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

Abstract

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 ($D_T$) and rotational ($D_R$) diffusion coefficients within polyethylene oxide solutions (0 to 3 wt. %) and human bronchial epithelial cell (hBEC) mucus (0 to 6.4 wt. %). Interpolation of $D_T$ and $D_R$ 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, $D_T$ and $D_R$ monotonically decrease with increasing concentration. $D_R$ is more sensitive than $D_T$ 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 $D_R$ measurements.

Conclusions: The extended dynamic range afforded by simultaneous measurement of $D_T$ and $D_R$ 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.

Keywords: gold nanorods; mucus; optical coherence tomography; particle diffusion; polyethylene oxide.