Electrolysis: processes – compositions used therein – and methods – Electrolytic analysis or testing – Involving enzyme or micro-organism
Reexamination Certificate
2000-03-10
2001-08-28
Bell, Bruce F. (Department: 1741)
Electrolysis: processes, compositions used therein, and methods
Electrolytic analysis or testing
Involving enzyme or micro-organism
C205S778000, C205S781000, C205S792000, C205S793000, C204S403060, C204S415000, C204S291000, C600S309000, C600S345000, C600S353000
Reexamination Certificate
active
06280604
ABSTRACT:
FIELD OF THE INVENTION
The present invention generally relates to the field of electrochemical detection of nitric oxide and, in preferred embodiments, includes materials for constructing electrodes, microelectrodes, and ultramicroelectrodes (all hereinafter referred to as “electrodes”) that exhibit an increased response to nitric oxide after a period of electrochemical conditioning and that chemically increase the concentration of nitric oxide available for detection at the electrode surface and/or catalytically increase the rate constant for the electrolysis of nitric oxide.
In addition, the present invention relates to nitric oxide detector systems that incorporate said nitric oxide electrodes, as well as to the methods herein described for using such detector systems. These systems and methods may be employed usefully to detect nitric oxide in any biological or non-biological liquid sample and/or in any biological system (e.g., near or within a whole organism, tissue, group of cells, individual cell, sub-cellular component, or in any fluid within, bathing or withdrawn from an organism).
BACKGROUND OF THE INVENTION
Nitric oxide (NO.) is a short-lived, free radical gas that has recently been shown to play a fundamental role in biological processes, resulting in a demand for accurate and precise techniques for its detection.
Methods for detecting nitric oxide in biology and medicine include spectrophotometry, chemiluminescence, and paramagnetic resonance. But these techniques generally do not permit rapid measurement at the site of NO. production and therefore are not ideal for following the brief course of production and decay that characterizes the metabolism of nitric oxide in biological samples or systems. Electrochemical detection, however, can follow such transient processes, and several electrodes have been developed for the direct electrochemical detection of nitric oxide.
Recently issued U.S. Pat. No. 5,980,705 (incorporated by reference hereinto) discloses certain novel electrodes and methods for detecting nitric oxide. In general, such electrodes have a surface region formed of a metal which complexes with nitric oxide when exposed to a nitric oxide-containing fluid and exhibit maximal nitric oxide response after being electrochemically conditioned.
SUMMARY OF THE INVENTION
Broadly, the present invention relates to electrodes constructed from materials that exhibit an enhanced response to nitric oxide (after conditioning according to the above-cited U.S. Pat. No. 5,980,705 and/or conditioning and pre-conditioning as described herein) and that may also meet one or more of the following four criteria: 1. form electrically-conducting or electrically-semiconducting oxides (see Example I); 2. exhibit an enhanced response to nitric oxide in the presence of chloride (see Example II); 3. exhibit an enhanced response to nitric oxide after a period of electrochemical pre-conditioning followed by conditioning (see Example III); 4. permit indirect detection of nitric oxide (see Example IV).
The present invention also relates to detector systems that employ, as one or more of their components, the novel nitric oxide electrodes of this invention (see Example V). The detector systems of this invention may usefully detect in vivo, in humans or animals, normal processes or pathological conditions that result in an increase or decrease in nitric oxide production, such as, for example, bacteremia, septicemia, autoimmune diseases, stroke, heart attack, tissue injury, surgical trauma, and vascular penetration (see Example VI).
Most preferably, the electrodes of this invention may be prepared from ruthenium, or have a coating prepared from ruthenium on a core of supporting material. The ruthenium may be combined with one or more other materials as may be desired. Alternatively, electrodes of this invention may be prepared from materials or mixtures of materials other than ruthenium, such that the resulting electrodes exhibit an enhanced response to nitric oxide and also meet one or more of the four criteria listed above. Such materials, in principle, include all metals, metaloids, and non-metals, but most particularly the six metals of the so-called platinum group (elements having atomic numbers 44-46 and 76-78) and the transition group metals, as well as metals, metaloids, and non-metals capable of forming electrically-conducting or electrically-semiconducting oxides, including oxides discussed in Tsuda, N. et al., (1990)
Electronic Conduction in Oxides
. Berlin: Springer-Verlag, the entire content of which is expressly incorporated hereinto by reference.
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Incorporation of Anionic Metalloprorphyrins Into Poly(Pyrrole-Alkylammonium) Films—Part 2. Characterization of the Reactivity of The Iron(III) Porphyrininc-Based Polymer; Fethi Bedioui, Yves Bouhier, Chistian Sorel, Jacques Devynck, Liliane Coche-Guerente, Alain Deronzier and Jean Claude Moutet; Laboratoire d'Electrochimie Analytique et Appliquée (U.R.A. No. 216 du C.N.R.S.), Ecole Nationale Supérieure de chimie de Paris, 11 Rue
Allen Barry W.
Coury Louis A.
Piantadosi Claude A.
Bell Bruce F.
Duke University
Nixon & Vanderhye P.C.
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