CN101589307A - Sorting of microdevices - Google Patents

Abstract

Particles or other microdevices are disposed in an array having discreet regions (e.g. magnetic bars), oriented within a magnetic field, and then sorted through application of a removing force under conditions that remove a proper subset of the microdevices from the array as a function of differing orientations of the microdevices. Methods are also contemplated for using magnetic patterns to sort collections of microdevices by magnetic complementarity. Preferred methods use a capture and release process to sort microdevices (microdevices), and unlike conventional sorters, do not require high particle flow rates. Also contemplated are microdevice libraries in which microdevices have mutually distinct magnetic codes, and a region with a mutually distinct polymeric or other chemical moiety.

Description

The classification of microdevice

The application advocates the right of priority of U.S. Provisional Application sequence number 60/886370 that on January 24th, 2007 applied for and the U.S. Provisional Application sequence number of applying for January 24 60/886373.

Technical field

The present invention relates to use muscle power that the collection (collection) of microdevice is categorized into subclass.

Background technology

Normally used particle classifying (sorting) technology is based on the motion of particle by device or passage.The classification rate dependent is in the flow velocity of particle, and high flow velocity may damage particle.Because the classification particle in narrow the passage that is enough to guide particle flux be slow and easily passage stop up, so in fact the passage of Shi Yonging in fact on diameter greater than the particle that will be classified.The classification that obtains is handled and is usually directed to use static charge that particle is directed to specific stream, but this method is not suitable for intensive particle.Most systems depends on and read the next particle of discerning of optical signalling (being generally fluorescence) in classification process.Can obtain 10 when examining (cell) and particle classifying device ⁶The rank particle/minute speed, this speed refers to the detection of particle, becomes high-purity fraction (fraction) usually than slow two rank of this speed or more multistage magnitude separate particles.

The application is with reference to different patents, patented claim and public publication.The full content of these projects is hereby expressly incorporated by reference.Wherein by with reference to the definition that is incorporated into term in this reference or use under the situation inconsistent or opposite with the definition of the term that provides at this, use is in the use of this term that provides and the definition of the term in the non-application reference.

Summary of the invention

The invention provides a kind of system and method, wherein particle or other microdevice are disposed in the have zone of dispersion array of (for example magnetic stripe), at the magnetic field interior orientation, and under the situation of the suitable subclass that from array, removes microdevice, remove power and classify, as the different directed functions of microdevice by application.

Aspect of preferred embodiment, at least some zone of dispersions can be alignd fully appearing as one or more bands, depart from this band and are directed but another or a plurality of zone are parallel to.Can separate adjacent area easily by the interior zone distance of 0.1 to 500 μ m.Unless obviously different with context, all scopes described herein all comprise end points.

The zone preferably comprises the parallel in fact bar of magnetic material, and it can be by permanent or only temporarily be magnetized.Bar can have combination in any low or high coercivity and low or high remanent magnetism.Given zone can comprise 1,2,3 or such bar of higher number.

Preferred sorting technique comprises following steps: the set of location microdevice on array; In the mode of the subclass that changes microdevice and the magnetic interaction between the described array with magnetic field application to microdevice; And the subclass that selectively removes described microdevice from described array.The step that can carry out five these using magnetic forces at least and selectively remove.

In fact, array can be used to carry out combinatorial chemistry.For example, can provide a plurality of magnetic orientable microdevice, each all has the active site at high relatively chemical activity (" chemical activity position "), and each comprises single and the code light uniqueness; Microdevice is divided at least the first set and second set; Reactive site at first set and the microdevice of second set is carried out different reactions, reconfigures then to the microdevice of small part first set and second set.Can repeat this processing for third and fourth set.Meet foregoing description, special consideration at least some microdevices of can classifying at least in part as the function of locating on array, use and support 10,10 ³, 10 ⁶Or the code of higher number selection.Consider that also the step that can use classification is divided at least the three set and the 4th set to help the microdevice in first set that will reconfigure and second set.

Consider that from another viewpoint theme of the present invention can comprise and uses magnetic pattern by the classify method of collection of microdevice of magnetic complementarity.Preferable methods is used to catch and discharge and is handled the microdevice of classifying, and unlike traditional classifier, does not need high particle flux speed.The size of Particle Density is not disturbed the classification by the magnetic complementarity.Because can in batch processing, carry out classification, can obtain to classify and the very high effective speed-10 that separates ⁹Rank microdevice/second.This is than traditional FACS (cytological classification of fluorescence-activation) or based on the high 4-6 of the speed rank of liquid blood cell count equipment.In addition, though some specific embodiments can be benefited from the application of light fetch equipment, many embodiment of subject matter do not need to use such equipment.

The physical embodiments of considering can comprise following element:

1) set of the microdevice of magnetic coding.Described microdevice comprises not magnetizable substrate and comprises the magnetizable material that magnetic can be distinguished code.The scope of single microdevice size is to less than 1 micron from 500 microns.

2) the classification chip by the magnetic complementarity, can be divided into subclass with the set of microdevice, comprises combination and uncombined microdevice.Described classification chip comprises substrate and the diacritic coding region of magnetic.In a preferred embodiment, each classification chip all comprises a plurality of coding regions.Coding region can be identical with its adjacent encoder zone in fact, or can be different with the adjacent encoder zone.

3) magnetic field generator.Described field generator can be an electromagnetism, perhaps can comprise permanent magnet or the combination of the two.Preferred embodiment comprises can produce balanced electromagnetic generator on the surface of classification chip.

4) forcer is used for removing uncombined microdevice from the classification chip.Preferred embodiment comprises independent use fluid force or the forcer that is used in combination with the magnetic force generator.

Subject matter also comprises display packing, comprising: the set of microdevice is provided, and the set of different microdevices comprises different magnetic codes; Provide to have and the structure the formation array at position of first and second of different magnetic code complementation, microdevice is joined described array; And, make the different subclass of microdevice select first and second positions respectively to described arrayed applications external magnetic field.Such method can advantageously comprise 8 extra at least positions of structuring the formation, described extra at least 8 structure the formation the position with from the first and second different magnetic code complementations of structuring the formation the position.

Also consider the microdevice storehouse, comprise first, second and the 3rd microdevice at least, each microdevice has different magnetic code mutually, and the zone with different mutually chemical parts.In such storehouse, the chemical part of difference can be condensate (peptide or nucleic acid) or non-polymeric body mutually.In addition, subject matter comprises that invent in the storehouse, the chemical entities of R and D by using.

For the invention of summing up claim protection and advantage compared with prior art, some purpose and the advantage of subject matter have been described at this.Certainly, should be understood that not all such purpose or advantage can obtain according to any specific embodiment.Thus, for example, one of skill in the art will recognize that can be by obtaining or the mode in this advantage that represents or one group of advantage optimized embodies or carries out inventive concept, and need not acquisition in other purpose or the advantage of this embodiment or hint.

Whole embodiment described here is in the scope of subject matter.These and other embodiment will be by apparent for those of ordinary skills from following detailed description of preferred embodiment with reference to the accompanying drawings, and theme is not limited to disclosed any certain preferred embodiment.

Description of drawings

Fig. 1. left panel: comprise 2 (every has three finger ends) magnetic codes and non-magneto-optic sign indicating number (OCR character 437) towards the microdevice of the same type last and direction that faces down.Magnetic code is symmetrically located in the microdevice about x axle and y axle (major axis of microdevice), but is located asymmetrically in apart from 1 micron of the bottom surface of microdevice with apart from the position of 1.8 microns of the end faces of microdevice about the z axle.Be positioned under the end face 0.46 micron position in the magnetic key element (element) on (arraying) chip of structuring the formation.The center panel: in the field of structuring the formation that occurs towards on and structuring the formation of the microdevice that faces down mix the major axis that is parallel to magnetic stripe.Right panel: the identical view in the process of using the lifting field (z axle) that only promotes prone microdevice.

Fig. 2 A-2C. six key elements of position encoded mechanism (n=6): A. (k=1) and two key elements (k=2) code enumerate expression; B. three key elements (k=3) code enumerates expression; C. four elements (k=4), five key elements (k=5) and six key elements (k=6) code enumerates expression.

Fig. 3. 10 pairs of three elements quadratures of the encoding mechanism shown in Figure 2 that is suitable for classifying pattern of structuring the formation.

Fig. 4. corresponding to 18 position codes of 36 position codes.By each 6 position code is used three elements (k=3), can obtain 20 expression (shown in Fig. 2 B) to each 6 position code.Such code can be used to the tripeptides storehouse of encoding, and this tripeptides storehouse comprises amino acid whose all combinations of naturally-occurring.

Fig. 5. four position encoded mechanism (n=4): for the expression of enumerating of a key element (k=1), two key elements (k=2), three key elements (k=3) and four elements (k=4) code.

Fig. 6. the example of asymmetric microdevice.Microdevice comprise the asymmetrical shape of magnetic key element or asymmetric arrangement or its two.The magnetic key element can comprise magnetic code and magnetic calibration key element; In these examples, magnetic calibration key element is illustrated as thick bar.

Fig. 7. comprise 8 position encoded mechanism (n=8) microdevice enumerate expression, these 8 encoding mechanisms comprise 5 key elements (k=5) and the asymmetric bar of structuring the formation.

Fig. 8. 35 couple, the four key element quadratures of the microdevice shown in Figure 7 that is suitable for the classifying pattern of structuring the formation.

Fig. 9. produce the synoptic diagram of many separation (split) classification processing of four groups of microdevices.Separate in the classification processing, the microdevice pond is divided in groups, and group is further divided more.In this example, this pond at first is divided into two son groups, and each son group further is divided into two groups then.

