A Microfluidic Model of Biomimetically Breathing Pulmonary Acinar Airways

Summary

Soft-lithography was utilized to produce a representative true-scale model of pulmonary alveolated airways that expand and contract periodically, mimicking physiological breathing motion. This platform recreates respiratory acinar flows on a chip, and is anticipated to facilitate experimental investigation of inhaled aerosol dynamics and deposition in the pulmonary acinus.

Abstract

Quantifying respiratory flow characteristics in the pulmonary acinar depths and how they influence inhaled aerosol transport is critical towards optimizing drug inhalation techniques as well as predicting deposition patterns of potentially toxic airborne particles in the pulmonary alveoli. Here, soft-lithography techniques are used to fabricate complex acinar-like airway structures at the truthful anatomical length-scales that reproduce physiological acinar flow phenomena in an optically accessible system. The microfluidic device features 5 generations of bifurcating alveolated ducts with periodically expanding and contracting walls. Wall actuation is achieved by altering the pressure inside water-filled chambers surrounding the thin PDMS acinar channel walls both from the sides and the top of the device. In contrast to common multilayer microfluidic devices, where the stacking of several PDMS molds is required, a simple method is presented to fabricate the top chamber by embedding the barrel section of a syringe into the PDMS mold. This novel microfluidic setup delivers physiological breathing motions which in turn give rise to characteristic acinar air-flows. In the current study, micro particle image velocimetry (µPIV) with liquid suspended particles was used to quantify such air flows based on hydrodynamic similarity matching. The good agreement between µPIV results and expected acinar flow phenomena suggest that the microfluidic platform may serve in the near future as an attractive in vitro tool to investigate directly airborne representative particle transport and deposition in the acinar regions of the lungs.

Introduction

A detailed quantification of respiratory flow dynamics in the distal, alveolated regions of the lungs is paramount towards understanding airflow mixing in the pulmonary acinus and predicting the fate of inhaled aerosols in the deepest airways^1–3. This latter aspect is of particular concern when addressing on the one hand the hazards of inhaled pollutant particles or conversely in seeking novel strategies for improved and targeted drug delivery of inhaled therapeutics to localized lung sites^{4, 5} as well as for systemic delivery.

To date, respiratory flows in the deep pulmonary acinar regions have been typical....

Protocol

1. Master Fabrication

1. Use deep reactive ion etching (DRIE) of a silicon on insulator (SOI) wafer to fabricate a master silicon wafer as described in former works^{32, 33}.
   NOTE: DRIE is preferred to standard SU-8 micromachining due to the high aspect ratio features (40 µm wide and 90 µm deep trenches).

2. Casting and Sealing of the Microfluidic Device

1. Mix PDMS and curing agent at a 10:1 weight ratio inside a clean small container such as a plastic weighing dish.
2. Degas the mixture in a desiccator under vacuum until all air bubbles are removed.
   NOTE: Prepare e....

Results

Computer-aided design (CAD) and microscope images of the in vitro acinar platform are presented in Fig. 1. The biomimetic acinar model features five generations of branching rectangular channels lined with alveolar-like cylindrical cavities (Fig. 1). Here, the model generations are numbered from generation 1 (for the most proximal generation) to generation 5 (for the most distal generation). Note that only the channel inlet leading to generation 1 is open to the outer environmen.......

Discussion

A critical feature of the microfluidic acinar platform presented here is its ability to reproduce physiologically-realistic breathing motions that give rise to physiological flow profiles and velocities within acinar ducts and within alveoli. Since the microfluidic channels are produced with a relatively low aspect ratio (i.e., w_d/h ≈ 3.9, where w_d is the duct width and h is the duct height), the measured flows show more plug-like .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Polydimethylsiloxane (PDMS) and curing agent	Dow Corning	(240)4019862	Sylgard® 184 Silicone Elastomer Kit
Plastipak 2 ml syringe	BD	300185
Norm-Ject Luer slip 1 ml syringe	Henke Sass Wolf	4010-200V0
1 mm Biopsy punch	Kai Medical	BP-10F
Laboratory Corona Treater	Electro-Technic Products	BD-20AC
PHD Ultra Syringe pump	Harvard apparatus	703006
Dyed red rqueous fluorescent particles	Thermo-Scientific		Uncatalloged 0.86 µm beads were used
Glycerin AR	Gadot	830131320
FlowMaster MITAS micro-particle image velocimetry (µPIV) system	LaVision	1108630