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Open Access Publications from the University of California

Scholarly Works (14 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2010)

There is a growing need for technology that can control microscale oxygen gradients onto a tissue or culture sample in vitro. This dissertation introduces the oxygen microgradient chip (OMA), which employs electrolysis to generate oxygen microgradients within cell culture without forming bubbles. Dissolved oxygen generated at noble microelectrodes patterned on a chip surface diffuses through a gas-permeable silicone membrane and is dosed into cell culture. The amount of generated oxygen is directly proportional to a current flowing across the electrodes and thus can be controlled with high precision. By real-time modulation of the current, spatial profile of the oxygen concentration microgradient can be modified during an experiment. Distinct microgradients generated by different electrodes can be superimposed to pattern arbitrary and multi-dimensional oxygen concentration profiles with microscale resolution. Design of the OMA is based on simulation results of diffusion and physical considerations. Microfabrication, assembly process, and improvements of the early OMA are presented. Use of an oxygen-sensitive fluorophore film verifies that the measured microgradients in OMA match simulation results. Generation of reactive oxygen species during the electrolysis is also considered and quantified. This technology enables the biological study of gradient-related effects. Three different, well-known biological models are introduced to demonstrate how the microtechnology enables new types of experiments. Lastly, we explore the effect of oxygen gradients on muscle progenitor cells having half-deficiency of superoxide dismutase-1 (SOD1) enzyme. Another type of oxygen gradient chip that utilizes atmospheric oxygen is developed and used in this experiment. Myotube formation of the SOD1 heterozygote myoblasts decreased significantly compared to that of wild-type myoblasts, indicating that the oxygen stress on SOD1 heterozygote myoblasts induces defective cellular function on differentiation.

    Cover page: Oxygen Concentration Microgradients for Cell Culture
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2017)
    Major clinical challenges associated with islet transplantation for type 1 diabetes include shortage of donor organs, poor engraftment due to ischemia, and need for immunosuppressive medications. Semipermeable membrane capsules can immunoprotect transplanted islets by blocking passage of the host's immune components while providing exchange of glucose, insulin, and other small molecules. However, capsules-based diffusive transport often exacerbates ischemic injury to islets by reducing the rate of oxygen and nutrient transport. We previously reported the efficacy of a newly developed semipermeable ultrafiltration membrane, the silicon nanopore membrane (SNM) under convective-driven transport, in limiting the passage of pro-inflammatory cytokines while overcoming the mass transfer limitations associated with diffusion through nanometer-scale pores. In this study, we report that SNM-encapsulated mouse islets perfused in culture solution under convection outperformed those under diffusive conditions in terms of magnitude (1.49-fold increase in stimulation index and 3.86-fold decrease in shutdown index) and rate of insulin secretion (1.19-fold increase and 6.45-fold decrease during high and low glucose challenges), respectively. Moreover, SNM-encapsulated mouse islets under convection demonstrated rapid glucose-insulin sensing within a physiologically relevant time-scale while retaining healthy islet viability even under cytokine exposure. We conclude that encapsulation of islets with SNM under convection improves islet in vitro functionality. This approach may provide a novel strategy for islet transplantation in the clinical setting.
      Cover page: Glucose-Stimulated Insulin Response of Silicon Nanopore-Immunoprotected Islets under Convective Transport.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2018)
      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.
        Cover page: Slit pores preferred over cylindrical pores for high selectivity in biomolecular filtration
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2017)
        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.
          Cover page: Silicon nanoporous membranes as a rigorous platform for validation of biomolecular transport models
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2018)
          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.
            Cover page: Silicon Micropore‐Based Parallel Plate Membrane Oxygenator
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2017)
            Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet viability and functionality due to inadequate mass transfer resulting in islet hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration-based BAP devices possess enhanced glucose-insulin kinetics, the polymer membranes used in these devices provide inadequate ultrafiltrate flow rates and result in excessive thrombosis. Here, we report the silicon nanopore membrane (SNM), which exhibits a greater hydraulic permeability and a superior pore size selectivity compared to polymer membranes for use in BAP applications. Specifically, we demonstrate that the SNM-based intravascular BAP with ∼10 and ∼40 nm pore sized membranes support high islet viability (>60%) and functionality (<15 minute insulin response to glucose stimulation) at clinically relevant islet densities (5700 and 11 400 IE per cm2) under convection in vitro. In vivo studies with ∼10 nm pore sized SNM in a porcine model showed high islet viability (>85%) at clinically relevant islet density (5700 IE per cm2), c-peptide concentration of 144 pM in the outflow ultrafiltrate, and hemocompatibility under convection. These promising findings offer insights on the development of next generation of full-scale intravascular devices to treat T1D patients in the future.
              Cover page: An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport.
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2017)
              Correction for 'An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport' by Shang Song et al., Lab Chip, 2017, 17, 1778-1792.
                Cover page: Correction: An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2019)
                We report wafer-scale growth of atomically thin, three-dimensional (3D) van der Waals (vdW) semiconductor membranes. By controlling the growth kinetics in the near-equilibrium limit during metal-organic chemical vapor depositions of MoS2 and WS2 monolayer (ML) crystals, we have achieved conformal ML coverage on diverse 3D texture substrates, such as periodic arrays of nanoscale needles and trenches on quartz and SiO2/Si substrates. The ML semiconductor properties, such as channel resistivity and photoluminescence, are verified to be seamlessly uniform over the 3D textures and are scalable to wafer scale. In addition, we demonstrated that these 3D films can be easily delaminated from the growth substrates to form suspended 3D semiconductor membranes. Our work suggests that vdW ML semiconductor films can be useful platforms for patchable membrane electronics with atomic precision, yet large areas, on arbitrary substrates.
                  Cover page: Atomically thin three-dimensional membranes of van der Waals semiconductors by wafer-scale growth.
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2016)
                  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.
                    Cover page: Diffusive Silicon Nanopore Membranes for Hemodialysis Applications
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2018)
                    We report 3D coherent diffractive imaging (CDI) of Au/Pd core-shell nanoparticles with 6.1 nm spatial resolution with elemental specificity. We measured single-shot diffraction patterns of the nanoparticles using intense x-ray free electron laser pulses. By exploiting the curvature of the Ewald sphere and the symmetry of the nanoparticle, we reconstructed the 3D electron density of 34 core-shell structures from these diffraction patterns. To extract 3D structural information beyond the diffraction signal, we implemented a super-resolution technique by taking advantage of CDI's quantitative reconstruction capabilities. We used high-resolution model fitting to determine the Au core size and the Pd shell thickness to be 65.0 ± 1.0 nm and 4.0 ± 0.5 nm, respectively. We also identified the 3D elemental distribution inside the nanoparticles with an accuracy of 3%. To further examine the model fitting procedure, we simulated noisy diffraction patterns from a Au/Pd core-shell model and a solid Au model and confirmed the validity of the method. We anticipate this super-resolution CDI method can be generally used for quantitative 3D imaging of symmetrical nanostructures with elemental specificity.
                      Cover page: Single-shot 3D coherent diffractive imaging of core-shell nanoparticles with elemental specificity.
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