Figure 10. produce the synoptic diagram of the series classification processing of four groups of microdevices.In this series classification was handled, the microdevice pond progressively was divided into group.In this example, the pond is divided into four groups.

Figure 11. use the classification chip (chip) of minimal amount to produce the synoptic diagram of the series classification processing of four groups of microdevices.Uncombined after the 3rd classification step (unbound) microdevice all is phase member on the same group.As a result, the final classification chip among Figure 10 is caught whole members of (capture) this group, and the chip of finally classifying not is necessary.

Figure 12. use the classification chip of minimal amount to produce the synoptic diagram of many separation classification processing of four groups of microdevices.Uncombined microdevice all is mutually on the same group or the member of son group after each classification step.As a result, three classification chips among Fig. 9 are caught whole members of this group or son group, and described three classification chips are not necessary.As shown in Figure 9 the classification chip is numbered.

Figure 13. produce the synoptic diagram that the many separation classification of four groups of microdevices is handled, wherein catch and every group of elution (eluted) from the classification chip.Shown in Fig. 9 and 12, the classification chip is numbered.

Figure 14. be suitable for four key element quadratures that encoding mechanism with the n=6 k=5 shown in Fig. 2 C is categorized into 15 set of three groups pattern of structuring the formation.

Figure 15. be shown as one 8 position code (top expression) of each two arrangement in position, and 16 position encoded spaces of two 4 position codes of each two arrangement in position (bottom expression).

Figure 16. four position encoded mechanism (n=4, k=3, m=2) enumerate expression.

Figure 17. upper panel: 8 position codes of each two arrangement in position (n=8 m=2).Lower panel: 8 position codes of each three arrangement in position (n=8 m=3).The universal expression that all possible position of expression, left side is filled, and the specific examples that k=7 expresses is represented on the right side.The magnetic key element has identical size in the microdevice shown in the panel of upper and lower.

Figure 18. the schematic illustration of structuring the formation of the low-coercivity microdevice on low-coercivity is structured the formation chip.The left side is illustrated in the pattern of the bar of structuring the formation on the chip of structuring the formation.The identical patterns of the microdevice of structuring the formation is represented to have in the right side.The direction of arrow indication external magnetic field.

Figure 19. on low-coercivity classification chip, comprise the schematic illustration of structuring the formation of the low-coercivity microdevice of the single key element codes in four positions (n=4 k=1).Pattern-all positions of structuring the formation that the left side is illustrated in the classification bar on the classification chip equate.The identical classification chip of the microdevice of all four codes that comprise the form of structuring the formation is represented to have in the right side.The direction of arrow indication external magnetic field.

Figure 20. on low-coercivity classification chip, comprise the schematic illustration of classification of the low-coercivity microdevice of the single key element codes in four positions (n=4 k=1).The left side expression is included in the microdevice of all four codes of four position codes of structuring the formation on the classification chip.The right side is illustrated in uses magnetic lift and the microdevice that removes lifting identical microdevice of structuring the formation afterwards.Only keeping these the microdevice-selection references with code of mending mutually with the classification chip is that a coding elements is aligned (align).The direction of arrow indication external magnetic field.

Figure 21. the schematic illustration of low-coercivity classification chip, the bar on the bar in the microdevice of wherein structuring the formation and the chip of structuring the formation is partly or entirely overlapping (overlap) simultaneously.

Figure 22. the actual expression of the part of low-coercivity classification chip, the bar on the bar in the microdevice of wherein structuring the formation and the chip of structuring the formation will be simultaneously partly or entirely overlapping.On the right side is a pair of microdevice that can be classified on the classification chip; The top microdevice mates five pattern on the classification chip fully, and the bottom microdevice only mates two bars on the classification chip simultaneously.

Figure 23. the actual expression that classification is handled.The part of the classification chip of left panel: Figure 21 and 22 shown types comprises the mixing of structuring the formation of two different microdevices of type shown in Figure 22; Center panel: the identical view in the process of using the lifting field that only promotes a microdevice; Right panel: in applicating fluid power with the identical view after (uncombined) microdevice that removes lifting.

Figure 24. the schematic illustration of structuring the formation of the low-coercivity microdevice on high coercivity is structured the formation chip.The microdevice that left side expression is structured the formation when parallel with the direction of magnetization of magnetic key element on the chip of structuring the formation when external field is aligned.The right side represent when external field be aligned and the chip of structuring the formation on the direction of magnetization antiparallel of magnetic key element the time microdevice of structuring the formation.The direction of arrow indication external magnetic field.

Figure 25. on high coercivity classification chip, comprise 15 key element code (n=32 k=15 of 32 positions;＞565 hundred sign indicating numbers all ages) the schematic illustration of structuring the formation of low-coercivity microdevice.Pattern-all positions of structuring the formation that the left side is illustrated in the classification bar on the classification chip equate.The identical classification chip of the microdevice that comprises 32 position codes of structuring the formation is represented to have in the right side.The direction of arrow indication external magnetic field.The external magnetic field is aligned parallel with the direction of magnetization of magnetic key element on the chip of classifying.

Figure 26. on high coercivity classification chip, comprise the schematic illustration of classification of low-coercivity microdevice of the 15 key element codes (n=32 k=15) of 32 positions.The left side expression is included in the microdevice of 32 position codes of structuring the formation on the classification chip.The right side is illustrated in uses magnetic lift and the microdevice that removes lifting identical microdevice of structuring the formation afterwards.Only keeping those the microdevice-selection references with code of mending mutually with the classification chip is more than or equal to 8 coding elements that are aligned.The direction of arrow indication external magnetic field

Figure 27. the schematic illustration of the part of high coercivity classification chip, wherein each position of structuring the formation is unique.

Figure 28. comprise the structure the formation schematic illustration of a part of low-coercivity classification chip in place of two differences.On the right side is a pair of microdevice that can structure the formation on the classification chip.

Figure 29. comprise the structure the formation actual expression of a part of low-coercivity classification chip in place of two differences.On the right side is a pair of microdevice that can structure the formation on the classification chip.

Figure 30. the part of the classification chip of expression Figure 28 and the type shown in 29, comprise the actual expression that the nonrandomness that mixes of structuring the formation of two different microdevices of type shown in Figure 29 is structured the formation and handled.

Embodiment

Definition

Unless otherwise defined, as used herein all scientific and technical terminologies have with the present invention under technical field in the identical implication of those of ordinary skill institute common sense.Be hereby expressly incorporated by reference at these all patents of quoting, application, disclosed application and other public publication full content.If definition in this application with at this in conjunction with opposite or inconsistent as the definition in all patents, application, disclosed application and other public publication quoted, definition so in this application is better than by with reference to the definition that is incorporated into this.If definition is not the definition that proposes in this application and conflict occurs in the definition that is hereby expressly incorporated by reference, adopt those definition that in the patent of the application on the same day of No. the 12/018319th, the unsettled U.S. Patent application of " Microdevice Arrays Formed by Magnetic Assenbly " by name, provide.

At this, " coercivity " of material refers to magnetization at material and has been tending towards the magnetization of this material being reduced to the intensity of zero required applying a magnetic field after saturated.Coercivity is that unit is measured usually with the oersted.The magnetic field bigger than the coercivity of material must be applied to this material, changes magnetized direction to force it." high coercivity " material is commonly referred to as permanent magnet.

At this, " magnetized predetermined preferred (preferential) axle " means magnetized preferred axes, and it can be scheduled to by the manufacturing processing of microdevice and the knowledge of design." the predetermined magnetization preferred axes " of microdevice is the basic sides of the design of this microdevice, and for example, the bar shaped key element of the CoTaZr that uses in many examples that the application represents has the predetermined magnetization preferred axes of the major axis that is parallel to magnetic stripe." predetermined magnetization preferred axes " is the attribute of microdevice of geometric configuration, composition and structural arrangements that depends on the magnetic key element of microdevice.The bar shaped key element of the CoTaZr that uses in many examples that the application represents has the predetermined magnetization preferred axes of the major axis that is parallel to bar; On the contrary, the traditional magnetic bead with magnetic material of stochastic distribution does not have predetermined magnetization preferred axes.The magnetization (with its absolute value) that produces along predetermined magnetization preferred axes greater than or equal at least to go up the magnetization that produces along any other of microdevice.Usually, for rotation under the magnetized interaction of magnetic field that applies and generation or directed itself microdevice of the present invention, Duo 20% at least than the polarization of the microdevice of other generation along at least one along the magnetization (with its absolute value) of the generation of the predetermined magnetization preferred axes of microdevice.Preferably, should Duo 50%, 70% or 90% at least than the polarization of the microdevice of other generation along the magnetization (with its absolute value) of the generation of the predetermined magnetization preferred axes of microdevice of the present invention along at least one.More preferably, lack 2 times, 5 times, 10 times, 20 times, 50 times even 100 times along the magnetization (with its absolute value) of the generation of the predetermined magnetization preferred axes of microdevice of the present invention than the polarization as many as of the microdevice of other generation along at least one.At this, " quadrature " set of classification chip is group with spatial division, makes that all members in the group can be caught ((bound) that remain combination) by a member of quadrature category set by selecting the magnetic selection benchmark rightly.

