps insert in the hole metal tube, as the fluid connection of reaction tank and external fluid loop (for example disperser or gathering-device).On the other hand, entrance and exit also can be a passage at the reaction tank endpiece (width by micron to millimeter).A plurality of pipes of arranging with band shape are connected with above-mentioned passage.Example sound field shown in Fig. 4-field flow separating reaction pond can be used as the example in a sound field-dielectric-field flow separating reaction pond.At this moment, a single input port (hole) is positioned at the bottom surface of reaction tank.Two outlets 180 and 190 are positioned at the top cover and the bottom surface of reaction tank, are the thin thin passages that cutting obtains on wall.Many pipes of arranging with band shape are used for linking to each other with the outlet of these passages.Two outlets that are arranged in top cover and bottom are corresponding to being used for tripping device (Springston et al, 1987 that field flow separates; Lee et al, 1989; Levin and Giddings, 1991).
C, exemplary method
C.1. sound field-field flow separates, and sound field-electrophoresis-field flow separates and separates batch operation with sound field-dielectric-field flow
In batch operation, a sound field-field flow separates (perhaps sound field-electrophoresis-field flow separates or sound field-dielectric-field flow separation) reaction tank by the pre-loaded mounting medium of inlet.Hybrid fine particles sample (for example 100uL) injects or inserts the medium of reaction tank by input port.Separate for sound field-field flow, use suitable sound field state, then particulate is in the equilibrium position that can reach them under the influence of sound power and other power in the time in appointment.Sound field in the reaction tank is to obtain by suitable electric signal and piezoelectric sensor.Separate for sound field-electricity-field flow, add suitable electric field and sound field, then particulate is in sound power, and the influence of electrophoretic force and other power reaches their equilibrium position in down will be at the appointed time.Separate for sound field-dielectric-field flow, add suitable dielectrophoresis field and sound field, then particulate reaches their equilibrium position in a period of time under the influence of sound field power, dielectrophoresis force and other power.This step is known as " relaxation " (Giddings, 1981, Giddings, 1993) in typical field flow detachment process.At relaxation stage (Fig. 9 A), particulate of different nature under the afterburning influence, in reaction tank, be in different equilibrium positions.For thermal diffusion effect concerning the balance position of particulate is equipped with the small size particulate (or object) of material impact,, the equilibrium position of dissimilar particulates distributes corresponding to the equilibrium concentration of different particle type.After the relaxation step, flowing of fluid just is established, and the particulate that is in differing heights is driven through reaction tank with different speed.In this process, keep the condition of impressed field constant.Leave the difference of reaction tank time according to particulate, particulate of different nature is separated into a plurality of subgroups (Fig. 9 B).Fig. 9 A, 9B are presented at a rectangle sound field-field flow and separate batch process in (or electrophoresis-field flow separates, or dielectric-field flow separates) sectional view.Fig. 9 A is presented in the relaxation process, and particulate 800 and 850 is placed at various height under the effect of impressed field.Fig. 9 B shows and then relaxation process, sets up fluid and distribute after (being velocity distribution 780) in reaction tank, and particulate 800 surpasses particulate 850, therefore will leave reaction tank as far back as outlet 795 places.Fluid flows and realizes by mounting medium being injected reaction tank inlet 790.
Batch mode is common mode of operation concerning most of field flows separate.Particulate can leave reaction tank from single outlet or a plurality of outlet (for example one at the reaction tank top cover, another is in the reaction tank bottom surface).Can directly be used for collecting two separated portions at top cover and bottom surface to two outlets.The relaxation step is unnecessary under some application scenario.To type, possible particulate just can reach their balance height in very of short duration time after being introduced into reaction tank according to particle mixture.In this case, particulate just can be separated with batch fashion, and do not need the relaxation step.
Like this, flow point on the scene from utilize sound field power to separate an object to may further comprise the steps with batch fashion: 1) set up device described in the invention; 2) ingress port by described device imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium; 3) sample that will contain material to be identified injects the interior mounting medium of reaction tank; 4) piezoelectric sensor is applied at least one road electric signal that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power to be applied on the material; 5) ingress port by device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; Described material in described mounting medium is to be distributed in perpendicular to mounting medium to move through on the reaction tank direction, and recognition material is to realize in the difference that moves through distributing position on the reaction tank direction perpendicular to mounting medium according to material.This sound field flow point can be used in to various sound fields-field flow tripping device described in the invention from batch mode.
In above-mentioned sound field-field flow separates batch processing mode, be preferably in mounting medium introduced and make before its reaction tank of advancing according to a certain velocity distribution, earlier on the piezoelectric sensor that causes sound field power on the said object, applying electric signal so that the object to be separated edge direction vertical with mounting medium direct of travel in reaction tank is placed into the equilibrium position.
Flow point on the scene comes separating objects that batch processing mode be may further comprise the steps from middle application electrophoretic force harmony field force: 1) set up device described in the invention.2) ingress port by described device imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium; 3) sample that will contain material to be identified injects the interior mounting medium of reaction tank; 4) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an electric field, thereby causes having at least an electrophoretic force to be applied on the described material; 5) ingress port by device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; Described material in described mounting medium is to be distributed in perpendicular to mounting medium to move through on the reaction tank direction, and recognition material is to realize in the difference that moves through distributing position on the reaction tank direction perpendicular to mounting medium according to material.Various sound field-electrophoresis described in the invention-field flow tripping device all can separate in the batch processing mode at sound field-electrophoresis-field flow to be used.
In above-mentioned sound field-electricity-field flow separates batch processing mode, be preferably in mounting medium introduced and make before its reaction tank of advancing according to a certain velocity distribution, earlier on electrode member that causes dielectrophoresis force on the said object and the piezoelectric sensor that causes sound field power, applying electric signal so that the object to be separated edge direction vertical with mounting medium direct of travel in reaction tank is placed into the equilibrium position.
