Laser speckle particle sizer informs the size distribution of tissue granularities

Size characterization is critical in pharmaceutical and clinical applications, yet current methods struggle to map particle size distributions within intact biological specimens in nm–µm range. Dynamic Light Scattering (DLS), the industry standard, is limited to dilute, transparent, low-viscosity suspensions and lacks sensitivity to slower dynamics in viscous media or tissue. We introduce a laser Speckle PARticle SizEr (SPARSE) that leverages the spatio-temporal analysis of polarized speckle to estimate particle sizes in opaque biofluids and tissues. Backscattered speckle patterns are captured at two polarization states, and their intensity envelope and autocorrelation are calculated. A polarized Monte-Carlo ray tracing model simulates these attributes across biologically relevant parameters, identifying metrics that inform size and refractive index. SPARSE results correlate strongly with DLS in polybead and milk phantoms and with smear microscopy in increasingly hypertonic blood. In breast carcinoma, SPARSE distinguishes adipose, fibrous, and epithelial compartments, showing promise as a noninvasive diagnostic tool.