Evaluation of silicon membranes for extracorporeal membrane oxygenation (ECMO).

While extracorporeal membrane oxygenation (ECMO) is a valuable therapy for patients with lung or heart failure, clinical use of ECMO remains limited due to hemocompatibility concerns with pro-coagulatory hollow fiber membrane geometries. Previously, we demonstrated the feasibility of silicon nanopore (SNM) and micropore (SµM) membranes for transport between two liquid-phase compartments in blood-contacting devices. Herein, we investigate various pore sizes of SNM and SµM membranes - alone or with a polydimethylsiloxane (PDMS) protective coating - for parameters that determine suitability for gas exchange. We characterized the bubble or rupture point of these membranes to determine sweep gas pressures at which gas emboli would form. The smallest pore size SNM and the SµM with PDMS coating could be pressurized in excess of 260 cmHg without rupture, which is comparable to hollow fiber sweep gas pressures. Oxygen flux for the SµM with and without PDMS was insignificantly different at 0.0306 ± 0.0028 and 0.0297 ± 0.0012 mL/min, respectively, while SNM flux was significantly lower at 0.0149 ± 0.0040 mL/min. However, the area-normalized mass transfer coefficient of the SNM was 338 ± 54 mL O2 m-2 min-1 cmHg-1 - an order of magnitude higher than that of the SµM with and without PDMS (57.3 ± 5.5 and 55.6 ± 2.2 mL O2 m-2 min-1 cmHg-1). Ultimately, we conclude that SµM-PDMS may make effective membranes for ECMO, since they are both mechanically robust and capable of high oxygen flux.

Silicon Micropore-Based Parallel Plate Membrane Oxygenator.

Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SµM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM-PDMS membranes was 3.03 ± 0.42 mL O2 min-1 m-2 cm Hg-1 with pure water and 1.71 ± 1.03 mL O2 min-1 m-2 cm Hg-1 with blood. An analytic model to predict gas transport was developed using data from the bench-top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM-PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.

Silicon nanoporous membranes as a rigorous platform for validation of biomolecular transport models.

Microelectromechanical systems (MEMS), a technology that resulted from significant innovation in semiconductor fabrication, have recently been applied to the development of silicon nanopore membranes (SNM). In contrast to membranes fabricated from polymeric materials, SNM exhibit slit-shaped pores, monodisperse pore size, constant surface porosity, zero pore overlap, and sub-micron thickness. This development in membrane fabrication is applied herein for the validation of the XDLVO (extended Derjaguin, Landau, Verwey, and Overbeek) theory of membrane transport within the context of hemofiltration. In this work, the XDLVO model has been derived for the unique slit pore structure of SNM. Beta-2-microglobulin (B2M), a clinically relevant "middle molecular weight" solute in kidney disease, is highlighted in this study as the solute of interest. In order to determine interaction parameters within the XDLVO model for B2M and SNM, goniometric measurements were conducted, yielding a Hamaker constant of 4.61× 10-21 J and an acid-base Gibbs free energy at contact of 41 mJ/m2. The XDLVO model was combined with existing models for membrane sieving, with predictions of the refined model in good agreement with experimental data. Furthermore, the results show a significant difference between the XDLVO model and the simpler steric predictions typically applied in membrane transport. The refined model can be used as a tool to tailor membrane chemistry and maximize sieving or rejection of different biomolecules.

Thermodynamic analysis of osmotic energy recovery at a reverse osmosis desalination plant.

Recent years have seen a substantial reduction of the specific energy consumption (SEC) in seawater reverse osmosis (RO) desalination due to improvements made in hydraulic energy recovery (HER) as well as RO membranes and related process technologies. Theoretically, significant potential for further reduction in energy consumption may lie in harvesting the high chemical potential contained in RO concentrate using salinity gradient power technologies. Herein, "osmotic energy recovery" (OER) is evaluated in a seawater RO plant that includes state-of-the-art RO membranes, plant designs, operating conditions, and HER technology. Here we assume the use of treated wastewater effluent as the OER dilute feed, which may not be available in suitable quality or quantity to allow operation of the coupled process. A two-stage OER configuration could reduce the SEC of seawater RO plants to well below the theoretical minimum work of separation for state-of-the-art RO-HER configurations with a breakeven OER CAPEX equivalent to 42% of typical RO-HER plant cost suggesting significant cost savings may also be realized. At present, there is no commercially viable OER technology; hence, the feasibility of using OER at seawater RO plants remains speculative, however attractive.

Characterization of human islet function in a convection-driven intravascular bioartificial pancreas.

Clinical islet transplantation for treatment of type 1 diabetes (T1D) is limited by the shortage of pancreas donors and need for lifelong immunosuppressive therapy. A convection-driven intravascular bioartificial pancreas (iBAP) based on highly permeable, yet immunologically protective, silicon nanopore membranes (SNM) holds promise to sustain islet function without the need for immunosuppressants. Here, we investigate short-term functionality of encapsulated human islets in an iBAP prototype. Using the finite element method (FEM), we calculated predicted oxygen profiles within islet scaffolds at normalized perifusion rates of 14-200 nl/min/IEQ. The modeling showed the need for minimum in vitro and in vivo islet perifusion rates of 28 and 100 nl/min/IEQ, respectively to support metabolic insulin production requirements in the iBAP. In vitro glucose-stimulated insulin secretion (GSIS) profiles revealed a first-phase response time of <15 min and comparable insulin production rates to standard perifusion systems (~10 pg/min/IEQ) for perifusion rates of 100-200 nl/min/IEQ. An intravenous glucose tolerance test (IVGTT), performed at a perifusion rate of 100-170 nl/min/IEQ in a non-diabetic pig, demonstrated a clinically relevant C-peptide production rate (1.0-2.8 pg/min/IEQ) with a response time of <5 min.