Flow point on the scene comes separating objects that batch processing mode be may further comprise the steps from middle application dielectrophoresis force harmony field force: A) set up device described in the invention; B) ingress port by described device imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium; C) sample that will contain material to be identified injects the interior mounting medium of reaction tank; D) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an electric field, thereby causes having at least a dielectrophoresis force to be applied on the described material; E) piezoelectric sensor is applied another road electric signal at least that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power to be applied on the described material; F) ingress port by device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; Described material in described mounting medium is to be distributed in perpendicular to mounting medium to move through on the reaction tank direction, and recognition material is to realize in the difference that moves through distributing position on the reaction tank direction perpendicular to mounting medium according to material.Any one uses the device of foregoing invention can carry out the batch operation that sound field-dielectric-field flow separates.
In " batch processing " operation that above-mentioned use sound field-dielectric-field flow separates, preferably be applied on the material to be identified by electrode being applied electric signal generation dielectric power earlier, and be applied on the material to be identified by piezoelectric sensor being applied electric signal generation sound field power, make species distribution to be identified on the direction that flows perpendicular to fluid and be in equilibrium state, import medium then, to form (step f) before the velocity distribution.
In the batch operation that above-mentioned use sound field-electrophoresis-field flow separates or sound field-dielectric-field flow separates, same, preferably apply different electric signal to produce sound field power, electrophoretic force, or dielectrophoresis force.
In the batch operation that above-mentioned use sound field-electrophoresis-field flow separates or sound field-dielectric-field flow separates, sound field power, electrophoretic force or dielectrophoresis force can produce simultaneously, also can produce in proper order.
C.2. the continuous-mode operation that sound field-field flow separates, sound field-electrophoresis-field flow separates, sound field-dielectric-field flow separates
In continuous-mode operation, the particulate biased sample imports to sound field-field flow continuously by ingress port to be separated in the reaction tank of (perhaps sound field-electrophoresis-field flow separation, sound field-dielectric-field flow separate).Separate for sound field-field flow, under suitable sound field effect, particulate can be in the equilibrium position in reaction tank under the effect of sound field power and other power (as gravity, fluid lift force etc.).Sound field power in the reaction tank is to obtain by piezoelectric sensor being applied suitable electric signal.Separate for sound field-electrophoresis-field flow, under suitable electric field, sound field effect, particulate can make particulate be in the equilibrium position in reaction tank under the effect of sound field power, electrophoretic force and other power (as gravity, fluid lift force etc.).Separate for sound field-dielectric-field flow, under suitable dielectric electric field, sound field effect, particulate can make particulate be in the equilibrium position in reaction tank under the effect of sound field power, dielectrophoresis force and other power (as gravity, fluid lift force etc.).Getting two kinds of particulate samples separates in sound field-field flow and separates in (perhaps sound field-electrophoresis-field flow separates, sound field-dielectric-field flow separates) reaction tank and analyze.Separating the particulate that is in higher equilibrium position in (perhaps sound field-electrophoresis-field flow separation, sound field-dielectric-field flow separate) reaction tank will flow out from the higher position of outlet at sound field-field flow, and being in the particulate that hangs down the equilibrium position in reaction tank will flow out from the lower position of outlet.Like this, particle mixture just by continuous be divided into two-layer.Obviously, need separate fluid in the reaction tank outlet.(Springston?et?al，1987；Lee?et?al，1989；Levin?and?Giddings，1991)。
If a plurality of outlets are arranged at top and bottom at reaction tank, just can collect a plurality of field flows.In the example of Figure 10, an outlet 870 is arranged at the top of reaction tank, and two outlets 880 and 890 are arranged at the bottom.Like this, this reaction tank just can be used for separating the particulate more than three kinds or three kinds.This reaction tank can be sound field-field flow separating reaction pond, also can be that sound field-electrophoresis-field flow separates, sound field-dielectric-field flow separating reaction pond.Exist a fluid velocity to distribute 860 in the reaction tank.
Because the effect of the various power that apply, particulate 900 is in the highest position in flowing through the process of reaction tank, therefore flows out from top exit 870.And because the effect of the various power that apply, particulate 910 is in minimum position in flowing through the process of reaction tank, therefore flow out from outlet at bottom 880.Another kind of 920 of particulates mediate, and like this, it just flows out from another outlet 890 of bottom.This operation is corresponding with the field flow piece-rate system of using tripping device.(Springston?et?al，1987；Lee?et?al，1989；Levin?and?Giddings，1991)。
Flow point on the scene from may further comprise the steps in handling by applying continuous mode that sound field power separates material: a) obtain a described in the present invention sound field-field flow tripping device; B) mounting medium that will contain material to be identified of the ingress port by described device imports in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; C) excite the generation sound wave by piezoelectric sensor being applied at least one road electric signal that produces by electric signal generator, thereby cause having at least one to put on that the sound field power on the material has a component that moves through the reaction tank direction perpendicular to mounting medium in the described mounting medium.Described material in described mounting medium is to be distributed in perpendicular to mounting medium to move through on the reaction tank direction, comes recognition material according to material in the difference that moves through distributing position on the reaction tank direction perpendicular to mounting medium.The continuous mode that this sound field-field flow separates can be used for arbitrary sound field-field flow tripping device.
