Toward microfluidic integration of respiratory and renal organ support in a single cartridge.

BACKGROUND: Extracorporeal organ assist devices provide lifesaving functions for acutely and chronically ill patients suffering from respiratory and renal failure, but their availability and use is severely limited by an extremely high level of operational complexity. While current hollow fiber-based devices provide high-efficiency blood gas transfer and waste removal in extracorporeal membrane oxygenation (ECMO) and hemodialysis, respectively, their impact on blood health is often highly deleterious and difficult to control. Further challenges are encountered when integrating multiple organ support functions, as is often required when ECMO and ultrafiltration (UF) are combined to deal with fluid overload in critically ill patients, necessitating an unwieldy circuit containing two separate cartridges. METHODS: We report the first laboratory demonstration of simultaneous blood gas oxygenation and fluid removal in single microfluidic circuit, an achievement enabled by the microchannel-based blood flow configuration of the device. Porcine blood is flowed through a stack of two microfluidic layers, one with a non-porous, gas-permeable silicone membrane separating blood and oxygen chambers, and the other containing a porous dialysis membrane separating blood and filtrate compartments. RESULTS: High levels of oxygen transfer are measured across the oxygenator, while tunable rates of fluid removal, governed by the transmembrane pressure (TMP), are achieved across the UF layer. Key parameters including the blood flow rate, TMP and hematocrit are monitored and compared with computationally predicted performance metrics. CONCLUSIONS: These results represent a model demonstration of a potential future clinical therapy where respiratory support and fluid removal are both realized through a single monolithic cartridge.

Characterization of main pulmonary artery and valve annulus region of piglets using echocardiography, uniaxial tensile testing, and a novel non-destructive technique.

Characterization of cardiovascular tissue geometry and mechanical properties of large animal models is essential when developing cardiovascular devices such as heart valve replacements. These datasets are especially critical when designing devices for pediatric patient populations, as there is often limited data for guidance. Here, we present a previously unavailable dataset capturing anatomical measurements and mechanical properties of juvenile Yorkshire (YO) and Yucatan (YU) porcine main pulmonary artery (PA) and pulmonary valve (PV) tissue regions that will inform pediatric heart valve design requirements for preclinical animal studies. In addition, we developed a novel radial balloon catheter-based method to measure tissue stiffness and validated it against a traditional uniaxial tensile testing method. YU piglets, which were significantly lower weight than YO counterparts despite similar age, had smaller PA and PV diameters (7.6-9.9 mm vs. 10.1-12.8 mm). Young's modulus (stiffness) was measured for the PA and the PV region using both the radial and uniaxial testing methods. There was no significant difference between the two breeds for Young's modulus measured in the elastic (YU PA 84.7 ± 37.3 kPa, YO PA 79.3 ± 15.7 kPa) and fibrous regimes (YU PA 308.6 ± 59.4 kPa, YO PA 355.7 ± 68.9 kPa) of the stress-strain curves. The two testing techniques also produced similar stiffness measurements for the PA and PV region, although PV data showed greater variation between techniques. Overall, YU and YO piglets had similar PA and PV diameters and tissue stiffness to previously reported infant pediatric patients. These results provide a previously unavailable age-specific juvenile porcine tissue geometry and stiffness dataset critical to the development of pediatric cardiovascular prostheses. Additionally, the data demonstrates the efficacy of a novel balloon catheter-based technique that could be adapted to non-destructively measure tissue stiffness in situ.

Relationship Between Central Venous Catheter Protein Adsorption and Water Infused Surface Protection Mechanisms.

Central venous catheters (CVCs) are implanted in the majority of dialysis patients despite increased patient risk due to thrombotic occlusion and biofilm formation. Current solutions remain ineffective at preventing these complications and treatment options are limited and often harmful. We present further analysis of the previously proposed water infused surface protection (WISP) technology, an active method to reduce protein adsorption and effectively disrupt adsorbed protein sheaths on the inner surface of CVCs. A WISP CVC is modeled by a hollow fiber membrane (HFM) in a benchtop device which continuously infuses a saline solution across the membrane wall into the blood flow, creating a blood-free boundary layer at the lumen surface. Total protein adsorption is measured under various experimental conditions to further test WISP performance. The WISP device shows reduced protein adsorption as blood and WISP flow rates increase (P < 0.040) with up to a 96% reduction in adsorption over the no WISP condition. When heparin is added to the WISP flow, protein adsorption (0.097[+0.035/-0.055] µg/mm2 ) is reduced when compared to both bolus administration and nondoped WISP, 0.406(+0.056/-0.065) µg/mm2 (P = 0.001) and 0.191 (+0.076/-0.126) (P = 0.029), respectively. Additionally, when heparinized WISP is applied to a preadsorbed protein layer, 0.375(+0.114/-0.164) µg/mm2 , it displays the ability to reduce the previously-adsorbed protein, 0.186(+0.058/-0.084) µg/mm2 (P = 0.0012), suggesting aptitude for intermittent treatments. The WISP technology not only shows the ability to reduce protein adsorption, but also the ability to remove preadsorbed material by effectively delivering drugs to the point of adsorption; functionalities that could greatly improve clinical outcomes.

Water Infused Surface Protection as an Active Mechanism for Fibrin Sheath Prevention in Central Venous Catheters.

Protein adhesion in central venous catheters (CVCs) leads to fibrin sheath formation, the precursor to thrombotic and biofilm-related CVC failures. Advances in material properties and surface coatings do not completely prevent fibrin sheath formation and post-formation treatment options are limited and expensive. We propose water infused surface protection (WISP), an active method for prevention of fibrin sheath formation on CVCs, which creates a blood-free boundary layer on the inner surface of the CVC, limiting blood contact with the CVC lumen wall. A hollow fiber membrane (HFM) in a benchtop device served as a CVC testing model to demonstrate the WISP concept. Porcine blood was pumped through the HFM while phosphate buffered saline (PBS) was infused through the HFM wall, creating the WISP boundary layer. Protein adherences on model CVC surfaces were measured and imaged. Analytical and finite volume lubrication models were used to justify the assumption of a blood-free boundary layer. We found a 92.2% reduction in average adherent protein density when WISP is used, compared with our model CVC without WISP flow. Lubrication models matched our experimental pressure drop measurements suggesting that a blood-free boundary layer was created. The WISP technique also provides a novel strategy for drug administration for biofilm treatment. Reduction in adherent protein indicates a restriction on long-term fibrin sheath and biofilm formation making WISP a promising technology which improves a wide range of vascular access treatments.