At this, " combination " microdevice is the microdevice that is in the process of the classification step of classification on the chip in the position of structuring the formation." uncombined " microdevice is the microdevice that is not in the process of the classification step of classification on the chip in the position of structuring the formation.In the classification step process, " structuring the formation " microdevice be by with the related microdevice that is maintained at the position on the surface that is parallel to the chip of classifying in fact of magnetic of classification chip magnetic." elution " microdevice is to be the more morning in classification is handled that " combination " still becomes " uncombined " microdevice in the step.Refer to the processing that on single classification chip, takes place in conjunction with, non-binding and elution.For example, the set of the microdevice of magnetic coding is placed on the classification chip and is structured the formation.Application is corresponding to the magnetic selection benchmark in magnetic field, and the surface that promotes and be oriented orthogonal in fact the classification chip by the surface from the classification chip causes the subclass of microdevice to become non-binding.Use certain type forcer to remove these uncombined microdevices.Forcer by applying a magnetic field and/or certain type comes the microdevice of the remaining combination of elution then.At this, non-binding first subclass that refers in the process that classification is handled the microdevice that removes from the classification chip, all subclass subsequently that remove from the classification chip are called as elution simultaneously.In some example, only uncombined subclass is corresponding to that damage and defective microdevice, and may not have the member.

Microdevice, embodiment

Microdevice comprises the code that the magnetic that makes this microdevice to be classified is distinguished.Described microdevice comprises magnetizable material, and can have magnetized preferred axes.Other feature also can be combined in the microdevice, but including, but not limited to light recognition coding pattern.But in United States Patent (USP) 7015047, enumerated the attribute of this microdevice that comprises light recognition coding pattern.United States Patent (USP) 7015047 has been discussed the subclass with the compatible microdevice of magnetic combined treatment.

Microdevice can have Any shape.They can have the polarization surface, but they do not need to have the polarization surface; They can be similar to pearl (bead).Flat disk is preferred embodiment a kind of.Make up the processing of structuring the formation for magnetic, being shaped as circle, square, ellipse, rectangle, hexagon, triangle and erose microdevice all is acceptable.Microdevice can be any suitable size.For example, the thickness of microdevice can be from about 0.1 micron to about 500 microns.Preferably, the thickness of microdevice can be from about 1 micron to about 200 microns.More preferably, the thickness of microdevice can be from about 1 micron to about 50 microns.In a particular embodiment, microdevice is the form with rectangle of the surface area of (for example 1000 microns multiply by 1000 microns) from about 10 square microns to about 1000000 square microns.In another particular embodiment, microdevice is to have from about 1 micron irregularly shaped to about 500 microns single dimension.

Microdevice can comprise one or more magnetizable key elements.Microdevice can have predetermined magnetization preferred axes.

Each magnetic key element in microdevice can have any width, length, thickness and shape.Each magnetic key element in microdevice can be made up of the different materials with similar or different magnetic attributes.

Can in microdevice of the present invention, use the magnetisable material that is fit to arbitrarily.In an example, the magnetizable material of use is paramagnetic material, ferrimagnetic material, ferromagnetic material or the material of super paramagnetic.Preferably, magnetizable material is a transistion metal compound, perhaps the alloy of iron, nickel, copper, cobalt, manganese, tantalum, zirconium for example.In preferred example, magnetizable material is a metal oxide.Further preferred example comprises ferronickel (NiFe) and cobalt.Extra preferable material is the alloy of cobalt, for example CoTaZr alloy, ferro-cobalt (CoFe) alloy, cobalt ferronickel (CoNiFe) alloy, cobalt niobium zirconium (CoNbZr) alloy, cobalt niobium hafnium (CoNbHf) alloy and cobalt tantalum hafnium (CoTaHf) alloy.Preferably, such feature is the bar shaped with magnetized preferred axes.Term " bar " also comprises the shape that is similar to bar and irregular a little but can represent the shape of magnetized preferred axes, for example taper of Yan Changing except rectangular shape.It is solid that bar needs not be, and can comprise cutout as described below or hole.But magnetizable material can be placed on the not magnetizable substrate the inside (being wrapped in the inside) that comprises microdevice fully, comprise outside the not magnetizable substrate of microdevice be connected to this not magnetizable substrate or be in any position between the two fully.Preferably, magnetizable material is figuratum, for example uses little processing or lithography technique, makes that its 3D shape is the known features of the design of microdevice.

Because microdevice is used to measure in liquid is structured the formation form, the advantage that they have is can use traditional liquid and globule treating apparatus (for example pipettor) and by component (aliquoted) and distribution (dispensed) easily.They are not auto correlations when as a result, being desirably in shortage magnetic field.Thus, low remanent magnetism (staying the magnetization in the medium after removing the external magnetic field) is the quality of expecting.The for example cobalt-base alloy of CoTaZr and iron oxide (Fe ₃O ₄) be the preferred example that satisfies the magnetic material of this condition.

In a preferred embodiment, microdevice comprises the non-magnetic substrate of being made up of multilayer, as describing in the United States Patent (USP) 7015047.This non-magnetic substrate can comprise other characteristic, comprises light coding pattern and well.Can comprise extra characteristic, and any one of the big measure feature of those and the plane little manufacturing device compatibility used in for example microelectromechanical systems (MEMS) can be combined on the non-magnetic substrate of microdevice.In a preferred embodiment, microdevice comprises the circuit that electrically contacts pad and allow to utilize the MEMS type sensor in the microdevice.This circuit preferably is made up of the inner electrical conductor material that surrounds of the substrate of microdevice, makes only to expose contact pad and sensor element on the surface of microdevice.Lip-deep contact pad at microdevice can be used to by the complementary contact pad on the chip of structuring the formation microdevice is connected to power supply and/or senser element.In a preferred embodiment, place circuit with distinct configuration in each microdevice, the connection between the complementary pad on the microdevice contact pad and the chip of structuring the formation can be used to determine the identity of microdevice thus.

In one embodiment, microdevice comprises the surface of chemical reaction, and this surface is suitable for adhering to chemistry or biological part (moiety).In another embodiment, this surface appears in well or the impression (indentation).In one embodiment, make by silane (for example TSL 8330, glycidoxy-propyltrimethoxy silane) on this surface.In another embodiment, reaction surface produces by the mercaptan (for example, 11 sulfydryl undecanoic acids) that comprises reagent.In another embodiment, reaction surface is the unimolecular layer (for example being mentioned at " the Formationand structure of self-assembled monolayers " of chem..Rev.96:1533-1544 (1996) with in by " the Self-assembeled monolayers of thiolates on metal as aform of nanotechnology " of people such as Love at Chem.Rev.105:1103-1169 (2005) by Ulman) from combination.Can use batch technology (for example set of the microdevice of in the aqueous solution of appropriate reagent, placing, silane for example is with reaction of formation surface on the silicon oxide surface of the exposure of microdevice) reaction of formation surface on microdevice.Alternatively, before discharging, silicon chip can generate (making the process of handling or afterwards) reaction surface at microdevice at microdevice.Reaction surface can be applied to all microdevices (for example by gas or liquid phase place silanization) on the silicon chip, perhaps the use location specifies deposition (for example ink-jet) or mask (photoetch) to be applied to the ad-hoc location of silicon chip, makes reaction surface only be applied to the subclass of the microdevice on the silicon chip or only is applied to the ad-hoc location of each microdevice.In a further embodiment, the processing of such position appointment can be used to produce unique compound on each microdevice.Such technology is widely used in and produces that DNA is little to structure the formation and put down in writing well in the literature that (for example Pirrung is at Chem.Rev.97, people such as " Spatially addressable combinatorial libraries " among the 473-448 (1997) and Gao are at Biopolyers, " the In situ synthesis of oligonucleotidemicroarrays " among the 73:579-596 (2004)).In a further embodiment, the position of reaction surface on microdevice can be figuratum.Can generate such pattern by mask; materials used protects the surface not revised in mask; for example one deck photoresist can be used to around the silicon dioxide well, and photoresist is dissolved to represent the surface that is not silylated after the silanization on well surface then.Also can obtain pattern, for example can produce gold surface, react the only surface after the generation carboxylation on gold with carboxylated alkyl sulfhydryl at silica surface by using different materials.Single microdevice can comprise one or more figuratum reaction surfaces.Such method also is documented in manufacturing and the Chemistry Literature, is applied to the little manufacturing of structuring the formation of DNA and protein especially.In extra embodiment, chemical reaction surface is corresponding to use connector (linker) molecule in solid phase synthesis.Many such connector molecules are that known (for example Jung.G is at Combinatorial Chemistry for the application in combinatorial chemistry field, Weinheim, Wiley-VCH, in 1999, and people such as Dolle is at Journal of Combinatorial Chemistry, among the 9:855-902 (2007) " comprehensive survey of chemical libraries for drug discovery and cheminalbiology; 2006 " quote in)

When the microdevice that comprises the magnetic key element is placed in the external magnetic field, in microdevice, produce magnetic dipole.Because microdevice has magnetized preferred axes, so unless be prevented from, microdevice will rotate so that its magnetized preferred axes is alignd with the magnetic line of force of external magnetic field.Unlike traditional magnetic bead, when microdevice is placed on the external magnetic field of rotation, microdevice will rotate also in fact as little stirring bar.As a result, away from any consideration about row's battle array, the expectation microdevice reacts on the external magnetic field consumingly.The magnetic key element of being made up of the material with high saturation of for example coTaZr alloy is a preferred embodiment.