In separating, sound field-electrophoresis-field flow may further comprise the steps in handling: A) described in the present invention sound field-electrophoresis-field flow tripping device by applying continuous mode that sound field power separates material.B) ingress port by described device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; C) excite the generation electric field by electrode being applied at least one road electric signal that produces by electric signal generator, thereby cause having at least one to put on that the electrophoretic force on the material has a component that moves through the reaction tank direction perpendicular to mounting medium in the described mounting medium; D) excite the generation sound field by piezoelectric sensor being applied other at least one road electric signal that produces by electric signal generator, thereby cause having at least one to put on that the sound field power on the material has a component that moves through the reaction tank direction perpendicular to mounting medium in the described mounting medium.Described material in described mounting medium is to be distributed in perpendicular to mounting medium to move through on the reaction tank direction, comes recognition material according to material in the difference that moves through distributing position on the reaction tank direction perpendicular to mounting medium.The continuous mode that this sound field-electrophoresis-field flow separates can be used for arbitrary sound field-electrophoresis-field flow tripping device.
In separating, sound field-dielectrophoresis-field flow may further comprise the steps in handling: A) obtain a described in the present invention sound field-dielectric-field flow tripping device by applying continuous mode that sound field power separates material.B) ingress port by described device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution; C) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an inhomogeneous field, thereby causes having at least a dielectrophoresis force that is applied on the described material to have a component that moves through the reaction tank direction perpendicular to mounting medium; D) piezoelectric sensor is applied another road electric signal at least that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced a sound field, thereby causes having at least a sound field power that is applied on the described material to have a component that moves through the reaction tank direction perpendicular to mounting medium; Described material in described mounting medium is to be distributed in perpendicular to mounting medium to move through on the reaction tank direction, comes recognition material according to material in the difference that moves through distributing position on the reaction tank direction perpendicular to mounting medium.The continuous mode that this sound field-field flow separates can be used for arbitrary sound field-field flow tripping device.The continuous mode that this sound field-dielectrophoresis-field flow separates can be used for arbitrary sound field-dielectrophoresis-field flow tripping device.
D. power
Although we do not wish that theory and mechanism that north is described here fetter, and below introduce the various power that several present apparatus and method are utilized.
D.1. sound field radiant force
The sound field radiant force is a kind of can being used in the fluid, is used to catch, the contactless power of manipulation, movable corpuscle.The sound field power of utilizing ultrasound wave to produce has the operation that particulate carries out: collect red blood cell (Yasuda et al, 1997), collect micron-sized tygon particulate (0.3 to 10 micron of diameter, Yasuda and Kamakura, 1997), collect dna molecular (Yasuda et al, 1996C), the collection in enormous quantities, semicontinuous of pair cell and precipitation (Pui, et al, 1995).By the competition between electrostatic force and the sound field radiant force, can separate different sizes and charged particles the tygon particulate (Yasuda et al, 1996A, B).In addition, when utilizing the sound field radiant force that mammalian cell is handled, observe ion penetrating (for red blood cell, Yasuda et al, 1997), produce antibody (for the hybrid oncocyte, Pui.et al, 1995).In manipulation process, pair cell does not cause or causes minimum injury.
By on piezoelectric sensor, applying AC signal, can in a sound field-field flow separating reaction pond (perhaps sound field-electrophoresis-field flow separation, sound field-dielectrophoresis-field flow separating reaction pond), produce a standing wave plane.Same, cross and on piezoelectric sensor, apply AC signal, can in a sound field-field flow separating reaction pond (perhaps sound field-electrophoresis-field flow separation, sound field-dielectrophoresis-field flow separating reaction pond), produce a sound field with standing wave component.We check the sound field radiant force that particulate is subjected to now in stationary field.Suppose that standing wave is to be based upon in the liquid on the specific direction (for example, Z direction).The variation of standing wave on the Z direction can be shown with following table:
Δp(z)＝p
0?sin(kz)cos(ωt)
Wherein Δ p represents the sound field pressure on the Z direction, p
0Represent the sound field pressure intensity, k represents wave number (2 π/λ, wherein λ is a wavelength), and z represents the distance of pressure node, and ω represents angular frequency, and t represents the time.The theory that proposes according to Yoshioka and Kawashima nineteen fifty-five, in the stationary field of a static state, the sound field radiant force that acts on a spherical particle can be represented with following formula (to see that K.Yoshioka and Y.Kawashima are at Acustica, 1955, Vol.5, pages 167-173:Acoustic radiation pressure on acompressible sphere):
Wherein r is the radius of particulate, E
AcousticBe the mean energy density of sound field, A is a constant, represents with following formula:
ρ wherein
mAnd ρ
pRepresent particulate and density of medium, γ
mAnd γ
pRepresent the acoustic impedance of particulate and medium.A represents the sound field polarization parameter here.Acoustic impedance is defined as the density (ρ of material
mAnd ρ
pRepresent particulate and density of medium) and the velocity of sound (C
mAnd C
pRepresent medium and particulate in the velocity of sound) product (γ
m=ρ
mC
mAnd γ
p=ρ
pC
p).
When A＞0, particulate is located to move to the pressure node (z=0) of standing wave.
When A＜0, particulate is located to move to the pressure node (z=0) away from standing wave.
Clearly, when being placed on the particulate of different densities and acoustic impedance in the stationary field, they are subjected to different sound field radiant forces.For example: according to the sound field energy distribution of having set up, diameter is that the sound field radiant force that 10 microns particulate is subjected to changes from 0.01 to 1000pN.
At K.Yoshioka and Y.Kawashima at Acustica, 1955, Vol.5, pages 167-173: in " Acoustic radiation pressure on a compressible sphere ", also described the sound field radiant force that particulate is subjected in the wave sound field of being expert at.Utilize these theories, those experts that utilize sound field to carry out particle manipulating just can analyze and calculate the suffered sound field radiant force of particulate.
