CN1715918B - Configurable dynamic three dimensional array - Google Patents

Configurable dynamic three dimensional array Download PDF

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CN1715918B
CN1715918B CN 200510081431 CN200510081431A CN1715918B CN 1715918 B CN1715918 B CN 1715918B CN 200510081431 CN200510081431 CN 200510081431 CN 200510081431 A CN200510081431 A CN 200510081431A CN 1715918 B CN1715918 B CN 1715918B
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probe
array
light trapping
light
probes
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CN1715918A (en
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戴维·格里尔
沃德·洛佩斯
刘易斯·格鲁贝尔
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Arryx Inc
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    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
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    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
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    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00664—Three-dimensional arrays
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    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0454—Moving fluids with specific forces or mechanical means specific forces radiation pressure, optical tweezers
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Abstract

The present invention relates generally to a configurable array of probes for assaying targets within a fluid. The probes are contained within optical traps which allows for alterations in the selection and re-configuration of the quantity or quality of probes in the array. Moreover, the array is dynamic in that once configured the optical traps may allow for independent repositioning of a given optical trap and contained probe.

Description

Configurable dynamic three dimensional array
The application is to be on April 12nd, 2002 applying date, and application number is 02816288.9, and denomination of invention is divided an application for the Chinese invention patent application of " configurable dynamic three dimensional array ".
The background of invention
Mentioned the document of various public publications in the bracket in whole application.In order to describe the situation of the technical field of the invention more fully, in this application as a reference in conjunction with whole disclosures of the document of these public publications.
Technical field
The present invention relates generally to probe array.Especially, the present invention relates to a kind of system and method, this system and method has used a plurality of light trappings, may be or may not be the configurable dynamic probe array that combines with substrate to form one.
Background technology
The array of promising reaction probe (reactive probes) is used for analyzing with other chemistry and biological test and tests and has very long history.For example, array is through being usually used in science of heredity, and biological chemistry and field of biology are to analyze the sample (being called target) of biology or chemical material.Analyzed sample often only can provide quite little amount.This limited supply of some materials has caused the development of microarray, and this microarray is used for providing highdensity relatively probe at a little array, with in the small amount of sample the target analysis.
The microarray that is used for the test of biomaterial usually is called as biochip.Two main about Application of Biochips is: about the extraction of the sequence information of a special nucleic acid, that is, no matter nucleic acid is corresponding to the full gene group of a biosome, an individual gene, or the part (U.S. Pat 6,025,136) of an individual gene; Evaluation with the gene expression formula.(referring to Schena, Ad.et al. " Quantitative monitoring of gene expressionpattems with a complimentary DNA microarray ", Science 270 (5235): 467-70 (Oct.20,1995); D.J.and Winzeler, E.A., " Genomics; geneexpression and DNA arrays ", Nature 405 (6788): 827-836 (2000) and Ekins, R.and Chu, F.＜RTI W., " Microarrays:their origins andapplications ", Trends in Biotechnology 17:217-18 (1999) .)
That conventional microarray comprises the oligonucleotide probe or wire or two-dimensional structure are attached on the flat surfaces of a solid support (substrate).Dissimilar oligonucleotide are fixed in the substrate with preposition.Thereby microarray is in case form, and the position of the position of probe and any target of reacting with probe thus is known all the time.Probe fixing or by being called as synthetic (in situ photolithography the synthesis) (U.S. Pat 5 of original position photolithography technology, 837,832 and US5,143,854) the directly synthetic oligonucleotide of technology is realized to substrate, or has been synthesized back fixedly realizing by oligonucleotide at it.
A shortcoming of such microarray is their linearity or the two-dimensional structure surf zone that provides limited probe to be fixed, thereby the density of the probe of analyzing target has been set a restriction.Under the situation of the hybridization of the DNA between target (DNA or DNA fragment) and the probe (fixing oligonucleotide), the rate controlled that hybridization speed can be contacted with probe by target.Therefore, the density of probe is high more, and the speed of hybridization is big more.
Second shortcoming of such microarray is that the method by their structure causes.In case microarray prepares, the type of probe and quantity are also just fixing.
In the another kind of method that the target in a spot of sample is analyzed, probe stationary is on the surface of globule shape basic unit.(Kambara ﹠amp; Mitsuhashi. unsettled patent WO00/61198) each comprises the globule label that has nothing in common with each other of a different probe, thereby, after finishing analysis, allow by differentiating the target (seeing WO 00/71243) what label which globule has discern each probe and combine.
By mobile globule physically, probe stationary is in guide rod simultaneously, kapillary, and groove, or in the hole in the thin plate, clean the globule that has target then, the homogeneity of globule and probe is held.Though the on-plane surface characteristic of globule provides bigger surf zone to interact than micro probe array for target really, but globule still must keep predetermined order with keeping the supporting globule of which probe or the globule that probe must connect in The whole analytical process, and after analysis the record of the homogeneity of checked each globule to determine its homogeneity.
The another one shortcoming of microarray and globule analysis is to need the probe physical fixation to substrate.In some cases, this fixing itself and also naturally and understandably change probe, or influence the process that probe is used for analysis.In other cases, during the initial analysis or afterwards, if the homogeneity of known probe in the The whole analytical process, and the structure of array can change easily, can obtain the information of change that the quality and quantity of probe is wanted so.Yet no matter microarray still is the globule analysis, this change all is impossible.
In irrelevant technical field, be known that with a plurality of produced simultaneously smooth tweezers trapped particle optically.(see and be presented to Grier﹠amp; The U.S. Pat 6,055,106 of Dufresne) the light tweezer uses the gradient force of a branch of light to come trapped particle based on the specific inductive capacity of particle.For energy being reduced to minimum, the particle with the specific inductive capacity that is higher than surrounding medium can move to the zone of light tweezer, and there electric field intensity is the highest.
