Solid-state electronics and single-molecule biophysics

Biomolecular systems are traditionally studied using ensemble measurements and fluorescence-based detection. Among the most common in vitro applications are DNA microarrays to identify target gene expression profiles [1] and enzyme-linked immunosorbent assays (ELISA) to identify proteins [2]. While much can be determined with ensemble measurements, scientific and technological interest is rapidly moving to single-molecule techniques. When probing at the single-molecule level, observations can be made about the inter- and intramolecular dynamics that are usually hidden in ensemble measurements. In molecular diagnostic, single-molecule techniques often do not require amplification and simplify sample preparation. The most popular single-molecule techniques based on fluorescence [3, 4] are fundamentally limited in resolution and bandwidth by the countable number of photons emitted by a single fluorophore (typically on the order of 2500 photons/sec). Instrumentation is complex, expensive, and large-form-factor. Furthermore, most optical probes photobleach, limiting observation times and pump powers. Single-molecule measurements of the kinetics of fast biomolecular processes are often unavailable through fluorescent techniques, as they lack the required temporal resolution.