Piezoelectric sensor is made with piezoelectric.When outside piezoelectric to applying mechanical force deformation takes place, piezoelectric can produce electric field (this is called piezoelectric effect or generator effect).Opposite, piezoelectric is applied electric field can produce a mechanical stress (this is called electricity and causes blockage effect or engine effect).Piezoelectric effect is found in 1880 by Pierre Curie and his fraternal Jacques.The reason of explaining is the electric polarization that the displacement of ion has caused the material structure unit.When applying electric field, ion is replaced by electrostatic force, causes the mechanical sex change of whole material.Like this, in a sound field-field flow separation or sound field-electrophoresis-field flow separation or sound field-dielectrophoresis-field flow tripping device, piezoelectric sensor is applied AC signal, and the vibrations that produce on the sensor just are coupled in the liquid in the reaction tank so, cause producing in the reaction tank sound wave.Such sound wave may have capable ripple and standing wave component.
In the past, utilized sound wave in medium, particulate to be separated.For example: U.S. Patent No. 4523682 has been introduced a kind of big or small to difference in the sound wave reaction tank, the method that different densities and particulate of different nature separate.The full text of U.S. Patent No. 4523682 is quoted by this patent in the mode of list of references.U.S. Patent No. 4523682 has been described the apart of particulate of different nature in sound wave.The characteristics of utilizing the apparatus and method that sound wave among the present invention-field flow separates be can be from potpourri separating particles, and obtain pure particulate samples.And in U.S. Patent No. 4523682, can only come separating particles by the position of particulate in the sound wave reaction tank.
D.2 electrophoretic force
The electric field that applies in the external world
In, to the electrostatic force F of particulate
ECan represent with following formula:
Q wherein
pRepresent the effective charge on the particulate.The charge polarity of particulate and the direction that applies electric field have determined the direction of the electrostatic force that particulate is subjected to.
D.3 dielectrophoresis force
Be in the inhomogeneous field dielectrophoresis force F that the particulate that radius is r is subjected to
DEPzCan represent with following formula:
E wherein
RmsBe the root-mean-square value of electric field intensity, ε
mBe the penetrating rate of dielectric of medium, χ
DEPBe the polarization parameter of particulate, represent with following formula:
" Re " represents real.Symbol
Be compound penetrating rate, (for particulate x=p, for medium x=m).Parameter ε
pAnd σ
pBe the effective penetrating rate and the effective conductivity of particulate.These parameters are determined by frequency.For example, a cell is because the polarization of cell membrane has effective conductivity and effective penetrating rate by the frequency decision.
Above-mentioned equation to dielectrophoresis force also can be write:
Wherein p (z) is the square wave field distribution of a unit pulse voltage (V=1V) on electrode.
In a sound field-dielectrophoresis-field flow tripping device, can produce an inhomogeneous field by the lip-deep microelectrode of reaction tank being applied AC signal.For the electrod-array of an alternating expression, dielectric power is roughly pressed exponential damping on the vertical direction of electrode plane.This can be from Huang et al, and 1997 draw.
On a sound field-dielectrophoresis-field flow separating reaction pond vertical direction, particulate or cell with different dielectric characteristic (being penetrating rate and conductance) will be subjected to different dielectric power.For the particulate of handling with dielectrophoresis (comprising cell), the dielectric power that acts on a diameter and be on 10 microns the particulate changes between 0.01 to 1000pN.
(Huang et al, Biophys.J.Vol.73, p1118-1129,1997. in the dielectrophoresis of former report-field flow isolation technics; Wang et al., Biophys.J.Vol.74, p2689-2701,1998.), in the convection cell velocity distribution position of particulate influence/control/when handling, only used the negative sense dielectrophoresis.This is because the forward dielectrophoresis may cause treating that particulate is adsorbed or captures electrode surface.But in the sound field-dielectrophoresis in the present invention-field flow separation method or the device, forward dielectrophoresis and negative sense dielectrophoresis can use.。Because by add provide can spatial variations the sound field radiant force, can control to particulate in the fluid and go.Here, the forward dielectrophoresis can be by the sound field radiant force institute balance of spatial variations.
D.4 fluid lift force
In a sound field-field flow separating reaction pond (perhaps sound field-electrophoresis-field flow separating reaction pond or sound field-dielectrophoresis-field flow separating reaction pond) of carrying out separation of particles and analysis, can form a fluid velocity and distribute.All be far longer than in the rectangle reaction tank of its height in length and width, can form a parabola shaped laminar flow fluid and distribute.Such velocity distribution can be represented with following formula:
V wherein
mIt is fluid velocity apart from reaction tank bottom z height.H is the height of reaction tank,＜V
mBe the mean flow rate of fluid in reaction tank.If a particulate is by the fluid transport that such velocity distribution is arranged, and this particulate is positioned at from reaction tank bottom or very near position, top, and it will be subjected to a fluid lift force F
Lift(this reflection pond horizontal positioned or near horizontal positioned).If during the distance of particulate and reaction tank bottom very little (for example, highly be in 200 microns the reaction tank, 10 microns particulate apart from the bottom less than 1 micron), fluid lift force can make particulate leave pool wall (Williams et al., 1992; 1994; 1996; 1997).This power is used in classical supermembrane-field flow isolation technics.Because fluid lift force is in the sedimentation equilibrium of forces, particulate is placed to the differing heights (for example, Ratanathanawongs S.K.and Giddings, 1992, Williams et al, 1996) in the reaction tank.As everyone knows, when the distance of particulate and pool wall increased, fluid lift force decayed to zero, but in nearer distance, still should consider its influence.
