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4 March 2013Towards single molecule detection using photoacoustic microscopy
Recently, a number of optical imaging modalities have achieved single molecule sensitivity, including photothermal
imaging, stimulated emission microscopy, ground state depletion microscopy, and transmission microscopy. These
optical techniques are based on optical absorption contrast, extending single-molecule detection to non-fluorescent
chromophores. Photoacoustics is a hybrid technique that utilizes optical excitation and ultrasonic detection, allowing it to
scale both the optical and acoustic regimes with 100% sensitivity to optical absorption. However, the sensitivity of
photoacoustics is limited by thermal noise, inherent in the medium itself in the form of acoustic black body radiation. In
this paper, we investigate the molecular sensitivity of photoacoustics in the context of the thermal noise limit. We show
that single molecule sensitivity is achievable theoretically at room temperature for molecules with sufficiently fast
relaxation times. Hurdles to achieve single molecule sensitivity in practice include development of detection schemes
that work at short working distance, <100 microns, high frequency, <100 MHz, and low loss, <10 dB.
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Amy M. Winkler, Konstantin Maslov, Lihong V. Wang, "Towards single molecule detection using photoacoustic microscopy," Proc. SPIE 8581, Photons Plus Ultrasound: Imaging and Sensing 2013, 85811A (4 March 2013); https://doi.org/10.1117/12.2004265