Microfluidic S nitrosothiol Sensor

PROJECT SUMMARY This Small Business Innovation Research SBIR Phase I project aims to develop an accurate rapid and commercially available microfluidic sensor that measures low molecular weight S nitrosothiols in biological samples S nitrosothiols RSNOs the primary transporters of nitric oxide NO in physiology play a critical role for NOandapos s bioactivity Homeostatic control of low molecular weight RSNOs especially S nitrosoglutathione is lost in many disease states Such dysfunction is thought to contribute to the underlying disease pathology Despite the promise of low molecular weight RSNOs as mechanistic biomarkers no simple to use standardized tools currently exist for measuring these compounds There are vast disagreements in the literature regarding the reference ranges for low molecular weight RSNOs complicating the clinical understanding of these species As a result RSNOs have been identified as candidate biomarkers for many inflammatory and respiratory diseases Yet little work has validated these findings or determined their clinical utility A standardized accurate facile and commercially ready device to measure RSNOs would enable important clinical research A simple to use device could resolve fundamental questions regarding the formation and degradation of RSNOs in disease and help further a general understanding of RSNOsandapos roles in cellular physiology signaling and apoptosis To address the gap in acceptable RSNO measurement techniques we have begun to develop an innovative straightforward and inexpensive device for measuring RSNOs in small volumes of biological fluids The device is based on our core technology a microfluidic NO sensor Using a visible light emitting diode LED the RSNOs are photolytically broken down to NO which is then detected electrochemically In this format the signal generated from NO oxidation is proportional to the RSNO content in the original sample Employing visible light photolysis along with our microfluidic NO sensor presents several key advantages our microfluidic sensor requires minimal sample volume L and reduces interference from other common electroactive species the use of visible light to cleave RSNOs as opposed to UV light mediated strategies developed by others does not generate contamination from photolytic reduction of endogenous nitrate and our sensor features two working electrodes providing us with a tool to determine and thus remove the background signal associated with each unique sample matrix Leveraging our core competencies in NO chemistry and measurement we have assembled a talented team of analytical chemists and clinical researchers to develop a simple to use inexpensive device that can measure RSNOs in biologic samples Once developed this device will enable new clinical research that evaluates S nitrosothiols as clinical biomarkers for disease PROJECT NARRATIVE S nitrosothiols are endogenous physiologic transporters of nitric oxide and are promising biomarkers for vascular respiratory and inflammatory disease However low cost and easy to use tools to measure S nitrosothiols are lacking The objective of this project is to develop an accurate commercially available lab on a chip device that enables rapid detection of S nitrosothiols in biological samples