High optical nonlinearity enables super-resolution imaging through scattering layers

Imaging through scattering layers remains one of the key challenges in optical microscopy, particularly in biological tissues where light scattering degrades image resolution and contrast. We demonstrate that uniting intrinsic properties of multiply scattered light [1] with a high optical non-linearity (such as offered by avalanching nanoparticles, ANPs [2]) yields, rather surprisingly, super-resolution, low-background imaging behind opaque, strongly scattering layers. In our approach, a continuous wave 1064 nm laser illuminates the sample containing nonlinear labels through a strongly scattering layer, creating a random speckle field; individual speckle grains are diffraction-limited in their size. Due to the statistical distribution of speckle grain intensities and the steep nonlinear response of the ANPs, only the brightest speckle grain induces detectable emission. This effectively creates a single sub-diffraction excitation spot without requiring any ballistic light. Raster-scanning this spot across the sample is enabled by the angular memory effect [3], and images are acquired in a simple epi-detection configuration, analogous to two-photon microscopy. In contrast to standard