Single-molecule studies reveal important molecular characteristics, including kinetics and dynamics of molecular reactions, hidden in the heterogeneous, unsynchronized populations that characterize most ensemble techniques. Optical techniques, especially fluorescence microscopy techniques, have been the most popular approaches to observe single-molecules providing three-dimensional visualization of multiple molecules simultaneously. However, sophisticated instrumentation hinders broader applications of this technology into cost-effective sensors. In contrast, electronic detection approaches have the potential to support large multiplexed arrays of sensors with fully integrated detection electronics. Field-effect transistors (FETs) allow label-free, real-time detection of molecules by transducing the intrinsic charge of molecules into the conductance of the device. In this talk, we present an electronic single-molecule system which enables miniaturization of multiplexed and massively parallel assays. We employ a single-walled carbon nanotube (SWCNT) as a sensing interface and fabricate 100-mm wafer-scale FET arrays by placing nanotubes using spin-casting. For genomic assays, detection is achieved with a single-stranded DNA (ssDNA) probe molecule which is functionalized onto the SWCNT. We have established a point-functionalization approach that is electrically controllable and applicable to many devices in parallel in arrays. We demonstrated direct observation of the covalent bonding process between the SWCNT and the aryl-diazonium ion at the single-event level, which was followed by probe ssDNA immobilization. The device transduces single DNA hybridization events by detecting the intrinsic negative charge of the DNA molecule. Also, biasing the surrounding electrolyte relative to the device enables electrical DNA melting (e-melting) by inducing a repulsive charge on the SWCNT. Other probe molecules expand the utility of the approach. For example, an aptamer probe allows small molecule detection by monitoring substantial conformational change associated with small-molecule binding to the aptamer structure.

Massively parallel single-molecule detection platform using nano-electronics

2019 Fall National Meeting

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