CN1545561A - Configurable dynamic three dimensional array - Google Patents

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 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.

1. FIELD OF THE INVENTION

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 and the configurable dynamic probe array of substrate bonded to form one.

2. the discussion of correlative technology field

The array of promising reaction probe (reactive probes) is used for analyzing with other chemistry and bioassay and tests and has very long history.For example, array is through being usually used in genetics, 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 an organism, an individual gene, or the part (U.S. Pat 6,025,136) of an individual gene; Evaluation with the genetic expression formula.(referring to Schena, Ad.et al. " Quantitative monitoring of gene expressionpatterns 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-dirnentional 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-dirnentional 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 (fixed oligonucleotide), the rate-controlling 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 identity 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 identity of checked each globule to determine its identity.

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 identity 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 inductivity of particle.For energy being reduced to minimum, the particle with the specific inductivity that is higher than surrounding medium can move to the zone of light tweezer, and there strength of electric field 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 inductivity 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 strength of electric field, 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 (vacuum doughunt).Optical gradient is a radial, 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 absorptivity 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, itself and optics whirlpool are of the same clan on macroscopic view.To such an extent as to the light cage forms that a time average ring of light tweezer comes too by force can not captive particle around too big or reflectivity, its specific inductivity is lower than surrounding medium.Yet, 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 procedure 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 identity 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.

Brief 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 (patterning) 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 identity of probe the time, can change probe spatial relation 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 identity of probe by the identity 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 identity of the probe that is comprised in the chain maintenance light trapping.

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.

Accompanying drawing is described

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 sketch chart 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.

Detailed description of preferred 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 optoelectronic equipment, 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, colloidal is from the promotion of assembling and survey 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 photodiode, the process light that medium produced or the beamlet of other energy,, its medium is diffracted to two bundles or more beamlet with it.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 cross section 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 modulated, 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, cell 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, be complementary structure (complimentary structure)) reaction, as hybridization, and be detected.Target material also includes, but not limited to oligonucleotide, polynucleotide, chemical compound, protein, fat, polysaccharide, ligand, cell, antibody, antigen, cell 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 small-particle, or the small-particle of Else Rule.The material that constitutes suitable substrate includes, but not limited to controlled pore glass (control pore glass), pottery, silica, titanium dioxide, latex, plastics, polystyrene for example, vinyl toluene (methylstyrene), polymethylmethacrylate, paramagnetic material, thoriosol, graphite, tetrafluoroethylene, cross-linked dextran, agarose for example, Mierocrystalline 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 adherent probe, unbonded probe, the perhaps combination of adherent and unbonded probe.If any, select what mixture of bonding and non-bonding probe, may partly be subjected to the influence of the physical property of probe.Particularly, the character of some probe, skin cells for example can be changed into not bonding with substrate.On the contrary, for example proteinic effect of other probe can be by removing substrate maintenance probe/proteinic the 3rd structure and being used better.

Fig. 1 has shown and has been used for analysis of biological material and configurable arrays 8 substrate adherent probe 500-504.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 sketch chart 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 apparatus 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, promptly light beam 31, from laser apparatus 102 and be redirected so that the A ' zone from the beam splitter 30 continues to the regional A on the phase pattern optical element (phase patterning optical element) 22.Then, each beamlet of being produced of phase pattern optical element 22 is through the area B of the back aperture 28 that is positioned at condenser lens 12.Beamlet is assembled by condenser lens 12.Consequent focuson light beam forms light trapping 1000-1004 by being created in three-dimensional and comprising and control the necessary gradient condition of probe.For the sake of clarity, five groups of probes, beamlet and light trappings have only been shown among Fig. 1, 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 apparatus as laser beam 100.The available laser apparatus comprises solid laser, diode pumping laser device, gas laser, dyestuff (dye) laser apparatus, Alexandria (alexanderite) laser apparatus, free electron laser, VCSEL laser apparatus, diode laser, the Ti-sapphire laser, doping YAG laser apparatus, doping YLF Lasers device, diode pumping YAG laser apparatus and flash lamp pumping YAG laser apparatus.Is preferred at 10mW to the diode pumping Nd:YAG laser apparatus 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 rays, 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 dichroscope, optical energy gap speculum (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 ' zone of beam splitter 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 planar back aperture 28 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, speculum, 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 electric motor (not shown) rotation.Static phase medelling optical element in the embodiment shown in fig. 4 has fixed surface 41 and zone of dispersion (discreet regions) 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: computer generates diffraction pattern, phase shift material, the liquid crystal phase shift array, micro mirror array comprises 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.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 primary 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 converting the Gaussian pattern to 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 by being that the inert material constitutes for substrate.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 property 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 with the substrate adherent probe that has mark by handle 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 identity of probe can be known or the identity 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 predetermined 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 backscattering (polarized lightback scattering), the former is used for estimating surely chemical identity, the latter is suitable for measuring the size of internal structure, for example the nucleus size.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, computer 38 can be used to analyze spectroscopic data, and be used to discern suspicious carcinous, before the cancer and/or non-carcinous cell type.Computer can adopt information to comprise selecteed cell type with the direct light trap then.Involved cell then can be according to the reaction of the cell that is comprised and target (for example other cell, antibody, antigen and other biomaterial, or medicine and other pharmaceutical chemicals) or bonding, and with the probe in performing an analysis.Those of skill in the art will recognize that the methodology that is used to inquire about with concentrated cell can be changed according to the parameter special to cancer cells, be used for inquiry and/or separate blastomere, cell or other material, and do not deviate from this