D.5 sound field-field flow separation, sound field-electrophoresis-field flow separate each dynamic balance in sound field-dielectric-field flow separating reaction pond
In the sound field-field flow separating reaction pond of a horizontal positioned or level of approximation placement, the fluid along continuous straight runs flows.In vertical direction, particulate is subjected to three power, i.e. F
Acoustic, F
LiftAnd settling capacity
When these dynamic balances:
F
acoustic(z)+F
lift(z)+F
G＝0
If particulate is stressed is zero, and particulate will stop to move up and down.Owing to be subjected to sound field power and fluid lift force by highly decision, particulate stressed be zero position h
EqBalance.This position still be the more important thing is by density of particle, acoustic impedance and particle size decision by the decision of sound field energy distribution.Particulate with heterogeneity (density, acoustic impedance, size), balance at various height.And in fluid with different speed motion (V
p, by h
EqDecision).Therefore, flow through the asynchronism(-nization) (t of reaction tank
p=L/V
p).Similarly analysis also can be used for the sound field-field flow separating reaction pond of out-of-level placement.In this case, the settling capacity effect that is subjected in fluid velocity distributes of particulate is with above-mentioned different.Have only the sedimentation component of force to the position of particulate in velocity distribution by influence.Because have only the settling capacity action direction to become the component of 90 degree angles just to work with the flow motion direction.
In the sound field-electrophoresis-field flow separating reaction pond of a horizontal positioned or level of approximation placement, the fluid along continuous straight runs flows.In vertical direction, particulate is subjected to four power, i.e. F
Acoustic, F
E, F
LiftAnd settling capacity
When these dynamic balances:
F
acoustic(z)+F
E+F
lift(z)+F
G＝0
If particulate is stressed is zero, and particulate will stop to move up and down.Owing to be subjected to sound field power and fluid lift force by highly decision, particulate stressed be zero position h
EqBalance.This position by the sound field energy distribution, apply electric field intensity decision, but the more important thing is by density of particle, acoustic impedance and particle size decision.Particulate with heterogeneity (density, acoustic impedance, size), balance at various height.And in fluid with different speed motion (V
p, by h
EqDecision).Therefore, flow through the asynchronism(-nization) (t of reaction tank
p=L/V
p).Compare with electrophoresis-field flow shunting, added the sound field radiant force in the equilibrium equation.Similarly analysis also can be used for the sound field-electrophoresis-field flow separating reaction pond of out-of-level placement.In this case, the settling capacity effect that is subjected in fluid velocity distributes of particulate is with above-mentioned different.Have only the sedimentation component of force to the position of particulate in velocity distribution by influence.Because have only the settling capacity action direction to become the component of 90 degree angles just to work with the flow motion direction.
By the comparison of sound field radiant force and electrostatic force (electrophoretic force), Yasuda et al. (1996A, B) proof in 750 microns high reaction tanks, can different sizes, with the tygon particulate apart of different electric charges apart from the time 20 microns.
Same, in the sound field-dielectric-field flow separating reaction pond of a horizontal positioned or level of approximation placement, the fluid along continuous straight runs flows.Particulate each equilibrium equation in sound field-dielectric-field flow separating reaction pond is:
F
acoustic(z)+F
DEP(z)+F
lift(z)+F
G＝0
The same, particulate is stressed to be that zero position is balance height h
EqThis position by the sound field energy distribution, apply inhomogeneous field intensity decision, but the more important thing is by density of particle, acoustic impedance and particle size decision.Particulate with heterogeneity (density, acoustic impedance, size), balance at various height.And in fluid with different speed motion (V
p, by h
EqDecision).Therefore, flow through the asynchronism(-nization) (t of reaction tank
p=L/V
p).Compare with dielectrophoresis-field flow shunting, added the sound field radiant force in the equilibrium equation.Similarly analysis also can be used for the sound field-electrophoresis-field flow separating reaction pond of out-of-level placement.Similarly analysis also can be used for the sound field-dielectric-field flow separating reaction pond of out-of-level placement.In this case, the settling capacity effect that is subjected in fluid velocity distributes of particulate is with above-mentioned different.Have only the sedimentation component of force to the position of particulate in velocity distribution by influence.Because have only the settling capacity action direction to become the component of 90 degree angles just to work with the flow motion direction.
Based on single (greatly) particulate during above-mentioned analysis, the diffusional effect of particulate has been left in the basket.Sound field-field flow is separated, sound field-electrophoresis-field flow separates, and sound field-dielectric-field flow separation method is for the separation of particulate and describe the operation (little of molecular level) that also can use small particle.Improvement to above-mentioned analysis should be considered diffusional effect.For example, in the distribution of Yasuda et al. (1996A) particle concentration in one dimension ultrasonic standing wave field and electric field, just considered the diffusional effect of particulate.Considered under the situation of spread of particles effect that at these particulate CONCENTRATION DISTRIBUTION decision Z-TEK is in vertical direction planted the elution time of based fine particles surely.On the vertical direction of fluid, can in the works that many field flows separate, see (for example: Caldwell and Gao, 1993, Giddings 1993) from the theoretical analysis of the CONCENTRATION DISTRIBUTION under the effect to small particle flow point on the scene.Those carry out the expert that molecule separates and analyzes with small particle at the use flow point from technology, and utilize sound field/electrophoresis/dielectrophoresis effect to carry out the expert of separation of particles, can be at any time sound field-field flow separates to utilizing, sound field-electrophoresis-field flow separates, sound field-dielectric-field flow separates and is used for that molecule separates with small particle and theoretical analysis is carried out in analysis.
Claims (77)
- A flow point on the scene from utilize the device of sound field power recognition material, this device comprises:A) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank;B) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite and produce sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
- 2. according to the device described in the claim 1, comprise a plurality of ingress ports.
- 3. according to the device described in the claim 1, comprise a plurality of outlet ports.
- 4. according to the device described in the claim 1, wherein said outlet port is connected with gathering-device or identification apparatus.
- 5. according to the device described in the claim 1, the length that the design feature of wherein said reaction tank is defined as reaction tank is fully greater than the height and the width of reaction tank.
- 6. according to the device described in the claim 1, also comprise a plurality of piezoelectric sensors.
- 7. according to the device described in the claim 6, wherein said a plurality of piezoelectric sensors are to excite by identical or different electric signal.
