In situ pulmonary mucus hydration assay using rotational and translational diffusion of gold nanorods with polarization-sensitive optical coherence tomography.

Significance: Assessing the nanostructure of polymer solutions and biofluids is broadly useful for understanding drug delivery and disease progression and for monitoring therapy. Aim: Our objective is to quantify bronchial mucus solids concentration (wt. %) during hypertonic saline (HTS) treatment in vitro via nanostructurally constrained diffusion of gold nanorods (GNRs) monitored by polarization-sensitive optical coherence tomography (PS-OCT). Approach: Using PS-OCT, we quantified GNR translational (DT) and rotational (DR) diffusion coefficients within polyethylene oxide solutions (0 to 3 wt. %) and human bronchial epithelial cell (hBEC) mucus (0 to 6.4 wt. %). Interpolation of DT and DR data is used to develop an assay to quantify mucus concentration. The assay is demonstrated on the mucus layer of an air-liquid interface hBEC culture during HTS treatment. Results: In polymer solutions and mucus, DT and DR monotonically decrease with increasing concentration. DR is more sensitive than DT to changes above 1.5 wt. % of mucus and exhibits less intrasample variability. Mucus on HTS-treated hBEC cultures exhibits dynamic mixing from cilia. A region of hard-packed mucus is revealed by DR measurements. Conclusions: The extended dynamic range afforded by simultaneous measurement of DT and DR of GNRs using PS-OCT enables resolving concentration of the bronchial mucus layer over a range from healthy to disease in depth and time during HTS treatment in vitro.

OCT particle tracking velocimetry of biofluids in a microparallel plate strain induction chamber.

SIGNIFICANCE: Imaging biofluid flow under physiologic conditions aids in understanding disease processes and health complications. We present a method employing a microparallel plate strain induction chamber (MPPSIC) amenable to optical coherence tomography to track depth-resolved lateral displacement in fluids in real time while under constant and sinusoidal shear. AIM: Our objective is to track biofluid motion under shearing conditions found in the respiratory epithelium, first validating methods in Newtonian fluids and subsequently assessing the capability of motion-tracking in bronchial mucus. APPROACH: The motion of polystyrene microspheres in aqueous glycerol is tracked under constant and sinusoidal applied shear rates in the MPPSIC and is compared with theory. Then 1.5 wt. % bronchial mucus samples considered to be in a normal hydrated state are studied under sinusoidal shear rates of amplitudes 0.7 to 3.2 s - 1. RESULTS: Newtonian fluids under low Reynolds conditions (Re ∼ 10 - 4) exhibit velocity decreases directly proportional to the distance from the plate driven at both constant and oscillating velocities, consistent with Navier-Stokes's first and second problems at finite depths. A 1.5 wt. % mucus sample also exhibits a uniform shear strain profile. CONCLUSIONS: The MPPSIC provides a new capability for studying biofluids, such as mucus, to assess potentially non-linear or strain-rate-dependent properties in a regime that is relevant to the mucus layer in the lung epithelium.