Development of a Multifunctional Electrochemical Probe for Detection of Anticoagulants in Whole Blood

摘要

The ability to rapidly and accurately monitor anticoagulant drugs such as heparin is critical for cardiac surgical patients. Unfortunately, this is quite challenging due to the narrow therapeutic window and heterogenous molecular weight of heparin; which has led to heparin being the second most common ICU medication error. Currently the most widely used method to monitor heparin is the activated partial thromboplastin time (aPTT), however, this is an indirect measurement of heparin dose and requires blood sampling with long turnaround times. Here we develop a minimally invasive, multifunctional electro-optical fiber optic for the detection of heparin. These probes have a local optical channel for in situ optical spectroscopy and electrical channel for quantitative electrochemical sensing. To enhance the electrochemical surface area of the fiber optic, and provide a porous medium for ion transport and support matrix for the immobilization of heparin-complexing dyes, highly conductive polymer layers were developed that can be electrochemically deposited on the probes. Strong cathodic current changes, and attenuation of light through the medium are observed in heparin-spiked buffer solutions when heparin complexes with the dye molecules, and the degree of change can be correlated to heparin concentration. Electrical sensing were also carried out in human whole blood and used to extract heparin concentrations in real time. Given the small footprint of the electro-optic fiber optic probes, they can be inserted through an intravenous catheter to provide a novel in situ solution to rapid, quantitative monitoring of heparin dose in the bloodstream.