Scope of 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 channel, 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 video 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, computer 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 computer 38 uses optical data stream is converted to numerical data stream by the photodetector or the processing of any suitable device of monitoring intensity.

In order to construct array, operator 36 and/or computer 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 identity of each probe keeps, and no matter light trapping is positioned at probe where.

In a preferred embodiment, computer 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, and it also comprises fluid medium 3000.The array of probe 500-504 is suspended in the medium 3000 their volume (containment) by light trapping 1000-1004.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 predetermined 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 first location P1 that comprises probe 500-503.

For probe 500-502 is moved to second position P2 from first location 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 predetermined position.By constructing second group of group light trapping at the suitable first location 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 predetermined position P3 of second group of predetermined position P2 to the, from four groups of predetermined position P4 of the 3rd group of predetermined position P3 to the, from five groups of predetermined position P5 of the 4th group of predetermined position P4 to the.The timed 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 adherent 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 backscattering.Computer 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,, select to abandon which probe and collect which probe by computer 38 and/or operator 36.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 finished analysis then from chief cell 10 via exporting 18 eliminatings or washing.Under other situation, at least some still are contained in the probe of light trapping, are utilized again 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 computer 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.The 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 dichroscope 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 tube end 151 by optical fiber 150.The light beam (not shown) of exporting from the collimator 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 dichroscope 58 forms the optical data stream (not shown) by the lower section 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, has wherein assembled the mini-system that is used to form light trapping 50, is labeled as 60 usually.The nosepiece 54 that has attached shell 52 thereon is directly installed in the microscope by the base that supports nosepiece 54a and 54b.Shell and its inclusion are fixed to nosepiece 54a and 54b with the optical element 51 that links to each other, and the rest part 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 set of lenses 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 (157)

1, the method for a kind of configuration and tracking probe array comprises:

In container, produce at least two movably light trappings;

At least two probes are provided in container;

Select at least two probes to be used for the inclusion of the probe array that light trapping inside comprised;

With catching each selected probe one of in the light trapping, be contained in the probe array of light trapping inside with configuration packet; And,

Comprise the position of the light trapping of probe, the position of at least one captive probe in the tracking array by monitoring.

2, the method in the claim 1 further comprises by moving the light trapping that comprises tracked probe and changes the position of at least one tracked probe.

3, the method in the claim 1, wherein light trapping is by two or more light tweezers, the optics whirlpool, the optics bottleneck, optical rotator or light cage constitute.

4, the method in the claim 2, wherein each light trapping can move independently.

5, the method in the claim 2, wherein each light trapping moves by computer control.

6, the method in the claim 4, wherein each light trapping moves by computer control.

7, the method in the claim 4, wherein at least one probe combines with the substrate that indicates the wavelength specific markers, and this at least one probe is by utilizing this mark of spectral measurement and utilizing spectral measurement to select this at least one bonded probe.

8, the method in the claim 4, wherein at least two probes have different combinations or response characteristic each other, and by selecting at least one probe, by traveling probe preposition and use the position of segregate probe to select this probe in the container by isolating probe according to the different combination of probe or response characteristic.

9, the method in the claim 8, wherein preposition is the daughter cell of physics.

10, the method in the claim 8, wherein preposition is the optical daughter cell.

11, the method in the claim 1 further comprises, introduces at least one target in the container, and determines that each captive probe and each target are with or without reaction therein.

