Multiple-property composite beads and preparation and use thereof

Abstract

This invention relates generally to the field of moiety or molecule isolation, detection and manipulation and library synthesis. In particular, the invention provides a bead, which bead comprises: a) a magnetizable substance; and b) an electrically conductive substance or an optical labeling substance. Methods and kits for isolating, detecting and manipulating moieties and synthesizing libraries using the beads are also provided.

1 - 32 . (canceled)  
     
     
         33 . A method for isolating a moiety, which method comprises: 
 a) providing a bead, which bead comprises a magnetizable substance, an optical labeling substance and a binding partner that is capable of binding to a moiety to be isolated;    b) contacting a sample containing or suspected of containing of said moiety with said bead provided in step a) under conditions allowing binding between said moiety and said binding partner; and    c) recovering said bead from said sample,    whereby the identity of said isolated moiety is assessed by analyzing said optical labeling substance comprised in said bead.    
     
     
         34 . The method of  claim 33 , wherein the optical labeling substance is a quantum dot.  
     
     
         35 . The method of  claim 33 , wherein the moiety is a cell, a cellular organelle, a virus, a molecule and an aggregate or complex thereof.  
     
     
         36 . The method of  claim 33 , wherein the bead is recovered from the sample by a magnetic field, centrifugation or filtration.  
     
     
         37 . The method of  claim 33 , wherein a plurality types of moieties are isolated by using a plurality types of beads, each type of the beads contains a binding partner that is capable of binding to a member of the plurality types of the moieties.  
     
     
         38 . The method of  claim 33 , wherein the sample is a fluid sample.  
     
     
         39 . The method of  claim 33 , wherein the isolation is conducted in a liquid container selected from the group consisting of a beaker, a flask, a cylinder, a test tube, an enpindorf tube, a centrifugation tube, a culture dish, a multiwell plate and a filter membrane.  
     
     
         40 . The method of  claim 33 , further comprising a step of recovering said isolated moiety from said bead.  
     
     
         41 . The method of  claim 33 , wherein the binding partner specifically binds to the moiety.  
     
     
         42 . A method for manipulating a moiety, which method comprises: 
 a) providing a bead, which bead comprises (a) a magnetizable substance, and (b) an electrically conductive substance or an optical labeling substance, and which further comprises a binding partner that is capable of binding to a moiety to be manipulated;    b) coupling said moiety to said bead provided in step a) via binding between said moiety and said binding partner to form a moiety-bead complex; and    c) manipulating said moiety-bead complex with a dielectrophoresis, a traveling-wave dielectrophoresis and/or a magnetic force,    thereby said moiety is manipulated.    
     
     
         43 . The method of  claim 42 , wherein the moiety-bead complex is manipulated in a chip format and the manipulation is effected through a combination of a structure that is external to the chip and a structure that is built-in in the chip.  
     
     
         44 . The method of  claim 42 , wherein the moiety to be manipulated is selected from the group consisting of a cell, a cellular organelle, a virus, a molecule and an aggregate or complex thereof.  
     
     
         45 . The method of  claim 42 , wherein the manipulation is selected from the group consisting of transportation, focusing, enrichment, concentration, aggregation, trapping, repulsion, levitation, separation, fractionation, isolation and linear or other directed motion of the moiety.  
     
     
         46 . The method of  claim 42 , wherein the moiety is not directly manipulatable by a dielectrophoresis, a traveling-wave dielectrophoresis and/or a magnetic force.  
     
     
         47 . The method of  claim 42 , wherein neither the moiety nor the binding partner is directly manipulatable by a dielectrophoresis, a traveling-wave dielectrophoresis and/or a magnetic force.  
     
     
         48 . The method of  claim 42 , wherein at least two types of moieties are manipulated.  
     
     
         49 . The method of  claim 48 , wherein the moieties are manipulated via a plurality of types of corresponding beads.  
     
     
         50 . The method of  claim 48 , wherein the moieties are manipulated sequentially or simultaneously.  
     
     
         51 . The method of  claim 42 , further comprising a step of recovering said isolated moiety from said bead.  
     
     
         52 . The method of  claim 42 , wherein the bead comprises an optical labeling substance and the method further comprises a step of assessing the identity of the manipulated moiety by analyzing the optical labeling substance comprised in the bead.  
     
     
         53 . The method of  claim 52 , wherein the optical labeling substance is a quantum dot.  
     
     
         54 . The method of  claim 51 , wherein the bead comprises an optical labeling substance and the method further comprises a step of assessing the identity of the isolated moiety by analyzing the optical labeling substance comprised in the bead.  
     
     
         55 . The method of  claim 54 , wherein the optical labeling substance is a quantum dot.  
     
     
         56 . The method of  claim 42 , wherein the binding partner specifically binds to the moiety.  
     
