(Plenary) Electrochemical/Optical Sensors in Medicine: Meeting Needs for the 21st Century
Authors: Meyerhoff Mark E. 
Published: July 2021

Over the past 40 years, miniaturized potentiometric and amperometric sensors for ions (K+, Ca++, Na+, Mg++, Cl-, H+), gases (O2 and CO2), and nutrients/metabolites (glucose, lactate, creatinine, urea) have revolutionized the practice of critical care medicine by providing tools to measure an array of these physiologically important species, simultaneously, in small volumes of undiluted whole blood. Indeed, all modern point-of-care whole blood analyzers used in hospitals worldwide now employ electrochemical sensor arrays as either single-use or multi-use devices for near-patient testing, especially in operating rooms, emergency rooms, intensive care units, etc. Some of the same or similar chemistries have also been adapted to create either single-use or continuous monitoring optical sensors (fluorescence, etc.). Further, nearly all blood glucometers as well as newer implantable subcutaneous glucose sensors now use electrochemical measurement principles to provide accurate glucose concentrations for millions of diabetic patients each and every day. A brief overview of these existing electrochemical/optical sensor technologies that have already had such a great impact in medicine will be provided during the introductory portion of this lecture.
At the same time, there remain a number of unmet needs in medicine where electrochemical/optical chemical sensing devices could still play important analytical roles. Therefore, in the major portion of this presentation, the following research projects ongoing in our laboratories at the University of Michigan will be highlighted: 1) recent efforts to utilize electrochemical sensors for measurement of polyionic drugs and associated contaminants (including the anticoagulant heparin, low-molecular weight heparin, and inflammatory over-sulfated chondroitin sulfate (OSCS) contaminants in biomedical heparin preparations);1-2 2) research aimed at utilizing the same chemistry employed to make ion and polyion selective electrochemical sensors to create optical sensing films as well as optical sensing microfluidic devices that are able to quantitate species in volumes of << 1 µL;3 3) research related to the development of implantable electrochemical sensors for ions, gases, glucose, lactate, etc. that emit low levels of nitric oxide (NO) (a potent anti-platelet and antimicrobial agent) and that can potentially be used to continuously monitor critical care species intravenously in ICU patients with improved accuracy (see Fig. 1);4 and 4) efforts to use improved electrochemical/amperometric gas phase sensors for detecting nitric oxide (NO) in exhaled nasal/oral breath and also the use of NO and nitrogen dioxide (NO2) sensors to monitor and feedback control the levels of therapeutic gas phase NO being generated by novel photochemical and electrochemical gas phase generators.5-6 These gas phase NO generators can potentially replace use of very high cost compressed gas cylinders containing NO to provide controlled levels of NO gas on-demand for inhalation therapy of patients with pulmonary hypertension (including infants) and for use in the sweep gas of oxygenators to prevent clotting and Systemic Inflammatory Response Syndrome (SIRS) in patients undergoing open heart surgery.
Literature Cited:

L. Wang, S. Buchanan and M. E. Meyerhoff, “Rapid Detection of High Charge Density Polyanion Contaminants in Biomedical Heparin Preparations Using Potentiometric Polyanion Sensors,” Anal. Chem., 80, 9845-9847 (2008).

K. Gemene and M. E. Meyerhoff, “Reversible Detection of Heparin and Other Polyanions by Pulsed Chronopotentiometric Polymer Membrane Electrode,” Anal. Chem., 82, 1612-1615 (2010).

X. Wang, M. Sun, S. A. Ferguson, J. D. Hoff, Y. Qin, R. C. Bailey, and M. E. Meyerhoff, “Ionophore-Based Biphasic Chemical Sensing in Droplet Microfluidics,” Angew. Chem. Int. Ed., 58, 1-6 (2019).

M. Frost and M. E. Meyerhoff, “Real-Time Monitoring of Critical Care Analytes in the Bloodstream with Chemical Sensors: Progress and Challenges,” Ann. Rev. Anal. Chem., 8, 171-192 (2015).

J. Zajda, N. J. Schmidt, Z. Zheng, X. Wang and M. E. Meyerhoff, “Evaluation of Amperometric Platinized-Nafion-Based Gas Phase Sensor for Determining Nitric Oxide (NO) Levels in Exhaled Human Nasal Breath,” Electroanalysis 30, 1602-1607 (2018).

Y. Qin, J. Zajda, H. Ren, J. Toomasian, T. Major, A. Rojas-Pena, B. Carr, T. Johnson , J. Haft, R. H. Bartlett, A. Hunt, N. Lehnert, and M. E. Meyerhoff, “Low Cost Portable Gas Phase Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Within the Sweep Gas/Cardiotomy Suction Air During Cardiopulmonary Bypass Surgery,” Mol. Pharmaceutics, 14, 3762-3771 (2017).

Figure 1. Comparison of average error of PO2 levels using amperometric IV-oxygen sensing catheters with (n=4) and without (n=4) NO release chemistry placed into the arteries of pigs for 20 h. % deviation calculated vs. measurements made on discrete whole blood samples (heparinized syringe) on Radiometer blood-gas/electrolyte analyzer.

Figure 1