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 (DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math>) and rotational (DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math>) diffusion coefficients within polyethylene oxide solutions (0 to 3 wt. %) and human bronchial epithelial cell (hBEC) mucus (0 to 6.4 wt. %). Interpolation of DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> and DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> 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.
Conclusions
The extended dynamic range afforded by simultaneous measurement of DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> and DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> 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.
Results
In polymer solutions and mucus, DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> and DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> monotonically decrease with increasing concentration. DRDR<math><mrow><msub><mrow><mi>D</mi></mrow><mrow><mi>R</mi></mrow></msub></mrow></math> is more sensitive than DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> 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 DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> measurements. Conclusions: The extended dynamic range afforded by simultaneous measurement of DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> and DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> 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.
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 (DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math>) and rotational (DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math>) diffusion coefficients within polyethylene oxide solutions (0 to 3 wt. %) and human bronchial epithelial cell (hBEC) mucus (0 to 6.4 wt. %). Interpolation of DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> and DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> 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, DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> and DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> monotonically decrease with increasing concentration. DRDR<math><mrow><msub><mrow><mi>D</mi></mrow><mrow><mi>R</mi></mrow></msub></mrow></math> is more sensitive than DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> 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 DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> measurements. Conclusions: The extended dynamic range afforded by simultaneous measurement of DTDT<math><mrow><msub><mi>D</mi><mi>T</mi></msub></mrow></math> and DRDR<math><mrow><msub><mi>D</mi><mi>R</mi></msub></mrow></math> 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.