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Doppler frequency shifts associated with the motions in cells range from mHz to Hz, requiring ultra-stable interferometry to capture frequency offsets at several parts in 1018. Common-path interferometers minimize the influence of mechanical disturbances when the signal and reference share common optical elements. In this paper, multi-mode speckle self-referencing via a Fresnel biprism demonstrates frequency stability down to 1 mHz. A low-coherence NIR source creates an OCT-like pseudo-coherence-gate in Fourier-domain holography without phase stepping, and the Fourier reconstruction of the self-referencing speckle fields produces an image-domain autocorrelation of the target. Fluctuation spectroscopy of dynamic speckle is performed on a semi-solid lipid emulsion that captures Brownian thermal signatures and on feline tissue culture that measures active intracellular transport. The extension of biodynamic imaging to lower frequencies opens the opportunity for studies of cell crawling in macroscopic living tissues.
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Coherent light scattering from cellular dynamics in living tissues
Abstract This review examines the biological physics of intracellular transport probed by the coherent optics of dynamic light scattering from optically thick living tissues. Cells and their constituents are in constant motion, composed of a broad range of speeds spanning many orders of magnitude that reflect the wide array of functions and mechanisms that maintain cellular health. From the organelle scale of tens of nanometers and upward in size, the motion inside living tissue is actively driven rather than thermal, propelled by the hydrolysis of bioenergetic molecules and the forces of molecular motors. Active transport can mimic the random walks of thermal Brownian motion, but mean-squared displacements are far from thermal equilibrium and can display anomalous diffusion through Lévy or fractional Brownian walks. Despite the average isotropic three-dimensional environment of cells and tissues, active cellular or intracellular transport of single light-scattering objects is often pseudo-one-dimensional, for instance as organelle displacement persists along cytoskeletal tracks or as membranes displace along the normal to cell surfaces, albeit isotropically oriented in three dimensions. Coherent light scattering is a natural tool to characterize such tissue dynamics because persistent directed transport induces Doppler shifts in the scattered light. The many frequency-shifted partial waves from the complex and dynamic media interfere to produce dynamic speckle that reveals tissue-scale processes through speckle contrast imaging and fluctuation spectroscopy. Low-coherence interferometry, dynamic optical coherence tomography, diffusing-wave spectroscopy, diffuse-correlation spectroscopy, differential dynamic microscopy and digital holography offer coherent detection methods that shed light on intracellular processes. In health-care applications, altered states of cellular health and disease display altered cellular motions that imprint on the statistical fluctuations of the scattered light. For instance, the efficacy of medical therapeutics can be monitored by measuring the changes they induce in the Doppler spectra of livingex vivocancer biopsies.
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- Award ID(s):
- 2200186
- PAR ID:
- 10493866
- Publisher / Repository:
- IOP Publishing
- Date Published:
- Journal Name:
- Reports on Progress in Physics
- Volume:
- 87
- Issue:
- 3
- ISSN:
- 0034-4885
- Format(s):
- Medium: X Size: Article No. 036601
- Size(s):
- Article No. 036601
- Sponsoring Org:
- National Science Foundation
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