Device and methods of using device for detection of hyperammonemia

• US 10,620,187 B2
• Filed: 03/23/2018
• Issued: 04/14/2020
• Est. Priority Date: 08/30/2013
• Status: Active Grant

• Current Assignee: Children's National Medical Center, United States Department Of Health And Human Services, University of Maryland, College Park
• Original Assignee: University of Maryland, College Park
• Inventors: Ayyub, Omar Bilal, Behrens, Adam Michael, Kofinas, Peter, Summar, Marshall Lynn, Cabrera-Luque, Juan Manuel, Cunningham, Gary, Simeonov, Anton, Marugan, Juan
• Primary Examiner(s): Kosson, Rosanne
• Application Number:
  US15/933,834
• Publication Number:
  US 20180284099A1
• Time in Patent Office: 753 Days
• CPC Class Codes: G01N 21/78 producing a change of colour
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• CPC Class Codes: G01N 27/3275 Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
• CPC Class Codes: G01N 2800/04 Endocrine or metabolic disorders
• CPC Class Codes: G01N 33/4925 measuring blood gas content, e.g. O2, CO2 , HCO3
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH

Abstract

The present disclosure relates to a biosensor capable of measuring the total concentration of one or a plurality of ammonia or ammonium ions with the use of indophenol reagents in the presence of an ionomer. In some embodiments, the biosensor comprises a perfluorinated membrane that comprises an ionomer in contact with an alkali buffer in a vessel configured to receive a sample, such as whole blood. The disclosure also relates to a method of detecting or quantifying the ammonia or ammonium ion concentration in whole blood in a point of care bio sensor without reliance on gas chromatography or any measurement that takes more than about twenty minutes.

Claims

1. A method of quantifying a concentration of ammonia or ammonium ion in a sample comprising contacting a sample of bodily fluid to a biosensor, wherein the biosensor comprises:

(i) at least a first and second vessel;

(ii) a fluid exchange opening positioned between the first and the second vessel;

(iii) at least one conduit in fluid communication with the at least first vessel, the at least one conduit configured to receive a fluid from a point external to the biosensor; and

(iv) a membrane positioned at the fluid exchange opening;

wherein the membrane comprises an ionomer;

wherein the at least one conduit is configured to hold a sample volume from about 5 μ

l to about 100 μ

l; and

wherein the first vessel or the second vessel comprises, individually or in combination;

a hypohalite, an alkali buffer, and at least one phenolic reagent or indophenol related compound;

wherein the sample is in contact with the biosensor for a sufficient period of time to allow modification of the phenolic reagent or indophenol related compound to become modified into a phenolic or indophenol reaction product.

2. The method of claim 1, wherein the method does not comprise exposing the sample of bodily fluid to any external stimuli or reagent prior to contacting the sample to the biosensor.

3. The method of claim 1, wherein the sample of bodily fluid is whole blood from a subject.

4. The method of claim 1, further comprising comparing a concentration value obtained by the contacting step to a threshold value associated with one or more metabolic diseases.

5. The method of claim 4, wherein the metabolic disease is hyperammonemia.