- 8. according to the device described in the claim 6, wherein said a plurality of piezoelectric sensors are to be contained on the inside surface or outside surface of reaction tank.
- 9. according to the device described in the claim 6, wherein said a plurality of piezoelectric sensors be arranged in one with mounting medium by on the fully parallel plane of the moving direction of reaction tank.
- 10. according to the device described in the claim 1, the wherein said electric signal generator that is used to excite piezoelectric sensor to produce sound field power can be exported the electric signal of different amplitudes and frequency.
- 11. according to the device described in the claim 1, wherein said reaction tank comprises a pipe.
- 12. according to the device described in the claim 11, wherein said one or more piezoelectric sensors are to be distributed on the inside surface of pipe.
- 13. according to the device described in the claim 11, wherein said piezoelectric sensor, or most of piezoelectric sensors wherein are to be distributed on the outside surface of pipe.
- 14. according to the device described in the claim 1, wherein said reaction tank comprises a top cover, a bottom surface and two sidewalls.
- 15. according to the device described in the claim 14, the velocity distribution of wherein said mounting medium diverse location in reaction tank is para-curve or approximate parabolical distribution.
- 16. according to the device described in the claim 14, a wherein said piezoelectric sensor or a plurality of piezoelectric sensor are to be arranged on the reaction tank top cover.
- 17. according to the device described in the claim 14, a wherein said piezoelectric sensor or a plurality of piezoelectric sensor are to be arranged on the reaction tank bottom surface.
- 18. according to the device described in the claim 14, a wherein said piezoelectric sensor or a plurality of piezoelectric sensor are to be arranged on the interior facing surfaces of reaction tank.
- 19. according to the device described in the claim 14, the height between wherein said reaction tank top and the bottom is the half-wavelength of sound wave standing wave.
- 20. according to the device described in the claim 14, wherein said two parts that sidewall is the packing ring between top wall and base wall, and on packing ring, have passage.
- 21. according to the device described in the claim 20, wherein said passage be shaped as rectangle, ellipse or circular.
- 22. according to the device described in the claim 20, wherein said width of channel is between 1 millimeter to 20 centimetres, the height of passage is between 20 microns to 10 millimeters, and the length of passage is between 1 centimetre to 200 centimetres.
- 23. a flow point on the scene from utilize the device of sound field power recognition material, this device comprises:A) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank;B) have at least a piezoelectric sensor to be positioned at certain part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
- 24. a flow point on the scene from utilize the device of sound field power recognition material, this device is by constituting with lower member:A) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank;B) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
- 25. a flow point on the scene from utilize the device of electrophoretic force harmony field force recognition material, this device is by constituting with lower member:A) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank;B) have at least two electrodes to form the part of described reaction tank, wherein said electrode can excite the generation electric field by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the electrophoretic force on the material in the described mounting medium, this electrophoretic force has the component perpendicular to the mounting medium moving direction;C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
- 26., comprise plural electrode according to the device described in the claim 25.
- 27. according to the device described in the claim 25, each electrode in the wherein said plural electrode all is connected on the electrical lead in the electrical lead bus that is electrically connected with electric signal generator individually.
- 28. according to the device described in the claim 25, wherein said electrode is to be distributed on the reaction tank vertical or horizontally.
- 29. according to the device described in the claim 25, wherein said distribution of electrodes is on the inside surface of reaction tank.
- 30. according to the device described in the claim 25, wherein said electrode be arranged in one with the fully parallel plane of the moving direction of mounting medium by reaction tank on.
- 31. according to the device described in the claim 25, wherein said electrode forms an electrod-array, described electrod-array can be a mutual dislocation formula electrod-array, mutual dislocation formula castle electrod-array has the mutual dislocation formula electrod-array of cycle apex and has the mutual dislocation formula electrod-array on cycle circular arc top.
- 32. according to the device described in the claim 25, wherein said electrode is a metal level that is deposited on the reaction tank surface.
- 33. according to the device described in the claim 32, wherein said metal can be a gold, platinum, aluminium, chromium, titanium, copper and silver.
- 34. according to the device described in the claim 25, the wherein said electric signal generator that is used for exciting electrode generation electrophoretic force is one and can exports the galvanic direct voltage source of different amplitudes or the alternating-current voltage source that can export different amplitudes, phase place.
- 35. according to the device described in the claim 25, the wherein said electric signal that is used for exciting electrode generation electrophoretic force is the ac signal of a direct current electric signal or a low frequency.
- 36. according to the device described in the claim 25, wherein said reaction tank comprises a pipe.
- 37. according to the device described in the claim 36, a wherein said electrode and/or piezoelectric sensor, or a plurality of electrode and/or piezoelectric sensor are to be distributed on the inside surface of pipe.
- 38. according to the device described in the claim 36, a wherein said piezoelectric sensor, or a plurality of piezoelectric sensor is to be distributed on the outside surface of pipe.
- 39. according to the device described in the claim 25, wherein said reaction tank comprises a top cover, a bottom surface and two sidewalls, and a described electrode and/or piezoelectric sensor, or a plurality of electrode and/or piezoelectric sensor are to be distributed on the top cover of reaction tank.
- 40. according to the device described in the claim 25, wherein said reaction tank comprises a top cover, a bottom surface and two sidewalls, and a described electrode and/or piezoelectric sensor, or a plurality of electrode and/or piezoelectric sensor are to be distributed on the bottom surface of reaction tank.
- 41. according to the device described in the claim 25, a wherein said electrode and/or piezoelectric sensor, or a plurality of electrode and/or piezoelectric sensor are to be arranged in the reaction tank on the facing surfaces.
