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.

TECHNICAL FIELD

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.

BACKGROUND ART

The preparation and use of magnetically responsive beads are known in the art. See. e.g., U.S. Pat. Nos. 4,285,819, 4,582,622, 4,795,698, 5,091,206, 5,795,470, 5,648,124, and 5,834,121. Carbon beads have been used as HPLC packing materials and coating filler. Quantum dots have found their applications in bioanalysis just recently. Quantum dot nanocrystals are nanometer scale particles that are neither small molecules nor bulk solids. Their composition and small size (a few hundred to a few thousand atoms) give these dots extraordinary optical properties, which can be readily customized by changing the size or composition of the dots. This property is the basis for encoding using quantum dots.

Microarray, biochips, and high throughput bioassays have experienced rapid progress during last several years. There are two types of biochips: passive and active biochips. Passive biochips refer to those on which chemical or biochemical reactions are dependent on passive diffusion of sample molecules. Active biochips, on the other hand, allow versatile functions of molecular manipulation, interaction, hybridization reaction and separation by external forces through means such as microfluidic manipulation and electrical manipulation of molecules. When functional beads are used as molecular carrier, the beads are manipulated on the active chips.

Although beads technology has found wide applications in separation and analysis, there is a limited supply of various beads, especially those suitable to be used with active biochips, e.g., multiple-forces chips. The present invention addresses this and other related needs in the art.

DISCLOSURE OF THE INVENTION

In one aspect, the present invention is directed to a bead, which bead comprises:

a) a magnetizable substance; and b) an electrically conductive substance or an optical labeling substance.

In another aspect, the present invention is directed to a method for isolating a moiety, which method comprises: a) providing a bead comprising 1) a magnetizable substance, 2) an optical labeling substance, and preferably 3) 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 bead and/or 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.

In still another aspect, the present invention is directed to a method for manipulating a moiety, which method comprises: a) providing a bead comprising 1) a magnetizable substance, 2) an electrically conductive substance, and preferably 3) 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, preferably in a chip format, thereby said moiety is manipulated. The above method for manipulating a moiety can be readily extended to manipulating multiple moieties by using multiple types of beads, each type of which is targeted to one type of moieties to be manipulated.

In yet another aspect, the present invention is directed to a kit for manipulating a moiety, which kit comprises: a) a bead comprising 1) a magnetizable substance, 2) an electrically conductive substance or an optical labeling substance, and preferably 3) a binding partner that is capable of binding, or capable of specifically binding, to a moiety to be manipulated; and b) a means for generating a physical force for manipulating said moiety-bead complex.

In yet another aspect, the present invention is directed to a kit for manipulating a moiety in a chip format, which kit comprises: a) a bead comprising 1) a magnetizable substance, 2) an electrically conductive substance or an optical labeling substance, and preferably 3) a binding partner that is capable of binding, or capable of specifically binding, to a moiety to be manipulated; and b) a chip on which a moiety-bead complex can be manipulated.

In yet another aspect, the present invention is directed to a method for detecting a moiety, which method comprises: a) providing a bead comprising 1) a magnetizable substance, 2) an optical labeling substance, and preferably 3) 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 bead and/or said binding partner; and c) detecting binding between said moiety and said bead and/or said binding partner, whereby the presence or amount of said moiety is assessed by analysis of binding between said moiety and said bead and/or said binding partner and the identity of said moiety is assessed by analyzing the optical labeling substance comprised in the bead. The above method for detecting a moiety can be readily extended to detecting multiple moieties by using multiple types of beads, each type of which is targeted to one type of moieties to be detected and each of which has a unique optical labeling substance.

In yet another aspect, the present invention is directed to a method for synthesizing a library, which method comprises: a) providing a plurality of beads of the present invention, each of said beads comprising a magnetizable substance and an optical labeling substance that corresponds to an entity to be synthesized on said bead; and b) synthesizing said entities on said beads, wherein said beads are sorted after each synthesis cycle according to said optical labeling substances and the sorted beads are then subjected to appropriate synthesis reaction in the next synthesis cycle according to said entities to be synthesized on said beads, 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. A library that is synthesized according to the above method is also provided.

In yet another aspect, the present invention is directed to 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, wherein said unique optical labeling substance on each of said beads corresponds to an entity to be synthesized on each of said beads; and b) synthesizing said entities 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 corresponds to said unique optical labeling substance on each of said beads.

In yet another aspect, the present invention is directed to a method for generating an antibody library, which method comprises: a) contacting a library synthesized according to the above method with a plurality of antibodies; and b) selecting and/or recovering the antibodies that specifically bind to the entities of the above library.

Claim 1 of 25 Claims

1. A bead, which bead comprises: a) a magnetizable substance; and b) an electrically conductive substance, and an optical labeling substance selected from the group consisting of a fluorescent substance, a scattered-light detectable particle and a quantum dot; wherein the bead has a size of at least 0.1 .mu.m.
 

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