12, the method in the claim 11, wherein captive probe is a biomaterial.

13, the method in the claim 11, wherein captive probe is a chemical compound.

14, the method in the claim 12, it hits is biomaterial.

15, the method in the claim 12, it hits is chemical compound.

16, the method in the claim 13, it hits is biomaterial.

17, the method in the claim 13, it hits is chemical compound.

18, the method in the claim 12, wherein captive probe is an oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or their combination.

19, the method in the claim 14, it hits is oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or their combination.

20, the method in the claim 16, it hits and is selected from by oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, in the group that RNA or they constitute one or more.

21, the method for claim 1 further comprises, probe all combines with substrate.

22, the method for claim 1 comprises that further probe all directly caught by light trapping.

23, the method for claim 1 comprises that further at least some probes combine with substrate and at least some probes do not combine with substrate.

24, the method for claim 21 further comprises, by moving the position of at least two tracked probes in the light trapping change array that comprises probe.

25, the method for claim 1 further comprises the optical data stream that produces with the corresponding data of identity and position of at least one light trapping.

26, the method for claim 24, wherein each light trapping can move independently.

27, the method for claim 24, wherein each light trapping mobile be subjected to computer-controlled.

28, the method for claim 25 further comprises with computer receiving optical data stream.

29, the method for claim 28 further comprises and uses the Computer Analysis optical data stream.

30, the method for claim 29, wherein computer moving according at least one light trapping of analysis and guidance of optical data stream.

31, the method for claim 25 further comprises optical data stream is converted to vision signal.

32, the method for claim 31 further comprises and uses the computer receiving video signals.

33, the method for claim 32 further comprises and uses the Computer Analysis vision signal.

34, the method for claim 33 comprises that further the analysis and utilization computer according to vision signal instructs moving of one or more light trappings.

35, the method for claim 31, wherein vision signal is used to produce image.

36, the method for claim 35 comprises that further the operator observes image, and instructs moving of one or more light trappings based on image observation.

37, the method for claim 25, wherein data are spectroscopic datas.

38, the method for claim 37 comprises that further the analysis and utilization computer based on spectroscopic data instructs moving of one or more light trappings.

39, the method for claim 24, wherein light trapping is by two or more light tweezers, the optics whirlpool, the optics bottleneck, optical rotator or light cage form.

40, the method for claim 26, wherein each light trapping moves by computer control.

41, the method for claim 24 is wherein by spectral measurement mark and utilize results of spectral measurements to select at least one probe.

42, the method for claim 24, wherein at least two probes have combination or the response characteristic that is different from each other, and select at least one probe by isolating this probe, by traveling probe preposition and use the position of segregate probe to select this probe in the container according to the different combination of probe or response characteristic.

43, the method in the claim 42, wherein preposition is the daughter cell of physics.

44, the method in the claim 42, wherein preposition is the optical daughter cell.

45, the method in the claim 169, wherein captive probe is a biomaterial.

46, the method in the claim 169, wherein captive probe is a chemical compound.

47, the method in the claim 46, it hits is biomaterial.

48, the method in the claim 46, it hits is chemical compound.

49, the method in the claim 45, it hits is biomaterial.

50, the method in the claim 45, it hits is chemical compound.

51, the method in the claim 45, wherein captive probe is an oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or its combination.

52, the method in the claim 47, it hits is oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or its combination.

53, the method in the claim 49, it hits and is selected from by oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, in the group that RNA or its constitute one or more.

54, the method for claim 24, its middle probe all combines with substrate.

55, the method for claim 24, its middle probe does not all combine with substrate.

56, the method for claim 24, wherein at least some probes combine with substrate and at least some probes do not combine with substrate.

57, a kind of method of analysis of biological material comprises:

Produce at least two movably light trappings at internal tank;

Fluid medium is provided in container;

At least two probes that are used for biomaterial are provided in fluid medium;

Select at least two probes to be used for the inclusion of array;

Follow the tracks of each selecteed probe with one of light trapping;

At least one comprises the target of biomaterial in the introducing container; With,

Determine each captive probe and each target response or not reaction.

58, the method for claim 57 further comprises the position that comprises the light trapping of probe by monitoring, follows the tracks of the position of at least one captive probe.

59, the method for claim 57, wherein captive probe comprises biomaterial.

60, the method for claim 57, wherein captive probe comprises chemical compound.

61, the method for claim 59, wherein captive probe is an oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or its combination.

62, the method for claim 57, it hits is oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, cDNA, RNA or its combination.

