Point-of-Care Analysis of Blood Ammonia with a Gas-Phase Sensor

Abstract

Elevated blood ammonia (hyperammonemia) may cause delirium, brain damage, and even death. Effective treatments exist, but preventing permanent neurological sequelae requires rapid, accurate, and serial measurements of blood ammonia. Standard methods require volumes of 1 to 3 mL, centrifugation to isolate plasma, and a turn-around time of 2 h. Collection, handling, and processing requirements mean that community clinics, particularly those in low resource settings, cannot provide reliable measurements. We describe a method to measure ammonia from small-volume whole blood samples in 2 min. The method alkalizes blood to release gas-phase ammonia for detection by a fuel cell. When an inexpensive first-generation instrument designed for 100 μL of blood was tested on adults and children in a clinical study, the method showed a strong correlation (R 2 = 0.97) with an academic clinical laboratory for plasma ammonia concentrations up to 500 μM (16 times higher than the upper limit of normal). A second-generation hand-held instrument designed for 10–20 μL of blood showed a near-perfect correlation (R 2 = 0.99) with healthy donor blood samples containing known amounts of added ammonium chloride up to 1000 μM. Our method can enable rapid and inexpensive measurement of blood ammonia, transforming diagnosis and management of hyperammonemia.

Alkylammonium Cation Affinities of Nitrogenated Organobases: The Roles of Hydrogen Bonding and Proton Transfer

“…Our calculations predict that imidazole 13 has higher alkylammonium affinity than pyrazole 17 and pyridine 23 (Figure 6). Along the same line, the imidazole derivatives (13)(14)(15)(16) show higher ACA values than the pyrazoles (17)(18)(19)(20)(21)(22). The electron-density donation to the azacycle by the incorporation of methyl groups to the imidazole and pyrazole leads towards higher ACA values whereas the presence of electron-withdrawing groups provokes a decrease of its alkylammonium affinities (see 20-22 columns, top).…”

“…Hydrogen bonding [1–3] is an omnipresent interaction in topics as varied as the structural stability of life molecules, [4–7] molecular recognition, [8–10] enzyme catalysis [11,12] or the properties of water [13] . Proton transfers and hydrogen bonds involving ammonium cations are essential processes in chemistry and biochemistry [14–21] . The ubiquity of amino functionalities in life molecules such as proteins, DNA and RNA, enzymes, phospholipids and in numerous bioactive compounds gives account for their importance.…”

“…[13] Proton transfers and hydrogen bonds involving ammonium cations are essential processes in chemistry and biochemistry. [14][15][16][17][18][19][20][21] The ubiquity of amino functionalities in life molecules such as proteins, DNA and RNA, enzymes, phospholipids and in numerous bioactive compounds gives account for their importance. Neurotransmitters [22][23][24] such as catecholamines serotonin, dopamine, norepinephrine and epinephrine, [25] and other biologically relevant molecules carry an amino function that under physiological conditions is usually protonated and thus in the form of an ammonium group, which is key to its biological function (Figure 1).…”

“…N-sp 2 organobases The organobase family with an interacting N-sp 2 atom was split into five categories: azoles (13)(14)(15)(16)(17)(18)(19)(20)(21)(22); azines (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36); amidines (37)(38)(39)(40)(41)(42)(43); guanidines (44)(45)(46)(47)(48) and azapolycycles (49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61). We start commenting the selected azoles and azines (Figure 5).…”

Highly Sensitive Tungsten Oxide Thin Film‐Based Field‐Effect Transistor for Real‐Time Monitoring of Dissolved Ammonia in Human Plasma

“…[2] Severity of liver cirrhosis has been monitored by the level of ammonia in human blood or plasma, [3,4] The excess concentration of ammonia in the venous blood of healthy adults and children potentially acts as a toxin, especially for central nervous system functioning, [5,6] The normal level of ammonia in healthy people's venous blood is ≈30 µM. [7] Even the mild increase in ammonia concentration from the normal level causes mood swings or memory loss. [8] The rapid increase in blood ammonia from the normal level may cause permanent brain damage or even death.…”