The classification chip, embodiment

The two forms the classification chip by magnetic material and non-magnetic material.The classification chip is carried out its function by first microdevice of structuring the formation, and being the attribute of the chip of structuring the formation of the special chip of structuring the formation-general and feature thus describes in the unsettled U.S. Patent application No.12/018319 of " the Microdevice Arrays Formed by MagneticAssembly " by name that apply on the same day with the application, and can be applied to classification chip disclosed herein.Can in the classification chip, use any suitable magnetizable material.In an example, the magnetizable material of use is paramagnetic material, ferrimagnetic material, ferromagnetic material or the material of super paramagnetic.Preferably, magnetizable material is a transistion metal compound, perhaps the alloy of iron, nickel, copper, cobalt, manganese, tantalum, zirconium for example.In preferred example, magnetizable material is a metal oxide.Further preferred example comprises ferronickel (NiFe) and cobalt.Extra preferable material is the alloy of cobalt, for example CoTaZr alloy, ferro-cobalt (CoFe) alloy, cobalt ferronickel (CoNiFe) alloy, cobalt niobium zirconium (CoNbZr) alloy, cobalt niobium hafnium (CoNbHf) alloy and cobalt tantalum hafnium (CoTaHf) alloy.Preferably, such feature is the bar shaped with magnetized preferred axes.In many application, the remanent magnetization in the classification chip is the quality of expectation.Be similar to microdevice, can be placed on the not magnetizable material the inside (being wrapped in the inside) that comprises the classification chip fully, comprising and still be connected to this not magnetizable material outside the not magnetizable material of the chip of classify or be in any position between the two fully at the magnetizable material of classification in the chip.Preferred embodiment is placed on the top of glass substrate with the magnetic key element, and uses silicon dioxide that it is surrounded, and makes silicon dioxide form flat or flat in fact surface.Further preferred embodiment is placed on the top of silicon substrate with the magnetic key element, and uses silicon dioxide that it is surrounded, and makes silicon dioxide form flat or flat in fact surface.

Though used the classification chip that comprises the CoTaZr bar with low remanent magnetism and low-coercivity in the example of the application's statement, these attributes are not necessary for the combination or the classification processing of magnetic array.Because high remanent magnetism will make microdevice magnetically be made up chaining or piece under the situation that lacks the external magnetic field, usually, not expect that microdevice comprises high remanent magnetism; Although can expect to be included in magnetic key element in the classification chip has described quality the array of field combination remains intact when structuring the formation to allow removing.

Each magnetic key element in the classification chip is made up of different designs.The magnetic key element can Any shape and size.Each magnetic key element can be different from all other key elements or comprise the subclass of such key element.Each magnetic key element can be made up of the different materials with similar or different magnetic attributes.Preferably, the magnetic key element can be the bar shaped with magnetized preferred axes.More preferably, the magnetic key element has predetermined magnetization preferred axes.Term " bar " also comprises the shape that is similar to bar and irregular a little but can represent the shape of magnetized preferred axes, for example taper of Yan Changing except rectangular shape.It is solid that bar needs not be, and can comprise cutout as described below or hole.

Preferred embodiment is the magnetic key element as the bar of being made up of height infiltration ferromagnetic material.These can be rectangle or rectangle in fact.As shown in Figure 1 with as the bar that comprises " finger piece " described in the United States Patent (USP) 7015047 is another preferred embodiment.These finger pieces can be (for example 1-2% of the whole length of bar) or (the almost whole length that for example comprises bar) grown that lacks or be between the two.

Not magnetizable substrate can be made up of any suitable material, comprises the combination of silicon, silicon dioxide, silicon nitride, plastics, glass, pottery, polymkeric substance, metal (for example gold, aluminium, titanium etc.) or other similar materials or these materials.In preferred example, described material is a silicon dioxide.In another preferred example, described material is a glass.Substrate can comprise single or multiple lift.The classification chip substrate can be but must not be flat or flat in fact.Can exist impression to guarantee the accurate calibration of described microdevice to allow microdevice " (seating) takes a seat " in the classification chip, this expects some application.For example, these impressions can have the plane of the smooth microdevice that is used to take a seat, and perhaps they can be to be used to take a seat the sphere of pearl or pearl microdevice.In a preferential embodiment, impression can be designed as with each shape that polarizes microdevice and is complementary, and for example, rectangular well is to keep the rectangle microdevice.

The number of the cloth lattice point of each cellar area depends on the size and the spacing of the magnetic key element on the classification chip.For example, be that the classification chip that 60 * 75 microns microdevice is structured the formation can be at every square millimeter of about 100 microdevices of structuring the formation to size shown in Figure 1.In other embodiments, density can be higher.For example, size is that 20 * 25 microns microdevice can be structured the formation and with the density classification of about 1000 microdevices of each square millimeter.

It not is to realize the necessary additional features of classification processing that the classification chip can comprise.With the device compatibility of flat little manufacturing arbitrarily on a large scale feature can be integrated on the not magnetizable substrate of classification chip, for example those that use in MEMS are (for example at Liu, C., Foundations of MEMS, PearsonPrentice Hall, Upper Saddle River, NJ, 2006; Gal-el-Hak, M., MEMS (MechanicalEngineering), CRC Press, Boca Raton, 2006 is described).Preferred example is the microchannel.Such passage can be used to from classification chip surface transmission and/or remove reagent and other material of for example microdevice.Extra preferred example comprise and have those electric light microsensors of in MEMS, using (for example at Gardner, people's such as J.W. Microsensors, MEMS, and Smart Device, JohnWiley﹠amp; Sons, West Sussex, 2001).

The classification chip the magnetic key element should with the magnetic key element complementation (complementary) of microdevice, but need be in size or the magnetic key element of mating microdevice in shape fully.

Make

Can use any microdevice and classification chip made of multiple processing.In a preferred embodiment, can use various traditional little processing and semiconductor making methods to make them.In United States Patent (USP) 7015047 and U.S. Patent application 2002/0081714, and in summary that photo-engraving process or MEMS manufacturing technology are discussed and textbook, describe and with reference to such method (for example at Banks, D., Microengineering, MEMS, and Interfacing:A practical Guide, CRC Press, 2006).

Recognizable magnetic code

The microdevice of magnetic coding comprises the recognizable code of the magnetic that makes microdevice to be classified.The recognizable code of magnetic be by the magnetic means can with other code of distinguishing.The recognizable code of magnetic the intensity of their magnetic material with or distribute on different.Preferred embodiment is included in the distribution of the magnetic key element in the substrate.Such distribution can be along any generation (wherein the x axle be the major axis (length) of microdevice for x, y or z, and the y axle is the axle (width) of second length of microdevice, and the z axle is the minor axis (highly) of microdevice).Fig. 1 represents how to distinguish the example that only comprises at the microdevice of those different on the position of the z axle magnetic key element of microdevice magnetic key elements.In this example, the microdevice of structuring the formation that comprises magnetic stripe stands to be parallel to the magnetic of major axis of the magnetic stripe in the chip field of structuring the formation of structuring the formation.Second magnetic field perpendicular to the plane of the chip of structuring the formation is provided then.Make their magnetic key element apart from 1.46 microns of the magnetic key elements of the chip of structuring the formation towards last microdevice, on the contrary, prone microdevice makes their magnetic key element apart from 2.26 microns of the magnetic key elements of the chip of structuring the formation.This difference on the distance cause structuring the formation chip magnetic key element and towards on microdevice and and prone microdevice between magnetic deviation enough big, make prone microdevice selectively to be promoted from the chip surface of structuring the formation by the magnetic means.

Magnetic code can only comprise single key element and remain diacritic (for example, when structuring the formation on the chip of structuring the formation in type shown in Figure 1, be diacritic) by the wall scroll magnet of 1 micron silica encapsulation and the wall scroll magnet that encapsulates by 1.1 micron silicas.Similarly, if the microdevice docking location on the classification chip has limited the motion of the microdevice (for example by well or post) of correct butt joint, so at x, the single constituent encoder in the y plane also is diacritic.In addition, different single key element codes is diacritic on size, shape and the material that comprises the magnetic key element.

It is identical in size that the magnetic key element of formation code does not need, as long as at the magnetic force that comprises the microdevice of correctly structuring the formation of wanting maintained code be included between the magnetic force of the microdevice of correctly structuring the formation of the code that unconjugated part will be removed and have discrete difference, make to exist appropriate thresholds to promote the microdevice that unconjugated microdevice keeps combination simultaneously.

Preferred embodiment is the x that the difference of distribution that is used for the magnetic material of diacritic code is present in microdevice, in the y plane.The example of such code is expressed and is comprised bar code.The form that number that two main compositions of bar code designing treatment are codes and code can be divided.

Space encoder

Definition is by the code sum of the space n coding that comprises the k key element in equation 1.

For example, consider in code shown in Figure 2, to have the bar code of 6 available positions.This is corresponding to the n=6 in equation 1.6 possible values that have k.For k=1, there are 6 possible codes; For k=2, there are 15 possible codes; For k=3, there are 20 possible codes; For k=4, there are 15 possible codes; For k=5, there are 6 possible codes; For k=6, only there is 1 possible code.In order to be the quadrature group with all code division, some subclass of bar must be used to catch.For k=1, space encoder can be divided into 2,3,4,5 or 6 groups, because can use quadrature to catch the combination in any of bar as shown in Figure 2.For example, consider that two quadratures are caught group as shown in Figure 3, each member comprises three bars.If the microdevice of each coding has and catches a bar of chip overlapping or zero bar-exist and one with each to catch chip overlapping, so with other member overlapping be exactly the zero bar.

For k=2, situation is more complicated.Use be divided into type as shown in Figure 3 two quadrature groups catch bar, the microdevice of each coding has and catches chip overlapping two, one or zero bar.For any given right, only exist to have 6 overlapping microdevice codes of two bars and will only have 9 codes that bar is overlapping, and can not be distinguished thus.Can always be to use trivial solution to classify, that is, only accurately mate the pattern of structuring the formation of a code, and such method can be as described below very useful.

