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Electrochemical aptamer-based sensors: leveraging the sensing platform for minimally-invasive microneedle measurements and fundamental exploration of sensor biofouling dynamics

Downs, Alexandra M.; Miller, Philip R.; Bolotsky, Adam; Staats, Amelia M.; Weaver, Bryan M.; Bennett, Haley L.; Tiwari, Sidhant; Kolker, Stephanie; Wolff, Nathan P.; Polsky, Ronen; Larson, Steven R.; Coombes, Kenneth R.; Sawyer, Patricia S.

The ability to track the concentrations of specific molecules in the body in real time would significantly improve our ability to study, monitor, and respond to diseases. To achieve this, we require sensors that can withstand the complex environment inside the body. Electrochemical aptamer-based sensors are particularly promising for in vivo sensing, as they are among the only generalizable sensing technologies that can achieve real-time molecular monitoring directly in blood and the living body. In this project, we first focused on extending the application space of aptamer sensors to support minimally-invasive wearable measurements. To achieve this, we developed individually-addressable sensors with commercial off-the-shelf microneedles. We demonstrated sensor function in buffer, blood, and porcine skin (a common proxy for human skin). In addition to the applied sensing project, we also worked to improve fundamental understanding of the aptamer sensing platform and how it responds to biomolecular interferents. Specifically, we explored the interfacial dynamics of biofouling – a process impacting sensors placed in complex fluids, such as blood.

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Microneedle electrochemical aptamer-based sensing: Real-time small molecule measurements using sensor-embedded, commercially-available stainless steel microneedles

Biosensors and Bioelectronics

Downs, Alexandra M.; Bolotsky, Adam; Weaver, Bryan M.; Foulk, James W.; Wolff, Nathan P.; Polsky, Ronen; Miller, Philip R.

Microneedle sensors could enable minimally-invasive, continuous molecular monitoring – informing on disease status and treatment in real-time. Wearable sensors for pharmaceuticals, for example, would create opportunities for treatments personalized to individual pharmacokinetics. Here, we demonstrate a commercial-off-the-shelf (COTS) approach for microneedle sensing using an electrochemical aptamer-based sensor that detects the high-toxicity antibiotic, vancomycin. Wearable monitoring of vancomycin could improve patient care by allowing targeted drug dosing within its narrow clinical window of safety and efficacy. To produce sensors, we miniaturize the electrochemical aptamer-based sensors to a microelectrode format, and embed them within stainless steel microneedles (sourced from commercial insulin pen needles). The microneedle sensors achieve quantitative measurements in body-temperature undiluted blood. Further, the sensors effectively maintain electrochemical signal within porcine skin. This COTS approach requires no cleanroom fabrication or specialized equipment, and produces individually-addressable, sterilizable microneedle sensors capable of easily penetrating the skin. In the future, this approach could be adapted for multiplexed detection, enabling real-time monitoring of a range of biomarkers.

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4 Results
4 Results