Chemistry: analytical and immunological testing – Heterocyclic carbon compound – Hetero-o
Reexamination Certificate
2001-08-03
2004-09-21
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Heterocyclic carbon compound
Hetero-o
C436S094000, C436S073000, C436S081000, C436S172000, C548S110000, C534S015000
Reexamination Certificate
active
06794195
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to indicator molecules for detecting the presence or concentration of an analyte in a medium, such as a liquid, and to methods for achieving such detection. More particularly, the invention relates to copolymer macromolecules containing relatively hydrophobic indicator component monomers, and hydrophilic monomers, such that the macromolecule is capable of use in an aqueous environment.
2. Description of the Related Art
Indicator molecules for detecting the presence or concentration of an analyte in a medium are known. Unfortunately, many of such indicators are insoluble or sparingly soluble in water. For example, U.S. Pat. No. 5,503,770 (James, et al.) describes a fluorescent boronic acid-containing compound that emits fluorescence of a high intensity upon binding to saccharides, including glucose. The fluorescent compound has a molecular structure comprising a fluorophore, at least one phenylboronic acid moiety and at least one amine-providing nitrogen atom where the nitrogen atom is disposed in the vicinity of the phenylboronic acid moiety so as to interact intramolecularly with the boronic acid. Such interaction thereby causes the compound to emit fluorescence upon saccharide binding. See also T. James, et al.,
J. Am. Chem. Soc.
117(35):8982-87 (1995). However, the compound described in example 2 of U.S. Pat. No. 5,503,770 (having formula (6)) is substantially insoluble in water, and as a practical matter requires the presence of an organic solvent such as methanol in order to work in a liquid environment.
Lack of sufficient aqueous solubility is a severe problem when dealing with applications in an aqueous environment, for example, in vivo applications. Thus, there remains a great need for adapting insoluble or sparingly soluble indicators for use in aqueous environments.
BRIEF SUMMARY OF THE INVENTION
In one aspect, the present invention is directed to an indicator macromolecule for detecting the presence or concentration of an analyte in an aqueous environment, said macromolecule comprising a copolymer of:
a) one or more indicator component monomers which individually are not sufficiently water soluble to permit their use in an aqueous environment for detecting the presence or concentration of said analyte; and
b) one or more hydrophilic monomers;
such that the macromolecule is capable of detecting the presence or concentration of said analyte in an aqueous environment.
In another aspect, the present invention is directed to a method for the production of an indicator macromolecule for detecting the presence or concentration of an analyte in an aqueous environment, said method comprising copolymerizing:
a) one or more indicator component monomers which individually are not sufficiently water soluble to permit their use in an aqueous environment for detecting the presence or concentration of said analyte; and
b) one or more hydrophilic monomers;
such that the resulting macromolecule is capable of detecting the presence or concentration of said analyte in an aqueous environment.
In another aspect, the present invention is directed to a method for detecting the presence or concentration of an analyte in a sample having an aqueous environment, said method comprising:
a) exposing the sample to an indicator macromolecule, said macromolecule comprising a copolymer of:
i) one or more indicator component monomers which individually are not sufficiently water soluble to permit their use in an aqueous environment for detecting the presence or concentration of said analyte; and
ii) one or more hydrophilic monomers;
such that the resulting macromolecule is capable of detecting the presence or concentration of said analyte in an aqueous environment, and wherein the indicator macromolecule has a detectable quality that changes in a concentration-dependent manner when said macromolecule is exposed to said analyte; and
b) measuring any change in said detectable quality to thereby determine the presence or concentration of said analyte in said sample.
In another aspect, the present invention provides a macromolecule which is capable of exhibiting an excimer effect, which comprises a copolymer of:
a) one or more excimer forming monomers, the molecular constituents of which are capable of exhibiting an excimer effect when suitably oriented with respect to each other; and
b) one or more other monomers;
such that the resulting macromolecule exhibits said excimer effect.
