A Wireless, Regeneratable Cocaine Sensing Scheme Enabled by Allosteric Regulation of pH Sensitive Aptamers

Abstract

A key challenge for achieving continuous biosensing with existing technologies is the poor reusability of the biorecognition interface due to the difficulty in the dissociation of analytes from the bioreceptors upon surface saturation. In this work, we introduce a regeneratable biosensing scheme enabled by allosteric regulation of a reengineered pH sensitive anti-cocaine aptamer. The aptamer can regain its affinity with target analytes due to proton-promoted duplex-to-triplex transition in DNA configuration followed by the release of adsorbed analytes. A Pd/PdH x electrode placed next to the sensor can enable the pH regulation of the local chemical environment via electrochemical reactions. Demonstration of a "flower-shaped", stretchable, and inductively coupled electronic system with sensing and energy harvesting capabilities provides a promising route to designing wireless devices in biointegrated forms. These advances have the potential for future development of electronic sensing platforms with on-chip regeneration capability for continuous, quantitative, and real-time monitoring of chemical and biological markers.

Technology Roadmap for Flexible Sensors

“…A resettable electrochemical sweat lactate sensor has been developed through reversible redox reactions in a biofuel cell . Regeneration of aptamers for cocaine sensing has been realized through pH-modulated conformational changes . Microfluidics are a promising platform for continuous-monitoring wearable biosensors.…”

“…232 Regeneration of aptamers for cocaine sensing has been realized through pH-modulated conformational changes. 233 Microfluidics are a promising platform for continuous-monitoring wearable biosensors. For instance, stretchable microfluidics can expel sweat from filled channels to enable multiple usage.…”

Recent progress in biosensor regeneration techniques

“…A recent study utilizes this mechanism for in vivo regeneration of cocaine sensors through mild shifts in pH levels. 32 The sensing is facilitated by a modified DNA sequence that includes a pH-sensitive domain at the 5′ end of the oligonucleotide for cocaine detection. As the pH level decreases, the formation of an intramolecular triplex interferes with the stem of the cocaine-aptamer complex that has a three-way junction structure, resulting in the liberation of the bound ligands (i.e., cocaine).…”

A DNA polymerase-powered self-propelled DNA walking strategy for one-step, amplified and dual-signal electrochemical target detection

“…Alternatively, some DNA-based isothermal amplication strategies, for example, rolling circle amplication (RCA), loopmediated isothermal amplication (LAMP), helicase dependent amplication (HDA), recombinase polymerase amplication (RPA), and strand displacement amplication (SDA), are popular for sensitivity improvement. [17][18][19][20] However, these strategies are usually based on the combined use of several nucleases, increasing the assay cost and the possibility of non-specic amplication. Also, these signal amplication means are more suitable for nucleic acid analysis by optical methods.…”