A Sensitive and Selective Microfluidic Nitrite Sensor

PROJECT SUMMARYNitriteonce thought to simply be an intermediate of nitric oxideNOsynthesishas emerged as an important mediator of redox control and a major storage form of NO produced in the vasculatureIt has become clear that nitrite itself is involved in the regulation of vascular toneespecially in response to hypoxiaAssays to measure nitrite are employed across a broad range of clinical research areas including those in asthmadiabetic ulcersinflammatory and infectious diseaseand traumatic brain injuryBecause of these ongoing areas as well as nitrite s important role in the vasculatureassays to measure nitrite have far reaching impact within the biomedical research communityDespite the widespread use of techniques to measure nitrite as both an indirect marker of NO production and a pool of NO generationcurrent techniques to measure this species require significant pre analytical processingare prone to interference from other speciesare incompatible with many sample matricesand suffer from limited dynamic range or inadequate limits of detectionA standardizedaccuratefacile and commercially ready device to measure nitrite would enable important clinical research for this compoundSuch a device could accelerate and enable new insights into nitrite both as a product and source of NO synthesisand potentially lead to the discovery of new diagnostic applications where nitrite holds valueTo address the significant pre analytical processing common to existing nitrite measurement techniqueswe have begun to develop an innovativestraightforward and inexpensive device for measuring nitrite in small volumes of biological fluidsThe device integrates our core device a microfluidic NO sensor with an additional electrode that selectively converts nitrite to NOIn this formatnitrite is selectively converted to NOand the gaseous NO product is detected electrochemically across an NO gas permeable membraneOn chip conversion of nitrite to NO gasfollowed by subsequent measurement of evolved NO offers several advantagesreduced interference from other common interfering species and matrices due to the selectivity of the membranesignal amplification with the potential for higher sensitivity and lower limits of detection relative to traditional electrochemical techniques that measure nitrite directlyandthe ability to account forand thus removethe background signal associated with each unique sample matrix through an additional working electrode that is isolated from the electrode used to convert nitrite to NOLeveraging our core competencies in NO chemistry and measurementwe have assembled a talented team to develop a simple touseinexpensive device that can measure nitrite in samples employed by the biomedical research community PROJECT NARRATIVE Nitrite is a product of nitric oxide synthesisa major pool of nitric oxide bioavailability in physiologyand a promising biomarker for vascularrespiratoryand inflammatory diseaseHoweverlow cost and easy touse tools capable of measuring nitrite at physiologic concentrations are lackingThe objective of this project is to develop an accuratecommercially available lab on a chip device that enables rapid detection of nitrite in biological samples