Drumming up single-molecule beats

Single-particle and single-molecule techniques have become invaluable tools to unravel complex chemical phenomena and biological processes. While fluorescence-based techniques have flourished due to advances in wavelength-dependent optical filtering and highly sensitive detectors (1), other methodologies (Fig. 1) have only recently achieved single-molecule sensitivity limits. A technique based on an oscillating nanodrum offers a promising new direction (2). Fig. 1. Various photothermal transducers for single-particle and single-molecule detection. ( A ) Nanomechanical resonator. A driven high-Q mechanical resonator oscillates at its stress-dependent frequency (red arrow). The photothermal plume produces thermal expansion, relieving stress and altering the resonance frequency measured by a Doppler vibrometer (green). ( B ) Surrounding medium. The heat plume produces a thermal plume (depicted by black circles) that a probe beam (green) scatters off of (dashed green arrows). The use of a high thermooptic coefficient medium (purple) enables sensitive detection. ( C ) Optical microresonator. A high-Q optical microresonator is photothermally heated, shifting the resonance condition monitored by a frequency-locked probe laser (green). ( D ) Atomic force microscope. A photothermal plume introduces thermal expansion in the sample, measured by deflection of the cantilever of the atomic force microscope (green arrow). ( E ) Surface plasmon resonance. Surface plasmons (green) are excited in a wide-field configuration. The thermal plume alters the local refractive index, shifting the plasmon. Room-temperature absorption-based techniques, while commonplace at the bulk level, offer significant challenges at the single-molecule level. A major obstacle arises when applying a typical transmission-type experimental geometry to single molecules from the extremely small single-molecule absorption cross-section, with a molecule yielding an almost imperceptible change in a large transmitted signal. At low temperature, … [↵][1]1To whom correspondence should be addressed. Email: rhg{at}chem.wisc.edu. [1]: #xref-corresp-1-1