Closed-Loop Intravenous Drug Administration Using Photoplethysmography

An optically-based injection control system has been developed for preclinical use for an intravenous drug delivery application. Current clinical drug delivery for oncology typically provides for intravenous administration without an awareness of achieved plasma concentration, yet interpatient variability produces consequences ranging from toxicity to ineffectual treatments. We report a closed-loop injection system integrating a pulse-photoplethysmograph to measure the concentration of an injected agent in the circulating blood system using a previously described technique. A proportional-derivative (PD) controller manages the injection rate in real-time. The target function for the controller is the population estimate of the pharmacokinetic model developed using Bayesian statistics describing the injection phase of a calibration set of 22 injections in mice. The controlled set of eight injections showed a reduction in variance from the target injection phase concentration profile of 74.8%.