RESUMEN
Microfluidic artificial lungs (µALs) are a new class of membrane oxygenators. Compared to traditional hollow-fiber oxygenators, µALs closely mimic the alveolar microenvironment due to their size-scale and promise improved gas exchange efficiency, hemocompatibility, biomimetic blood flow networks, and physiologically relevant blood vessel pressures and shear stresses. Clinical translation of µALs has been stalled by restrictive microfabrication techniques that limit potential artificial lung geometries, overall device size, and throughput. To address these limitations, a high-resolution Asiga MAX X27 UV digital light processing (DLP) 3D printer and custom photopolymerizable polydimethylsiloxane (PDMS) resin were used to rapidly manufacture small-scale µALs via vat photopolymerization (VPP). Devices were designed in SOLIDWORKS with 500 blood channels and 252 gas channels, where gas and blood flow channels were oriented orthogonally and separated by membranes on the top and bottom, permitting two-sided gas exchange. Successful devices were post-processed to remove uncured resin from microchannels and assembled with external tubing in preparation for gas exchange performance testing with ovine whole blood. 3D printed channel dimensions were 172 µm-tall × 320 µm-wide, with 62 µm-thick membranes and 124 µm-wide support columns. Measured outlet blood oxygen saturation (SO2) agreed with theoretical models and rated flow of the device was 1 mL min-1. Blood side pressure drop was 1.58 mmHg at rated flow. This work presents the highest density of 3D printed microchannels in a single device, one of the highest CO2 transfer efficiencies of any artificial lung to date, and a promising approach to translate µALs one step closer to the clinic.
Asunto(s)
Microfluídica , Intercambio Gaseoso Pulmonar , Ovinos , Animales , Intercambio Gaseoso Pulmonar/fisiología , Biomimética , Pulmón/fisiología , Impresión TridimensionalRESUMEN
The ability to cost-effectively produce large surface area microfluidic devices would bring many small-scale technologies such as microfluidic artificial lungs (µALs) from the realm of research to clinical and commercial applications. However, efforts to scale up these devices, such as by stacking multiple flat µALs have been labor intensive and resulted in bulky devices. Here, we report an automated manufacturing system, and a series of cylindrical multi-layer lungs manufactured with the system and tested for fluidic fidelity and function. A roll-to-roll (R2R) system to engrave multiple-layer devices was assembled. Unlike typical applications of R2R, the rolling process is synchronized to achieve consistent radial positioning. This allows the fluidics in the final device to be accessed without being unwrapped. To demonstrate the capabilities of the R2R manufacturing system, this method was used to manufacture multi-layer µALs. Gas and blood are engraved in alternating layers and routed orthogonally to each other. The proximity of gas and blood separated by gas permeable PDMS permits CO2 and O2 exchange via diffusion. After manufacturing, they were evaluated using water for pressure drop and CO2 gas exchange. The best performing device was tested with fresh whole bovine blood for O2 exchange. Three µALs were successfully manufactured and passed leak testing. The top performing device had 15 alternating blood and gas layers. It oxygenated blood from 70% saturation to 95% saturation at a blood flow of 3 mL min-1 and blood side pressure drop of 234 mmHg. This new roll-to-roll manufacturing system is suitable for the automated construction of multi-layer microfluidic devices that are difficult to manufacture by conventional means. With some upgrades and improvements, this technology should allow for the automatic creation of large surface area microfluidic devices that can be employed for various applications including large-scale membrane gas exchange such as clinical-scale microfluidic artificial lungs.