For k=3, reuse the bar collection of catching shown in Figure 3, the microdevice of each coding has and catches chip overlapping three, two, one or zero bar.Yet, unlike the example of k=2, can not divide three bars fifty-fifty, the result catches rightly for any, and each code only will have catches right at least two overlapping bars of a member with quadrature.Thus, can use 2 or more overlapping catching (selection) benchmark to divide space encoder fifty-fifty.

For k=4, the microdevice of each coding has and catch chip overlapping three, two or a bar, has the problem identical with k=2, and the existence use is any catches 9 codes that benchmark can not distinguish (with catching each right member overlapping two bars).

For k=5, it is overlapping that the microdevice of each coding has three or two bars.Can not divide five bars fifty-fifty, the result catches rightly for any, and each code only will have catches 3 overlapping bars of a right member with quadrature.Thus, overlapping catch benchmark and can be used to divide fifty-fifty space encoder for three.For k=6, only there is a code.

Except space encoder being divided into two equal groups, also there is other dividing mode, and can selects space encoder so that classifying space is applicable to application-specific.A simple example is that peptide is synthetic.If expectation produces whole combinations of abiogenous tripeptides, the ability (for each abiogenous amino acid whose group) that this needs 8000 codes and microdevice is divided into 20 groups.Fig. 4 represents the method (n=6 k=3) by such processing of encoding for the code of three separation of 20 group uses.Selection reference has become each expression for each code.This be aforesaid strong use of " trivial solution ".By closing the code of easy division, can generate the big code space of structuring the formation easily.

For example, examining and omiting target is the synthetic space encoder of DNA, and wherein expectation is divided into four groups.A plurality of copies that can be by using four member's codes as shown in Figure 5 (n=4 for example, k=1 or n=4, thereby k=3) use with above-mentioned example in identical method carry out and divide.

In order to be easy to discern the code of such demonstration is numbered.Yet shown pattern is symmetrical, and thus after rotation some codes can not distinguish with other codes, reduced the number of the diacritic code that can use for given space encoder thus.If expectation is used space encoder in more effective mode, exist to overcome symmetric multiple mode.Some examples have been shown among Fig. 6.These examples represent to use the alignment bars of asymmetrical multiple pattern.When alignment bars shown in Figure 6 is the alignment bars of bigger width, does not need such situation, and can use on width and the similar alignment bars of magnetic code width.Alternatively, if carrying out the processing of structuring the formation in shape with in the well of microdevice complementation, can use the microdevice of asymmetrical shape to eliminate symmetry in the code so.The global symmetry of microdevice is a problem.As a result, if the axle and the shape of symmetrical plane and code are all inconsistent, symmetrical code and symmetric shape can produce asymmetric microdevice.Fig. 6 represents some asymmetric microdevices.These examples are schematic rather than exhaustive.In a preferred embodiment, microdevice will comprise alignment bars.The placement of alignment bars can occur in any position of microdevice.In a further advantageous embodiment, microdevice comprises asymmetric alignment bars.In further preferred embodiment, microdevice will comprise alignment bars and asymmetric shape.Though Fig. 6 is illustrated in x, the asymmetric arrangement of the code in the y plane also can generate asymmetric arrangement by the asymmetric arrangement along the magnetic stripe of z axle (height of microdevice) in the microdevice as shown in Figure 1.

For the purpose of simplifying, in further illustrative example, in the time of the magnetic code in the demonstration microdevice, will use asymmetric right alignment bars.

The example that provides is so far directly encoded and is separated, but they do not utilize the space most effectively.Usually, to be divided into the classification application of the group of equal sizes for whole space, usually make the total number of positions (code space) in the magnetic code be even number (being divided exactly) the most simply by two, and the number of (key element) of the position that takies in code is an odd number, because this has guaranteed for example codes space n=6, k=3 and n=6, k=5, the sum of code can use being divided fifty-fifty based on the classification step of structuring the formation of two quadratures (not overlapping) as implied above.

Consider n=8, exist a lot of modes encode and the 8 location matrix codes of classifying-by from 8, selecting any four bars rather than the position be defined as a bar in per four positions, the maximum number destination code be / 4! Or 70.Using unique code is more complicated with the quadrature group that such expression is categorized as two equal sizes, because k is an even number as previously mentioned.This n=8 space encoder can be divided into the space of two n=4 or the space of four n=2, and each will comprise the code of 16 uniquenesses.Yet consider another example, select 5 bars from 8, this produces 56 codes, and because the value of k is an odd number, is divided into the group of two equal sizes easily.Fig. 7 represents that the exhaustive of this expression enumerate, and arranging subtend (referral) for convenience has been 1-56 by numeral.For two equal groups that the microdevice of these codings is structured the formation, can use the magnetic of forming by 4 bars bar of structuring the formation.Have at least three bars that align with classification chip magnetic microdevice will in conjunction with, remaining microdevice will be elution simultaneously.For example codes space shown in Figure 7, four bars that 35 uniquenesses that existence can be used are right.Fig. 8 represents to be used for the possible quadrature that whole space encoder is divided into two groups bar pattern of structuring the formation.Table 1 expression is for the structure the formation expressed intact of separating treatment of bar set of every pair of quadrature four.

Come each group is carried out the son division by repeat the classification processing with the different orthogonal collection.As a result, any given spatial division is become four groups, 6 classification step altogether that needs such as Fig. 9 are schematically shown in order to use three pairs of orthogonal sets.Yet, when spatial division is group, must not carry out final step, because remaining those microdevices all are phase members on the same group after penultimate stride.As a result, final separating step really is not a separating step, because it has caught whole members of target group.For example, when group was divided into four, as shown in figure 10, only as shown in figure 11 first three step was necessary.Similarly, when use was the classification chipset of two groups with spatial division, as shown in figure 12, only three steps were necessary.Thus, for the group with microdevice is divided into four groups, the sorting technique of separating sorting technique and sequential only needs three classification step more.Yet, may be an advantage in keeping final step because final step should be in front the step captive any microdevice remove, and remove any damage or defective microdevice.More separate classification and handle and still can only use five steps and keep this quality control treatments and exist.Such preferred embodiment is shown in Figure 13.

(use A, C, T, G)-this needs 1048576 codes (4 more with the set that has relatively produced all possible 10mer oligonucleotide that separates sorting technique to simple sequential sorting technique ¹⁰).Use four code methods will use code space and 40 classification step of 40.Use the sorting techniques of separating to use at least 23 space encoders (n=23 k=11 encode 1352078 patterns) and 50 classification step more.Application is depended in the appropriate selection of coding.

Have various other the encoding options that can be used, this allows the space to divide with the mode quilt that allows classification.This can relate to subclass-example shown in Figure 4 of selecting greater room, the subclass in three set expression n=18 k=9 spaces of n=6 k=3.Also can relate to the large-scale quadrature set of choosing the chip of structuring the formation that specific selection reference-existence can be used.For example, in Fig. 2 c, can be by using the quadrature shown in Fig. 2 C to n=6 k=5 group is divided into two equal groups, wherein selection reference is to use three bars to select three bars.Yet, select four bars by using four bars as shown in figure 14, identical space encoder can be divided into three equal groups.This example has proved that also when the classification processing was three quadrature groups with spatial division, each had two key elements common with any other member of this set at each classification chip of concentrating.

Space encoder also can be divided into more complicated encoding mechanism.Such example makes each position be represented as row and easier description by rearranging the space, wherein each row comprise key element more than a possible arrangement; The number of representing the element arrangements of each row by alphabetical m.Example shown in Figure 15 is represented 16 bar codes, comprises two collection of n=8 m=2 or n=4 m=2.The sum of definition code in the equation below:

For the set-point of n and m, the scope of the k value that existence can be used.For simple purpose, consider the lower panel of two set of expression n=4 m=2 among Figure 15.In order easily microdevice to be separated to four groups, can use k=1 to cause 64 codes.Yet k=3 is equivalent in spatial sub being divided into four groups, and causes 16 times of increases in space encoder, i.e. 1024 codes.Figure 16 represents to be used for 32 coding patterns that n=4 m=2 k=3 coding is expressed.

For example an advantage of the coding of those shown in Figure 15 and 16 expression is that they can more effectively utilize the space.Because in row, only use a bar, between bar, do not need the space so, and in fact the position can be overlapping in a large number.24 key elements that in the space of as shown in figure 15 fully independently 16 key element codes, can comprise as a result, identical size as shown in figure 17.Corresponding n=8, k=7, m=3 expresses will cause 17496 codes.This expresses 36% the code of having Duoed than n=16 k=8, and the n=16k=7 expression more friendly than classification Duoed above 50%.In form, it is the subclass that n=24 k=7 expresses that n=8, k=7, m=3 express.

In a preferred embodiment, pattern is included in the common set of the alignment bars on whole microdevices, makes no matter what its code is, all microdevices are all structured the formation on the classification chip.When each classification chip use was carried out the classification processing more than a pattern, preferred embodiment only used single code to each classification chip, makes that all positions of structuring the formation on the classification chip equate.This causes structuring the formation and is treated as unsettled U.S. Patent application No at by name " the Microdevice Arrays Formed by Magnetic Assembly " that submit on the same day with the application.The robust of describing in 12/018319 processing of structuring the formation.

The magnetic attribute that depends on the magnetic key element of the magnetic attribute of the magnetic key element on the classification chip and microdevice in the arrangement of the magnetic key element of classification on the chip.The preferred embodiment of microdevice is that their magnetic key element has low-coercivity and low remanent magnetism, makes the auto correlation that they can be not strong when lacking the external magnetic field.For such microdevice, can use to comprise large-scale magnetic Sorting Materials chip.Preferred embodiment is that the magnetic key element in the classification chip has low-coercivity.Structure the formation and the microdevice of classifying on the classification chip for the key element by these types, can use magnetic overlapping, wherein north and south poles is overlapping.Figure 18 represents to use the illustrative example of the magnetic stripe that such bar structures the formation.The illustrative example that Figure 19 and 20 expressions are handled by the classification of the low-coercivity key element of the microdevice of asymmetric alignment bars use n=4 k=1 coding.

