Method of fabricating a support with dry deposited compounds...

Coating processes – Direct application of electrical – magnetic – wave – or... – Electrostatic charge – field – or force utilized

Reexamination Certificate

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C427S475000, C427S485000

Reexamination Certificate

active

06368674

ABSTRACT:

The present invention relates to methods of reliably and reproducibly depositing reagents for conducting a chemical process onto a solid support, where in certain embodiments the reagents can be arrayed in a patterned array on the solid support, and to solid supports thereby produced. Further provided are controlled release packets, which can be arrayed on a solid support, for delaying or controlling the time after exposure of the containers to a liquid that it takes for the contents of the packets to dissolve. The methods of the invention use electrostatics and electrical fields to produce the supports and controlled release packets.
In conducting a variety of clinical, forensic, environmental, research, quality control and other assays or chemical processes, it is often desirable to conduct a variety of parallel reactions or processes, for example to accommodate a number of experimental samples and to accommodate control reactions. Each of these reactions or chemical processes typically needs a setup of the same reagents. Those who have worked in a clinical or other science laboratory will recognize that one of the most labor-intensive chores involves setting up an assay. This chore is also one of the prime suspects for a source of variability in an assay. Recognizing this, Eastman-Kodak developed clinical analyzers that take setup reagents from films produced by emulsion technology similar to that used to manufacture photographic films. These analyzers are now marketed by Johnson & Johnson Clinical Diagnostics (Raritan, N.J. and Rochester, N.Y.) as the Vitros brand analyzers. Emulsion technology is complex in its execution, and cannot readily form films with reagents that are not sufficiently stable or soluble in the wet emulsions used to produce the films. Further, this technology is limited to applying reagents to films and is not well suited to applying reagents in a pattern at separate locations on a support.
The present invention provides solid supports on which reagents for chemical processes are applied with a high degree of accuracy and reproducibility using electrostatic or controlled field deposition. Those reagents that are unstable in a solution can be deposited (a) as a dry powder, (b) by use of a limited exposure to a wet toner vehicle, or (c) by selection of a wet toner vehicle in which the reagents are more stable. In any of these cases, the reagents are stored in a non-liquid (“dry”) form layered on the solid support. These deposition processes allow two reagents which typically react or are otherwise incompatible with one another to be stored on the same support. For example, where the reagents do not have significant vapor pressures they can be deposited in the same layer while avoiding prolonged exposure to a reaction-promoting solution form. Alternatively, multiple layers which can include separating layers can be applied so as to minimize the exposure of the two reagents to one another.
Further provided are packets for reagents or other compounds, which reagents or other compounds are coated or admixed by controlled release layers. In one use, these reagents or other compounds can be released from the packets and into a liquid after other compounds have been dissolved. Thus, for example, a second antibody and detection reagents can be released only after time and reagents have been provided for supporting a binding reaction with a first antibody. Or in another example, reagents are delayed from dissolving into an assay until sufficient time has passed to allow experimental or control samples to be added to all of the reaction vessels.
SUMMARY OF THE INVENTION
In one embodiment, the invention provides a solid support having dry deposited thereon a first solid layer comprising at least a first compound, the compound for use in a chemical process conducted in a first solution. The invention allows stable forms where the first compound is not stable either (i) for storage in the first solution or (ii) in solution with one or more other compounds of the first layer.
In a second embodiment, the invention provides a tray or kit of wells adapted for conducting a chemical process, at least one well (and preferably two or more or all) has deposited thereon a first solid layer comprising one or more compounds for supporting a chemical process conducted in a first solution, wherein addition of the first liquid to each of the wells dissolves said one or more compounds.
The invention further provides a method of fabricating a solid support having deposited thereon a first solid layer comprising at least a first compound, the compound for use in a chemical process conducted in a first solution, comprising
creating an electromagnetic force for attracting particles having a first charge to a surface of the solid support, and
contacting the surface with the charged particles which comprise the material of the first layer.
The method can comprise: (1) in a first process, creating the electromagnetic force by directing ions of a second polarity opposite the first to the surface to create charges of the second polarity at the surface; or (2) in a second process, creating the electromagnetic force by generating an electrical field at a surface of the solid support. In these methods, the amount of material deposited can be monitored for instance by monitoring depositions onto a sensing electrode or monitoring the optical density or fluorescence or the deposited material, and when a target amount of deposition has occurred removing the electric field or removing non-adherent charged particles.
In a further embodiment, the invention provides a solid support having deposited thereon a first compound and a time-release composition, wherein upon exposure of the solid support to a first liquid in which the first compound is soluble the dissolution of the first compound is delayed by the presence of the time-release layer. A layer of material added over the time-release composition can include a second compound that is dissolved more quickly than the first compound.
In still another embodiment, the invention provides a method of conducting a chemical process in wells of a tray, wherein one or more of the wells is designated to receive a sample which can be dissolved in the first liquid, the method comprising
(i) providing the wells, which have deposited therein a time-release composition that comprises delayed-release reaction reagents that are soluble in the first liquid,
(ii) adding first liquid to all of the wells, and
(iii) adding, for example concurrently with step (ii) or thereafter, sample to the designated wells such that each designated well receives sample prior to a designated time period after addition of the first liquid to the well,
wherein the time-release composition assures that the delayed-release reaction reagents are substantially delayed from dissolving in the first liquid until after the designated time period.
Alternatively, the method can comprise
(a) providing the wells, wherein the time-release composition comprises reaction reagents that are soluble in the first liquid, and wherein the surface is further coated with a layer comprising early-release reaction reagents that are soluble in the first liquid, and
(b) adding first liquid to all of the wells and adding to sample to the designated wells,
wherein the time-release composition assures conditions for a first reaction process are first supported by a dissolution of the early-release reaction reagents and subsequently a dissolution of the delayed-release reaction reagents assures conditions for a second reaction process.
In another embodiment, the invention provides a solid support comprising on a surface thereof a non-overlapping pattern of first solid layers each comprising a first compound for use in a chemical process conducted in a solution or in vapor phase.


REFERENCES:
patent: 2933414 (1960-04-01), Beck
patent: 3754975 (1973-08-01), Spiller
patent: 3797739 (1974-03-01), Cowan
patent: 4072129 (1978-02-01), Bright et al.
patent: 4088093 (1978-05-01), Pan
patent: 4160257 (1979-07-01), Carrish
pat

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