- 42. a flow point on the scene from utilize the device of electrophoretic force harmony field force recognition material, this device comprises:A) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank;B) have at least two electrodes to form the part of described reaction tank, wherein said electrode can excite the generation electric field by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the electrophoretic force on the material in the described mounting medium, this electrophoretic force has the component perpendicular to the mounting medium moving direction;C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
- 43. a flow point on the scene from utilize the device of electrophoretic force harmony field force recognition material, this device to have to constitute with lower member:A) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank;B) have at least two electrodes to form the part of described reaction tank, wherein said electrode can excite the generation electric field by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the electrophoretic force on the material in the described mounting medium, this electrophoretic force has the component perpendicular to the mounting medium moving direction;C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
- 44. a flow point on the scene from utilize the device of dielectrophoresis force harmony field force recognition material, this device is by constituting with lower member:A) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank;B) have at least two electrodes to form the part of described reaction tank, wherein said electrode can excite by at least one road electric signal that is produced by electric signal generator and produce a non-uniform electric field, thereby cause at least one to put on the dielectrophoresis force on the material in the described mounting medium, this dielectrophoresis force has a component perpendicular to the mounting medium moving direction;C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
- 45., comprise plural electrode according to the device described in the claim 44.
- 46. according to the device described in the claim 45, each electrode in the wherein said plural electrode all is connected on the electrical lead in the electrical lead bus that is electrically connected with electric signal generator individually.
- 47. according to the device described in the claim 45, wherein said electrode further can also produce the space non-uniform electric field.
- 48. according to the device described in the claim 44, the electric signal that the wherein said electric signal generator output that is used for exciting electrode generation dielectrophoresis force has different amplitudes and phase place.
- 49. a flow point on the scene from utilize the device of dielectrophoresis force harmony field force recognition material, this device comprises:A) reaction tank comprises at least one ingress port and at least one outlet port, described reaction tank has such design feature, promptly when mounting medium was induced by this reaction tank, the translational speed of the described mounting medium of diverse location was different in reaction tank;B) have at least two electrodes to form the part of described reaction tank, wherein said electrode can excite by at least one road electric signal that is produced by electric signal generator and produce a non-uniform electric field, thereby cause at least one to put on the dielectrophoresis force on the material in the described mounting medium, this dielectrophoresis force has a component perpendicular to the mounting medium moving direction;C) have at least a piezoelectric sensor to form the part of described reaction tank, wherein said piezoelectric sensor can excite the generation sound wave by at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction.
- 50. a flow point on the scene from utilize the method for sound field power recognition material, this method comprises:A) obtain the device described in the claim 1;B) mounting medium that will contain material to be identified of the ingress port by device described in the claim 1 imports in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution;C) excite the generation sound wave by piezoelectric sensor being applied at least one road electric signal that produces by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction;Be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.
- 51. according to the method described in the claim 50, wherein said identification to material is to realize by the velocity distribution of mounting medium by reaction tank, the speed dependent that material moves in reaction tank is in its residing position in velocity distribution.
- 52. according to the method described in the claim 50, it is to depend on their positions velocity distribution that wherein said material moves out the time interval of coming from the outlet port of reaction tank.
- 53. according to the method described in the claim 50, it is to depend on their positions in velocity distribution that the outlet port of wherein said material from a plurality of outlet ports of reaction tank moves out the time interval of coming.
- 54., wherein act on gravity direction on the material perpendicular to the moving direction of mounting medium by reaction tank according to the method described in the claim 50.
- 55. according to the method described in the claim 50, wherein said material to be identified comprises cell, organelle, virus, molecule or their condensate or complex.
- 56. according to the method described in the claim 55, wherein said cell comprises zooblast, vegetable cell, mushroom cell, bacterial cell, cultured cell or recombinant cell.
- 57. according to the method described in the claim 55, wherein said organelle comprises nucleus, mitochondria, chloroplast, ribosomes, thick matter endoplasmic reticulum, golgiosome, lysosome, proteasome, excretion vesicles, vacuole or microsome.
- 58. according to the method described in the claim 55, wherein said molecule comprises inorganic molecule, organic molecule or their complex.
- 59. according to the method described in the claim 58, wherein said inorganic molecule comprises sodium, potassium, magnesium, calcium, chlorine, iron, copper, zinc, manganese, cobalt, iodine, molybdenum, vanadium, nickel, chromium, fluorine, silicon, tin, boron or arsenic ion.
- 60. according to the described method of claim 58, wherein said organic molecule comprises amino acid, peptide, protein, nucleosides, nucleotide, oligonucleotides, nucleic acid, vitamin, monose, oligosaccharides, carbohydrates, lipid or their compound.
- 61. according to the described method of claim 50, the size of wherein said material to be identified is between 0.01 micron to 1000 microns.
- 62. a flow point on the scene from utilize the method for sound field power recognition material, this method comprises:A) obtain the device described in the claim 1;B) ingress port by device described in the claim 1 imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium;C) sample that will contain material to be identified injects the interior mounting medium of reaction tank;D) piezoelectric sensor is applied at least one road electric signal that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power to be applied on the material;E) ingress port by device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium flow through reaction tank according to a kind of velocity distribution;Be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.
- 63. according to the method described in the claim 62, wherein saidly piezoelectric sensor is applied electric signal make its generation be applied to sound field power on the described material to have caused adding mounting medium and mounting medium is complied with before certain velocity distribution flows through reaction tank in reaction tank, the material in the mounting medium is shifted onto the equilibrium position on the direction vertical with the mounting medium moving direction.
- 64. a flow point on the scene from utilize the method for electrophoretic force harmony field force recognition material, this method comprises:A) obtain the device described in the claim 25;B) ingress port by device described in the claim 25 imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution;C) excite the generation electric field by electrode being applied at least one road electric signal that is produced by electric signal generator, thereby cause at least one to put on the electrophoretic force on the material in the described mounting medium, this electrophoretic force has the component perpendicular to the mounting medium moving direction;D) excite the generation sound wave by piezoelectric sensor being applied other at least one road electric signal that produces by electric signal generator, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction;Be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.
