Abstract
Clinical research shows that frequent measurements of both pH and lactate can help guide therapy and improve patient outcome. However, current methods of sampling blood pH and lactate make it impractical to take readings frequently (due to the heightened risk of blood infection and anemia). As a solution, we have engineered a subcutaneous pH and lactate sensor (PALS) that can provide continuous, physiologically relevant measurements. To measure pH, a sheet containing a pH-sensitive fluorescent dye is placed over 400 and 465 nm light-emitting diodes (LEDs) and a filter-coated photodetector. The filter-coated photodetector collects an emitted signal from the dye for each LED excitation, and the ratio of the emitted signals is used to monitor pH. To measure lactate, two sensing sheets comprising an oxygen-sensitive phosphorescent dye are each mounted to a 625 nm LED. One sheet additionally comprises the enzyme lactate oxidase. The LEDs are sequentially modulated to excite the sensing sheets, and their phase shift at the LED drive frequency is used to monitor lactate. In vitro results indicate that PALS successfully records pH changes from 6.92 to 7.70, allowing for discrimination between acidosis and alkalosis, and can track lactate levels up to 9 mM. Both sensing strategies exhibit fast rise times (< 5 min) and stable measurements. Multianalyte in vitro models of physiological disorders show that the sensor measurements consistently quantify the expected pathophysiological trends without cross talk; in vivo rabbit testing further indicates usefulness in the clinical setting.