Abolition of the need for end-users to perform sensor calibration proved key to the widespread use of home-glucose monitors. Motivated by this observation here we have adapted electrochemical aptamer-based (E-AB) sensors, a sensing technology that is far more general than the glucose monitor, to the problem of performing calibration-free in vivo measurements of molecules other than glucose. Specifically, we first demonstrate the ability of E-AB sensors to achieve the accurate and precise measurement of cocaine, ATP and kanamycin in vitro in undiluted whole blood, achieving clinically relevant accuracy (better than ±20%) in this sample matrix without the need to calibrate individual sensors. We then demonstrate similar, calibration-free accuracy (±30%) for ATP and kanamycin measurements with sensors placed in situ in the jugular veins of live rats over multi-hour measurements runs that achieve time resolution of seconds and concentration precision of a few micromolar.
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