Photonic lantern TIRF microscopy for highly efficient, uniform, artifact-free imaging.

We report a method for generating uniform, artifact-free total internal reflection fluorescence (TIRF) excitation via a photonic lantern. Our tapered waveguide, consisting of a multimode input and nine few-mode outputs, enables single-shot TIRF illumination from nine azimuthal directions simultaneously without the introduction of nonstationary devices. Utilizing the photonic lantern for multi-beam excitation provides a low-loss mechanism that supports a wide range of light sources, including high-coherence lasers and various wavelengths in the visible spectrum. Our excitation system also allows tuning of the TIRF penetration depth. The high-quality excitation produced by photonic lantern TIRF (PL-TIRF) enables unbiased imaging across the entire illumination field-of-view. The simplicity and robustness of our technique provides advantages over other TIRF approaches, which often have complicated setups with scanning devices or other impracticalities. In this paper we discuss the lantern design process, characterize its performance, and demonstrate flat-field super-resolution imaging and shadowless live-cell imaging using PL-TIRF.