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Non-invasively focusing light into strongly scattering media, such asbiological tissue, is highly desirable but challenging. Recently, wavefrontshaping technologies guided by ultrasonic encoding or photoacoustic sensinghave been developed to address this limitation. So far, these methods provideonly acoustic diffraction-limited optical focusing. Here, we introducenonlinear photoacoustic wavefront shaping (PAWS), which achieves opticaldiffraction-limited (i.e. single-speckle-grain) focusing in scattering media.We develop an efficient dual-pulse excitation approach to generate strongnonlinear photoacoustic (PA) signals based on the Grueneisen memory effect.These nonlinear PA signals are used as feedback to guide iterative wavefrontoptimization. By maximizing the amplitude of the nonlinear PA signal, light iseffectively focused to a single optical speckle grain. Experimental resultsdemonstrate a clear optical focus on the scale of 5-7 micrometers, which is ~10times smaller than the acoustic focus in linear dimension, with an enhancementfactor of ~6000 in peak fluence. This technology has the potential to providehighly confined strong optical focus deep in tissue for microsurgery ofParkinson's disease and epilepsy or single-neuron imaging and optogeneticactivation.

Nonlinear photoacoustic wavefront shaping (PAWS) for single speckle-grain optical focusing in scattering media