Deep-ultraviolet ptychographic pocket-scope (DART): mesoscale lensless molecular imaging with label-free spectroscopic contrast

TL;DR

DART is a portable, lensless deep-ultraviolet ptychographic system that provides high-resolution, label-free molecular imaging of biological specimens over large areas with femtogram sensitivity.

Contribution

The paper introduces DART, a novel handheld platform that combines lensless ptychography with deep-ultraviolet spectroscopy for label-free mesoscale molecular imaging.

Findings

Achieves 308-nm resolution across centimeter-scale areas.

Maps nucleic acids and proteins with femtogram sensitivity.

Provides detailed molecular contrast without external labels.

Abstract

The mesoscale characterization of biological specimens has traditionally required compromises between resolution, field-of-view, depth-of-field, and molecular specificity, with most approaches relying on external labels. Here we present the Deep-ultrAviolet ptychogRaphic pockeT-scope (DART), a handheld platform that transforms label-free molecular imaging through intrinsic deep-ultraviolet spectroscopic contrast. By leveraging biomolecules' natural absorption fingerprints and combining them with lensless ptychographic microscopy, DART resolves down to 308-nm linewidths across centimeter-scale areas while maintaining millimeter-scale depth-of-field. The system's virtual error-bin methodology effectively eliminates artifacts from limited temporal coherence and other optical imperfections, enabling high-fidelity molecular imaging without lenses. Through differential spectroscopic imaging at deep-ultraviolet wavelengths, DART quantitatively maps nucleic acid and protein distributions with femtogram sensitivity, providing an intrinsic basis for explainable virtual staining. We demonstrate DART's capabilities through molecular imaging of tissue sections, cytopathology specimens, blood cells, and neural populations, revealing detailed molecular contrast without external labels. The combination of high-resolution molecular mapping and broad mesoscale imaging in a portable platform opens new possibilities from rapid clinical diagnostics, tissue analysis, to biological characterization in space exploration.