Non-invasive tools for measuring metabolism and biophysical analyte transport: self-referencing physiological sensing

Biophysical phenomena related to cellular biochemistry and transport are spatially and temporally dynamic, and are directly involved in the regulation of physiology at the sub-cellular to tissue spatial scale. Real time monitoring of transmembrane transport provides information about the physiology and viability of cells, tissues, and organisms. Combining information learned from real time transport studies with genomics and proteomics allows us to better understand the functional and mechanistic aspects of cellular and sub-cellular systems. To accomplish this, ultrasensitive sensing technologies are required to probe this functional realm of biological systems with high temporal and spatial resolution. In addition to ongoing research aimed at developing new and enhanced sensors (e. g., increased sensitivity, enhanced analyte selectivity, reduced response time, and novel microfabrication approaches), work over the last few decades has advanced sensor utility through new sensing modalities that extend and enhance the data recorded by sensors. A microsensor technique based on phase sensitive detection of real time biophysical transport is reviewed here. The self-referencing technique converts non-invasive extracellular concentration sensors into dynamic flux sensors for measuring transport from the membrane to the tissue scale. In this tutorial review, we discuss the use of self-referencing micro/nanosensors for measuring physiological activity of living cells/tissues in agricultural, environmental, and biomedical applications comprehensible to any scientist/engineer.