The catching of other types that can be used for the optical acquisition particle comprises, but be not limited to, optics whirlpool (optical vortices), optics bottleneck (optical bottles), optical rotator (opticalrotators) and light cage (light cages). gradient of optics vortex arising around the zone of zero electric field, it is used to control the particle that specific inductive capacity is lower than surrounding medium, perhaps reflexive particle, perhaps the other types particle that is repelled by the light tweezer.In order to make its energy minimization, this particle can move to the minimum zone of electric field intensity, promptly at the suitable zero electric field region of the focus of the laser beam of shape.The optics whirlpool provides a zone that resembles very much the zero electric field in the hole in the Deep-fried doughnut (doughnut).Optical gradient is radially, has maximum electric field at the circumference of Deep-fried doughnut.The optics whirlpool is detained firmly small-particle in the hole of Deep-fried doughnut.Delay is by realizing at slip whirlpool on the small-particle of zero electric field line.
The optics bottleneck is different from the optics whirlpool and is that it only has one zero electric field in focus, and on the every other direction of focus, promptly in the end of whirlpool, non-zero electric field is arranged.The optics bottleneck can be used to catch atom and nanocluster, to such an extent as to they are owing to too little or absorbability can not be caught with optics whirlpool or light tweezer too by force.(J.Arlt?&?MJpadgett.“Gneration?of?a?beamwith?a?dark?focus?surrounded?by?regions?of?higher?intensity：The?opticalbottle?beam，”Opt.Lett.25，191-193，2000.)
Optical rotator is a kind of optical tooling of nearest record, and it provides a kind of pattern of catching the spiral arm of target.The change pattern can make captured object rotate.(L.paterson, M.P.MacDonald, RArlt, RSibbett, P.E.Bryant, and K.Dholakia, " Controlled rotation of optically trapped microscopicparticles; " Science 292,912-914,2001.) this class instrument can be used to control aspheric particle and drive the MEMs device or the nano-machine device.
Light cage (Neal U.S. Pat 5,939,716) in a broad aspect, to such an extent as to itself and optics whirlpool are of the same clan on macroscopic view. the time average ring that the light cage forms the light tweezer comes too by force can not captive particle around too big or reflectivity, yet its specific inductive capacity is lower than surrounding medium., be different from whirlpool, produced the non-zero electric field district. the optics whirlpool, though be similar to the light tweezer on using, principle of operation is opposite.
Existence is to the demand of a kind of analytical approach and system, wherein probe stationary to substrate the time, can not assessed the interaction of probe and target.Also have the demand of configurable to forming (with the configuration again) method and system of probe array, this method keeps the homogeneity of probe in The whole analytical process, and with the location independent of probe.The present invention satisfies the needs of these and other, and further relevant advantage is provided.
Summary of the invention
The invention provides a kind of structure, dispose and use novelty and the improved method and system of three-dimensional probe array.
In a container, produce light trapping.By making light beam, for example laser beam is oriented in an optical element and produces light trapping, and this optical element is by making up (patteming) its phase change light beam to produce beamlet.This beamlet scioptics conversely focuses on, and produces the necessary gradient condition of optical acquisition.Then, each has the probe adding container of known characteristic.Selection is used for the probe of given analysis, and each probe is by it being contained in the light trapping and chosen then.
The quality and quantity of probe that forms array removes by using light trapping to increase, or replaces probe and be easy to be reconfigured.In array, the arrangement of probe relative to each other also is dynamic because when keep selected forming array the homogeneity of probe the time, can change probe spatial relationship each other.Therefore, each probe of array and it also can be done as a whole in container or move on three-dimensional individually and can locate.
When probe keeps being included in the light trapping,,, can keep the homogeneity of probe by the homogeneity of knowing the light trapping that comprises probe also regardless of any change of its locus " in proper order " in array no matter whether it has been repositioned in the container.In addition, light trapping can be delivered to the another one light trapping to probe, and by that analogy, the optical acquisition of following the tracks of probe is simultaneously accommodated (custody) thereby the homogeneity of the probe that is comprised in the chain maintenance light trapping.
According to an aspect of the present invention, the method that a kind of configuration is provided and has followed the tracks of probe array comprises: produce at least two light trappings movably independently in container simultaneously; At least two probes are provided in container; Select at least two probes to be used for the inclusions of the probe array that light trapping inside comprised; Catch each selected probe, be contained in the probe array of light trapping inside with configuration packet for one with correspondence in the described light trapping; And, comprise the position of the light trapping of probe, the position of at least one captive probe in the tracking array by computer monitoring.
According to a further aspect in the invention, provide a kind of method of analysis of biological material to comprise: to produce at least two light trappings movably independently at internal tank; Fluid media (medium) is provided in container; At least two probes that are used for biomaterial are provided in fluid media (medium); Select at least two probes to be used for the inclusions of array; With corresponding in the described light trapping each selecteed probe of tracking; At least one comprises the target of biomaterial in the introducing container; With, determine each captive probe and each target response or not reaction; Wherein the probe that described target is reacted separates with remaining probe.
According to of the present invention more on the other hand, provide a kind of method that disposes probe array to comprise: to produce at least two light trappings movably independently at internal tank; Provide at least two probes at internal tank; With, by dispose the array of at least two probes with corresponding in the described light trapping each probe of selection; Wherein can revise described array by in described array, removing or increase at least one probe; Reach the position that comprises the light trapping of probe by computer monitoring, the position of following the tracks of at least one captive probe in the described array.