63, the method for claim 57 further comprises, the optical data stream of the corresponding data of identity and position of generation and at least one light trapping.

64, the method for claim 63 further comprises, by moving the position of at least one captive probe in the light trapping change array that comprises probe.

65, the method for claim 64, wherein each light trapping can move independently.

66, the method for claim 64, wherein each light trapping mobile be subjected to computer-controlled.

67, the method for claim 63 further comprises with computer receiving optical data stream.

68, the method for claim 67 further comprises and uses the Computer Analysis optical data stream.

69, the method for claim 68 further comprises and utilizes computer based moving in the one or more light trappings of analysis and guidance of optical data stream.

70, the method for claim 63 further comprises optical data stream is converted to vision signal.

71, the method for claim 70 further comprises and uses the computer receiving video signals.

72, the method for claim 71 further comprises and uses the Computer Analysis vision signal.

73, the method for claim 72 further comprises and utilizes computer based moving in the one or more light trappings of analysis and guidance of vision signal.

74, the method for claim 70, wherein vision signal is used to produce image.

75, the method for claim 74 comprises that further the operator observes image, and instructs moving of one or more light trappings based on image observation.

76, the method for claim 63, wherein data are spectroscopic datas.

77, the method for claim 76 further comprises and utilizes computer based moving in the one or more light trappings of analysis and guidance of spectroscopic data.

78, the method for claim 63, wherein light trapping is by two or more light tweezers, the optics whirlpool, the optics bottleneck, optical rotator or light cage form.

79, the method for claim 63, wherein at least one probe combines with substrate.

80, the method for claim 63, wherein at least one probe does not combine with substrate.

81, the method for claim 79, what wherein all had identical combination or a response characteristic indicates identical mark with substrate bonded probe.

82, the method for claim 81, wherein at least one mark is the wavelength particular dye.

83, the method for claim 82, wherein for selecting at least one probe, the spectral response by measuring the wavelength particular dye and utilize results of spectral measurements to select at least one and substrate bonded probe.

84, the method for claim 63, wherein at least two probes have different combinations or response characteristic each other, and isolate this probe according to the different combination of probe or response characteristic and select at least one probe, by traveling probe preposition and utilize the position of segregate probe to select this probe in the container.

85, the method in the claim 63, wherein preposition is the daughter cell of physics.

86, the method in the claim 84, wherein preposition is the optical daughter cell.

87, a kind of method that disposes probe array comprises:

Produce at least two movably light trappings at internal tank;

Provide at least two probes at internal tank; With,

By selecting each probe to dispose the array of at least two probes with one of light trapping.

88, a kind of method that disposes and dispose probe array comprises:

A directed focused beam on the phase pattern optical element to form a plurality of beamlets of locating 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, to produce movably light trapping in container on the condenser lens back aperture;

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;

Catch each chosen probe with one of light trapping, be contained in probe array in the light trapping with configuration packet; With

By moving the light trapping comprise probe, change the position that at least one is included in the interior probe of light trapping, be contained in probe array in the light trapping with configuration packet again.

89, the method for claim 90, wherein the phase pattern optical element has static surface.

90, the method for claim 91, wherein Jing Tai surface comprises two or more discrete zones.

91, the method for claim 90, wherein at least one position that is contained in the probe in the light trapping is changed by the zone of dispersion of the static surface that changes light beam and be directed to.

92, the method for claim 89, wherein static surface is basic continually varying.

93, the method for claim 89, wherein the position of at least one light trapping is by the zone of dispersion change of the static surface that changes light beam and be directed to.

94, the method for claim 89, wherein light beam change optical element is a grating, hologram, masterplate, polishing shape holographic filter, lens, speculum, prism, or wave plate.

95, the method for claim 90, wherein each zone of dispersion is a grating, hologram, masterplate, polishing shape holographic filter, lens, speculum, prism, or wave plate.

96, the method for claim 88, wherein the phase pattern optical element is dynamic.

97, the method for claim 96, wherein at least one position that is contained in the probe in the light trapping is changed by changing dynamic phasing medelling optical element.

98, the method for claim 97, wherein the form of at least one light trapping is changed by changing dynamic phasing medelling optical element.

99, the method for claim 97, wherein the light trapping of Gai Bianing is the light tweezer, optics whirlpool, optics bottleneck, optical rotator or light cage.

100, the method for claim 91, wherein the form of at least one light trapping changes by moving discrete static surface.

