UNEx-4Pi Method: Sidelobe-Free 3D Nanoscopy Breakthrough

Sidelobe-free deterministic 3D nanoscopy with λ/33 axial resolution has been a groundbreaking development in the field of super-resolution microscopy. The ability to achieve light-matter interaction in a highly confined space has been a long-standing challenge in physics and cutting-edge technologies. Various 3D microscopy modalities have been developed to break the diffraction limit and achieve super-resolution imaging by controlling fluorescence processes. These modalities offer different levels of lateral and axial resolution, but most suffer from limitations in achieving isotropic resolution.

The 4Pi microscopy was developed to address the axial resolution limitations by coherently adding the wavefronts of two opposing objectives. However, traditional 4Pi microscopy setups are complex and suffer from sidelobe issues due to interference nature, refractive index mismatches, and alignment challenges. The high-order nonlinear effect by multiphoton excitation has shown promise in achieving sub-diffraction resolution and suppressing sidelobes. Lanthanide-doped upconversion nanoparticles with photon avalanche properties have demonstrated exceptional nonlinear optical responses, making them ideal for achieving high-resolution imaging.

To overcome the limitations of traditional 4Pi microscopy and achieve a sidelobe-free, high-resolution 3D nanoscopy, a new method called UNEx-4Pi was developed. This method combines ultrahighly nonlinear excitation of photon avalanching nanoparticles with mirror-based bifocal vector field modulation. The theoretical studies and experimental results of the UNEx-4Pi concept have shown significant improvements in the sharpness of fluorescence spots and the suppression of sidelobes. The system demonstrated an extremely constringent focal spot without observed sidelobes, achieving an impressive axial resolution of λ/33 using a single low-power CW beam.

The UNEx-4Pi method has the potential to revolutionize super-resolution imaging, sensing, lithography, and data storage applications by enabling light-matter interaction in highly confined spaces. The simplicity, robustness, and high resolution capabilities of UNEx-4Pi make it a promising tool for advancing nanoscopic technologies. The integration of adaptive optics and further experimentation to enhance the performance and applications of UNEx-4Pi are underway, paving the way for new discoveries and innovations in the field of optical microscopy.