Array compositions and methods of making same

Details Array compositions and methods of making same Array compositions and methods of making same

2001-08-16

2004-08-03

Forman, B J (Department: 1634)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving nucleic acid

C435S007100, C435S283100, C435S287200, C435S287800, C435S288200, C435S288300, C435S288400, C435S288500, C422S068100, C422S105000

Reexamination Certificate

active

06770441

ABSTRACT:

FIELD OF THE INVENTION
The invention relates to sensor compositions comprising a composite array of individual arrays, to allow for simultaneous processing of a number of samples. The invention further provides methods of making and using the composite arrays. The invention provides microscope slide arrays and methods of making microscope slide arrays.
BACKGROUND OF THE INVENTION
There are a number of assays and sensors for the detection of the presence and/or concentration of specific substances in fluids and gases. Many of these rely on specific ligand/antiligand reactions as the mechanism of detection. That is, pairs of substances (i.e. the binding pairs or ligand/antiligands) are known to bind to each other, while binding little or not at all to other substances. This has been the focus of a number of techniques that utilize these binding pairs for the detection of the complexes. These generally are done by labeling one component of the complex in some way, so as to make the entire complex detectable, using, for example, radioisotopes, fluorescent and other optically active molecules, enzymes, quantum dots etc.
Of particular use in these sensors are detection mechanisms utilizing luminescence. Recently, the use of optical fibers and optical fiber strands in combination with light absorbing dyes for chemical analytical determinations has undergone rapid development, particularly within the last decade. The use of optical fibers for such purposes and techniques is described by Milanovich et al., “Novel Optical Fiber Techniques For Medical Application”, Proceedings of the SPIE 28th Annual International Technical Symposium On Optics and Electro-Optics, Volume 494, 1980; Seitz, W. R., “Chemical Sensors Based On Immobilized Indicators and Fiber Optics” in
C.R.C. Critical Reviews In Analytical Chemistry
, Vol. 19, 1988, pp. 135-173; Wolfbeis, O. S., “Fiber Optical Fluorosensors In Analytical Chemistry” in
Molecular Luminescence Spectroscopy, Methods and Applications
(S. G. Schulman, editor), Wiley & Sons, New York (1988); Angel, S. M.,
Spectroscopy
2 (4):38 (1987); Walt, et al., “Chemical Sensors and Microinstrumentation”,
ACS Symposium Series, Vol.
403, 1989, p. 252, and Wolfbeis, O. S.,
Fiber Optic Chemical Sensors
, Ed. CRC Press, Boca Raton, Fla., 1991, 2nd Volume.
More recently, fiber optic sensors have been constructed that permit the use of multiple dyes with a single, discrete fiber optic bundle. U.S. Pat. Nos. 5,244,636 and 5,250,264 to Walt, et al. disclose systems for affixing multiple, different dyes on the distal end of the bundle, the teachings of each of these patents being incorporated herein by this reference. The disclosed configurations enable separate optical fibers of the bundle to optically access individual dyes. This avoids the problem of deconvolving the separate signals in the returning light from each dye, which arises when the signals from two or more dyes are combined, each dye being sensitive to a different analyte, and there is significant overlap in the dyes' emission spectra.
U.S. Ser. Nos. 08/818,199 and 09/151,877 describe array compositions that utilize microspheres or beads on a surface of a substrate, for example on a terminal end of a fiber optic bundle, with each individual fiber comprising a bead containing an optical signature. Since the beads go down randomly, a unique optical signature is needed to “decode” the array; i.e. after the array is made, a correlation of the location of an individual site on the array with the bead or bioactive agent at that particular site can be made. This means that the beads may be randomly distributed on the array, a fast and inexpensive process as compared to either the in situ synthesis or spotting techniques of the prior art. Once the array is loaded with the beads, the array can be decoded, or can be used, with full or partial decoding occurring after testing, as is more fully outlined below.
In addition, compositions comprising silicon wafers comprising a plurality of probe arrays in microtiter plates have been described in U.S. Pat. No. 5,545,531.
SUMMARY OF THE INVENTION
The invention provides an array composition comprising a rigid support; a molded layer with at least a first assay location comprising discrete sites, where the molded layer is adhered to the rigid support; a layer of bonding agent adhering the rigid support to the molded layer; and a population of microspheres comprising at least a first and a second subpopulation, where the first subpopulation comprises a first bioactive agent and the second subpopulation comprises a second bioactive agent where the microspheres are randomly distributed on the sites.
The invention also provides a method for making an array composition containing at least a first assay location having discrete sites comprising the steps of contacting a surface of a template structure, the surface comprising one or more sets of projections, with a moldable material; removing the moldable material from the surface of the template structure, whereby the removed moldable material forms a molded layer with at least a first assay location comprising discrete sites; adhering the molded layer to a rigid support; and randomly distributing microspheres on the molded layer such that individual discrete sites comprise microspheres, where the microspheres comprise at least a first and a second subpopulation, where the first subpopulation comprises a first bioactive agent and the second subpopulation comprises a second bioactive agent.


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