Condensate Glucose Analyzer

Abstract

Systems and methods for analyzing glucose present in exhaled breath condensate (EBC). In certain embodiments, electrochemical- or coulometnc-based sensing technologies are used to analyze EBC for the presence and/or concentration of glucose. Based on the detected glucose m EBC, the subject invention provides systems and methods for non-invasive, accurate assessment of blood glucose levels.

1 - 26 . (canceled) 
     
     
         27 . An apparatus for monitoring blood glucose concentration and fluctuations therein in a living, breathing subject which comprises:
 a. a breath collection reservoir for collecting at least one breath or breath component from said living, breathing subject, said breath collection reservoir comprising or connected to a breath condensate collection reservoir;   b. said breath condensate collection reservoir comprising or connected to at least one sensor such that breath condensate from said at least one breath or breath component contacts said at least one sensor;   c. said at least one sensor comprising a means for measuring the concentration of glucose and of at least one dilutional indicator when contacted with breath condensate collected in said breath condensate collection reservoir;   d. said at least one sensor being operatively connected to at least one processor to which said sensor transmits signals representative of the sensed concentration of glucose and of said dilutional indicator in collected breath condensate in contact with said at least one sensor;   e. said processor, on receiving said at least one signal from said at least one sensor, calculating the blood concentration of glucose by dividing the measured glucose concentration in said breath condensate by the dilutional indicator concentration in said breath condensate and multiplying by a number which represents the concentration of said dilutional indicator in blood.   
     
     
         28 . The apparatus of  claim 27  wherein at least one or a combination of the following applies:
 a. the apparatus is non-invasive, portable, or both;   b. the breath collection reservoir comprises a means for extracting condensate from said at least one breath or breath component;   c. the breath collection reservoir is comprised within at least one breathing tube;   d. the at least one sensor comprises a hydrophilic hydrogel comprising at least one glucose-binding molecule selected from the group consisting of: antibodies, enzymes, oligonucleotides, peptides, or proteins;   e. the at least one sensor comprises one sensor for measuring glucose concentration in said breath condensate and another sensor for measuring the dilutional indicator concentration in said breath condensate;   f. the at least one sensor comprises microgravimetric sensor technology, electrochemical sensor technology, gas chromatography/mass spectrometry sensor technology, infrared spectroscopy sensor technology, ion mobility spectrometry sensor technology, thickness-shear mode sensor technology, photo-ionization sensor technology, amplifying fluorescent polymer sensor technology, fiber optic microsphere sensor technology, interdigitated microelectrode array sensor technology, microelectromechanical sensor technology, semiconductor gas sensor technology, conductive polymer gas sensor technology, surface acoustic wave gas sensor technology, and high electron mobility transistor-based sensor technology, linear flow sensor technology or combinations thereof;   e. the processor is operatively connected to an indicator means such that when said calculating is completed the output of said calculating is transmitted to said indicator which provides an indication of said blood glucose concentration of said subject from whom said at least one breath or breath component is collected;   f. the processor adjusts, by appropriate factors, for conversion of all units of measure such that the output of said calculating is provided by said processor in desired units of blood glucose concentration.   
     
     
         29 . The apparatus according to  claim 28  wherein at least one or a combination of the following applies:
 a. the breath component that is collected is the end tidal breath;   b. the glucose-binding molecule is selected from the group consisting of glucose-oxidase, glucose dehydrogenase, and glucose hexokinase or from glucose-6 phosphate dehydrogenase or hexokinase;   c. the means for extracting condensate from said breath or breath component comprises a Peltier device, which surrounds the collection reservoir or is otherwise in sufficient contact to achieve control over the temperature of said collection reservoir;   d. the means for extracting condensate from said breath or breath component extracts condensate by cooling said at least one exhaled breath sample or component thereof to a temperature below body temperature;   e. the dilutional indicator is a blood component which is tightly regulated in blood of the subject and which is present in said subject in substantially identical concentration in airway lining fluid and in blood.   
     
     
         30 . The apparatus according to  claim 29  wherein at least one or a combination of the following applies:
 a. the temperature below body temperature is a temperature selected from the group consisting of between 10 to 15 degrees Centigrade below body temperature or is a temperature between 20.6 degrees centigrade and −17.8 degrees centigrade;   b. the dilutional indicator is selected from chloride, sodium, potassium, urea, and combinations thereof;   c. the airway lining fluid from which said at least one exhaled breath or component thereof is comprised predominantly from alveolar lining fluid, fluid from capillary endothelial cells, and combinations thereof;   d. the data resulting from analysis of the sample of the patient's breath is recorded, transmitted or both;   e. the glucose concentration in the sample of the patient's breath is compared with a predetermined standard glucose concentration, wherein the predetermined standard glucose concentration is associated with a healthy patient;   f. the glucose concentration is determined to be abnormal;   g. the glucose concentration is communicated to the subject.   
     
