We are developing electrochemical biosensors that use a change in electron transfer properties of redox reporter-modified and surface-attached biomolecules (DNA or proteins) to transduce binding into a measurable response directly in complex matrices like undiluted whole blood. Oligonucleotide-based sensors are part of this class of electrochemical biosensors where a redox-reporter-modified, and surface-attached oligonucleotide changes conformation altering the reporter’s electron transfer. Oligonucleotide-based sensors have notable attributes for the detection of clinically relevant molecules including: 1) Rapid, quantitative, precise and single-step measurements of molecular targets directly in small undiluted whole blood volumes (i.e. finger-prick), as opposed to detection in hours in larger volumes of blood (i.e. venous draws) 2) Minimal resources and user input as opposed to laboratory-bound processes requiring trained personnel. To capitalize on these advantages, my research program aims at understanding and developing biosensors that can readily deploy at the point-of-care or allow real-time detection of molecular targets in complex matrices and directly in the living body.