I. Introduction
Biomolecular
systems are traditionally studied using fluorescence-based ensemble
measurements of the average characteristics of a relatively large number
of molecules. Among the most common in vitro
applications are DNA microarrays to identify 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 biomolecules at the single-molecule level,
dynamics can be observed which are usually hidden in ensemble
measurements. The most popular single-molecule techniques are also based
on fluorescence [3]. Though fluorescent probes are highly specific,
they use light as an intermediary between the biological system and
measurement electronics, which results in fundamental constraints in
resolution and bandwidth due to the countable number of photons emitted.
Single-molecule measurements of the kinetics of fast biomolecular
processes are often unavailable through fluorescent techniques, as they
lack the necessary temporal resolution.