Surface modification of microfluidic oxygenator units with an antithrombin-heparin (ATH) covalent complex for...

Respiratory distress syndrome (RDS) is a common complication affecting preterm and term neonates. To overcome issues caused by RDS, our group has developed an "artificial placenta" technology including a microfluidic lung assist device (LAD) built from single oxygenator units (SOUs). It is essential that the material surfaces within this system have reduced thrombogenicity when in contact with blood. In the present work, the surfaces of the polydimethylsiloxane (PDMS) microfluidic LAD were modified under flow conditions with an antithrombin-heparin covalent complex (ATH) using polydopamine (PDA) as a bio-adhesive. ATH uptake and stability on the surface were determined by radiolabelling and ATH heparin bioactivity was evaluated by measuring AT adsorption from plasma. ATH density on the surface was 0.21 ± 0.05 µg/cm² and the bound ATH was relatively stable in flowing blood with 76% remaining on the surface after two days. The specific heparin activity of the modified SOUs, in terms of AT adsorption from plasma, was 47.78 ± 10.63 ng/cm² compared to 11.56 ± 4.58 ng/cm² for PDMS-PDA SOUs, thereby demonstrating the efficacy of the ATH surface modification. The devices modified with ATH were resistant to clotting over a period of one hour in flowing plasma, and oxygen permeability was not compromised by the surface modifications. These results demonstrate that a previously developed PDA-ATH modification strategy can be translated from flat PDMS substrates to microfluidic SOUs under flow-based coating conditions, providing device-level anticoagulant function without measurably compromising membrane oxygen permeability under the conditions tested.