Aptamers and BSI for Sub-Microliter Analysis of Pharmaceuticals in Neonatal Urine

DESCRIPTION provided by applicant Neonatal and pediatric intensive care still involves performing painful needle punctures to obtain blood samples for routine clinical monitoring Pain management in the neonatal setting is often achieved by long term continuous intravenous infusion of morphine or related compounds It has become increasingly clear however that long term use of opioid compounds in neonates is likely to have significant deleterious neurological effects Unfortunately the very nature of neonates lower weight and incomplete and varied metabolic development complicates pharmacokinetic studies and modeling New analytical platforms are needed to enable studies of commonly used compounds in this patient population Non or minimally invasive microfluidic platforms with the ability to address multiple analytes in flexible manner have great promise in improving neonatal pain management and patient outcomes This project will apply a relatively new mode of detection backscattering interferometry BSI in conjunction with novel DNA aptamers binding agents to detect and quantify important opioids used for pain management in neonates as well as propofol an important agent used for general anesthesia We will also generate the necessary aptamers for detection of the urinary metabolites of these compounds The developed platform only requires microliter or less of urine and will enable studies and possibly personalized dosing of therapeutic compounds in neonates Because of our expertise to rapidly develop aptamers to small molecules in Phase II we will be in an excellent position to expand the menu of assays and translate them to the clinic with a recently developed benchtop BSI instrument PUBLIC HEALTH RELEVANCE Backscattering interferometry BSI is a recently developed technology for sensitive molecular detection developed by scientists at Vanderbilt University This project will develop a new system for rapid quantitation of pharmaceutical compounds and metabolites in the urine of newborns Because the system is microfluidic it requires less than microliter of sample and results are available in less than minute after sample introduction A new benchtop instrument has been recently developed which will allow us to rapidly translate the platform to the clinic or neonatal intensive care unit NICU in Phase II