101, the method for claim 100, wherein reformed light trapping is the light tweezer, optics whirlpool, optics bottleneck, optical rotator or light cage.

102, the method for claim 97, wherein the change of dynamic phasing medelling optical element is the variation in the hologram of encoding in its surface.

103, a kind of 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 inclusion 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; With

Be used for receiving the light beam of the inclusion of illumination container, and follow the tracks of moving and the monitor of inclusion of at least one light trapping.

104, the system of claim 103 further comprises, includes the container of an inlet.

105, the system of claim 103 further comprises, includes the container of an outlet.

106, the method for claim 8, its middle probe are to utilize by light trapping, flow passage or microscopic capillary mobile and segregate.

107, the method for claim 42, its middle probe are to utilize by light trapping, flow passage or microscopic capillary mobile and segregate.

108, the method for claim 84, its middle probe are to utilize by light trapping, flow passage or microscopic capillary mobile and segregate.

109, the method for claim 63, it hits and is selected from by oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, in the group that cDNA and RNA constitute one or more.

110, the method for claim 9, its middle probe are to utilize by light trapping, flow passage or microscopic capillary mobile and segregate.

111, the system of claim 103, wherein the phase pattern optical element is dynamic, and it further comprises:

First computer is to control the diffraction that is caused by the phase pattern optical element; With,

Second computer is to keep being contained in the record of each probe in the light trapping.

112, 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.

113, a kind of system that is used to form and follows the tracks of the light trapping that comprises the probe that is incorporated into target comprises:

With a plurality of probes of target bonded;

Be used to produce the light source of focused beam;

The container of substantially transparent;

The image light source is used for producing the light beam of the inclusion of illumination container;

Beam splitter is used for the light beam that orientation results from the inclusion of the focused beam of light source and the container that throws light on;

The phase pattern optical element, it is used to receive the light 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 changeable phase section and/or orientation to change at least one beamlet;

Condenser lens is used to assemble each beamlet and comprises light trapping with target bonded probe with formation; With

Monitor is used for receiving the light beam of the inclusion of illumination container, and follows the tracks of moving and inclusion of at least one light trapping.

114, the system of claim 113, its middle probe is a biomaterial.

115, the system of claim 113, its middle probe is a chemical compound.

116, the system in the claim 114, it hits is biomaterial.

117, the system in the claim 114, it hits is chemical compound.

118, the system in the claim 115, it hits is biomaterial.

119, the system in the claim 115, it hits is chemical compound.

120, the system in the claim 114, its middle probe is selected from by oligonucleotide, polynucleotide, protein, peptide, in the group that cDNA and RNA constitute one or more.

121, the system in the claim 116, it hits and is selected from by oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, in the group that cDNA and RNA constitute one or more.

122, the system in the claim 118, it hits and is selected from by oligonucleotide, polynucleotide, protein, polysaccharide, ligand, cell, antibody, antigen, honeycomb cell organelle, fat, blastomere, cell aggregation, microorganism, peptide, in the group that cDNA and RNA constitute one or more.

123, the method in the claim 2, wherein the mobile of at least one light trapping is selected from by the rotation in the fixed position, the rotation in the on-fixed position, in two dimension move and the group of the mobile formation in three-dimensional in one or more.

124, the method in the claim 2 further comprises by changing the surface of phase pattern optical element, moves the light trapping that comprises tracked probe.

125, the system in the claim 103, wherein the phase pattern optical element has static surface.

126, the system in the claim 125, wherein static surface comprises two or more zone of dispersions.

127, the system in the claim 126, wherein static surface is movably, so that focused beam is aimed at the chosen zone of static surface.

128, the method in the claim 2, wherein the phase pattern optical element has static surface, this static surface has two or more discrete zones, and the position of at least one light trapping is changed by the zone of dispersion of the static surface that changes light beam and be directed to.

129, the system in the claim 103, wherein the phase pattern optical element has basic continually varying static surface.

130, the system in the claim 127, wherein the phase pattern optical element is selected from and comprises grating, hologram, masterplate, light finishing hologram wave filter, lens, speculum, prism, or the group of wave plate.

131, the system in the claim 126, wherein each discrete zone is selected from and comprises grating, hologram, masterplate, light finishing hologram wave filter, lens, speculum, prism, or the group of wave plate.

132, the system in the claim 103, wherein the phase pattern optical element is dynamic.

133, the method in the claim 2, wherein the phase pattern dynamic element is dynamic, and changes the position that the phase pattern optical element changes at least one light trapping.

