Gerard F. Jones

Experimental characterization of next-generation expanded-bed adsorbents for capture of a recombinant protein expressed in high-cell-density yeast fermentation

Expanded‐bed adsorption (EBA) can be particularly useful in protein recovery from high‐cell‐density fermentation broth where conventional methods for harvest and clarification, such as continuous centrifugation and depth filtration, demand long processing times and are associated with high costs. In this work, the use of next‐generation high‐particle‐density EBA adsorbents, including two mixed‐mode resins, for the direct capture of a recombinant protein expressed in yeast at high cell densities is evaluated. Using classical experimental approaches and under different conditions (pH, salt, etc.), Langmuir isotherm parameters for these resins are obtained along with pore diffusivity values. Additional batch adsorption studies with Fastline® MabDirect, the resin that demonstrated the highest static binding capacity for the recombinant protein of interest under the conditions evaluated in this study, indicate competitive binding of nontarget proteins and approximately a 30% reduction in equilibrium binding capacity to 50 mg/mL settled bed in the presence of a 5%–10% cell concentration. Packed‐bed (PB) dynamic binding capacities for the MabDirect resin (25–40 mg/mL PB) were significantly higher than for the Fastline® HSA resin and for the MabDirect MM resin in expanded‐bed mode (5–10 mg/mL settled bed). Bed expansion behavior for the mMabDirect MM resin along with process yield and eluate purity are identified as a function of linear velocity and cell density, demonstrating process feasibility for pilot scale use.

Using a two species competitive binding model to predict expanded bed breakthrough of a recombinant protein expressed in a high cell density fermentation

Expanded Bed experiments were conducted using a mixed mode (MM) resin to capture and purify a recombinant protein produced in yeast fermentation. Expanded bed breakthrough profiles show an overshoot in column effluent concentration of the target protein in the presence of cells and other broth proteins, similar to that seen by other researchers when loading two competing species onto packed beds. In this research, a numerical model assuming negligible axial dispersion is developed and first validated for columns loads that contain only the target protein. This model is solved by finite differences in a unique way that uses an embedded analytical-solution to increase solution speed and stability. To model expanded bed breakthrough of the target protein in the actual cell broth, it was assumed that the other non-product proteins in the broth compete for MM resin binding sites and might be represented as a second “average” species via a traditional two-component competitive Langmuir isotherm. Estimates of the Langmuir constant and broth concentration of this second species were then calculated from batch adsorption data. Using these parameters for the second species, and other batch-derived parameters for the target protein with this resin, this unique numerical modeling approach provided results that compare favorably to experimental breakthrough data at various flow rates. Finally, the model was employed for a parameter sensitivity analysis that shows which process variables are most important in determining breakthrough time and the shape and magnitude of the concentration overshoot.

Application of Mathematical Modeling for Simulation and Analysis of Hypoplastic Left Heart Syndrome (HLHS) in Pre- and Postsurgery Conditions

This paper is concerned with the mathematical modeling of a severe and common congenital defect called hypoplastic left heart syndrome (HLHS). Surgical approaches are utilized for palliating this heart condition; however, a brain white matter injury called periventricular leukomalacia (PVL) occurs with high prevalence at or around the time of surgery, the exact cause of which is not known presently. Our main goal in this paper is to study the hemodynamic conditions under which HLHS physiology may lead to the occurrence of PVL. A lumped parameter model of the HLHS circulation has been developed integrating diffusion modeling of oxygen and carbon dioxide concentrations in order to study hemodynamic variables such as pressure, flow, and blood gas concentration. Results presented include calculations of blood pressures and flow rates in different parts of the circulation. Simulations also show changes in the ratio of pulmonary to systemic blood flow rates when the sizes of the patent ductus arteriosus and atrial septal defect are varied. These changes lead to unbalanced blood circulations and, when combined with low oxygen and carbon dioxide concentrations in arteries, result in poor oxygen delivery to the brain. We stipulate that PVL occurs as a consequence.

Experiments on the simultaneous two-phase liquid cooling of multiple simulated servers at differing vertical rack positions in steady state

An experimental study was conducted to examine the behavior of a refrigerant two-phase system for cooling multiple servers at differing vertical locations within a standard data center rack. In such racks, the vertically stacked servers may operate at different utilization levels and hence may have differing power dissipations. Furthermore, these distinct power dissipations may occur at differing vertical levels in the rack and may be time-dependent as a result of IT workload scheduling. A reliable two phase cooling system must operate in a stable and controllable fashion under these conditions and the design and characterization of such a system is the topic of this study. An experimental rig was developed for evaluating both pumped and non-pumped (thermosyphon) refrigerant two-phase systems for cooling simulated CPUs in both steady and transient scenarios, and with multiple simulated CPUs operating at distinct vertical positions. Each server flow branch was supplied by a common supply manifold, absorbing the heat at the CPUs using a mini-channel evaporator and returning the two-phase flow to a chilled water cooled plate condenser. Precise measurements were made of the mass flow rate to each branch as well as temperatures and pressures at all key system locations, allowing the identification of thermodynamic state at all relevant system positions. This paper presents preliminary experimental results for two simultaneously operating servers at different vertical positions and with different heat loads operating in steady state, in both pumped and non-pumped modes. It is shown that the system operation is stable in both modes for the two-server case. The flow rate branches evenly in the pumped case, with little effect of vertical position. In the non-pumped thermosyphon operation, flow rate to each server location is not affected by is power dissipation and vertical position.