- 65. according to the described method of claim 64, wherein said electrophoretic force harmony field force is produced simultaneously.
- 66. according to the described method of claim 64, wherein said electrophoretic force harmony field force is that order produces.
- 67. a flow point on the scene from utilize the method for electrophoretic force harmony field force recognition material, this method comprises:A) obtain the device described in the claim 25;B) ingress port by device described in the claim 25 imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium;C) sample that will contain material to be identified injects the interior mounting medium of reaction tank;D) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an electric field, thereby causes having at least an electrophoretic force to be applied on the described material;E) piezoelectric sensor is applied another road electric signal at least that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power to be applied on the described material;F) ingress port by device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution;Be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.
- 68. according to the method described in the claim 67, wherein saidly electrode is applied electric signal make it produce at least one electrophoretic force to be applied on the described material, piezoelectric sensor is applied electric signal to be made it produce at least one sound field power to be applied on the described material, caused in reaction tank, add mounting medium make mounting medium according to the velocity distribution form by before the reaction tank, the species distribution in the mounting medium perpendicular to mounting medium by the equilibrium position on the reaction tank direction.
- 69. according to the described method of claim 67, wherein said electrophoretic force harmony field force is produced simultaneously.
- 70. according to the described method of claim 67, wherein said electrophoretic force harmony field force is that order produces.
- 71. a flow point on the scene from utilize the method for dielectrophoresis force harmony field force recognition material, this method comprises:A) obtain the device described in the claim 44;B) ingress port by device described in the claim 44 imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution;C) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an inhomogeneous field, thereby causes having at least a dielectrophoresis force that is applied on the described material to have a component that moves through the reaction tank direction perpendicular to mounting medium;D) piezoelectric sensor is applied another road electric signal at least that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced a sound wave, thereby cause at least one to put on the sound field power on the material in the described mounting medium, this sound field power has the component perpendicular to the mounting medium moving direction;Be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.
- 72. according to the described method of claim 71, wherein said dielectrophoresis force harmony field force is produced simultaneously.
- 73. according to the described method of claim 71, wherein said dielectrophoresis force harmony field force is that order produces.
- 74. a flow point on the scene from utilize the method for dielectrophoresis force harmony field force recognition material, this method comprises:A) obtain the device described in the claim 44;B) ingress port by device described in the claim 44 imports to mounting medium in the reaction tank of device and is full of the entire reaction pond until mounting medium;C) sample that will contain material to be identified injects the interior mounting medium of reaction tank;D) electrode is applied at least one road electric signal that is produced by electric signal generator, wherein said exciting electrode has produced an electric field, thereby causes having at least a dielectrophoresis force to be applied on the described material;E) piezoelectric sensor is applied another road electric signal at least that is produced by electric signal generator, the wherein said piezoelectric sensor that excites has produced sound wave, thereby causes having at least a sound field power to be applied on the described material;F) ingress port by device imports to mounting medium in the reaction tank of device, and wherein said importing makes mounting medium pass through reaction tank according to velocity distribution;Be in described material in the described mounting medium in certain position that is shifted onto under the effect of power on the direction vertical, come recognition material according to the difference of material distributing position on this direction with the mounting medium moving direction.
- 75. according to the method described in the claim 74, wherein saidly electrode is applied electric signal make it produce at least one dielectrophoresis force to be applied on the described material, piezoelectric sensor is applied electric signal to be made it produce at least one sound field power to be applied on the described material, caused adding mounting medium and mounting medium is complied with before certain velocity distribution flows through reaction tank in reaction tank, the material in the mounting medium is shifted onto the equilibrium position on the direction vertical with the mounting medium moving direction.
- 76. according to the described method of claim 74, wherein said dielectrophoresis force harmony field force is produced simultaneously.
- 77. according to the described method of claim 74, wherein said dielectrophoresis force harmony field force is that order produces.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00130562 CN1221309C (en) | 2000-09-30 | 2000-09-30 | Apparatus for corpuscle field and flow separation by sound field force and other active force |
| EP01981809A EP1322953A2 (en) | 2000-09-30 | 2001-09-20 | Apparatuses and methods for field flow fractionation of particles using acoustic and other forces |
| AU2002213426A AU2002213426A1 (en) | 2000-09-30 | 2001-09-20 | Apparatuses and methods for field flow fractionation of particles using acoustic and other forces |
| PCT/US2001/042280 WO2002029400A2 (en) | 2000-09-30 | 2001-09-20 | Apparatuses and methods for field flow fractionation of particles using acoustic and other forces |
| CA 2422837 CA2422837A1 (en) | 2000-09-30 | 2001-09-20 | Apparatuses and methods for field flow fractionation of particles using acoustic and other forces |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00130562 CN1221309C (en) | 2000-09-30 | 2000-09-30 | Apparatus for corpuscle field and flow separation by sound field force and other active force |
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| CN1345624A CN1345624A (en) | 2002-04-24 |
| CN1221309C true CN1221309C (en) | 2005-10-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 00130562 Expired - Fee Related CN1221309C (en) | 2000-09-30 | 2000-09-30 | Apparatus for corpuscle field and flow separation by sound field force and other active force |
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| Country | Link |
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| CN (1) | CN1221309C (en) |
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| CP03 | Change of name, title or address |
Address after: Tsinghua Yuan, Haidian District, Beijing Co-patentee after: Capitalbio Corporation Patentee after: Tsinghua University Address before: Tsinghua Yuan, Haidian District, Beijing Co-patentee before: Boao Biochip Co., Ltd., Beijing Patentee before: Tsinghua University |
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| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20051005 Termination date: 20190930 |