# Computational structured illumination for high-content fluorescent and phase microscopy

## TL;DR

This paper introduces a computational speckle structured illumination microscopy technique that achieves high-resolution, large field-of-view imaging for both fluorescence and quantitative phase microscopy, enabling detailed biological analysis.

## Contribution

It presents a novel cost-effective speckle SIM method that jointly reconstructs fluorescence and phase images with 4x resolution enhancement over traditional systems.

## Key findings

- Achieves 700 nm fluorescence resolution and 1.2 μm phase resolution.
- Covers a large FOV of 2x2.7 mm^2 with high SBP.
- Effectively corrects for system imperfections during reconstruction.

## Abstract

High-content biological microscopy targets high-resolution imaging across large fields-of-view (FOVs). Recent works have demonstrated that computational imaging can provide efficient solutions for high-content microscopy. Here, we use speckle structured illumination microscopy (SIM) as a robust and cost-effective solution for high-content fluorescence microscopy with simultaneous high-content quantitative phase (QP). This multi-modal compatibility is essential for studies requiring cross-correlative biological analysis. Our method uses laterally-translated Scotch tape to generate high-resolution speckle illumination patterns across a large FOV. Custom optimization algorithms then jointly reconstruct the sample's super-resolution fluorescent (incoherent) and QP (coherent) distributions, while digitally correcting for system imperfections such as unknown speckle illumination patterns, system aberrations and pattern translations. Beyond previous linear SIM works, we achieve resolution gains of 4x the objective's diffraction-limited native resolution, resulting in 700 nm fluorescence and 1.2 um QP resolution, across a FOV of 2x2.7 mm^2, giving a space-bandwidth product (SBP) of 60 megapixels.