Measurement of blood ammonia from a finger or heel stick The goal is to develop a portable device that measures ammonia levels in blood obtained by fingeror heel stick, in the same way that diabetics measure their blood sugar levels. PAD will instantly diagnoseelevated blood ammonia (hyperammonemia), thus triggering treatment, and preventing ammonia-inducedbrain damage. PAD will permit finger and heel sticks, sparing children the trauma of venipuncture, andrequires only 0.02 ml (20 µL) blood volumes, conserving the blood of tiny infants. By contrast, the standard clinical laboratory test requires: proximity to a central laboratory (usually ina hospital) and 1 to 2 hours of turn-around time; intravenous cannulation by a trained phlebotomist; and atleast 3 ml of blood, or 300-fold more blood than PAD. PAD can have a major impact on child health. Rapid diagnosis and close monitoring of bloodammonia will guide treatments, from emergency hemodialysis, to intravenous ammonia scavengers, tohome medications. Hyperammonemia presents a risk to both child and adult populations in the U.S.: (1)20,000 children with mutations in any one of 44 genes; (2) 400,000 preterm infants born annually before 37weeks with immature livers; (3) 630,000 adults with liver cirrhosis; (4) 140,000 cancer patients receiving 5-fluorouracil chemotherapy; and (5) 6 million adults with obesity-associated nonalcoholic steatohepatitis(NASH). PAD uses a novel technology that adapts an inexpensive ($190) commercially available fuel cellgaseous ammonia detector for use with blood using a consumable cartridge containing K2CO3 to liberategaseous ammonia from the sample. Rapid diagnosis by PAD will protect brain function in many children.Treatment will improve when PAD is deployed to the bedside and outpatient clinics.Aim 1. Create and validate a cartridge production system capable of producing cartridges suitable forclinical studies Our specific aim is to develop an in-house cartridge production and assembly process that canproduce lot sizes of >5,000 cartridges that show less than 15% variability in K2CO3 loading and provide anammonia limit of quantification of â¤20 µM.1
Public Health Relevance Statement: Project narrative: Point-of-Care Blood Ammonia Measurement Using a Gas-Phase Fuel Cell Sensor Elevated blood ammonia is toxic to the brain, and if not treated within hours, can lead to permanent brain damage. The goal is to develop a device that measures ammonia in blood obtained by finger or heel stick procedure, thus addressing a critical unmet need for: (1) 20,000 children in the U.S. (700 infants born annually) with gene mutations leading to elevated blood ammonia; (2) patients seen in emergency rooms for altered mental status; and (3) 400,000 infants born annually before 37 weeks of gestation at risk due to immature liver function. The device will permit early diagnosis and prompt treatment of elevated ammonia, thus preventing brain damage in many children and improving the management and quality of life for patients with liver disease. 1
Project Terms: Acids ; Adult ; 21+ years old ; Adult Human ; adulthood ; Ambulatory Care Facilities ; Outpatient Clinics ; Ammonia ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Blood ; Blood Reticuloendothelial System ; Blood donor ; Blood Glucose ; Blood Sugar ; Blood Volume ; Brain ; Brain Nervous System ; Encephalon ; Cells ; Cell Body ; Centrifugation ; Centrifugation Fractionation ; Child ; 0-11 years old ; Child Youth ; Children (0-21) ; youngster ; Clinical Research ; Clinical Study ; Clinical Trials ; Confidence Intervals ; Cessation of life ; Death ; Diagnosis ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Emergency Situation ; Emergencies ; Exhibits ; Fingers ; Fluorouracil ; 5-FU ; 5-Fluracil ; 5FU ; Fluoro Uracil ; Fluoruracil ; Fluouracil ; Gases ; Genes ; Goals ; Heel ; Hemodialysis ; Hemodialyses ; Hospitals ; Infant ; Premature Infant ; infants born premature ; infants born prematurely ; premature baby ; premature infant human ; preterm baby ; preterm infant ; preterm infant human ; Laboratories ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Liver ; hepatic body system ; hepatic organ system ; Liver Cirrhosis ; Hepatic Cirrhosis ; Liver diseases ; Hepatic Disorder ; hepatic disease ; hepatopathy ; liver disorder ; Manuals ; Inborn Errors of Metabolism ; Hereditary Metabolic Disorder ; inborn metabolism disorder ; Mutation ; Genetic Alteration ; Genetic Change ; Genetic defect ; genome mutation ; Pain ; Painful ; Paper ; Patients ; Plasma ; Blood Plasma ; Plasma Serum ; Reticuloendothelial System, Serum, Plasma ; Production ; Publishing ; Quality of life ; QOL ; Risk ; Testing ; Time ; Transportation ; Work ; Generations ; Measures ; Liver Dysfunction ; Guidelines ; Blood specimen ; Blood Sample ; detector ; Pump ; sensor ; improved ; Procedures ; Clinical ; Phase ; Evaluation ; Training ; Hyperammonemia ; liver function ; Individual ; diabetic ; Measurement ; Brain Injuries ; Acquired brain injury ; brain damage ; brain-injured ; mental state ; mental status ; fluid ; liquid ; Liquid substance ; Venous ; Intravenous ; Hour ; System ; Emergency Department ; Emergency room ; Accident and Emergency department ; early detection ; Early Diagnosis ; Gene Alteration ; Gene Mutation ; Performance ; rapid diagnosis ; aqueous ; Venipunctures ; Speed ; novel technologies ; new technology ; Devices ; Sampling ; performance tests ; portability ; Cannulations ; µfluidic ; Microfluidics ; preventing ; prevent ; Address ; Data ; Detection ; Cancer Patient ; Collection ; Monitor ; Process ; Development ; developmental ; point of care ; design ; designing ; Population ; Trauma ; chemotherapy ; trial comparing ; commercialization ; nonalcoholic steatohepatitis ; NASH ; non-alcohol induced steatohepatitis ; non-alcoholic steato-hepatitis ; non-alcoholic steatohepatitis ; nonalcoholic steato-hepatitis ; 37 weeks gestation ; 37 weeks completed gestation ; Child Health ; adult obesity ; adult adiposity ; adults with obesity ; Home ; point of care testing ;