134, the method in the claim 4, wherein the phase pattern dynamic element is dynamic, and changes the position that the phase pattern optical element changes at least one light trapping.

135, the method in the claim 2, wherein the phase pattern dynamic element is dynamic, and to change the form that the phase pattern optical element changes at least one light trapping be the light tweezer, optics whirlpool, optics bottleneck, optical rotator or light cage.

136, the method in the claim 2, wherein the phase pattern optical element has static surface, and this static surface comprises two or more zone of dispersions, and the form of at least one light trapping is changed by mobile static surface.

137, the method in the claim 136, wherein the form of the light trapping of Gai Bianing is selected from by the light tweezer, optics whirlpool, optics bottleneck, the group that optical rotator or light cage constitute.

138, the system in the claim 132, wherein the phase pattern optical element is selected from least one in the group, this group comprises that computer generates diffraction pattern, phase shift material, liquid crystal phase shift array, micro mirror array, spatial light modulator, electro-optic deflector, acousto-optic modulator, distorting lens, reflection MEMS array.

139, the system in the claim 132 comprises that further a computer is with control dynamic phasing medelling optical element.

140, the system in the claim 103 comprises that further daughter cell is used to isolate the light trapping that at least one comprises probe in container.

141, the system in the claim 140, wherein daughter cell is the daughter cell of physics.

142, the system in the claim 150 further comprises a computer, forms the pattern optical element with change bit and changes the orientation of at least one beamlet and move corresponding light trapping to comprise probe.

143, the system in the claim 103, wherein light source is a laser, it is used to produce the focused beam with green spectral wavelength.

144, the system in the claim 103, wherein light source is a laser, it is used to produce the focused beam with visible light blue color spectrum wavelength.

System in 145 claims 103, wherein light source is a laser, it is used to produce the focused beam with visible light red spectrum wavelength.

146, the system in the claim 103, wherein light source produces and has the focused beam of about 400nm to the wavelength of about 1060nm scope.

147, the system in the claim 103, wherein light source is a laser beam.

148, the system in the claim 103 further comprises the computer that is used to receive optical data stream.

149, a kind of device that is used to form the light trapping array comprises:

Be used to produce the light source of light beam;

Condenser lens with top and bottom, back aperture is formed on described bottom;

The phase pattern optical element, it is used for the light beam of collectiong focusing, and it is diffracted at least two beamlets, and the phase pattern optical element has the back aperture that a surface is used for each beamlet is oriented in condenser lens;

First optical channel with first and second ends, first end communicates with the phase pattern optical element;

Second optical channel with first and second ends, first end intersects with second end of first optical channel;

The 3rd optical channel with first and second ends, first end communicates with second end of second optical channel;

First speculum, it is used to reflect the beamlet that sends from the phase pattern optical element and passes through first optical channel;

First group is transmitted Optical devices, and it is arranged in first optical channel, and it is collimated to receive the beamlet that first speculum is reflected;

Second group is transmitted Optical devices, and it is arranged in first optical channel, and it is collimated to receive the beamlet by first group of relay len;

Second speculum, it is positioned at the intersection point of first optical channel and second optical channel, and it is collimated with the beamlet of reflection by second group of transmission Optical devices and the 3rd optical channel; With

The 3rd speculum, its its be arranged within the 3rd optical channel, be used to reflect beamlet by the 3rd optical channel to the back aperture of condenser lens, thereby form the light trapping array.

150, the device of claim 149 further comprises, is used to produce the light source of illuminating bundle, and it is arranged on the top of proximity focusing lens.

151, the device of claim 150, wherein the 3rd speculum is a dichroic beam splitters, is used to guide the focused beam of light source generation and the light beam that light source produces.

152, the device of claim 149, wherein every group of transmission Optical devices are selected from single eyeglass in symmetrical clearance and symmetrical clearance doublet.

153, the device of claim 149, wherein every group is transmitted Optical devices and comprises the lens that are selected from the group that convex lens and concavees lens form.

154, the device of claim 149, wherein first and second groups of transmission Optical devices are symmetrical clearances, and keep at a certain distance away with combination as long shot.

155, the method for claim 25 further comprises and introduces at least one target of container, and determines that each captive probe and each target are with or without reaction therein.

156, the method consistent with claim 1 further comprises, by transmit probe from a light trapping to another light trapping, move at least one captive probe.

157, the method consistent with claim 1 further comprises, by transmit probe from first group of light trapping to second group of light trapping, move at least three captive probes.

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