A kind of configuration is provided and has disposed the method for probe array more on the other hand according to of the present invention, having comprised: a directed focused beam on the phase pattern optical element to form a plurality of beamlets from the phase pattern optical element; Directed these a plurality of beamlets pass through condenser lens to transmit beamlet, and assemble the beamlet that sends from condenser lens on the condenser lens back aperture, to produce independently movably light trapping simultaneously in container; A large amount of probes are provided in container; Select at least two probes to be used for being included in the content of the probe array in the light trapping; With in the described light trapping corresponding one catch each chosen probe, be contained in probe array in the light trapping with configuration packet; By moving the light trapping comprise probe, change the position that at least one is included in the probe in the described array, be contained in probe array in the light trapping with configuration packet again; Reach the position that comprises the light trapping of probe by computer monitoring, the position of following the tracks of at least one captive probe in the described array.
According to of the present invention more on the other hand, provide a kind of system that is used to form and follows the tracks of the light trapping that comprises probe to comprise: the light source that is used to produce focused beam; The container of substantially transparent; Be used for producing the image light source of light beam of the inclusions of illumination container; Be used for directed beam splitter; The phase pattern optical element, it is used to receive the focused beam from light source, and it is diffracted at least two beamlets, the phase pattern optical element has a surface and is used for the back aperture of directed each beamlet at condenser lens, and this surface is the phase section and/or the orientation that can change to change at least one beamlet; Be used to assemble the condenser lens of each beamlet with the light trapping that is formed for comprising probe; Be used in described container, providing the device of at least one target of forming by biomaterial; Be used for determining each probe of described light trapping and each target response or responseless device; Be used to follow the tracks of moving and the device of inclusions of described light trapping; And be used for the device that the probe that will described target be reacted and remaining probe separate.
Other features and advantages of the present invention will partly be mentioned in the following description with in the accompanying drawing, wherein describe and shown the preferred embodiments of the present invention, and partly, after the detailed description of carefully studying carefully below in conjunction with accompanying drawing, this for a person skilled in the art, this will be conspicuous, perhaps also can learn by practice of the present invention.Advantage of the present invention can be by the means pointed out especially in accompanying Claim with in conjunction with realizing and obtaining.
Description of drawings
Fig. 1 has shown the cut-away section side view of the system that forms configurable probe array.
Fig. 2 has shown the free probe that is included in the light trapping.
Fig. 3 has shown the skeleton diagram of the system that is used for forming probe array.
Fig. 4 has shown the light beam that changes element with a plurality of static zones.
Fig. 5 A has shown first effective exercise of probe.
Fig. 5 B has shown second effective exercise of probe.
Fig. 6 A has shown the composition view of the mini-system that is used to form light trapping.
Fig. 6 B has shown the inverted microscope that mini-system is housed of Fig. 6 A.
Embodiment
In order to describe principle of the present invention and operation, will describe in detail several specific embodiment of the present invention below.But, may do various changes, and scope of the present invention is not limited by following one exemplary embodiment.For example, though for gene order and DNA hybridization with particular reference to department of biology's analysis of unifying, but, be appreciated that the described below field of this method and system is practical equally, optical circuit Computer-Assisted Design, Manufacture And Test for example, nano composite material structure and test, the making of electrooptical device, the test of electronics constituent element, set of holographic data storage matrix (assembly) and test, chemical analysis, genome analysis, proteome analysis, the summary of combinatorial chemistry, the promotion of assembling certainly of colloid and detection non-biological material.
For convenience and as a reference but, in the following description book, use some technical term not as restriction.Brief definition is provided below:
A. " beamlet " is meant by a branch of light of orientation or other energy bundle, for example export the light beam that produces by the collimation of laser or light emitting diode, the process light that medium produced or the beamlet of other energy,, its medium is diffracted to two bundles or more beamlet with it. and the example of a beamlet will be the more higher order laser beam that diffraction goes out grating.
B. " phase section (Phase profile) " is meant the light in the xsect of light beam or beamlet or the phase place of other energy.
C. " phase patternization (Phase patterning) " refers to give the phase shift of the medelling of light beam or beamlet, this phase shift changes the phase sectional view of light beam or beamlet, it comprises, but be not limited to, diffraction, phase modulation (PM), pattern formation, beam splitting, convergence, dispersion, shaping, and other control bundle or beamlet.
D. " probe " refer to combine with target selectively or with biological or other chemical material of target response.Probe includes, but not limited to oligonucleotide, polynucleotide, chemical compound, protein, peptide, fat, polysaccharide, ligand, cell, antibody, antigen, organelle, fat, blastomere, cell aggregation, microorganism, cDNA, RNA or the like.
E. " target " is meant a kind of biology or other chemical material, and the existence of this material in sample combines with probe or target and probe reaction are surveyed with not existing by target.For example, the existence of the target that is formed by genetic material is that (it has for hybridizing necessary specific characteristic by the genetic material of target and the genetic material of probe, i.e. Hu Bu structure (complimentary structure)) reaction as hybridization reaction, and is detected.Target material also includes, but not limited to oligonucleotide, polynucleotide, chemical compound, protein, fat, polysaccharide, ligand, cell, antibody, antigen, organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or the like.
As shown in Figure 1, probe 500-504 can be by any suitable adhesion technique or rules (protocol), combine with any suitable substrate or react.A key property of suitable substrate is that it is a kind of material that can be comprised or handle by light trapping.Typical base of dielectric comprises globule, irregular granule, or the granule of Else Rule.The material that constitutes suitable substrate includes, but not limited to controlled pore glass (control pore glass), pottery, silica, titania, latex, plastics, polystyrene for example, methyl styrene (methylstyrene), polymethylmethacrylate, paramagnetic material, thoriosol, graphite, teflon, cross-linked dextran, agarose for example, cellulose, nylon, cross-linked micella, liposome, and capsule.
