Deep Speckle Holography Redefines Label-free Nanoparticle Phenotyping

TL;DR

Deep speckle holography is a novel, physics-informed method enabling simultaneous, label-free, multidimensional nanoparticle profiling in complex fluids with rapid, non-destructive measurements.

Contribution

It introduces deep speckle holography, a generative framework that profiles nanoparticle identity, size, and morphology from single measurements without purification or labeling.

Findings

Enables direct nanoparticle inference in native fluids without preprocessing.

Provides rapid (0.9 s) multidimensional readouts over a wide dynamic range.

Works across diverse samples including environmental and biological fluids.

Abstract

Nanoparticle metrology has long been constrained by the assumption that, in mixed and unprocessed fluids, particle size, morphology, composition, and species-specific abundance cannot be resolved simultaneously from a single label-free measurement. Here, we revisit this long-standing limitation by showing that complex forward speckle-holographic fields define an information-rich optical space for multidimensional particle signatures. We report deep speckle holography, a physics-informed generative framework that profiles particle identity, size, morphology, and species-resolved abundance from a single non-contact optical measurement. Across purified suspensions, mixed particle populations, environmental waters, human urine, and other unprocessed native fluids, the method enables direct nanoparticle inference without purification, labeling, or destructive preprocessing, delivering concurrent multidimensional readouts in 0.9 s over a dynamic range spanning 10 orders of magnitude. Deep speckle holography establishes a route toward direct label-free nanoparticle phenotyping in real-world fluids, moving nanoscale measurement beyond isolated-particle characterization toward multidimensional inference in complex mixtures, and expanding the scope of questions nanoscale measurement can address, from real-time tracking of nanoparticle transformations in living and environmental systems to non-invasive quality control of nanomedicine formulations, and beyond.