Webinar on May 12, 2021, 3:00 pm UTC+2
Photothermal Detection of Single Molecules and Single Gold Nanoparticles
The large mismatch between molecular sizes and optical wavelengths makes it hard to isolate optical signals from single small objects in condensed matter. The workhorse method for single-molecule detection remains fluorescence (or photoluminescence), but other methods based on scattering have appeared more recently .
Bright-field scattering (iSCAT) provides good signal-to-noise ratio in shot-noise-limited cases, but relies heavily on background subtraction. Photothermal contrast is a simpler and powerful way to subtract background, so that scattering by non-absorbing sample features is efficiently removed. After a short discussion of the principle, advantages and limitations of photothermal microscopy, I shall illustrate this technique with some of our results, including the detection of single quencher dye molecules , or that of weak changes of the absorption of a single gold nanorod due to adsorption of single non-absorbing protein molecules .
Photothermal microscopy, however, remains limited by the weak dependence, dn/dT, of the index of refraction of usual solids and liquids on temperature. It requires illumination intensities typically 1,000 times larger than fluorescence, which severely restricts photothermal imaging to the most photostable samples. Recently, several improvements of dn/dT have been proposed, in particular near-critical conditions  for photosensitive objects such as single conjugated polymer molecules.
Although more complex than single-beam microscopy methods, photothermal contrast offers the opportunity of complementary requirements on the heating and probing beams, which can be exploited for mid-infrared imaging with optical-limited resolution, or for chirality studies , where requirements on polarization purity and on high spatial resolution are fulfilled separately by the two beams.
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