Shown in another alternative embodiment that Fig. 2 shows, method of the present invention also comprises one of use or uses a plurality of light trappings 1005 (showing) not to be adhered to suprabasil one or more probe 505 (showing) to comprise.Should be understood that configurable array can only comprise bonding probe, unbonded probe, perhaps bonding and combination unbonded probe.If any, select what potpourri of bonding and non-bonding probe, may partly be subjected to the influence of the physical characteristics of probe.Particularly, the character of some probe, Skin Cell for example can be changed into not bonding with substrate.On the contrary, other probe is the effect of protein for example, can keep the 3rd structure of probe/protein and is used better by removing substrate.
Fig. 1 has shown that be used for analysis of biological material and the configurable arrays 8 bonding probe 500-504 of substrate.Use by the movably light trapping 1000-1004 of the beamlet 2000-2004 structure that focuses on probe configuration in chief cell (subject cell) 10.Chief cell 10 is the containers (vessel) by the material of substantially transparent structure, its allow beamlet by and do not influence the formation of light trapping.
What Fig. 3 showed is the skeleton diagram of the system of generation and the position that changes configurable probe array, is labeled as 20 usually.By propagating directional light, the laser beam 100 that produces by laser instrument 102 preferably, the A ' zone to the beam splitter 30 produces movably light trapping 1000-1004 (Fig. 1) in container 10.One of light beam, it is light beam 31, from laser instrument 102 and be redirected so as the A ' zone from the beam splitter 30 continue on the phase pattern optical element (phase patterning optical element) 22 regional A. then, each beamlet that phase pattern optical element 22 is produced is through the area B of the back aperture 28 that is positioned at condenser lens 12. and beamlet is assembled by condenser lens 12. and consequent focuson light beam forms light trapping 1000-1004. for the sake of clarity by being created in three-dimensional and comprising and control the necessary gradient condition of probe, five groups of probes have only been shown among Fig. 1, beamlet and light trapping, but should be understood that, according to the character of analyzing, the ability of the system of scope and other parameter and generation light trapping can be used more or less quantity.
Can use the energy of any suitable laser instrument as laser beam 100.Available laser instrument comprises solid-state laser, diode pumping laser device, gas laser, dyestuff (dye) laser instrument, Alexandria (alexanderite) laser instrument, free electron laser, VCSEL laser instrument, diode laser, the Ti-sapphire laser, doping YAG laser instrument, doping YLF Lasers device, diode pumping YAG laser instrument and flash lamp pumping YAG laser instrument.Is preferred at 10mW to the diode pumping Nd:YAG laser instrument of working between the 5W.The optimal wavelength that is used to form the laser beam 100 of the array of studying biomaterial comprises: infrared ray, near infrared ray, visual red (visible red), green, with visual indigo plant (visible blue) wavelength, the wavelength that has from about 400nm to about 1060nm is most preferred.
Beam splitter 30 is by dichroic mirror, optical energy gap catoptron (photonic band gapmirror), and omnidirectional reflector (omni directional mirror), or other similar device constitutes.Beam splitter 30 reflects selectively and is used to form the light wavelength of light trapping, and transmits other wavelength.Then, the part light that is reflected from the A ' of beam splitter zone is through the regional A of the phase pattern optical element 22 of coding, and these phase pattern optical elements 22 are arranged at basically with the back aperture 28 on the plane of condenser lens 12 joins in the plane 24 of knot.
When laser beam 100 was directed by phase pattern optical element 22, the phase pattern optical element produced a plurality of beamlets with altered phase section.According to the quantity and the type of the light trapping of wanting, this change can comprise diffraction, the wavefront shaping, and phase shift turns to (steering), disperses and convergence.Based on selected phase section, the phase pattern optical element can be used to produce the light trapping of following form: light tweezer, optics whirlpool, optics bottleneck, optical rotator, the two or more combinations in light cage and these forms.
Less and the embodiment that inside field strength is bigger from the periphery at the phase section of those beamlets in peripheral intensity, that too fills back aperture 28 is lower than about 15%, compare with filling back aperture 28 within reason, be used to form the light trapping that has greater strength in the periphery.
According to suitable phase pattern optical element how directional focusing light beam or other energy bundle, suitable phase pattern optical element be characterized as transmission or the refraction reflection.Transmission refraction optical element transmitted light beam or other energy bundle, and catadioptric optical element reflects light beam or other energy bundle.
The phase pattern optical element also can be categorized as have a static surface or have dynamic surface.The example of suitable static phase medelling optical element comprises that those have the optical element in one or more fixed surfaces zone, for example grating comprises scattered grating, reflection grating and transmission grating, hologram, comprise multicolor hologram, template, polishing shape hologram wave filter, multicolor hologram, lens, catoptron, prism, wave plate or the like.The phase pattern optical element 40 of static transmission as shown in Figure 4, is characterized by fixed surface 41.Yet in certain embodiments, the phase pattern optical element itself is movably, by relative laser beam travel(l)ing phase medelling optical element selecting suitable zone, thereby allow to select more than one fixed surface zone 42-46.Static phase medelling optical element can be fixed on axle (spinder) 47, and around a may command motor (not shown) rotation.Static phase medelling optical element in the embodiment shown in fig. 4 has fixed surface 41 and zone of dispersion 42-46.In other embodiment of static phase medelling optical element, no matter be transmission or reflection, fixed surface 41 has a heterogeneous surface that comprises the zone that continuously changes basically, perhaps the combination in zone of dispersion and the zone that continuously changes substantially.
Example with its function suitable static phase medelling optical element relevant with the time comprises: computing machine generates diffraction pattern, phase shift material, the liquid crystal phase shift array, micro mirror array, comprise the piston type micro mirror array, spatial light modulator, electro-optic deflector, acousto-optic modulator, distorting lens, reflection MEMS array or the like. because have dynamic phasing medelling optical element, so comprise the reformed hologram of medium encoder energy of phase pattern optical element, give focused beam with the phase shift of giving medelling, this causes the corresponding change at the phase section of focused beam, for example diffraction, or convergence. in addition, medium can be by the variation of change with the position of generation light trapping. and medium can change to move each light trapping independently, and this is the advantage of dynamic phasing medelling optical element.
