Label-Free Super-Resolution Microscopy with Coherent Nonlinear Structured-Illumination

Conventional structured-illumination microscopy provides up to a two-fold improvement in the achievable lateral resolution by spatially modulating the intensity profile of the illumination beam. However, the conventional structured-illumination scheme cannot be directly combined with label-free nonlinear coherent imaging modalities. Here we propose a way to overcome this limitation by generalizing the concept of structured-illumination microscopy to coherent nonlinear wide-field modalities, where the phase of the illumination beam is spatially modulated while interferometrically measuring the complex-valued scattered field. We demonstrate numerically how by using nonlinear processes of second-harmonic generation and third- harmonic generation up to four- and six-fold increases in the lateral resolution are possible, respectively. Since coherent nonlinear imaging modalities do not require use of labels, the demonstrated approach provides possibilities for biomedical applications benefitting from minimal sample preparation.