Do not consider whole magnetic induction density, the length of the bar on the chip of structuring the formation can be important with respect to the length of the bar on microdevice.Because concentrating near terminal " magnetic charge " of magnetic area, for low-coercivity classification chip, the interaction between the overlapping fully bar is mutual exclusion.Yet under situation overlapping between rectangular and the billet, interaction can attract, particularly when billet and rectangular central area are overlapping.When with shorter bar when overlapping rectangular ability with magnetic interaction of expectation can be used to create the chip design of structuring the formation, this has increased the interactional bulk strength of structuring the formation of expectation, and has improved the efficient of structuring the formation and classifying.In this process, the magnetic stripe of the microdevice of structuring the formation is fully overlapping with littler bar, simultaneously by with other two interactions that bar is overlapped and is devoted to expect.In a preferred embodiment, the length at bar overlapping fully on the array is littler by 50% than overlapping length on the microdevice of structuring the formation.In a preferred embodiment, the classification chip comprise alternately big bar and little.In further preferred embodiment, little less than 60% of the slit between bigger.Figure 21 represents to comprise the illustrative example of the classification chip of the magnetic stripe littler than the magnetic stripe on the microdevice that will be structured the formation.Figure 22 represents to use the classification chip that such pattern can be classified and the concrete instance of microdevice.In this example, the classification chip is definitely corresponding to a microdevice, and another microdevice only has two in five magnetic key elements and the chip of classifying is total.As a result, can use the selection reference of the magnetic key element of 3,4 or 5 alignment to distinguish these microdevices.The size of microdevice is 60 * 75 * 3 microns.Figure 23 represents the example of those microdevices of being classified.The part that the left panel of Figure 23 represents to be in the form of the structuring the formation chip of structuring the formation comprises every kind of microdevice among Figure 22.After using the lifting field, rise not complementary microdevice from the surface shown in the center panel.Applicating fluid power (the little volumetric pipette in chamber provides by experiment) removes the microdevice (removing unconjugated microdevice as described at Fig. 9-13) of rise.As described in Fig. 9-13, come the microdevice of " elution " combination then, to finish classification step by increasing lifting field and applicating fluid power.

Another preferred embodiment is that the magnetic key element in the classification chip has high coercivity.In order to use such key element on the classification chip, to structure the formation and the microdevice of classifying, can use magnetic overlapping.Overlapping different with the magnetic that occurs between the low-coercivity magnetic key element, at the overlapping specific direction that depends on the magnetic field externally of the magnetic between low-coercivity magnetic key element and the high coercivity magnetic key element.Figure 24 represents to use the illustrative example with the magnetic stripe of structuring the formation at the bar of the parallel or non-parallel external field that moves on the direction of magnetization of high coercivity key element.

For the high coercivity key element, do not need to exist the slit to structure the formation and to classify.Preferred embodiment is such layout: thus arrange that the magnetic key element does not provide well shape slit between the magnetic key element.The microdevice that Figure 25 and 26 expressions are being classified, wherein microdevice and classification chip satisfy this standard.In this example, (n=32 k=15) can comprise above 56,500 ten thousand different codes, but can use single classification chip effectively microdevice is divided into two groups of known composition space encoder.

Above-mentioned example is not used in restriction.Classification does not need to be divided into the group of identical size.In addition, in the continuous classification cycle, do not need to use identical benchmark.For example, first selects to comprise three set, and this set of three is being used to select to comprise these all microdevice patterns, and second select the step can be corresponding to needing four of Perfect Matchings, even 5, be used to select to comprise all combinations of three or more.Apparent to those skilled in the art, son is divided space encoder in every way.In addition, single classification chip can be used to divide the space by elution microdevice sequentially.Such order elution process relates to the microdevice of the more weak maintenance of elution continuously.For example, for example shown in Figure 7 in the code that comprises 5 magnetic key elements, can be from the group of single four element category with microdevice elution to four separation based on the number (1,2,3 or 4) of overlapping bar.For example, can making with such an order, elution process uses the classification chip of peanut to isolate appointment codes.

Also may make single microdevice be used for elution, thereby the microdevice of only microdevice in promoting the territory, place or peanut will be by elution by generating local the lifting.This can use little electromagnet or little permanent magnet to finish.Under high density is structured the formation condition, may promote more than a microdevice, still eluted microdevice can be structured the formation again with lower density, and re-treatment is to separate interested microdevice.In addition, can be used in combination order elution and the local field that promotes, to separate each microdevice apace.

Nonrandom structuring the formation

Can use more than a pattern each chip of classifying and carry out the classification processing.In this case, will by with the chip of structuring the formation on the magnetic complementarity of ad-hoc location come microdevice is structured the formation.In one embodiment, array comprises the subclass of magnetic code, and can use selection reference to select to be retained in the subclass of the microdevice of specific array position.In a further advantageous embodiment, the chip of structuring the formation comprises unique patterns with the corresponding magnetic key element of microdevice of each magnetic coding.Because the position of the microdevice of the specific coding on the chip of structuring the formation is to be determined by the position of its complementary magnetic pattern, so such array of particles no longer is at random.Figure 27 is illustrated in the structure the formation synoptic diagram of the such array on the chip of high coercivity, and wherein each position of structuring the formation is unique.Figure 28 has represented wherein to use the simpler low-coercivity of two different patterns of structuring the formation to structure the formation chip and the illustrative example of two microdevices can structuring the formation on array for example.Figure 29 represents the concrete instance corresponding to the illustrative example among Figure 28.Microdevice is 60 * 75 * 3 microns, and comprises 5 50 * 3 * 0.4 micron magnetic key element.The actual non-random array that Figure 30 represents to use microdevice shown in Figure 29 and the chip of structuring the formation forms.Microdevice is only structured the formation on the position on the array of the magnetic code that mates them fully.

Magnetic field generator

Magnetic field generator can be electromagnetism or can comprise permanent magnet or the combination of the two.Preferred embodiment comprises can produce balanced electromagnetic generator on the surface of classification chip.

The external magnetic field generator also can be electromagnetism or can comprise permanent magnet or the combination of the two.Initial step in classification is handled is structuring the formation of microdevice.In the unsettled United States Patent (USP) of by name " the Microdevice Arrays Formed by Magnetic Assembely " that submit on the same day with the application, please among the No.12/018319 this processing have been described.The adaptability of any specific external magnetic field generator depends on application-specific, particularly space encoder and selection reference.In a preferred embodiment, magnetic field generator is made of the solenoid group (for example Helmholtz coil) of nested (nested), and it is along a plurality of axle (for example x, y, z) guiding magnetic fields.

In a preferred embodiment, magnetic field generator comprises the solenoid group that each is nested, is similar to the Helmholtz coil, but will comprise that wherein each coil of Helmholtz coil can be regulated separately.In further preferred embodiment, coil comprises the magnetic core of iron for example or ferrite (ferrite).In a further advantageous embodiment, the magnetic field generation systems comprises the DC power supply of the output that can produce positive or negative polarity.In a further advantageous embodiment, the magnetic field generation systems comprise AC power supplies or with the frequency generator of the amplifier coupling that can drive solenoid.In further preferred embodiment, the magnetic field generation systems comprises the AC power supplies that is suitable for producing the degaussing pulse.

In a preferred embodiment, magnetic field generator is controlled, makes to carry out the order (for example solenoid group that encourages by the power supply by digital controllable) that magnetic field changes in programmable mode.

Be used to remove the forcer of uncombined microdevice

As shown in Figure 1, magnetic is distinguished combination and the uncombined state of microdevice can being separated into.Uncombined microdevice is the application lifting force to be not keep the microdevice of being structured the formation.

Because the dependence that magnetic interaction is adjusted the distance promotes the needed power of microdevice much larger than the power that microdevice is remained on the lifting state.As a result, when when the surface promotes uncombined microdevice, the magnetic field (for example z axle field) that keeps uncombined microdevice to make progress can be reduced, to weaken the magnetism intensity that uncombined microdevice is remained on the classification chip surface.When having reduced z axle field, can introduce bigger magnetic field deviation so that uncombined microdevice is drawn into collecting zone along arbitrary axis.Fluid force be have superiority and can use alone or be used in combination with magnetic field gradient-low z axle field (for example reduced after) even be in that the microdevice of upright form is easier to be removed-additionally splashing in the aqueous solution of alcohol to the chip surface of classifying also produce enough turbulent flows to remove uncombined microdevice.Result as shown in Figure 23, using the little volumetric pipette in laboratory is effective especially for removing uncombined microdevice.

Preferred embodiment comprises that those separately use fluid force or are used in combination with the magnetic force generator.Extra preferred embodiment comprises and using as the vibration force of description in the U.S. Patent application 20020137059, fluid force, sound power, electrophoresis (diaelectrophoretic) power etc.These power can be used singly or in combination, and these combinations can comprise the magnetic force generator.