Preferred dynamic optical elements comprises " the PAL-SLM series of X 7665 " that spatial light modulator for example Japanese Hamamatsu in pure phase position (phase-only) makes, perhaps " SLM512N15 ' and SLM512SA7 " that is made by the Boulder Nonlinear Systems of Layafette of the state of Colorado.These phase pattern optical elements are computer-controlled to produce beamlet 2000-2004 (Fig. 1) by the hologram that is coded in the medium, and wherein, this medium can be changed to produce the form of beamlet and chooser light beam.
In certain embodiments, be used to form the form of light trapping of array and/or the position of light trapping and be changed, and be configured thus and disposed again.This form can be changed into following form from its original form: light tweezer, optical vortex, optics bottleneck, optical rotator or light cage.Light trapping can move in two dimension or three-dimensional.
The phase pattern optical element can also be used to give laser a specific topological mode, for example, and by the Gaussian mode switch is become the Gaussian-Laguerre pattern.Therefore, a beamlet can be formed the Gaussian-Laguerre pattern, and another beamlet can be formed the Gaussian pattern.
Probe configuration is in container 10.Container 10 is chief cells that are made of the material of substantially transparent, the formation that this allows the beamlet process and does not influence light trapping.In those embodiment, at the substrate specific dye marker place of wavelength, chief cell should be transparent to this specific wavelength.In addition, chief cell should be made of the material that for substrate is inertia.For example, at the bottom of the bio-based, as cell, protein and DNA should not adhere on the surface of chief cell, and can be changed by material or destroy scarcely.
Have for combining with interested target and/or reacting that the probe of necessary special nature is selected to be covered in the configurable arrays to be increased to the container neutralization.In certain embodiments, probe and substrate bonding place, substrate is indicated the selection that mark (dyestuff specific as wavelength) is beneficial to probe.In a preferred embodiment, all bonding substrates with probe of identical adhesion characteristic or response characteristic indicate the mark of same type.When substrate indicated the wavelength specific markers, the selection of probe 500-504 can join in the container 10 by the bonding probe of handle and the substrate that has mark and finish.Then, as shown in Figure 3, the spectral measurement of the substrate that has mark of probe can be used for selecting (or not selecting) to be included in the probe of array.(Fig. 2) probe can not be adhered in the substrate and can be labeled in certain embodiments.
In the embodiment of the probe of selecting not to be labeled with formation all or part array, probe can in turn add in the container 10.Under such situation, the homogeneity of probe can be known or the homogeneity of probe can be learnt according to the time that adds probe by loading sequence.As selection, have the probe of different adhesion characteristics or response characteristic each other, can be isolated to different precalculated positions according to the difference of character.Then according to the choice of location probe of probe in container.
As seen in Figure 3, the spectrum of the sample of biomaterial can be finished with imaging lighting source 39, it not only is suitable for spectroscopy but also be suitable for polarized light back scattering (polarized lightback scattering), the former is used for estimating surely chemical homogeneity, the latter is suitable for measuring the size of inner structure, atomic nucleus size for example. in certain embodiments, use such spectroscopic method, cell is inquired about, and the cell that probe array is inquired about by the quilt of picking out is created. for example, computing machine 38 can be used to analyze spectroscopic data, and be used to discern suspicious carcinous, before the cancer and/or non-carcinous cell type. computing machine can adopt information to comprise selecteed cell type with the direct light trap then. and involved cell then can be according to the cell that is comprised and target (other cell for example, antibody, antigen, with other biomaterial, or medicine and other chemicals) reaction or bonding, and with the probe in performing an analysis. one skilled in the art will realize that, according to the parameter special to cancer cell, the methodology that is used to inquire about with concentrated cell can be changed, be used for inquiry and/or separate blastomere, cell or other material, and do not deviate from scope of the present invention.
In other embodiments, have probe mark or that do not have mark, the probe that does not have mark that for example has different bonding or response characteristics can be placed in a series of daughter cell 16 that is arranged in the container 10.In Fig. 1, for clarity sake, only shown a daughter cell.Yet, should be understood that, a plurality of such daughter cells can be provided.In certain embodiments, the border of daughter cell is made of light trapping.Many light trappings in correct orientation that place produce the optics daughter cell, and it can be carried out and physics daughter cell 16 identical functions.
The layout of the probe in the daughter cell 16 has adopted any suitable means, comprises and uses light trapping, by the fluid passage, moves by microscopic capillary or by other equivalent mechanism.In each daughter cell, one or more probes have been placed with identical bonding or response characteristic.Then, according to the daughter cell that comprises probe, select to be included in the probe in the array.
By in light trapping 1000-1004, comprising probe, use light trapping 1000-1004 to catch selected probe 500-504 then.Thereby one group of so involved probe is configured to the formation array.
The method and system of invention itself is provided for following the tracks of the semi-automatic or automatic process of moving of each light trapping and content.Should move and can pass through gamma camera, frequency spectrum, or optical data stream is monitored, it provides the selection of computer controlled manufacturing probe and is used to adjust the generation of light trapping information of type of the probe that light trapping comprises and the composition of the probe of formation array.In other embodiments, according to described the moving of predetermined mobile tracking by caused each light trapping of encoding phase medelling optical element.In addition, in certain embodiments, computing machine is used for keeping being included in the record of each probe of each light trapping.
Turn back to beam splitter 30, beam splitter 30 also provides the light beam 32 from imaging lighting source 39, and it forms the corresponding optical data stream of one or more beamlets that draws with location and position by the probe that light trapping comprised by chief cell 10.
