Glass manufacturing – Processes – Fusion bonding of glass to a formed part
Reexamination Certificate
1999-03-01
2001-03-06
Vincent, Sean (Department: 1731)
Glass manufacturing
Processes
Fusion bonding of glass to a formed part
C065S067000, C065S097000
Reexamination Certificate
active
06196026
ABSTRACT:
FIELD OF INVENTION
The invention relates to a glass multiple well assay plate for applications in biological or chemical assays.
BACKGROUND OF INVENTION
The relationship between structure and function of molecules is a fundamental issue in the study of biological and other chemical based systems. Structure-function relationships are important in understanding, for example, the function of enzymes, cellular communication, and cellular control and feedback mechanisms. Certain macromolecules are known to interact and bind to other molecules having a specific three-dimensional spacial and electronic distribution. Any macromolecule having such specificity can be considered a receptor, whether the macromolecule is an enzyme, a protein, a glycoprotein, an antibody, an oligonucleotide sequence of DNA, RNA or the like. The various molecules to which receptors bind are known as ligands.
Pharmaceutical drug discovery is one type of research that relies on the study of structure-function relationships. Much contemporary drug discovery involves discovering novel ligands with desirable patterns of specificity for biologically important receptors. Thus, the time to bring new drugs to market could be greatly reduced through the use of methods and apparatus which allow rapid generation and screening of large numbers of ligands.
A common way to generate such ligands is to synthesize libraries of ligands on solid phase resins. Since the introduction of solid phase synthesis methods for peptides, oligonucleotides, and other polynucleotides, new methods employing solid phase strategies have been developed that are capable of generating thousands, and in some cases millions of individual peptide or nucleic acid polymers using automated or manual techniques. These synthesis strategies, which generate families or libraries of compounds are generally referred to as “combinatorial chemistry” or “combinatorial synthesis” strategies.
The current storage format for compound libraries is a 96 well format well plate typically made from polypropylene and having rubber stopper sheets or hot seal covers. Certain processes and chemistries require that chemical reagents (which may be reactants, solvents, or reactants dissolved in solvents) be kept under inert or anhydrous conditions to prevent reactive groups from reacting with molecular oxygen, water vapor, or other agents. Examples of moisture sensitive chemistries include peptide chemistry, nucleic acid chemistry, organometallic, heterocyclic, and chemistries commonly used to construct combinatorial chemistry libraries. The solvent used for storage of synthesized chemicals is typically dimethylsulfoxide (DMSO).
Storage plates made from polymers have the disadvantage of being incapable of withstanding the extreme temperature variations that are sometimes required in combinatorial chemistry reactions and storage (between −20° and 370° C.).
Creating a multiwell plate from glass is a solution to this and other problems that are inherent in using polymers, such as sample interaction with the base polymer making up the plate. Glass, however cannot be injection molded and it is extremely difficult to press a gob of glass into a 96 well plate mold. One method currently used in producing a multiwell plate from glass involves a boring process. In this process, slabs of borosilicate glass conforming to the industry standard 96 well plate footprint are machined such that 96 individual wells are bored into the slab. This approach however is extremely costly.
Another method of making glass well plates involves vacuum thermoforming. By this method, small plates are produced from glass by vacuum thermoforming a thin glass sheet, as described in commonly assigned French Patent application
96-13530
. This technique offers well volumes of anywhere from 200 &mgr;ml to 0.1 &mgr;ml volume capacity per well. While these volumes may be convenient for high-throughput screening bioassay applications aimed at sample and reagent conservation, they are probably too small for chemical synthesis in organic solvent, the storage of drugs or drug candidates in organic solvent or long term storage where closure is required.
The potential for using sealable multiwell plates made of glass extend beyond use as a storage device for combinatorial chemistry. Glass multiwell plates may also be used for such tasks as: interfacing with instruments, extraction, derivatization, synthesis, and more.
SUMMARY OF INVENTION
It is therefore an object of the present invention to provide a multiwell plate that can be manufactured from glass in a cost effective way. Further, it is an object to provide a method of making a glass multiwell plate that can produce varied and unique well designs. It is another object to provide a glass multiwell plate having wells that can be sealed from the external environment, for example by means of a septa. It is yet another object of the present invention to provide a multiwell plate that can withstand great variations in temperature.
The present invention relates to a method of making a glass multiwell plate for use in biological and chemical assays, experimentation and storage. The method comprises the steps of: delivering and depositing a first length of a molten glass ribbon to a surface of a mold having a mold cavity possessing at least one well-forming depression and a peripheral surface, wherein the first length of ribbon overlies the mold cavity and the peripheral surface; causing the first length of ribbon to substantially conform to the contour of the mold cavity thereby forming at least one well in the first length; delivering and depositing a second length of the molten glass ribbon to the exposed surface of the earlier deposited first length of molten glass ribbon; and, puncturing a hole through the second length and over the approximate center of at least one well thereby forming a series of self contained wells that may be accessed through the hole in the second length.
The glass multiwell plate of the present invention comprises a substantially rectangular plate having a peripheral skirt and formed by a uniform sheet of glass having therein a plurality of wells, each well having sidewalls, a bottom and a top surface, the top surface defining a hole capable of being hermetically sealed by a sealing means such as a multi-plugged rubber mat.
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Anderson James G.
Dannoux Thierry L. A.
Beall Thomas R.
Corning Incorporated
Vincent Sean
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