Computational Modeling of Hypoplastic Left Heart Syndrome (HLHS) in Newborn Babies

Hypoplastic left heart syndrome (HLHS) is a congenital heart defect (CHD) in which left side of the heart is severely underdeveloped. To better understand this unique physiology, a computational model of the hypoplastic heart was constructed on the basis of compartmental analysis. Lumped parameter model of HLHS is developed based on the electrical circuit analogy. Model is made up of three parts: hypoplastic heart, pulmonary circulation and systemic circulation. Plots of blood pressure and flow for various parts of body show great match between predicted values and what we expected for the case of HLHS babies. Influence of patent ductus arteriosus (PDA) and ASD resistances on cardiac output and pulmonary to systemic flow was also studied. Results show that by increasing the PDA resistance causes more flow to pulmonary compartments and so the ratio increases. Blood flow increases by decreasing of pulmonary artery resistant. Increasing the PDA resistance causes decrease the cardiac output because of more resistance against blood occurs. Saturation increases by decreasing of pulmonary artery resistant.Copyright

Experimental Characterization of a Carbon Fiber Composite Material Heat Sink in Boiling Heat Transfer Using FC-72

The on-going trend towards increasing device performance while shrinking device size often results in escalating power densities and high operating temperatures. High operating temperatures may lead to reduced reliability and induced thermal stresses. Therefore, it is necessary to employ new and innovative thermal management techniques to maintain a suitable junction temperature at high power densities. For this reason, there is interest in a variety of liquid cooling techniques. This study analyzes a composite material heat sink. The heat sink consists of a very large number of small cross-section fins fabricated from carbon pitch fibers and epoxy. These carbon pitch fibers have a high thermal conductivity along the length of the fin. It is expected that the longer length will result in more heat transfer surface area and a more effective heat sink. This experimental study characterizes the thermal performance of the carbon-fiber heat sink in a two-phase closed loop thermosyphon using FC-72 as the operating fluid. The influence of heat load, thermosyphon fill volume, and condenser operating temperature on the overall thermal performance is examined. The results of this experiment provide significant insight into the possible implementation and benefits of carbon fiber heat sink technology in two-phase flow leading to significant improvements in thermal management strategies for advanced electronics. The carbon fiber heat sink yielded heat transfer coefficients in the range of 1300-1500 W/m2 K for heat fluxes in the range up to 3.2 W/cm2 . Resistances in the range of 0.20 K/W – 0.23 K/W were achieved for the same heat fluxes. Condenser temperature and fill ratio did not show a significant effect on any of the results.Copyright

Experimental Characterization of a Unique Carbon Fiber Brush Heat Sink in Two-Phase Heat Transfer

The performance enhancements and footprint decreases of advanced electronic devices result in soaring power densities which may in turn lead to elevated operating temperatures. As elevated device temperatures lead to decreased device reliability and increased thermal stresses, it is necessary to employ aggressive thermal management techniques to maintain an acceptable junction temperature at high power densities. For this reason, interest is growing in a variety of liquid cooling techniques This study analyzes an advanced engineered-material heat sink which provides significant improvements in thermal management strategies for advanced electronics. The heat sink consists of a very large number of small cross-section fins fabricated from carbon pitch fibers. For these carbon pitch fibers, the high thermal conductivity reduces the temperature drop along the length of the fin creating a longer effective fin length than for copper fins. The longer length results in more heat transfer surface area and a more effective heat sink. In liquid cooling, the rough surface of the fin will provide multiple bubble nucleation sites, strongly promoting active two-phase heat transfer over the entire fin surface. This surface enhancement is expected to lead to significant increases in performance over conventional heat sinks. This experimental analysis characterizes the thermal performance of the carbon-fiber heat sink in two-phase closed loop thermosyphon operation using FC72 as the operating fluid. The influence of power load, thermosyphon fill volume and condenser operating temperature on the overall thermal performance is examined. The results of this experiment provide significant insight into the possible implementation and benefits of carbon fiber heat sink technology in two-phase flow leading to significant improvements in thermal management strategies for advanced electronics.Copyright