Synthetic

Magnetic classification and structure the formation that synthetic and screening field provides significant advantage in the storehouse.Can be by compound directly being synthesized to the storehouse that produces on the microdevice based on particle.Solid phase synthesis process is widely used, and can make up the next and existing solid phase synthesis protocol-compliant of microdevice surface chemistry.Embodiment described here can be used to following the trail of microdevice in separation and the mixed method at random.In a preferred embodiment, can distribute specific synthesis step, the compound that must be synthesized is associated with specific magnetic code or part magnetic code microdevice.In a preferred embodiment, microdevice comprises the light code.This code can be a magnetic code, perhaps can be non-magnetosphere independently.Classification is handled and is caused showing all microdevices with the form of structuring the formation.Can utilize the feature of echoing mutually in classification process, to monitor microdevice with the detectable code of light.In a preferred embodiment, can carry out the light quality inspection with the checking precision of structuring the formation.In a further advantageous embodiment; can make to use up and to detect protection group (for example fluorescently-labeled) and carry out synthetic the processing; the light that maybe can carry out coupling validity can detect test, makes can estimate coupling validity (for example among " the Theone-bead-one-compound combinatorial method " of people at Chem.Rel.97:411-448 (1997) such as Lam description) in synthetic any step of handling.In a further advantageous embodiment, each microdevice has unique light code, the feasible coupling validity that can determine the compound on each microdevice in the synthetic step of handling.In a further advantageous embodiment, microdevice comprises magnetic group code independently to allow to collect the predetermined subset of code.

Embodiments of the invention provide aspect manufacturing and screening storehouse having the essential improvement of method now.The ability of Fast Classification and demonstration microdevice allows to produce and studies big compound and specify the particle storehouse.It is the storehouse of wherein compound in the storehouse being distributed to each particle before synthesis step that compound is specified the particle storehouse.Most storehouses based on particle are at random, relate to separating and the process of mixed type (described people such as Lam 1997).Yet, unless the storehouse that produces is " complete combination ", otherwise can not determine and separating and mixing the specific compound that comprises in the storehouse, mean that the storehouse comprises whole may the combination that makes up piece (for example amino acid, nucleosides etc.).Because such combinatorial libraries is big especially usually, in fact the pragmatize compound with hangar is unknown.By separate at each and blend step before and/or structure the formation afterwards, and the sign of the coding pattern by the microdevice identity of following the trail of microdevice can be determined the accurate composition with hangar.In addition, such information allows the identity of the compound on the microdevice of each coding to be known that it helps Screening Treatment.On the contrary, the compound specified bank allows the subclass of any desired of this storehouse inclusion compound.Such compound specified bank is to handle by the classification of guiding to produce, and wherein in synthetic each step of handling, the particle of known identities is directed into the particle reaction chamber.The storehouse of using NEXUS biosystem IRORI solid phase combinatorial chemistry synthesis system to produce is an example of being handled the extensive commercialization of the compound specified bank that produces by the classification of guiding.Commercial storehouse like this comprises usually and is less than 10000 compounds.

For example, consideration comprises the storehouse of the peptide (residuepeptide) of 10 residues of being made up of 20 spontaneous amino acid.In the storehouse, exist more than 10 ¹³Individual different possible peptide (20 ¹⁰).The storehouse based on particle at random need comprise than the more particle of possible compound, to have the storehouse that comprises all possible peptide.The random subset that can only comprise alternatively, the peptide of 10 residues with hangar.On the contrary, compound appointment particle storehouse can comprise any desired predetermined subset of the peptide of 10 residues, because the particle of each magnetic coding can be assigned to particular peptide.For example, the peptide storehouse that comprises 10 residues of all possible peptide in the human genome can be used to screen biological relevant processing, for example combination of enzyme spcificity, soluble recepter, antibodies, kinase activity etc.Have about 10 ⁷Individual like this by the peptide of human body gene group coding, still need comprise 10 with hangar ¹³Individual compound is to comprise these peptides.Omit filter such with the required high capacity of hangar, from 10 ¹³Also there is very big interference in the process of the peptide screening that individual non-physiology is relevant.On the contrary, can make up the compound specified bank only to comprise 10 ⁷The peptide of individual expectation.

Be except the identity of identification microdevice in the structure the formation additional advantage of microdevice of synthetic each step of handling, can also determine the measurement of the coupling validity of the synthesis step on each single microdevice by using nondestructively measuring (for example, colorimetric or fluorescence).For example, under the synthetic situation of peptide, use the experiment of formulating to determine at the finishing of the coupling of the level of single pearl people 1997 such as () Lam.Yet at Zhu Ku at random, owing to use the current pearl coding techniques whole storehouse of can not decoding routinely, the availability of this information is limited.The validity of determining the coupling step greater than pearl 95% or be in rank or purity or the composition that 95% of pearl can not be determined the main accessory substance on any single pearl.When explain obtain from research (for example screening function or activity) storehouse as a result the time, such particle appointed information is crucial.For example, the one group of microdevice that comprises very different primary products can comprise the similar accessory substance of remarkable quantity, and this is to cause owing to incomplete reaction takes place in synthetic different step.By following the trail of this information, can write down the distribution of accessory substance in each synthetic step.The ability that microdevice comprises the MEMS device of sensor or other types provides extra advantage by the substrate that allows microdevice and be used for synthesizing and analytical equipment in the research storehouse.

Following Example is used to prove the availability of these embodiment.Use 1,000 ten thousand microdevices to carry out storehouse synthetic of 100000 compounds.Microdevice comprises chemical reaction position (well that for example comprises the chemical reaction surface that shows appropriate connector).The magnetic space encoder that is used for class library has the expression greater than 100 ten thousand.The magnetic space encoder is divided, and makes to have at least 100000 magnetic Sort Codes and 10 group codes.The group code only is another mode of dividing the magnetic space encoder, makes the named aggregate of microdevice can be classified as group.In specific examples, will organize code and distribute unitedly to each Sort Code, make for 100 copies of each Sort Code in the storehouse just in time have 10 to comprise any specific group code.Thus, each microdevice have unique light code, the magnetic Sort Code of sharing by 100 other microdevices and the group code of sharing by 100 ten thousand other microdevices.Before beginning synthetic the processing, each compound that will be synthesized is assigned with the magnetic Sort Code.This distribution will be determined at synthetic each microdevice of each step of handling the reaction chamber that is placed.Microdevice is placed on the classification chip, and is classified into elution group (for example seeing Figure 13) and is placed on group in the appropriate reaction vessel at first synthesis step.After the appropriate reaction time, the flushing microdevice and with its structure the formation the classification chip on, and be placed on (for example microscope or fluorescence scanner) in the optical reader, determine they the light code and this optical code with being used to monitor that the fluorescence of reaction or the result of colorimetric estimation are recorded.Carry out another classification processing and begin next synthesis step.Repeat this processing up to synthetic (for example the storehouse of the peptide of 10 residues will need 10 such cycles) of finishing the storehouse.In the synthetic ending of handling, each light code has been determined the output and the profile of impurities of number percent.After synthetic, classify microdevice to produce 10 groups based on the group code of microdevice.Every group of 10 copies that comprise the magnetic code of each type.This handles 10 copies that produce the storehouse, and the copy in each storehouse comprises 10 copies of each compound, has wherein characterized the purity of compound synthetic on each microdevice.

Each microdevice comprises in the storehouse of unique light code therein, and each compound can be represented by a plurality of smooth codes (for example 10).This allows in synthetic processing procedure identification error and is analyzing in the process in storehouse and ignoring or recording error.For example, can monitor the light code on microdevice during the end of each step of structuring the formation of handling in classification, if comprising the microdevice of light code 2341 in the 8th step process of 15 steps processing, the result structured the formation by mistake, the composition of the compound on this microdevice is known so, and will can not suppose that also the analysis of other microdevice that comprises identical compound is unfavorable to sharing identical magnetic Sort Code for any analysis result of this microdevice thus.

The use of group code has significant advantage with respect to other methods of a plurality of copies that carry out the storehouse, because it has overcome when the Poisson distribution problem with the generation when organizing of a large amount of object random division.

Synthetic except carrying out the compound specified bank, embodiments of the invention also provide substantive improvement in manufacturing and screening aspect hangar.The whole advantages that are applied to the compound specified bank that obtain from the ability that shows particle with directed form also are applied to hangar.

The synthetic known predetermined composition and the ability in large-sized storehouse allow the execution sequence storehouse synthetic to discern compound of interest apace.For example, after screening first storehouse, can design the second new storehouse based on the result that research first storehouse obtains.Can continue the synthetic compound of the attribute that this processing has expectation up to the The selection result that obtains expectation and identification.Such synthetic compound comprises molecule, catalyzer of the molecule forbidden, medicine, combination etc.Any compound that can synthesize on carrier falls within the scope of the present invention.

Target is isolated

Embodiment described here can be used for isolating the interested any project that is connected to microdevice and can distinguishes by certain photoreduction process (directly or indirectly).Preferred example is the isolation of rare cell.The mixing of cell can be connected to microdevice, make a plurality of microdevices comprise individual cells.After structuring the formation, can comprise the microdevice of interested cell by the microdevice identification of light method (for example fluorescence) and those isolation.Can any step before light detects step aim at cell by signal.The cell of Ge Liing can be used to further analysis (for example gene representation, snp analysis, protein overview etc.) then.

Apparent to those skilled in the art, the more multiple changing type example except the embodiment that has described does not depart from scope of the present invention yet.In addition, when explaining the disclosure, all terms should be explained in the wideest possible mode consistent with the context.Particularly term " comprises " key element, composition or the step that should be interpreted as referring to non exhaustive form, the existence of key element, composition or step of indication reference, utilize or with not by the combination of other key element, composition or the step of clear and definite reference.When refer at least one something that chooses in instructions and the claim from the group that A, B, C... and N form, literal should be interpreted as only needing a key element from group, rather than A adds that N or B add N etc.

