Surface Modification of a Blood Contacting Polydimethylsiloxane Microfluidic Oxygenator

Abstract

Our collaborative lab group has conceptualized the 'artificial placenta', a lung assist device (LAD) for preterm and term neonates suffering from respiratory insufficiency. The device is connected to the infant by reopening the umbilical vessels, drawing blood through the extracorporeal LAD and back to the body using the natural pressure drop of the heart. Polydimethylsiloxane is the material of choice used for the LAD due to advantageous gas transfer properties; however, the inner microfluidic channels come into direct contact with blood. Therefore, surface modification is required to prevent coagulation. A novel antithrombin-heparin (ATH) covalent complex with high anticoagulant activity is used to coat the surface via the use of polydopamine (PDA) as a ‘bioglue.’ Dopamine has the ability to self-polymerize over many substrates (organic or inorganic) when subject to alkaline conditions in aqueous solution. The layer of PDA formed on the substrate (PDMS) may then be modified with specific proteins to create a bioactive surface. ATH modified onto PDMS discs via PDA showed strong monolayer coverage (0.23 μg/cm2) and remained relatively stable in blood up to 72 hours. When modified onto LAD oxygenator units via PDA and subject to flow conditions, ATH again showed strong monolayer coverage and remained in blood over 2 days. Specific bioactivity was also preserved. Another approach to surface modification is using tissue plasminogen activator (tPA) to induce fibrinolysis. Rather than preventing coagulation, a fibrinolytic surface could lyse clots as they form. tPA converts plasminogen into plasmin, which then degrades fibrin clots. PDMS-PDA discs modified with tPA in a similar manner to ATH showed strong surface coverage and stability in plasma, and tPA remained active against various activity assays. Eventually, a dual anticoagulant and fibrinolytic surface with ATH and tPA may be possible.