     
         57 - 59 . (canceled)  
     
     
         60 . A method for detecting a moiety, which method comprises: 
 a) providing a bead, which bead comprises a magnetizable substance, an optical labeling substance and a binding partner that is capable of binding to a moiety to be detected;    b) contacting a sample containing or suspected of containing of said moiety with said bead provided in step a) under conditions allowing binding between said moiety and said binding partner; and    c) detecting binding between said moiety and said binding partner,    whereby the presence or amount of said moiety is assessed by analysis of binding between said moiety and said binding partner and the identity of said moiety is assessed by analyzing the optical labeling substance comprised in the bead.    
     
     
         61 . The method of  claim 60 , wherein the optical labeling substance is a quantum dot.  
     
     
         62 . The method of  claim 60 , wherein the moiety is a cell, a cellular organelle, a virus, a molecule and an aggregate or complex thereof.  
     
     
         63 . The method of  claim 60 , wherein a plurality of moieties is detected by using a plurality of beads, each of the beads contains a binding partner that is capable of binding to a member of the plurality of the moieties.  
     
     
         64 . The method of  claim 63 , wherein the presence, amount or identity of said moieties are detected simultaneously.  
     
     
         65 . The method of  claim 60 , wherein the sample is a fluid sample.  
     
     
         66 . The method of  claim 60 , wherein the sample is contacted with the bead in a liquid container selected from the group consisting of a beaker, a flask, a cylinder, a test tube, an enpindorf tube, a centrifugation tube, a culture dish, a multiwell plate and a filter membrane.  
     
     
         67 . The method of  claim 60 , wherein the binding partner specifically binds to the moiety.  
     
     
         68 . A method for synthesizing a library, which method comprises: 
 a) providing a plurality of beads, wherein each of said beads comprises an optical labeling substance that corresponds to an entity to be synthesized on said bead and a magnetizable substance; and    b) synthesizing said entities on said beads, wherein said beads are sorted after each synthesis cycle according to said optical labeling substances,    whereby a library is synthesized, wherein each of said beads contains an entity that corresponds to an optical labeling substance on said bead and the sum of said beads collectively contains a plurality of entities that is predetermined before the library synthesis.    
     
     
         69 . The method of  claim 68 , wherein the optical labeling substance is a quantum dot.  
     
     
         70 . The method of  claim 68 , wherein the beads further comprises an element that facilitates and/or enables manipulation of the beads and/or the bead/synthesized entity complexes.  
     
     
         71 . The method of  claim 70 , wherein the element is selected from the group consisting of a cell, a cellular organelle, a virus, a microparticle, an aggregate or complex of molecules and an aggregate or complex thereof.  
     
     
         72 . The method of  claim 68 , wherein the beads further comprise a molecular tag.  
     
     
         73 . The method of  claim 72 , wherein the molecular tag is a DNA sequence or an antibody.  
     
     
         74 . The method of  claim 68 , wherein each of the beads contains a single synthesized entity.  
     
     
         75 . The method of  claim 68 , wherein the synthesized entities are selected from group consisting of peptides, proteins, oligonucleotides, nucleic acids, vitamins, oligosaccharides, carbohydrates, lipids, small molecules, or a complex or combination thereof.  
     
     
         76 . The method of  claim 68 , wherein the synthesized library comprises a defined set of entities that are involved in a biological pathway, belongs to a group of entities with identical or similar biological function, expressed in a stage of cell cycle, expressed in a cell type, expressed in a tissue type, expressed in an organ type, expressed in a developmental stage, entities whose expression and/or activity are altered in a disease or disorder type or stage, or entities whose expression and/or activity are altered by drug or other treatments.  
     
     
         77 . The method of  claim 68 , wherein the synthesized library comprises a defined set of DNA fragments.  
     
     
         78 . The method of  claim 77 , wherein each of the DNA fragments in the synthesized library comprises at least 10, 15, 20, 25, 50, 75, 100, 200 or 500 nucleotides.  
     
     
         79 . The method of  claim 68 , wherein the synthesized library comprises a defined set of protein or peptide fragments.  
     
     
         80 . The method of  claim 79 , wherein each of the protein or peptide fragments in the synthesized library comprises at least 10, 15, 20, 25, 50, 75, 100, 200 or 500 amino acids.  
     
     
         81 . A library that is synthesized according to the method of  claim 68 .  
     
     
         82 . A method for generating an antibody library, which method comprises: 
 a) contacting the library of  claim 81  with a plurality of antibodies;    b) selecting and/or recovering the antibodies that specifically bind to the entities of the library of  claim 81 .    
     
     
         83 . The method of  claim 82 , wherein the plurality of antibodies is derived from a phage display library.  
     
     
         84 . A method for synthesizing a library, which method comprises: 
 a) providing a plurality of beads, each of said beads comprising a magnetizable substance, an electrically conductive substance and a unique optical labeling substance; and    b) synthesizing an entity on said beads, wherein said beads are identified after each synthesis cycle according to said unique optical labeling substances,    whereby a library is synthesized, wherein each of said beads contains an entity that can be identified according to said unique optical labeling substance on each of said beads.    
     
     
         85 . A library that is synthesized according to the method of  claim 84 .  
     
     
         86 - 88 . (canceled)