Our microneedle-based devices support high-frequency molecular measurements on human subjects. To show this, we first fixed a phenylalanine-detecting devices onto a subject's arm and initiated data collection. After an initial set of measurements were collected, the subject was allowed to move and to complete light, everyday tasks while periodically returning to the potentiostat to perform further measurements over the course of 5 h. During this entire period, the sensor remained coupled to dermal ISF (figure ). While we performed these measurements the peak current decreased. This decrease is expected as it is seen regularly in in-vitro testing in serum, presumably as foulants diffuse to the sensing surface and reduce electron transfer. The disc-electrode device detected the increase in ISF phenylalanine levels associated with an oral challenge (25 mg/kg) within 20 min, which then plateaued. This is consistent with the known physiology of phenylalanine, as previous, blood- draw-based studies reported a rapid increase in plasma phenylalanine with heightened levels sustained thereafter (figure ). We do, however, observe a mild drift in signal after phenylalanine uptake (>30 min post ingestion)), presumably due to sensor degradation (figure ). This degradation could be potentially resolvable using our recently reported methods to improve sensor longevity to greater than one week . Throughout this work we made significant compromises to achieve high-frequency, on-body dose-response measurements. For example, when challenged free in solution, our phenylalanine aptamer sensor achieves greater signal gain and peak currents at higher square-wave frequencies (> 60 Hz; SI figure ). However, at frequencies above 120 Hz the peak current of our microneedle devices is either indistinguishable from noise or does not respond to challenge with phenylalanine. Because of this, which could be due to the capacitive-resistance charging effects present when including the epidermis into the electrical circuit, we collected our onbody data using a 10 Hz square-wave frequency. By limiting our measurements to this single frequency we are unable to determine absolute phenylalanine concentrations because we cannot employ calibration free measurement techniques . Ultimately, we could mitigate this effect by moving the counter electrode onto the backside of the microneedle substrate to remove the epidermis from the device circuit.