Table 1

Claims (according to the modification of the 19th of treaty)

International office receives (04.08.2008) on August 4th, 2008

1. the method for the microdevice of classifying comprises:

Microdevice with the diacritic device code of magnetic is provided;

Provide and have the array that comprises the magnetic area code and apply the discrete coding region of magnetic force;

Use described magnetic force to come about the directed microdevice in described zone, as the function of device and area code; And

Under the situation of the suitable subclass that removes microdevice from described array, use the power that removes to the microdevice that has been directed, as the different directed functions of microdevice.

2. method according to claim 1, wherein, microdevice has the longest linear dimension of 0.1 to 500 μ m, comprises 0.1 μ m and 500 μ m.

3. method according to claim 1 further comprises and reuses magnetic force and use the step that removes step.

4. method according to claim 1 further comprises the set that utilizes microdevice, the magnetic space encoder of at least 10 selections of described microdevice utilization support.

5. method according to claim 1 further comprises the set that utilizes microdevice, described microdevice utilization support at least 10 ³The magnetic space encoder of individual selection.

6. method according to claim 1 further comprises the set that utilizes microdevice, described microdevice utilization support at least 10 ⁶The magnetic space encoder of individual selection.

7. method according to claim 1 further comprises and utilizes each all to comprise the set that size and size have the magnetic material of at least 1.2 length breadth ratio and have the microdevice of predetermined magnetization preferred axes.

8. method according to claim 1 wherein, uses the step of the directed microdevice of magnetic force to comprise to make the member of the subclass of microdevice to erect with respect to the microdevice outside the described subclass.

9. sorting technique comprises:

Use has the diacritic device code of magnetic, predetermined magnetization preferred axes and utilizes the microdevice of the magnetic space encoder that can support at least 10 selections; And

Use magnetic force to come directed microdevice, as the function of device and area code about coding region with magnetic area code.

10. method according to claim 1, wherein, microdevice has the longest linear dimension of 0.1 to 500 μ m, comprises 0.1 μ m and 500 μ m; And at least some microdevice utilization supports at least 10 ³The magnetic space encoder of individual selection.

11. method according to claim 9, wherein, at least some microdevice utilization supports at least 10 ⁶The magnetic space encoder of individual selection.

12. sorting technique:

The location has the set that magnetic can be distinguished the microdevice of device code on the array with the coding region that comprises the magnetic area code;

In the mode of the subclass that changes microdevice and the magnetic interaction between the described array with magnetic field application to microdevice, as the function of device and area code; And

Selectively remove the subclass of described microdevice from described array.

13. method according to claim 1, wherein, each microdevice in described set has the longest linear dimension of 0.1 to 500 μ m, comprises 0.1 μ m and 500 μ m, and the chemical activity position.

14. method according to claim 13 further comprises the step that repeats five using magnetic forces at least and selectively remove.

15. method according to claim 13 further comprises the set that utilizes microdevice, described microdevice utilizes a plurality of magnetic coding regions, the space encoder of at least 10 selections of described a plurality of magnetic coding region utilization supports.

16. a method of carrying out combinatorial chemistry comprises:

Provide a plurality of magnetic orientable microdevice, each microdevice comprises the chemical reaction position, and each microdevice comprises magnetic code;

Use the magnetic orientation of microdevice that microdevice is divided at least the first set and second set;

Reactive site at first set and the microdevice of second set is carried out different reactions, reconfigures then to the microdevice of small part first set and second set;

Microdevice during the magnetic orientation of use microdevice is gathered first set and second that reconfigures is divided at least the three set and the 4th set; And

Reactive site at the 3rd set and the microdevice of the 4th set is carried out different reactions, reconfigures then to the microdevice of small part the 3rd set and the 4th set.

17. method according to claim 16 further comprises to small part being classified to fewer microdevices, as the function of the orientation of the such microdevice on array.

18. method according to claim 16 comprises that further the step of using classification is divided at least the three set and the 4th set to help the microdevice in first set that will reconfigure and second set.

19. method according to claim 17, wherein, at least some code supports at least 10 ³Individual different selection.

20. method according to claim 16, wherein, at least some code supports at least 10 ⁶Individual different selection.

21. a display packing comprises:

The set of microdevice is provided, and the set of different microdevices comprises that different magnetic can distinguish the device code;

Provide to have and comprise and the structure the formation array at position of first and second of the magnetic position code of different components code complementation;

Microdevice is joined described array; And

To described arrayed applications external magnetic field, make the different subclass of microdevice select first and second positions respectively, as the function of device and position code.

22. method according to claim 21 further comprises 8 extra at least positions of structuring the formation, described extra at least 8 structure the formation the position with from the first and second different magnetic code complementations of structuring the formation the position.

23. storehouse, comprise first, second and the 3rd microdevice, each microdevice has mutual different magnetic can distinguish the device code, and zone with different mutually chemical parts, and the array that further comprises the position of structuring the formation, wherein at least one position comprises the magnetic position code with the device code complementation of first microdevice.

24. storehouse according to claim 23, wherein, each mutual different chemical part is a condensate.

25. storehouse according to claim 23, wherein, each mutual different chemical part is peptide or nucleic acid.

26. chemical entities of studying by the storehouse of using claim 23.

Claims (26)

1. the method for the microdevice of classifying comprises:

Array with zone of dispersion is provided, and described zone of dispersion applies magnetic force;

Use described magnetic force to come about the directed microdevice in described zone; And

Under the situation of the suitable subclass that removes microdevice from described array, use the power that removes to the microdevice that has been directed, as the different directed functions of microdevice.

2. method according to claim 1, wherein, microdevice has the longest linear dimension of 0.1 to 500 μ m, comprises 0.1 μ m and 500 μ m.

3. method according to claim 1 further comprises and reuses magnetic force and use the step that removes step.

4. method according to claim 1 further comprises the set that utilizes microdevice, the magnetic space encoder of at least 10 selections of described microdevice utilization support.

5. method according to claim 1 further comprises the set that utilizes microdevice, described microdevice utilization support at least 10 ³The magnetic space encoder of individual selection.

6. method according to claim 1 further comprises the set that utilizes microdevice, described microdevice utilization support at least 10 ⁶The magnetic space encoder of individual selection.

7. method according to claim 1 further comprises utilizing to have the set that predetermined magnetization preferred axes and length breadth ratio are at least 1.2 microdevice.

8. method according to claim 1 wherein, uses the step of the directed microdevice of magnetic force to comprise to make the member of the subclass of microdevice to erect with respect to the microdevice outside the described subclass.

9. sorting technique comprises:

Use has predetermined magnetization preferred axes and utilizes the microdevice of the magnetic space encoder that can support at least 10 selections; And

Use the directed microdevice of magnetic force.

10. method according to claim 1, wherein, microdevice has the longest linear dimension of 0.1 to 500 μ m, comprises 0.1 μ m and 500 μ m; And at least some microdevice utilization supports at least 10 ³The magnetic space encoder of individual selection.

11. method according to claim 9, wherein, at least some microdevice utilization supports at least 10 ⁶The magnetic space encoder of individual selection.

12. sorting technique:

The set of location microdevice on array;

In the mode of the subclass that changes microdevice and the magnetic interaction between the described array with magnetic field application to microdevice; And

Selectively remove the subclass of described microdevice from described array.

13. method according to claim 1, wherein, each microdevice in described set has the longest linear dimension of 0.1 to 500 μ m, comprises 0.1 μ m and 500 μ m, and the chemical activity position.

14. method according to claim 13 further comprises the step that repeats five using magnetic forces at least and selectively remove.

15. method according to claim 13 further comprises the set that utilizes microdevice, described microdevice utilizes a plurality of magnetic coding regions, the space encoder of at least 10 selections of described a plurality of magnetic coding region utilization supports.

16. a method of carrying out combinatorial chemistry comprises:

Provide a plurality of magnetic orientable microdevice, each microdevice comprises the chemical reaction position, and each microdevice comprises magnetic code;

Use the magnetic orientation of microdevice that microdevice is divided at least the first set and second set;

Reactive site at first set and the microdevice of second set is carried out different reactions, reconfigures then to the microdevice of small part first set and second set;

Microdevice during the magnetic orientation of use microdevice is gathered first set and second that reconfigures is divided at least the three set and the 4th set; And

Reactive site at the 3rd set and the microdevice of the 4th set is carried out different reactions, reconfigures then to the microdevice of small part the 3rd set and the 4th set.

17. method according to claim 16 further comprises to small part being classified to fewer microdevices, as the function of the orientation of the such microdevice on array.

18. method according to claim 16 comprises that further the step of using classification microdevice in first set that will reconfigure and second set is divided at least the three and gathers and the 4th set.

19. method according to claim 17, wherein, at least some code supports at least 10 ³Individual different selection.

20. method according to claim 16, wherein, at least some code supports at least 10 ⁶Individual different selection.

21. a display packing comprises:

The set of microdevice is provided, and the set of different microdevices comprises different magnetic codes;

Provide and have and the structure the formation array at position of first and second of different magnetic code complementation;

Microdevice is joined described array; And

To described arrayed applications external magnetic field, make the different subclass of microdevice select first and second positions respectively.

22. method according to claim 21 further comprises 8 extra at least positions of structuring the formation, described extra at least 8 structure the formation the position with from the first and second different magnetic code complementations of structuring the formation the position.

23. a storehouse comprises first, second and the 3rd microdevice, each microdevice has different magnetic code mutually, and the zone with different mutually chemical parts.

24. storehouse according to claim 23, wherein, each mutual different chemical part is a condensate.

25. storehouse according to claim 23, wherein, each mutual different chemical part is peptide or nucleic acid.

26. chemical entities of studying by the storehouse of using claim 23.

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