Libraries of Encoded beads, each Member Noncovalently Associated with Multiple Identical Molecules, Viruses or Cells

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GSJ: Received June 6 2005: http://wbabin.net/saba/saba51.htm

Libraries of Encoded beads, each Member Noncovalently Associated with Multiple Identical Molecules, Viruses or Cells

James Saba

The use of beads as a means of synthetically creating combinatorial libraries is well know. Also well know is the use of light as a means of cleaving the library members from the beads so as to produce soluble library members.

Highly effective means of screening libraries of beads has also been reported. Some involve randomly distributing the beads, such as in a gel (1). Another involves positions the beads in wells (2). The use of spraying to position beads has also been described (3).

One problem with these techniques is that the kinds of chemical libraries that can be synthesized is limited.

Herein is disclosed a means to taking advantage of bead screening techniques, without the synthetic limitations. In essence instead of synthesizing the library on the beads, a previously synthesized set of molecules (including macromolecules) is noncovalently associated with particles, such as by absorption or encapsulation.

Figure 1 attempts to describe the process of creating such a library of beads.

We start with a microtiter plate, the wells of which have different solubilized molecules. The molecules can be as diverse as desired, which allow us to tap into the vast chemical libraries of NIH and the pharmaceutical companies.

Into each well is placed a bead, perferably encoded. Various means of encoding are known, and in this example let us assume we are using quantum dots (4). In it conceivable that a code need not be used, in that residual molecules in an active bead could be directly identified.

Subsequently, the beads noncovalently absorb their respective molecules. After absorption, the beads are removed and perhaps dried.

Of importance are the beads which are just one form of the particles envisioned herein. Another important particle is a capsule. Particles can designed to be slow release, or to release their contents upon stimulation such as with light or heat.

Figure 2 exemplifies screening of the library produced in Figure 1.

Also apparently novel and encompassed in the present invention, are particle libraries where each particle comprises multiple identical viruses or cells. Furthermore, a particle encapsulating multiple identical cells may be such that it is porous only the the secreted products of the cells.

This invention is considered valuable and a US patent application is anticipated to be filed in the very near future. However, it is hoped that others with laboratory facilities will investigate its full potential, perhaps even to establish a collaboration with the inventor.

The following condensed provisional claims are an attempt to encompass important aspects of this invention.

Claims

1) A library of encoded particles each member thereof in noncovalent association with multiple identical molecules, viruses, or cells.

2) The library of claim 1 wherein the molecules are relatively small synthetic organic compounds.

3) A method of screening the library of claim 1 or 2, comprising distributing the particles in a nonrandom or random array.

4) The method of claim 3 which involves spraying.

References

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Addendum 6/7/05

The following important references (1,2) were just uncovered. The methods are similar in character to the use of gel pads (3). However, these investigators have done an excellent job in working out the details of utilizing cell lawns.

1) Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens.
Bailey, et al Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16144-9

2) Small molecule microarrays
Sabatini & Stockwell US Patent Appl 20030032203 Feb 13, 2003

3) Gel pad arrays and methods and systems for making them.
Taylor, et al US Patent Appl 20040253613