Super-resolution imaging has facilitated groundbreaking discoveries by surpassing classical limitations. However, the commonly employed fluorescence-based approach exhibits inherent drawbacks, such as low labeling efficiency and potential toxicity. To address these challenges, we propose photothermal relaxation localization (PEARL) microscopy, a broadly applicable label-free chemical imaging technique that exploits the unique temporal characteristics of sub-diffraction limit objects. These features can be extracted through higher harmonic demodulation, effectively transcending the diffraction limit. Unlike existing methods, PEARL demonstrates a highly linear power dependence, enabling enhanced signal levels without the need for high peak power. Furthermore, PEARL's applicability extends to virtually any absorptive material. Experimental validations encompassing a range of materials, from gold nanoparticles to subcellular droplets, corroborate PEARL's ability to achieve superior resolution. In summary, PEARL introduces a versatile and potent optical super-resolution imaging technique with the potential to catalyze advancements across diverse scientific domains.
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Delong Zhang (2024) studied this question.
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