Field performance metric(s) optimization

Abstract

Introduction: In contrast to methods for monitoring physical vital signs, such as pulse, respiration rate, and body temperature, the ability to monitor molecules indicative of health or performance status has greatly lagged. Specifically, until recently, technologies able to monitor specific molecules in the body in real-time were limited to the detection of only a few metabolites (glucose, lactate, and oxygen) and no hormones or protein biomarkers. This is because all prior molecular monitoring technologies relied on the specific chemical or enzymatic reactivity of their targets to generate a signal, rendering it impossible to generalize them to new targets. Methods: Human technological prowess notwithstanding, the ability to monitor arbitrary molecules in the body continuous and in real-time is a solved problem: the human body, for example, utilizes hundreds of receptors that respond quantitatively to specific molecular cues without exploiting their chemical or enzymatic reactivity. To achieve this, nature has invented two critical “tricks.” The first is the combinatorial chemistry of biopolymers (proteins, nucleic acids), with which it can generate high-affinity, high-specificity receptors against almost any water-soluble target. The second is the use of conformation-linked signalling, in which the binding of a target molecule alters the shape of the receptor, producing in turn an easily detected output1,2. Motivated by these arguments, recent advances in biosensors have exploited the same two tricks. Results: Using the combinatorial chemistry of biomolecules to generate high-performance receptors and our growing understanding of biomolecular physics to re-engineering them such that they undergo binding-induced conformational changes, recent advances in the field of biosensors has enabled, for the first time, the high-frequency, real-time measurement of specific molecules in living bodies via an approach that is agnostic to the reactivity of the target and thus can be generalized to new targets3,4. Discussion/conclusions: The newly achieved ability to monitor arbitrary molecules continuously and in real-time in the human body provides unprecedented opportunities to both identify the biomarkers correlative of health and performance status and to monitor them in real-time. Acknowledgements: Biosensor research in Prof. Plaxco’s group at UCSB has been supported by the U.S. Office of Naval Research and the NIH. References 1Lubin AA, Plaxco KW. Folding-based electrochemical biosensors: the case for responsive nucleic acid architectures. Acc Chem Res 2010; 43:496–505. https://doi.org/10.1021/ar900165x 2Plaxco KW, Soh HT. Switch based biosensors: a new approach towards real-time, in vivo molecular detection. Trends in Biotech 2011; 29:1-5. https://doi.org/10.1016/j.tibtech.2010.10.005 3Arroyo-Curras N, Somerson J, Vieira P, et al. Real-time measurement of small molecules in awake, ambulatory animals. Proc Natl Acad Sci USA 2017; 114:645–650. https://doi.org/10.1073/pnas.1613458114 4Idili A, Gerson J, Kippin T, et al. Seconds-resolved, in situ measurements of plasma phenylalanine disposition in living rats. Anal Chem 2021; 93:4023-4032. https://doi.org/10.1021/acs.analchem.0c05024