Laser Speckle Particle Sizer (SPARSE) Informs the Size Distribution of Tissue Granularities

Particle sizing of biomaterials and tissues holds profound implications across diverse industrial and clinical disciplines. Conventional approaches such as dynamic light scattering (DLS) are restricted to dilute liquids, and unable to assess particle size distribution in intact, untampered biomaterials and tissues in their native state. Here, we introduce the laser Speckle PARticle SizEr (SPARSE), which leverages the size-dependent attributes of polarized back-scattered laser speckle to characterize the average radius of a continuum of endogenous scattering particles, in the 10nm-10um range, in biological fluids and soft tissues in their native state. The SPARSE approach exploits cross- and co-polarized attributes of spatial and temporal laser speckle intensity fluctuations to quantify the average particle size in various specimens, including polystyrene microspheres, milk, whole blood specimens, and intact soft tissues, without prior knowledge or explicit account of refractive index and scattering concentrations. Through scanning the laser beam across the tissue surface, we establish the capability of SPARSE to evaluate a spatial map of heterogenous scattering particle sizes with a resolution of a few 10s of 𝜇m that closely mirrors histopathological microstructures in benign and carcinoma breast tissue specimens. By enabling the size characterization of intact tissues and biomaterials across a continuum of granularities, non-destructively in native specimens, SPARSE opens substantial opportunities for quality control in industrial applications, drug development, and advanced clinical diagnostics.