Real-time assessment of fluid flow generated by appendage movements of Daphnia using standing square-wave chronamperometry.

Standing square-wave chronoamperometry (SSWCA) was applied to the analysis of the microfluid flow generated by the movement of the appendages of the Crustacea Daphnia. This novel approach provided for the first time real-time assessment and analysis of the breathing rate/fluid flow of individual organisms. An electrochemical tracer was delivered into the fluid inflow of the organism and a carbon fiber microelectrode placed in the fluid outflow's path. The variation of the net concentration/flux of the electroactive tracer, dopamine, at the electrode surface was measured with SSWCA. The observed chronoamperometric peaks (with fine structure) of the outflow are seen as a direct representation of appendage movement and, too, the workings and responses of the organism to its environment, e.g., external stimuli such as food or chemicals. It was concluded that SSWCA follows primarily the variation of the convective component of the Nernst-Plank equation for flux and, to lesser extent, diffusion and migration. In this work, SSWCA can clearly be used to monitor changes in the Daphnia-generated fluid outflow on a different time scale than was previously possible. This new application of SSWCA is faster and likely more accurate than using high-speed video.

Slit pores preferred over cylindrical pores for high selectivity in biomolecular filtration.

Microelectromechanical systems (MEMS) have enabled the fabrication of silicon nanopore membranes (SNM) with uniform non-overlapping "slit shaped" pores. The application of SNM has been suggested for high selectivity of biomolecules in a variety of medical filtration applications. The aim of this study was to rigorously quantify the differences in sieving between slit pore SNM and more commonly modeled cylindrical pore membranes, including effects of the extended Derjaguin, Landau, Verwey, and Overbeek (XDLVO) interactions. Applying equations derived for SNM in previous work, we compare the partition coefficient of slit and cylindrical pore membranes while accounting for both steric and XDLVO interactions. Simple, steric approximations demonstrate that slit pore membranes exhibit significantly lower partition coefficients than cylindrical pore models. Incorporating XDLVO interactions results in an even more marked difference between slit pore and cylindrical pore membranes. These partition coefficients were used to evaluate changes in beta-2-microglobulin (B2M) selectivity. The data demonstrate that XDLVO interactions increase the selectivity advantage that slit pores possess over cylindrical pores, particularly for larger values of the acid-base decay constant. Finally, the bovine serum albumin (BSA) to B2M selectivity ratio was investigated. The selectivity ratio appears larger in slit pores than cylindrical pores for all cases, indicating that slit pores are particularly well suited for hemofiltration applications. The results of this study have significant implications for the application of SNM in membrane processes where highly selective separation of biomolecules is desirable.

The redox couple of the cytochrome c cyanide complex: the contribution of heme iron ligation to the structural stability, chemical reactivity, and physiological behavior of horse cytochrome c.

Contrary to most heme proteins, ferrous cytochrome c does not bind ligands such as cyanide and CO. In order to quantify this observation, the redox potential of the ferric/ferrous cytochrome c-cyanide redox couple was determined for the first time by cyclic voltammetry. Its E0' was -240 mV versus SHE, equivalent to -23.2 kJ/mol. The entropy of reaction for the reduction of the cyanide complex was also determined. From a thermodynamic cycle that included this new value for the cyt c cyanide complex E0', the binding constant of cyanide to the reduced protein was estimated to be 4.7 x 10(-3) L M(-1) or 13.4 kJ/mol (3.2 kcal/mol), which is 48.1 kJ/mol (11.5 kcal/mol) less favorable than the binding of cyanide to ferricytochrome c. For coordination of cyanide to ferrocytochrome c, the entropy change was earlier experimentally evaluated as 92.4 J mol(-1) K(-1) (22.1 e.u.) at 25 K, and the enthalpy change for the same net reaction was calculated to be 41.0 kJ/mol (9.8 kcal/mol). By taking these results into account, it was discovered that the major obstacle to cyanide coordination to ferrocytochrome c is enthalpic, due to the greater compactness of the reduced molecule or, alternatively, to a lower rate of conformational fluctuation caused by solvation, electrostatic, and structural factors. The biophysical consequences of the large difference in the stabilities of the closed crevice structures are discussed.

Diffusive Silicon Nanopore Membranes for Hemodialysis Applications.

Hemodialysis using hollow-fiber membranes provides life-sustaining treatment for nearly 2 million patients worldwide with end stage renal disease (ESRD). However, patients on hemodialysis have worse long-term outcomes compared to kidney transplant or other chronic illnesses. Additionally, the underlying membrane technology of polymer hollow-fiber membranes has not fundamentally changed in over four decades. Therefore, we have proposed a fundamentally different approach using microelectromechanical systems (MEMS) fabrication techniques to create thin-flat sheets of silicon-based membranes for implantable or portable hemodialysis applications. The silicon nanopore membranes (SNM) have biomimetic slit-pore geometry and uniform pores size distribution that allow for exceptional permeability and selectivity. A quantitative diffusion model identified structural limits to diffusive solute transport and motivated a new microfabrication technique to create SNM with enhanced diffusive transport. We performed in vitro testing and extracorporeal testing in pigs on prototype membranes with an effective surface area of 2.52 cm2 and 2.02 cm2, respectively. The diffusive clearance was a two-fold improvement in with the new microfabrication technique and was consistent with our mathematical model. These results establish the feasibility of using SNM for hemodialysis applications with additional scale-up.