Non-fluorescent molecular super-resolution imaging system based on photothermal relaxation localization microscopy

Abstract

The present invention discloses a non-fluorescent molecular super-resolution imaging system based on photothermal relaxation localization microscopy, which includes a pump light source, a detection light source, a microscope, a photodetector, a multi-harmonic signal extraction device, and an imaging processing device. The detection light, modulated by the photothermal effect of the target sample and the dissipation of photothermal energy, undergoes multi-harmonic demodulation, and then super-resolution imaging is performed based on the high-harmonic signals extracted from the frequency domain. This method enables super-resolution imaging of light-absorbing molecules or structures without fluorescent labels, fundamentally resolving several limitations of conventional super-resolution imaging, such as photobleaching, labeling efficiency, and labeling selectivity of fluorescent molecules. Furthermore, it fundamentally eliminates various limitations of super-resolution fluorescence, such as the need for specially designed fluorescent molecules and photodamage caused by high-power lasers.

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