Then, the supervisory 34a of vision that optical data stream can the person of being operated 36, utilize spectroscopy equipment 34b and/or video monitoring 34c to observe, be converted to vision signal, monitoring or analysis.Optical data stream 32 can also be used for computing machine 38 uses optical data stream is converted to digital data stream by the photodetector or the processing of any suitable device of monitoring intensity.
In order to construct array, operator 36 and/or computing machine 38 can be adjusted the hologram by phase pattern optical element 22 codings, to guide moving of each light trapping to obtain selected probe and to catch it.A plurality of light trappings that have involved probe form the component of the array of configuration, and as for the component or the position of probe, according to user's needs, this array can dispose again.Use optical data stream, the position of one or more captive probes can be identified, and their position can be monitored.Based on such information, the surface of phase pattern optical element can be changed, and is changed independently in certain embodiments, comprises the form of the one or more light trapping of probe with change.
In addition, in the array position of one or more captive probes can by monitoring comprise it the position of light trapping and tracked.Then, use such information, by changing the surface of phase pattern optical element, in the array any given probe independently reorientation in chief cell, and by comprising the light trapping of probe, it is known that the homogeneity of each probe keeps, and no matter light trapping is positioned at probe where.
In a preferred embodiment, computing machine 38 is before capture probe and all control moving of light trapping afterwards.In other embodiments, optical data stream at first is converted to vision signal, and it is used for producing and the corresponding image of array then, and the operator observes image to control moving of at least one light trapping based on image then.
With reference to figure 1 and 3, for analyzing, first batch of target T1-T5 adds chief cell 10 by inlet 14, its array that also comprises fluid media (medium) 3000. probe 500-504 is suspended in the medium 3000 their volume (containment) by light trapping 1000-1004. and in order to increase the chance of reacting with target T1-T5, probe can correspondingly with the mobile phase of light trapping move around chief cell.
For example, in one embodiment, probe 500-504 is rotated the medium 3000 by comprising target T1-T5.By comprising probe optically, with physically comprise opposite, and in chief cell 10 traveling probe, probe and the interactional chance of each target have increased, and have therefore improved speed and the efficient analyzed.
Shown among Fig. 5 A and the 5B by sequentially producing the array of several groups of light trapping traveling probe 500-502.In the embodiment that Fig. 5 A shows, shown simple linear the moving of probe array, its P1 configuration along the line, P1 has represented the precalculated position.Move through probe is transferred to second group from first group of light trapping, the 3rd group, finish for the 4th group then.Be on the first area 42 of phase pattern optical element 40, to produce with reference to 4, the first groups of light trappings of figure in addition by directed laser beam.When the beamlet that sends when first area 42 passed through condenser lens, they had formed first group of light trapping at the primary importance P1 that comprises probe 500-503.
For probe 500-502 is moved to second place P2 from primary importance P1, static phase medelling optical element 40 is around axle 47 rotations, so that laser beam is aimed at second area 43, produces second group of light trapping at P2 place, corresponding second group of precalculated position.By constructing second group of group light trapping at the suitable primary importance P1 place of closing on, probe can be delivered to second group of light trapping from first group of light trapping.By rotatable phase medelling optical element to aim at and the corresponding appropriate area 42-46 of position P1-P5 that wants, can continue to transmit probe successively from three groups of precalculated position P3 of second group of precalculated position P2 to the, from four groups of precalculated position P4 of the 3rd group of precalculated position P3 to the, from five groups of precalculated position P5 of the 4th group of precalculated position P4 to the.The time interval between the termination of one group of light trapping and the generation of next group should continue for some time, and is delivered to next group light trapping to guarantee probe before drift.
This moving of probe can be used for rotation (troll) probe by medium, thereby increases target and the interactional chance of probe in the medium.Such simple another zone that can also be used for from daughter cell 16 (Fig. 1) traveling probe to chief cell 10 of moving perhaps isolates probe in the daughter cell 16.
In the embodiment that Fig. 5 B shows, shown probe close on leniently arrive narrow staggered mobile.Probe staggered move with as produce with reference to the akin mode of the described mode of Fig. 5 A.Yet, present two probes 500 and the 502 generation light trappings that are disposed of first area 42 usefulness P1 along the line,, and the 3rd probe 501 is configured in P2, promptly between top two probes, but spaced apart with line P1.When probe is delivered to second group and move to second and subsequently position from first group of light trapping, the permission probe that is staggered of probe is clogged thick and fast and needn't be placed one group of trap simultaneously in the position of closing on very much from two probes, otherwise can cause probe to be contained in the wrong light trapping.
In case target and probe interact, can use spectrographic technique research target.Those spectrum with probe (that is, those and target response or bonding probe) of positive result can obtain by using image illumination 39, and for example this is suitable for non-resilient spectroscopy (inelasticspectroscopy) or polarized light back scattering.Computing machine 38 can be analyzed the target that spectroscopic data is wanted with identification, and guiding phase pattern element removes to isolate the target that those are wanted.One skilled in the art will realize that the methodology that is used to isolate target according to spectroscopic data can be changed, with according to from target and/or the available out of Memory of optical data stream, discern and/or isolate target, and do not deviate from scope of the present invention.
When finishing analysis, by computing machine 38 and/or operator 36, which probe selection is abandoned and is collected which probe. and the characteristic of the configuration again of array allows given light trapping and involved probe to move selectively. in some cases, medium 3000 and unbonded target can be from chief cell 10 via exporting 18 eliminatings or washing, finish analysis then. under other situation, at least some still are contained in the probe of light trapping, again utilized further to analyze with other target. according to the parameter of analyzing, this technology can be used for being determined as the situation of the probe of plus or minus. also in the other situation, because be reconfigured the other probe that light trapping can be used to get rid of non-bonding probe and obtain to be used for further experiment about the quantity of the probe that forms array and the array of characteristic probe.