     
         31 . The apparatus according to  claim 27  wherein:
 a. the apparatus is non-invasive, portable, or both;   b. the breath collection reservoir comprises a means for extracting condensate from said at least one breath or breath component;   c. the breath or breath component is end-tidal breath;   d. the at least one sensor comprises one sensor for measuring glucose concentration in said breath condensate and another sensor for measuring the dilutional indicator concentration in said breath condensate;   e. the at least one sensor comprises a hydrophilic hydrogel comprising at least one glucose-binding molecule selected from the group consisting of: antibodies, enzymes, oligonucleotides, peptides, or proteins, or wherein the at least one sensor comprises microgravimetric sensor technology, electrochemical sensor technology, gas chromatography/mass spectrometry sensor technology, infrared spectroscopy sensor technology, ion mobility spectrometry sensor technology, thickness-shear mode sensor technology, photo-ionization sensor technology, amplifying fluorescent polymer sensor technology, fiber optic microsphere sensor technology, interdigitated microelectrode array sensor technology, microelectromechanical sensor technology, semiconductor gas sensor technology, conductive polymer gas sensor technology, surface acoustic wave gas sensor technology, and high electron mobility transistor-based sensor technology, linear flow sensor technology or combinations thereof; and   f. the processor is operatively connected to an indicator means such that when said calculating is completed the output of said calculating is transmitted to said indicator which provides an indication of said blood glucose concentration of said subject from whom said at least one breath or breath component is collected;   
     
     
         32 . The apparatus according to  claim 31  wherein:
 a. the glucose-binding molecule is selected from the group consisting of glucose-oxidase, glucose dehydrogenase, and glucose hexokinase;   b. the means for extracting condensate from said breath or breath component comprises a Peltier device, which surrounds the collection reservoir or is otherwise in sufficient contact to achieve control over the temperature of said collection reservoir;   c. the means for extracting condensate from said breath or breath component extracts condensate by cooling said at least one exhaled breath sample or component thereof to a temperature below body temperature; and   d. the dilutional indicator is a blood component which is tightly regulated in blood of the subject and which is present in said subject in substantially identical concentration in airway lining fluid and in blood.   
     
     
         33 . The apparatus according to  claim 32  wherein:
 a. the temperature below body temperature is a temperature selected from the group consisting of between 10 to 15 degrees Centigrade below body temperature or is a temperature between 20.6 degrees centigrade and −17.8 degrees centigrade;   b. the dilutional indicator is selected from chloride, sodium, potassium, and combinations thereof; and   c. the airway lining fluid from which said at least one exhaled breath or component thereof is comprised predominantly from alveolar lining fluid, fluid from capillary endothelial cells, and combinations thereof.   
     
     
         34 . A non-invasive, portable glucose monitoring device according to  claim 27  comprising:
 a) at least one collection reservoir for collecting at least one exhaled breath sample, wherein said collection reservoir comprises a sensor and a signaling means, said sensor, said signaling means or both either comprising or being in operative communication with at least one processor; and   b) a means for extracting condensates from the exhaled breath sample, wherein said sensor is equipped to identify glucose and at least one solute in the extracted condensate, and where the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same solute in blood to determine a dilution factor to be utilized in correlating the concentration of glucose in blood with the glucose identified in the extracted condensate by multiplying said dilution factor with the concentration of glucose in said condensate.   
     
     
         35 . A non-invasive, portable glucose monitoring device comprising at least one processor and at least one collection reservoir for extracting and collecting condensate from at least one exhaled breath sample, wherein said collection reservoir comprises a sensor and a signaling means, wherein said sensor is equipped to identify glucose and at least one solute in the extracted condensate, and where the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same solute in blood to determine a dilution factor to be utilized in correlating the concentration of glucose in blood with the glucose identified in the extracted condensate by multiplying said dilution factor with the concentration of glucose in said condensate. 
     
     
         36 . A method for measuring the glucose concentration in blood from an exhaled breath sample of a subject which comprises:
 a. collecting at least one exhaled breath sample or component thereof from said subject;   b. extracting condensate from said at least one exhaled breath sample;   c. contacting said condensate with a glucose sensor to determine a glucose concentration in said condensate and with an electrolytic sensor to determine a concentration of at least one electrolyte in said condensate, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood;   d. obtaining the ratio of said concentration of said at least one electrolyte in said condensate with the concentration of said at least one electrolyte in blood; and   e. multiplying said ratio with said glucose concentration in said condensate to obtain the glucose concentration in the blood of said subject.   
     
     
         37 . The method according to  claim 36  wherein said at least one exhaled breath sample or component thereof is an end tidal breath sample. 
     
     
         38 . The method according to  claim 37  wherein said electrolyte is selected from the group consisting of chloride, sodium, potassium and combinations thereof. 
     
     
         39 . The method according to  claim 38  wherein said electrolyte is chloride. 
     
     
         40 . The method according to  claim 36  wherein said method is used to detect hyperglycemia, hypoglycemia or both and fluctuations between hyperglycemia and hypoglycemia. 
     
     
         41 . A method for monitoring blood glucose concentration which comprises using the apparatus according to  claim 27 . 
     
     
         42 . A method for monitoring blood glucose concentration which comprises:
 a. collecting from a subject a breath or breath component in a breath collection reservoir, said breath collection reservoir comprising or connected to a breath condensate collection reservoir;   b. contacting breath condensate collected in said breath condensate collection reservoir with at least one sensor;   c. measuring the concentration of glucose and of at least one dilutional indicator by contacting said breath condensate collected in said breath condensate collection reservoir with said at least one sensor;   d. using the measured concentration of glucose and the at least one dilutional indicator from collected breath condensate in contact with said at least one sensor to calculate the blood concentration of glucose by dividing the measured glucose concentration in said breath condensate by the dilutional indicator concentration in said breath condensate and multiplying by a number which represents the concentration of said dilutional indicator in blood.