image: Figure | DART enables label-free molecular imaging with quantitative virtual staining. (a) Mesoscale molecular imaging demonstration showing the DART system (inset) acquiring data across a centimeter scale field of view. The topographic height map reveals sample variations from 590 to 635 μm. The recovered nucleic acid mass distribution (0-50.53 femtograms) and protein mass distribution (0-796.90 femtograms) are quantitatively mapped at each pixel without any external labels or stains. (b) Virtual staining based on the quantitative molecular maps produces familiar histological appearances, with nucleic acids (blue) corresponding to cell nuclei and proteins (purple) representing cytoplasm. This physics-based approach provides explainable and reproducible results directly derived from measured molecular content, unlike black-box AI methods.
Credit: Guoan Zheng et al.
For centuries, biological imaging has relied on dyes and fluorescent labels to visualize cellular structures -- a practice that not only alters samples but can delay critical medical decisions. Traditional staining can take 20-30 minutes during surgery, potentially delaying critical decisions about tumor margins. Even routine pathology requires lengthy preparation protocols that modify the very molecules being studied.
In a new paper published in eLight, a team of scientists led by Professor Guoan Zheng from the University of Connecticut, has developed the deep-ultraviolet ptychographic pocket-scope (DART) -- a handheld platform that transforms molecular imaging through intrinsic deep-ultraviolet spectroscopic contrast.
DART changes the imaging paradigm by exploiting a fundamental property of biology: DNA and proteins naturally absorb specific wavelengths of deep-ultraviolet light. By imaging at 266 and 280 nanometers -- wavelengths where nucleic acids and proteins have distinct absorption signatures -- DART creates quantitative molecular maps with femtogram precision without any external labels.
“DART provides molecular information instantly, and because it’s based on intrinsic molecular properties rather than dye binding, the results are inherently quantitative and reproducible,” explains Zheng.
The system achieves remarkable specifications in a handheld form factor: 308-nanometer resolution, centimeter-scale field of view, and millimeter-scale depth of field. This combination, impossible with conventional microscopy, enables comprehensive tissue imaging without mechanical refocusing.
A key feature of DART is its ‘virtual staining’ capability. Unlike AI-based approaches that can generate artifacts or hallucinate features, DART's virtual stains derive directly from measured molecular content. The system quantifies nucleic acid and protein masses with femtogram accuracy, then translates these measurements into familiar histological appearances.
“We’re essentially giving clinicians molecular X-ray vision,” notes Zheng. “hey can see not just cell structures, but the actual protein and DNA distributions that define cellular identity and pathological states.”
The implications extend beyond terrestrial laboratories. The compact, label-free design makes DART ideal for space missions, where monitoring astronaut health and studying microbial adaptation under microgravity are critical challenges. The device could also enable field diagnostics in resource-limited settings where traditional staining infrastructure is unavailable.
The team achieved these capabilities through several technical innovations. They modified commercial image sensors to improve deep ultraviolet sensitivity. A disorder-engineered coded surface converts high-angle scattered light into detectable signals. Most critically, their ‘virtual state’ algorithm eliminates artifacts from LED coherence limitations and optical imperfections.
Looking forward, the researchers envision expanding DART’s wavelength range for finer molecular discrimination and developing endoscopic versions for in-vivo imaging. The technology could transform pathology workflows, enable real-time surgical guidance, and open new frontiers in space biology -- all while preserving samples in their natural, unaltered state.
The convergence of computational imaging, spectroscopy, and miniaturization embodied in DART represents more than incremental progress. It offers a fundamentally new way to observe biology: directly, quantitatively, and without perturbation.
Journal
eLight
Article Title
Deep-ultraviolet ptychographic pocket-scope (DART): mesoscale lensless molecular imaging with label-free spectroscopic contrast