Analyzer for nitric oxide in exhaled breath with multiple-use sensor

Abstract

A high-sensitivity analyzer for nitric oxide in exhaled breath at levels of 200 ppb or less with a sensor containing cytochrome C is rendered capable of multiple uses without the need for installing a new sensor for each use. This capability is achieved by regenerating the analyzer after each use by purging the sensor and surrounding regions with NO x -free air in a controlled manner, preferably in pulses separated by equilibration periods.

1 . An apparatus for analyzing a succession of samples of exhaled breath for nitric oxide concentration, said apparatus comprising:
 a sensor configured to optically differentiate between samples containing different nitric oxide levels;   a NO x  filter;   a breath intake port;   a pump that draws gas across said nitric oxide sensor;   a switching valve that directs gas flow through said apparatus, said switching valve comprising first and second valve positions,   said first valve position communicating said sensor, said NO x  filter, and atmospheric air and isolating said sensor from said breath intake port, so that the pump draws atmospheric air through said NO x  filter to convert said atmospheric air to substantially NO x -free air and draws said NO x  -free air across said sensor, and   said second valve position communicating said sensor with said breath intake port, so that said pump draws breath from said breath intake port across said sensor while bypassing said NO x  filter; and   a controller that controls said switching valve to alternate between said first valve position and said second valve position to purge the sensor with the substantially NO x -free air between sample analyses.   
     
     
         2 . The apparatus of  claim 1 , further comprising a temperature controller that equilibrates temperature of said sensor to a selected temperature within the range of about 25° C. to about 35° C. 
     
     
         3 . The apparatus of  claim 1 , wherein the temperature is equilibrated for a duration of from about one minute to about fifteen minutes after the purging. 
     
     
         4 . The apparatus of  claim 1 , further comprising a CO 2  filter, and wherein said first valve position further communicates said CO 2  filter with said sensor, said NO x  filter, and atmospheric air, and said second valve position further communicates said CO 2  filter with said sensor and said breath intake port. 
     
     
         5 . The apparatus of  claim 1 , wherein said controller controls both said switching valve and said pump and activates said pump in pulses separated by intervals of selected duration. 
     
     
         6 . The apparatus of  claim 5 , wherein each purge comprises a succession of pulses of the pump to draw said NO x -free air across said sensor separated by static intervals with substantially no gas flow through said apparatus. 
     
     
         7 . The apparatus of  claim 6 , wherein each purge comprises from two said pulses to ten said pulses, each pulse ranging in duration from about one second to about ten seconds, and said static intervals ranging in duration from about ten seconds to about 3 minutes. 
     
     
         8 . The apparatus of  claim 6 , wherein each purge comprises from two said pulses to five said pulses, each pulse ranging in duration from about two seconds to about six seconds, and said static intervals ranging in duration from about thirty seconds to about two minutes. 
     
     
         9 . The apparatus of  claim 1 , further comprising a diffusion barrier leading from said sensor to the atmosphere. 
     
     
         10 . The apparatus of  claim 9 , wherein said diffusion barrier is a gas discharge conduit leading from said sensor to the atmosphere, said gas discharge conduit having an inner diameter of less than 0.25 cm 2  and a length greater than 10 cm. 
     
     
         11 . The apparatus of  claim 1 , wherein the sensor comprises a desiccant that maintains a controlled moisture level in the sensor without affecting the ability of the apparatus to differentiate between samples containing different nitric oxide levels 
     
     
         12 . The apparatus of  claim 11 , wherein said desiccant is molecular sieve 3A. 
     
     
         13 . The apparatus of  claim 1 , wherein said NO x  filter comprises a packed bed of potassium permanganate. 
     
     
         14 . The apparatus of  claim 1 , wherein said NO x  filter is a packed bed of solid granules of an NO x  adsorbent. 
     
     
         15 . The apparatus of  claim 14 , wherein the NO x  adsorbent is selected from one of alumina, calcium carbonate, calcium oxide, calcium sulfate, barium oxide, sodium carbonate, sodium phosphate, potassium carbonate, or a molecular sieve. 
     
     
         16 . The apparatus of  claim 1 , wherein said NO x  filter is in cartridge form. 
     
     
         17 . The apparatus of  claim 1 , wherein the sensor comprises:
 (i) a protein that binds nitric oxide contained in exhaled breath and that undergoes an optically detectable change upon so binding, said protein immobilized in a porous inert matrix at a protein concentration that together with said matrix porosity causes exhaled breath containing 200 ppb or less of nitric oxide to produce said optically detectable change, and   (ii) a desiccant that maintains a controlled moisture level in said matrix without affecting the ability of the apparatus to differentiate between samples containing different nitric oxide levels.   
     
     
         18 . The apparatus of  claim 17 , wherein said NO x  filter comprises a packed bed of potassium permanganate. 
     
     
         19 . The apparatus of  claim 17 , wherein said NO x  filter is a packed bed of solid granules of an NO x  adsorbent. 
     
     
         20 . The apparatus of  claim 19 , wherein the NO x  adsorbent is selected from one of alumina, calcium carbonate, calcium oxide, calcium sulfate, barium oxide, sodium carbonate, sodium phosphate, potassium carbonate, or a molecular sieve. 
     
     
         21 . The apparatus of  claim 17 , wherein said NO x  filter is in cartridge form. 
     
     
         22 . The apparatus of  claim 17 , wherein said desiccant is molecular sieve 3A. 
     
     
         23 . The apparatus of  claim 17 , wherein said protein is cytochrome C. 
     
     
         24 . The apparatus of  claim 17 , wherein said protein is cytochrome C and said matrix is a xerogel or an aerogel. 
     
     
         25 . The apparatus of  claim 17 , wherein said protein is cytochrome C, said matrix is a xerogel or an aerogel, and said cytochrome C and matrix together form a monolith with a concentration of from about 1 mg to about 40 mg cytochrome C per cubic centimeter of said monolith, a monolith pore diameter of from about 2 nm to about 10 nm, and a monolith surface area of from about 550 m 2 /g to about 650 m 2 /g.