In certain embodiments, there is no need to change from static light beam each zone generation beamlet of optical element 40, perhaps mobile beam changes optical element 40 on a prescribed direction.As an alternative, change the position that regional order can change this group light trapping.
What Fig. 6 A showed is the stereographic map that is used to form the small-sized system of light trapping, is labeled as 50 usually.Phase pattern optical element 51 is dynamic optical elements, have reflection, dynamic surface, it also is " a PAL-SLM series of X 7665 " that the spatial light modulator of pure phase position is for example made by Japanese Hamamatsu, perhaps " SLM512N15 ' and SLM512SA7 " that is made by the BoulderNonlinear Systems Lafayette of the state of Colorado.These dynamic optical elements have the reflecting surface of codified, and wherein computing machine can be controlled the hologram that is formed on wherein.
Fig. 6 A has shown the mini-system that is used to form light trapping, and optical element 51 alignment housings 52 or be attached on the shell 52 provide the first optical frequency road 53a by this shell 52.Other end 53c and the second perpendicular optical frequency road 53d that the one end 53b in the first optical frequency road is in close proximity to optical element 51, the first optical frequency roads interact and communicate.The second optical frequency road is formed among the base 54a of the microscope lens that turntable (turret) or " nosepiece (nosepiece) " 54b are installed.Nosepiece 54b is suitable for being assembled to Nixon TE 200 series microscope (not shown).The second optical frequency road communicates with the 3rd optical frequency road 55a that also is orthogonal to the second optical frequency road.The 3rd optical frequency road 55a laterally by nosepiece 54a, and is parallel to object lens focusing lens 56 from the top surface of nosepiece 54b.Condenser lens has the top and forms the bottom of back aperture 57.What insert the 3rd optical frequency road between the back aperture 57 of the second optical frequency road and condenser lens is dichroic mirror beam splitter 58.Other parts that are used to form light trapping 50 in mini-system comprise first mirror M 1, its reflection is passed through the first optical frequency road from the beamlet that the phase pattern optical element sends, first group that is arranged in the first optical frequency road is transmitted optical devices TO1, it is collimated to receive the beamlet of first mirror M, 1 reflection, second group that is arranged in the first optical frequency road is transmitted optical devices TO2, it is collimated to receive the beamlet by first group of relay len TO1, with second mirror M 2 at the intersection point place that is positioned at the first optical frequency road and the second optical frequency road, it is collimated with the beamlet of reflection by second group of transmission optical devices TO2 and the 3rd optical frequency road 55a.
In order to produce light trapping, guided laser bundle (not shown) comes out and reflects the dynamic surface 59 that leaves optical element 51 from collimator end 151 by optical fiber 150.The light beam (not shown) of exporting from the collimating apparatus terminal 151 of optical fiber 150 is diffracted into a plurality of beamlet (not shown) by the dynamic surface 59 of optical element 51.The numbering type of each beamlet and direction can be controlled and change by the hologram that change is coded in the dynamic surface medium 59.Beamlet reflects first mirror M 1 then and transmits optical devices TO1 through first group, transmits optical devices TO2 along the first optical frequency road 53a through second group and arrives second mirror M 2; Be oriented at then on the spectroscope 58 up to the back aperture 57 of object lens 56, assembled, form the necessary optical gradient condition of light trapping thereby produce by object lens 56.Be used for imaging, that part of light that is decomposed by dichroic mirror 58 forms the optical data stream (not shown) by the lower part of the 3rd optical frequency road 55b.
Less and among the bigger embodiment of the field strength inside at the phase section of those its neutron light from the periphery in peripheral intensity, that too fills back aperture 57 is lower than about 15%, compare with filling back aperture 57 within reason, be used to form the light trapping that has around than hard intensity.
Shown in Fig. 6 B is the stereographic map of Nixon TE 200 series microscope, wherein assembled the mini-system that is used to form light trapping 50, usually being labeled as 60. nosepieces 54 that have attached shell 52 thereon is directly installed in the microscope by the base that supports nosepiece 54a and 54b. and shell and its inclusions are fixed to nosepiece 54a and 54b with the optical element 51 that links to each other, the remainder that adjusts the telescope to one's eyes seldom or do not need to require change and improves. for imaging, above object lens 56, can provide light source.
First and second groups are transmitted optical devices TO1 and TO2 and have been shown each and comprise two lens elements.Lens can be protruding or recessed.Can select different and the type that changes and the lens of quantity, the single eyeglass (symmetrical air spacedsinglets) in for example symmetrical clearance, symmetry dual eyeglass in clearance (symmetrical air spaced doublets) and/or other lens or lens combination are to realize the transmission of image from first mirror M, 1 to second mirror M 2.In certain embodiments, first and second groups are transmitted optical devices is symmetrical clearance doublets, and its combination spaced apart is as long shot.
Owing in above system and device and method, can do certain change and not deviate from scope of the present invention, so all are contained in the content in the above description, shown in drawing and description, can be interpreted as illustrative, and unrestricted meaning.

Claims (10)

1. a configuration and the method for following the tracks of probe array comprise:
In container, produce at least two light trappings movably independently simultaneously;
At least two probes are provided in container;
Select at least two probes to be used for the inclusions of the probe array that light trapping inside comprised;
Catch each selected probe, be contained in the probe array of light trapping inside with configuration packet for one with correspondence in the described light trapping; And,
Comprise the position of the light trapping of probe, the position of at least one captive probe in the tracking array by computer monitoring.
2. the method in the claim 1, wherein captive probe is a chemical compound.
3. the method in the claim 1, wherein captive probe is an oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or their combination.
