Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals
Reexamination Certificate
1997-09-30
2002-10-22
Ponnaluri, Padmashri (Department: 1627)
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
C205S081000, C205S118000, C205S123000, C205S136000, C422S068100, C422S082010, C435S091500, C435S091500, C435S091500, C435S091500
Reexamination Certificate
active
06468806
ABSTRACT:
FIELD OF THE INVENTION
The present invention generally relates to methods and apparatus for the parallel deposition, synthesis and screening of an array of diverse materials at known locations on a single substrate surface. More specifically, the invention is directed to potential masking systems and methods for applying a spatially varying potential across a substrate to deliver different materials to spatially addressable locations on the substrate.
BACKGROUND OF THE INVENTION
The discovery of new materials with novel chemical and physical properties often leads to the development of new and useful technologies. Currently, there is a tremendous amount of activity in the discovery and optimization of materials, such as superconductors, zeolites, magnetic materials, phosphors, nonlinear optical materials, thermoelectric materials, high and low dielectric materials and the like. Unfortunately, even though the chemistry of extended solids has been extensively explored, few general principles have emerged that allow one to predict with certainty the composition, structure, and reaction pathways for the synthesis of such solid state compounds.
The preparation of new materials with novel chemical and physical properties is at best happenstance with our current level of understanding. Consequently, the discovery of new materials depends largely on the ability to synthesize and analyze new compounds. Given approximately 100 elements in the periodic table that can be used to make compositions consisting of three, four, five, six or more elements, an incredibly large number of possible new compounds remains largely unexplored. As such, there exists a need in the art for a more efficient, economical and systematic approach for the synthesis of novel materials and for the screening of such materials for useful properties.
One of the processes whereby nature produces molecules having novel functions involves the generation of large collections (libraries) of molecules and the systematic screening of those collections for molecules having a desired property. An example of such a process is the humoral immune system which in a matter of weeks sorts through some 10
12
antibody molecules to find one which specifically binds a foreign pathogen (Nisonoff et al.,
The Antibody Molecule
(Academic Press, New York, 1975)). This notion of generating and screening large libraries of molecules has recently been applied to the drug discovery process.
Using this logic, methods have been developed for the synthesis and screening of large libraries of up to 10
14
molecules of peptides, oligonucleotides and other small molecules. Geysen et al., for example, have developed a method wherein peptide syntheses are carried out in parallel on several rods or pins (
J. Immun. Meth
. 102:259-274 (1987), incorporated herein by reference for all purposes). Generally, the Geysen et al. method involves functionalizing the termini of polymeric rods and sequentially immersing the termini in solutions of individual amino acids. In addition to the Geysen et al. method, techniques have recently been introduced for synthesizing large arrays of different peptides and other polymers on solid surfaces. Pirrung et al. have developed a technique for generating arrays of peptides and other molecules using, for example, light-directed, spatially-addressable synthesis techniques (U.S. Pat. No. 5,143,854 and PCT Publication No. WO 90/15070, incorporated herein by reference for all purposes). In addition, Fodor et al. have developed, among other things, a method of gathering fluorescence intensity data, various photosensitive protecting groups, masking techniques, and automated techniques for performing light-directed, spatially-addressable synthesis techniques (Fodor et al., PCT Publication No. WO 92/10092, the teachings of which are incorporated herein by reference for all purposes).
Using these various methods, arrays containing thousands or millions of different elements can be formed (U.S. patent application Ser. No. 08/805,727, filed Dec. 6, 1991, the complete disclosure of which is incorporated herein by reference for all purposes). As a result of their relationship to semiconductor fabrication techniques, these methods have come to be referred to as “Very Large Scale Immobilized Polymer Synthesis,” or “VLSIPS™” technology. Such techniques have met with substantial success in screening various ligands such as peptides and oligonucleotides to determine their relative binding affinity to a receptor such as an antibody.
The solid phase synthesis techniques currently being used to prepare such libraries involve the sequential coupling of building blocks to form the compounds of interest. For example, in the Pirrung et al. method polypeptide arrays are synthesized on a substrate by attaching photo-removable groups to the surface of the substrate, exposing selected regions of the substrate to light to activate those regions, attaching an amino acid monomer with a photo-removable group to the activated region, and repeating the steps of activation and attachment until polypeptides of the desired length and sequence are synthesized. These solid phase synthesis techniques cannot readily be used to prepare many inorganic and organic compounds.
In PCT WO 96/11878, the complete disclosure of which is incorporated herein by reference, methods and apparatus are disclosed for preparing a substrate with an array of diverse materials deposited in predefined regions. Some of the methods of deposition disclosed in PCT WO 96/11878 include sputtering, ablation, evaporation, and liquid dispensing systems. Using the disclosed methodology, many classes of materials can be generated combinatorially including inorganics, intermetallics, metal alloys, and ceramics.
In order to provide an efficient approach to synthesizing and screening new materials, a method of forming arrays of materials with varying chemical composition, concentration, stoichiometry and thickness at known locations on a substrate is desirable.
SUMMARY OF THE INVENTION
The present invention provides methods and apparatus for depositing various components onto a substrate to form an array of diverse materials, the materials being deposited in predefined regions. In particular, the present invention provides potential masking methods and systems which generate spatially varying electric, magnetic and/or chemical potentials across a substrate. These spatially varying potentials are used to deposit patterned combinatorial libraries in which the individual materials vary in chemical composition, concentration, stoichiometry, and/or thickness.
Once an array is prepared, a variety of characterization techniques may be used to rapidly screen and/or characterize the large number of materials contained on the array. A few of the material properties which may be easily investigated using this system include conductivity, super-conductivity, resistivity, thermal conductivity, anisotropy, hardness, crystallinity, optical transparency, magnetoresistance, permeability, frequency doubling, photoemission, coercivity, and dielectric strength. As a result of this rapid screening process, new compositions with new physical properties can be quickly identified. Once identified, a variety of well known methods can be used to prepare the materials on a larger scale.
Systems of the present invention comprise one or more source materials and a potential assembly for applying a spatially varying potential across a substrate, thus enabling components of the source materials to be deposited at spatially addressable locations on the substrate. The components may be deposited either in discrete arrays or in continuously varying patterns. Although the present invention potentially has the ability to create any number of different materials on a single array, typically an array will contain more than 9 different materials. Typically the array will contain at least 50 different materials, although for specific applications the array may contain more than 100 different materials, more than 10
3
different material
Danielson Earl
Devenney Martin
McFarland Eric
Warren Christopher J.
Dobrusin & Thennisch PC
Ponnaluri Padmashri
Symyx Technologies Inc.
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