Towards Ultrasensitive Stochastic Sensing of Lead Ions in Blood

INVESTIGATOR: Jiyeon Kim, University of Rhode Island
MENTOR: Brett Lucht, University of Rhode Island

SCIENTIFIC THEME: Environmental Health Sciences

ABSTRACT: This project will develop a novel technology for ultrasensitive and rapid analysis of nanomolar lead ions (Pb2+) in the blood by stochastically detecting individual Pb2+-selective polymeric nanoemulsions (NEs) at a nanopipet electrode. Lead exposure is extremely dangerous for children, and can cause severe damage to their brains and nervous systems, resulting in behavior and learning disabilities, slow-growth, headaches, and hearing problems.  The project employs technology developed by the PI, monodisperse polymeric NEs doped with Pb2+-selective ionophores and dispersed in a blood sample to quickly extract Pb2+ into the NEs by taking advantage of fast ion-diffusion from the blood sample to NEs. Importantly, the phase-boundary potential developed across the Pb2+-loaded NE/blood interface depends on the Pb2+ concentration as given by the Nernst equation. This potential will be measured using a nanopipet electrode filled with an organic electrolyte solution to determine the blood lead concentration. Each time when a Pb2+-loaded NE collides at the nanopipet-supported blood/organic interface, the interfacial potential synchronizes with the phase-boundary potential of the NE. The interfacial potential returns to an original value as the NE desorbs from the interface, thereby yielding a spike response. Accordingly, specific aims are: Specific Aim 1 Develop and optimize this new sensor technology by employing stochastic electrochemistry and polymeric NEs doped with Pb2+-selective ionophores, and evaluate its sensitivity, selectivity, detection limit, and response time in a physiological buffer solution containing possible interfering ions, and Specific Aim 2 Apply the new sensor technology to measure nanomolar Pb2+ in blood samples by employing  a standard caprine blood sample certified by the National Institute of Standards and Technology and validate by statistically comparing the results with those obtained by using ICP-MS. If successful, this project will achieve a detection limit of ~0.25 µg/dL (12 nM), over an order of magnitude more sensitive than the current technology (LeadCare II). Owing to the unprecedentedly high sensitivity, this project will have enormous impact on point-of-care blood lead testing as well as on the neurotoxicological studies of lead exposure.

HUMAN HEALTH RELEVANCE: Both children and adults are vulnerable to the effects of lead. Particularly, children under the age of 5 are at risk, because their body, brain, and metabolism are still developing. Childhood lead exposure is estimated to contribute to about 600,000 new cases of children with intellectual disabilities every year. Chronic lead exposure in adults can result in cataracts, nerve disorders, muscle and joint pain memory or concentration problems. Therefore, the nanomolar level determination of the blood lead concentration in this project is crucial for the investigation of suspected cases of lead intoxication especially for the child health.