Laser speckle particle sizer (SPARSE) informs the size distribution of tissue granularities

Tissues and biomaterials are composed of particles, including cells, nuclei, organelles, protein aggregates, lipid vesicles, and fibers. The size distribution of tissue particles and granularities is altered in various pathologies. These granularities span a wide range from nano- to micrometer scale, posing a unique challenge in quantifying the continuum of particles sizes in intact tissue. We introduce laser Speckle PARticle SizEr (SPARSE), a noncontact optical technique that enables particle sizing over 10 nanometer-to-10 micrometer range, through analyzing the spatiotemporal attributes of polarized laser speckle, back-scattered from biofluids and tissues. We demonstrate that SPARSE effectively quantifies the average particle sizes in milk, blood, and intact tissue without a prior knowledge of particles' refractive indices or concentrations. Through beam scanning, particle size distribution is mapped in benign and malignant breast tissues with high resolution (~100 micrometer), mirroring histopathological microstructures. By enabling particle sizing in intact biomaterials and tissues, SPARSE holds broad potential for applications across nanomedicine, diagnostics, and biotechnology.