4. the method for an analysis of biological material comprises:
Produce at least two light trappings movably independently at internal tank;
Fluid media (medium) is provided in container;
At least two probes that are used for biomaterial are provided in fluid media (medium);
Select at least two probes to be used for the inclusions of array;
With corresponding in the described light trapping each selecteed probe of tracking;
At least one comprises the target of biomaterial in the introducing container; With,
Determine each captive probe and each target response or not reaction;
Wherein the probe that described target is reacted separates with remaining probe.
5. the method for claim 4, wherein captive probe is an oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or its combination.
6. method that disposes probe array comprises:
Produce at least two light trappings movably independently at internal tank;
Provide at least two probes at internal tank; With,
By dispose the array of at least two probes with corresponding in the described light trapping each probe of selection;
Wherein can revise described array by in described array, removing or increase at least one probe; And
Comprise the position of the light trapping of probe, the position of following the tracks of at least one captive probe in the described array by computer monitoring.
7. a configuration and dispose the method for probe array again comprises:
A directed focused beam on the phase pattern optical element to form a plurality of beamlets from the phase pattern optical element;
Directed these a plurality of beamlets pass through condenser lens to transmit beamlet, and assemble the beamlet that sends from condenser lens on the condenser lens back aperture, to produce independently movably light trapping simultaneously in container;
A large amount of probes are provided in container;
Select at least two probes to be used for being included in the content of the probe array in the light trapping;
With in the described light trapping corresponding one catch each chosen probe, be contained in probe array in the light trapping with configuration packet;
By moving the light trapping comprise probe, change the position that at least one is included in the probe in the described array, be contained in probe array in the light trapping with configuration packet again; And
Comprise the position of the light trapping of probe, the position of following the tracks of at least one captive probe in the described array by computer monitoring.
8. system that is used to form and follows the tracks of the light trapping that comprises probe comprises:
Be used to produce the light source of focused beam;
The container of substantially transparent;
Be used for producing the image light source of light beam of the inclusions of illumination container;
Be used for directed beam splitter;
The phase pattern optical element, it is used to receive the focused beam from light source, and it is diffracted at least two beamlets, the phase pattern optical element has a surface and is used for the back aperture of directed each beamlet at condenser lens, and this surface is the phase section and/or the orientation that can change to change at least one beamlet;
Be used to assemble the condenser lens of each beamlet with the light trapping that is formed for comprising probe;
Be used in described container, providing the device of at least one target of forming by biomaterial;
Be used for determining each probe of described light trapping and each target response or responseless device;
Be used to follow the tracks of moving and the device of inclusions of described light trapping; And
Be used for the device that the probe that will react to described target and remaining probe separate.
9. the method for claim 2 wherein is based on the predetermined mobile of caused each light trapping of encoding phase medelling optical element, follows the tracks of moving of captive probe.
10. the system in the claim 8, wherein the phase pattern optical element is selected from and comprises grating, hologram, masterplate, polishing shape hologram wave filter, lens, catoptron, prism, or the group of wave plate.
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Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE20306138U1 (en) 2003-04-16 2003-09-04 Monajembashi, Shamci, Dr., 69126 Heidelberg Preparation of biological target cells, with auxiliary erythrocytes, has a glass carrier for use with a multi-beam laser as optical tweezers for manipulation to examine the cell elasticity
EP1687663A4 (en) * 2003-10-28 2010-03-31 Arryx Inc System and method for manipulating and processing materials using holographic optical trapping
US7449679B2 (en) * 2003-10-28 2008-11-11 Arryx, Inc. System and method for manipulating and processing materials using holographic optical trapping
GB0416498D0 (en) 2004-07-23 2004-08-25 Council Cent Lab Res Councils Optically controllable device
WO2008034102A2 (en) 2006-09-15 2008-03-20 Haemonetics Corporation Surface mapping by optical manipulation of particles in relation to a functionalized surface
WO2008140758A1 (en) * 2007-05-10 2008-11-20 Pacific Biosciences Of California, Inc. Methods and systems for analyzing fluorescent materials with reduced autofluorescence
JP2010538645A (en) * 2007-09-11 2010-12-16 アリックス インク Combined method and apparatus for sorting objects
EP2185261A4 (en) * 2007-09-13 2013-08-28 Arryx Inc Methods and apparatuses for sorting objects in forensic dna analysis and medical diagnostics
PL2280875T3 (en) * 2008-04-23 2012-10-31 Signode Int Ip Holdings Llc Strapping device with a gear system device
US9644229B2 (en) * 2012-06-18 2017-05-09 Sobru Solutions, Inc. Microorganism evaluation system
CN109239937A (en) * 2018-09-15 2019-01-18 天津大学 A kind of optical tweezer automation control device
CN113053556A (en) * 2021-03-10 2021-06-29 暨南大学 Biological micromotor array with reconfigurability and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1166600A (en) * 1996-11-26 1997-12-03 中国科学院上海光学精密机械研究所 Optical suspension measuring system
US5776674A (en) * 1995-06-05 1998-07-07 Seq, Ltd Chemical biochemical and biological processing in thin films
US6055106A (en) * 1998-02-03 2000-04-25 Arch Development Corporation Apparatus for applying optical gradient forces

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3102523B2 (en) * 1992-10-12 2000-10-23 日本電信電話株式会社 Fine particle array control method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5776674A (en) * 1995-06-05 1998-07-07 Seq, Ltd Chemical biochemical and biological processing in thin films
CN1166600A (en) * 1996-11-26 1997-12-03 中国科学院上海光学精密机械研究所 Optical suspension measuring system
US6055106A (en) * 1998-02-03 2000-04-25 Arch Development Corporation Apparatus for applying optical gradient forces

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CN1715918A (en) 2006-01-04
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EP1412519A2 (en) 2004-04-28
JP2004532991A (en) 2004-10-28
HK1078933A1 (en) 2006-03-24
WO2003001178A3 (en) 2003-02-27
WO2003001178A2 (en) 2003-01-03
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NZ530239A (en) 2006-08-31

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