38 research outputs found

    Multi-Disciplinary Hands-On Desktop Learning Modules and Modern Pedagogies

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    Our team’s research focuses on fundamental problems in undergraduate education in terms of how to expand use of well researched, yet still “new”, teaching pedagogies of ‘sensing’ or ‘hands-on’, ‘active’ and ‘problem-based learning’ within engineering courses. It is now widely accepted that traditional lectures ARE NOT best for students – yet that is what the community almost universally does. To address this issue we are developing new Desktop Learning Modules (DLMs) that contain miniaturized processes with a uniquely expandable electronic system to contend with known sensor systems/removable cartridges, as well as, unknown expansions to the project. We have shown that miniaturized mimics of industrial-scale equipment produce process data that agree with correlations developed for large-scale equipment. We are now adapting concepts shown efficacious in a single chemical engineering course to a variety of engineering classes within civil, mechanical, bio- and electrical engineering. Some examples of new hands-on learning applications in chemical engineering include a boiler / condenser and evaporative and shell & tube heat exchangers. In bioengineering, we are developing prognostic devices for separating Prostate Cancer Tumor Cells (PCTCs) from blood, sensing for the presence of PCTCs, a thermoregulation simulated limb cartridge for studying kinematics of heat flow and heat distribution in human extremities, and immunoaffinity neuron-like ion selective electrodes. In civil engineering, the DLMs illustrate open channel flow units and a solar powered Rankine cycle is underway in mechanical engineering. We are implementing DLMs along with team learning pedagogy. In this paper we will present technical aspects surrounding development of a large number of new learning cartridges. While the assessment strategies being developed are broadly applicable we will just present one instance, with the civil engineering cartridge, of the identification of misconceptions and experimental design for assessing the impact of the DLM on learning. The assessment includes a pre- and post-test assessment to determine improvement in understanding basic concepts and persistence and/or repair of misconceptions

    A flow perfusion bioreactor with controlled mechanical stimulation: Application in cartilage tissue engineering and beyond

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    To repair articular cartilage (AC) defects in osteoarthritic patients, one approach is to engineer three-dimensional grafts with physicochemical properties similar to endogenous AC. Such grafts can be grown in bioreactors that provide environmental conditions favoring chondrogenesis. Studies show mechanical stimulation during the culturing process greatly enhances development of functional engineered grafts. A review of literature on bioreactor options reveals a lack of capacity to simultaneously stimulate cells with a combination of shear stress and oscillating hydrostatic pressure, both of which are important parts of the in vivo AC environment. It is hypothesized that combining both forces in a new bioreactor design will contribute to better AC tissue growth. In this paper, we provide a brief review of bioreactors and describe a new computer-controlled perfusion and pressurized bioreactor system, and the novelty of its control programming features for service in a host of applications. We briefly summarize results on synergistic effects in employing perfusion, oscillating hydrostatic pressure in a scaffold free environment and with the addition of encapsulation for inducing chondrogenesis. We further describe efforts to modify the newly developed system to include a continuous flow and pressurized centrifugal mode to enhance further the capabilities for inclusion of very high shear stresses. Applications for several other cell and tissue engineering approaches are discussed.&nbsp

    Fluid Flow through a High Cell Density Fluidized-Bed during Centrifugal Bioreactor Culture

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    An increasing demand for products such as tissues, proteins, and antibodies from mammalian cell suspension cultures is driving interest in increasing production through high-cell density bioreactors. The centrifugal bioreactor (CCBR) retains cells by balancing settling forces with surface drag forces due to medium throughput and is capable of maintaining cell densities above 10(8) cells/mL. This article builds on a previous study where the fluid mechanics of an empty CCBR were investigated showing fluid flow is nonuniform and dominated by Coriolis forces, raising concerns about nutrient and cell distribution. In this article, we demonstrate that the previously reported Coriolis forces are still present in the CCBR, but masked by the presence of cells. Experimental dye injection observations during culture of 15 μm hybridoma cells show a continual uniform darkening of the cell bed, indicating the region of the reactor containing cells is well mixed. Simulation results also indicate the cell bed is well mixed during culture of mammalian cells ranging in size from 10 to 20 μm. However, simulations also allow for a slight concentration gradient to be identified and attributed to Coriolis forces. Experimental results show cell density increases from 0.16 to 0.26 when centrifugal force is doubled by increasing RPM from 650 to 920 at a constant inlet velocity of 6.5 cm/s; an effect also observed in the simulation. Results presented in this article indicate cells maintained in the CCBR behave as a high-density fluidized bed of cells providing a homogeneous environment to ensure optimal growth conditions

    Kinetic Simulation of a Centrifugal Bioreactor for High Population Density Hybridoma Culture

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    Demand for increasingly complex post-translationally modified proteins, such as monoclonal antibodies (mAbs), necessitates the use of mammalian hosts for production. The focus of this paper is a continuous centrifugal bioreactor (CCBR) capable of increasing volumetric productivity for mAb production through high density hybridoma culture, exceeding 10 8 cells/mL. At these extreme densities environmental conditions such as substrate and inhibitor concentrations rapidly change, dramatically affecting growth rate. The development of a kinetic model predicting glucose, mAb, lactate, and ammonium concentrations based on dilution rate and cell density is shown in this paper. Additionally, it is found that pH affects both growth rate and viability, and a range of 6.9 to 7.4 is needed to maintain growth rate above 90% of the maximum. Modeling shows that operating an 11.4 mL CCBR inoculated with 2.0 × 10 7 cells/mL at a dilution rate of 1.3 h −1 , results in a predicted growth rate 82% of the maximum value. At the same dilution rate increasing density to 6.0 × 10 7 cells/mL decreases the predicted growth rate to 60% of the maximum; however, by increasing dilution rate to 6.1 h −1 the growth rate can be increased to 86% of the maximum. Using the kinetic model developed in this research the concentration of glucose, mAb, lactate, and ammonium are all predicted within 13% of experimental results. This model and an understanding of how RPM impacts cell retention serve as valuable tools for maintaining high density CCBR cultures, ensuring maximum growth associated mAb production rates

    A Study of the Coriolis Effect on the Fluid Flow Profile in a Centrifugal Bioreactor

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    Increasing demand for tissues, proteins, and antibodies derived from cell culture is necessitating the development and implementation of high cell density bioreactors. A system for studying high density culture is the centrifugal bioreactor (CCBR) which retains cells by increasing settling velocities through system rotation, thereby eliminating diffusional limitations associated with mechanical cell retention devices. This paper focuses on the fluid mechanics of the CCBR system by considering Coriolis effects. Such considerations for centrifugal bioprocessing have heretofore been ignored; therefore a simpler analysis of an empty chamber will be performed. Comparisons are made between numerical simulations and bromophenol blue dye injection experiments. For the non-rotating bioreactor with an inlet velocity of 4.3 cm/s, both the numerical and experimental results show the formation of a teardrop shaped plume of dye following streamlines through the reactor. However, as the reactor is rotated the simulation predicts the development of vortices and a flow profile dominated by Coriolis forces resulting in the majority of flow up the leading wall of the reactor as dye initially enters the chamber, results confirmed by experimental observations. As the reactor continues to fill with dye, the simulation predicts dye movement up both walls while experimental observations show the reactor fills with dye from the exit to the inlet. Differences between the simulation and experimental observations can be explained by excessive diffusion required for simulation convergence, and a slight density difference between dyed and un-dyed solutions. Implications of the results on practical bioreactor use are also discussed
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