In yet another aspect, the present invention provides a method for producing a macromolecule which is capable of exhibiting an excimer effect, which method comprises copolymerizing:
a) one or more excimer forming monomers, the molecular constituents of which are capable of exhibiting an excimer effect when suitably oriented with respect to each other; and
b) one or more other monomers;
such that the resulting macromolecule exhibits said excimer effect.
In yet another aspect, the present invention provides a method for detecting the presence or concentration of an analyte in a sample, said method comprising:
a) exposing the sample to an indicator macromolecule, said macromolecule comprising a copolymer of:
i) one or more indicator component monomers, the molecules of which are capable of exhibiting an excimer effect when suitably oriented with respect to each other, and which are also capable of detecting the presence or concentration of an analyte; and
ii) one or more other monomers;
such that the resulting macromolecule exhibits said excimer effect, and wherein the indicator macromolecule has a detectable quality that changes in a concentration-dependent manner when said macromolecule is exposed to said analyte; and
b) measuring any change in said detectable quality to thereby determine the presence or concentration of said analyte in said sample.
REFERENCES:
patent: 6002954 (1999-12-01), Van Antwerp et al.
patent: 6011984 (2000-01-01), Van Antwerp et al.
patent: 6344360 (2002-02-01), Colvin et al.
Appleton, B. et al., “Detection of Total Sugar Concentration Using Photoinduced Electron Transfer Materials: Development of Operationally Stable, Reusable Optical Errors”,Sensors and Actuators, 2000, pp. 302-304.
Aoki, T. et al., “Effect of Phenylboronic Acid Groups in Copolymers on Endothelial Cell Differentiation into Capillary Structures”,J. Biomater. Sci. Polymer Edn, 1997, vol. 9., No. 1, pp. 1-14.
Burgemeister, T., et al., “Fast Thermal Breaking and Formation of a B-N Bond in 2-(Aminomethyl)benzeneboronates,”Chem. Ber., 1981, vol. 114, pp. 3403-3411.
Hisamitsu, I. et al., “Glucose-Responsive Gel from Phenylborate Polymer and Poly(Vinyl Alcohol): Prompt Response at Physiological pH Through the Interaction of Borate with Amino Group in the Gel”,Phamaceutical Research, 1997, vol. 14, No. 3, pp. 289-293.
Kataoka, K. et al., “Novel Sensing System for Glucose Based on the Complex Formation Between Phenylborate and Fluorescent Diol Compounds”,J. Biochem., 1995, vol. 117, pp. 1145-1147.
Kataoka, K. et al., “Totally Synthetic Polymer Gels Responding to External Glucose Concentration: Their Preparation and Application to On-Off Regulation of Insulin Release”,J. Am. Chem. Soc., 1998, vol. 120, pp. 12694-12695.
Kitano, S., et al., “Glucose-Responsive Complex Formation Between Poly(vinyl alcohol) and Poly(N-vinyl-2-pyrrolidone) with Pendent Phenylboronic Acid Moieties”,Makromol. Chem. Rapid Commun., 1991, vol. 12, pp. 227-233.
Kikuchi, A., et al., “Glucose-Sensing Electrode Coated with Polymer Complex Gel Containing Phenylboronic Acid”,Anal. Chem., 1996, vol. 68, pp. 823-828.
Peterson, J. et al., “Fiber Optic pH Probe for Physiological Use”,Anal. Chem., 1980, vol. 52, pp. 864-869.
Sandanayake, K., et al., “Two Dimensional Photoinduced Electron Transfer (PET) Fluorescence Sensor for Saccharides”,Chemistry Letters, 1995, pp. 503-504.
Shino, D., et al., “Amine Effect on Phenylboronic Acid Complex with Glucose Under Physiological pH in Aqueous Solution”,J. Biomater. Sci. Polymer Edn., 1996, vol. 7, No. 8, pp. 697-705.
Soundararajan, S., et al., “Boronic Acids fo
Cole Monique T.
Moran Michael J.
Rothwell Figg Ernst & Manbeck
Sensors for Medicine & Science, Inc.
Warden Jill
LandOfFree
Detection of analytes in aqueous environments does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Detection of analytes in aqueous environments, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Detection of analytes in aqueous environments will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3237696