(Invited) Optimising CNT-FET Biosensor Design: Tuning Biomolecule Interfaces for Aptamer-Biomarker Sensing and Beta-Lactamase Detection

Abstract

We will present different strategies to control the assembly of single walled carbon nanotube (SWCNT)-biomolecule interfaces towards the fabrication of bioelectronic devices, with a focus on the real-time biosensors with engineered aptamer and protein interfacing. In particular, we will report on the fabrication of nanoscale biosensing devices designed to present biorecognition moieties (aptamers and proteins) in defined orientations; this allowed us to control the local electrostatic surface presented within the Debye length, and thus modulate the conductance gating effect upon binding incoming targets, from biomarkers associated to stress and (neuro) trauma, to classes of enzyme relevant to antimicrobial resistance (beta-lactamases).Our efforts focused in particular on using beta-lactamase binding protein (BLIP2) as receptor due to its potential as a biosensor for the most common antibiotic degrading enzymes, the beta-lactamases (BLs). Attaching BLIP2 at single designed residues positions directly to SCNTs using genetically encoded phenyl azide photochemistry, our devices were able to successfully detect the two different BLs, TEM-1 and KPC-2. The changes in conductance closely matched the predicted electrostatic profile sampled by the CNTs on BL binding.These studies highlight the key role transducer-biomolecule interfaces play in biosensing devices, and the need to control and tune by design the electrostatic gating, for more effective and optimal CNT-FET biosensor construction.