A microfluidic respiratory assist device with high gas permeance for artificial lung applications

Abstract

One of the principal challenges in artificial lung technology has been the ability to provide levels of oxygen and carbon dioxide exchange that rival those of the natural human lung, while mitigating the deleterious interaction between blood and the surface of the synthetic gas exchange membrane. This interaction is exacerbated by the large oxygenator surface area required to achieve sufficient levels of gas transfer. In an effort to address this challenge, microfluidics-based artificial lung technologies comprising stacked microchannel networks have been explored by several groups. Here we report the design, fabrication and initial testing of a parallel plate multilayered silicone-based microfluidic construct containing ultrathin gas exchange membranes, aimed at maximizing gas transfer efficiency while minimizing membrane-blood contact area. The device comprises a branched microvascular network that provides controlled wall shear stress and uniform blood flow, and is designed to minimize blood damage, thrombosis and inflammatory responses seen in current oxygenators. Initial testing indicates that flow distribution through the multilayer structure is uniform and that the thin membrane can withstand pressures equivalent to those expected during operation. Oxygen transfer using phosphate buffered saline as the carrier fluid has also been assessed, demonstrating a sharp increase in oxygen transfer as membrane thickness is reduced, consistent with the expected values of oxygen permeance for thin silicone membranes.

Kinetics of sickle cell biorheology and implications for painful vasoocclusive crisis

“…1A). The O 2 concentration was controlled by exchanging gas flow in the channel through the PDMS membrane, which is gaspermeable (33). Although it is known (34) that the morphology of sickled cells depends on the DeOxy rate, we observed heterogeneity in cell morphology at the same DeOxy rate.…”

Microfluidic Organ‐on‐a‐Chip Technology for Advancement of Drug Development and Toxicology

“…This issue was addressed by Kniazeva et al, [ 29 ] who created a microfl uidic design to maximize gas transfer, with the goal of working towards creating an artifi cial lung or a lung assistant device. The design consisted of a small branched network of channels representing the microvascular system, with an ultrathin membrane separating the microvascular network from the channel representing oxygen fl ow.…”

“…Human alveolar epithelial/microvascular endothelial cells [7] Observing cellular injury through both solid and fl uid mechanical stress A549, AEC [28] Producing suitable levels of gas transfer for artifi cial lung applications N/A [29] Gaseous exchange in vascular network through creation of free-standing membranes N/A [31] Optimizing fl ow and gaseous exchange through use of a vascular scaffold N/A [30] Intestine Toxicity/Drug Testing µCCA model to study GI tract and predict drug toxicity Caco-2 and HepG2/C3A [36] Testing drug permeability in the intestinal epithelial cell membrane through use of microhole trapping Caco-2 [44] Functional analysis Use of hydrogels as a platform for cultivated cells in a GI tract design Caco-2 [38] Functional model for potential integration in a body-on-a-chip design Analyzing signals through bacteria-cell interaction in GI tract HeLa S3 [39] Effects of shear stress, monocyte-EC adhesion, and monocyte transmigration on a vasculature system PAEC, RAW264.7, THP-1 [66] Bone Marrow Toxicity/Drug Testing Radiation-induced toxicity effects on a bone marrow-on-a-chip hematopoietic and adipocyte cells [67] Cancer/Tumor Toxicity/Drug Testing Studying chemotherapy resistance using a lung cancer microfl uidic model Recreating prostate cancer microenvironment using fl uid shear stress…”

Organs-on-a-chip for drug discovery

“…Kniazeva et al [26] have recently applied microfluidics to combine capillary channels for blood delivery with a large membrane for the exchange of oxygen. The resulting device contained interdigitated layers of blood and oxygen filled channels that can be stacked to produce a 3D lung architecture, which could not be generated using standard macroscale approaches.…”