Continuous culture and downstream processing of algae with recycle: An integrated large-scale approach for production of renewable crude oil

In order to have a significant impact on energy security and reduction of greenhouse gasses, the production of advanced biofuels must be increased to billions of gallons per year. Scale up of phototrophic algae bioprocessing for renewable oil production has been attempted for decades and has recently reached new levels of performance and scale. For over three years, Sapphire has successfully operated the world’s largest algae farm, consisting of 100 acres of ponds in New Mexico, used to feed an integrated conversion and extraction unit based on high temperature liquefaction technology. All aspects of the process are run on a continuous basis, including the recycle of water and nutrients from the harvest and extraction units back to the ponds. Typical oil refineries process 8 – 80 million liters of crude oil per day, on a continuous basis for up to 5 years non-stop, 24 hours per day. In order to be a significant source of crude oil to even a single refinery, productivity of an algal biorefinery must be at least 0.8 to 8 million liters of renewable crude per day. Furthermore, the manufacturing cost of the “green crude” must be at or below the current price of petroleum plus any carbon credits and/or renewable energy credits. The high productivity and low cost targets will be met only with robust, large-scale, continuous bioprocessing on an integrated basis with recycle of water and nutrients. This talk will first introduce key aspects of biofuels bioprocessing, in contrast and comparison to biopharmaceutical bioprocessing. This includes the impact of raw material costs versus product value, and the resulting need for phototrophic culture as well as continuous integrated recycle of water and nutrients. Methods to continuously maintain a target co-culture or ecosystem, in open ponds, free of unwanted predators, competitors, and pests, will also be discussed. Challenges regarding phototrophic growth of algae, such as mixing and light penetration, will be presented in context and comparison to typical heterotrophic growth of microorganisms and animal cells in closed vessels. Trends in productivity and future prospects for the field will be presented, including the potential use of genetically-modified organisms

Ignorant empiricism in cell culture engineering: 30 years of expensive lessons

Although cell culture engineering has generally been quite successful, the path forward was not steady, but instead has had many stalls and diversions. These have largely been due to approaches based upon ignorant empiricism --- i.e., it just seems to work, but we don\u27t know why . As it turns out, ignorant empiricism often goes hand-in-hand with performance barriers that are not identified and thus not overcome for years. Examples will be discussed such as early sparging, agitation, and cell line handling protocols that limited the impact of nutrient enrichment and modern medium development. Until such barriers were identified and overcome, industrial cell culture could not have met the cost requirements and market demands for monoclonal antibody therapeutics. Ignorant empiricism also led to the expensive development and testing of many creative but operationally complex and impractical bioreactor designs, as will be shown. It also led to both near and complete stock outs of life saving drugs as well as the failure and take-over of a major biopharmaceutical company. Lastly, it continues to lead to unexpected run failures, operational crises, and process performance variability, including unacceptable variability in product quality. This talk will cover 30 years of expensive lessons learned, including some being learned only now

Now you see me...

A report discussing the development of a series of film resources for use in undergraduate nurse educatio

Hydrodynamic effects on animal cells in microcarrier bioreactors by Matthew Shane Croughan.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1988.Includes bibliographical references.Ph.D

Student nurses’ preparation and negotiation of transition to the Registered Nurse role. Are there any factors that influence or inhibit this successful negotiation and transition?A systematic review

The aim of this systematic review is to review and determine the student nurse preparation and negotiation of their readiness to qualify as a registered nurse on the Nursing and Midwifery Council register. There is consideration given with aspects and elements explored that determine the influences that lead to success of this transition and the success or inhibitors of this negotiation alongside transition from student nurse to the registered nurse role. The aim of this review therefore, is to critically review the evidence to identify if there are any factors that negotiate the preparation and transition from student nurse to the registered nurse role.The objectives of this review are as follows:To conduct a comprehensive literature search and identify evidence that is relevantTo appraise critically the quality of identified evidence and analyse the findings to ascertain if there are any factors that negotiate the preparation and transition from student nurse to the registered nurse role and whether the factors influence or inhibit this transition To determine and explore the factors that influence or inhibit success or failure encompassed within the student nurse transition to registered nurs

Directional dark field retrieval with single-grid x-ray imaging

Directional dark-field imaging is an emerging x-ray modality that is sensitive to unresolved anisotropic scattering from sub-pixel sample microstructures. A single-grid imaging set-up can be used to capture dark-field images by looking at changes in a grid pattern projected upon the sample. By creating analytical models for the experiment, we have developed a single-grid directional dark field retrieval algorithm that can extract dark-field parameters such as the dominant scattering direction, and the semi-major and -minor scattering angles. We show that this method is effective even in the presence of high image noise, allowing for low dose and time sequence imaging

A fast implicit X-ray diffusive-dark-field retrieval method using a single mask and exposure

Complementary to conventional and phase X-ray radiography, dark-field imaging has become central in visualizing diffusive scattering signal due to the spatially-unresolved texture within an object. To date most diffusive-dark-field retrieval methods require either the acquisition of multiple images at the cost of higher radiation dose or significant amounts of computational memory and time. In this work, a simple method of X-ray diffusive dark-field retrieval is presented, applicable to any single-mask imaging setup, with only one exposure of the sample. The approach, which is based on a model of geometric and diffusive reverse-flow conservation, is implicit and non-iterative. This numerically fast methodology is applied to experimental X-ray images acquired using both a random mask and a grid mask, giving high quality reconstructions that are very stable in the presence of noise. The method should be useful for high-speed imaging and/or imaging with low-flux sources

Engineering characterization of a versatile vertical-wheel bioreactor for cell and gene therapy

An ideal, versatile bioreactor for cell and gene therapy should be capable of growing cells across a range of formats, such as freely floating in suspension, in aggregates of various target sizes, and also on porous or solid carriers of various sizes. It should work well with cells and multi-cellular structures that are particularly shear sensitive. Ideally, it should be a well-mixed vessel with a homogenous culture environment. To achieve these low shear and mixing objectives, the bioreactor should be capable of suspending aggregates and solid carriers, as well as provide good mixing, at low power inputs per volume. Furthermore, in order to harvest attached cells when needed, it should also be capable of rapidly applying a uniform target high shear environment to viably remove cells from solid carriers. To achieve these objectives, a single-use bioreactor system using an innovative Vertical-Wheel technology has been developed. The first design hypothesis was that a large vertical wheel, when rotated at relatively close clearance to a circular tank bottom, could provide homogeneous liquid mixing, as well as uniform suspension of solid carriers or cellular aggregates, at lower power input per volume than traditional stirred tanks. The second design hypothesis was that the same vertical wheel design could be used to viably harvest cells from solid carriers by simply turning up the rotation speed to a target level for a short period of time. In this talk, we present data directly testing both of these hypotheses. Experimental data will be presented showing the measured power curves for the novel vertical wheel design, as well as the resulting power levels required to achieve uniform fluid mixing and suspension of solid microcarriers across a range of scales, from 0.5 liters to 80 liters. Data will also be shown regarding the ability of this system to viably harvest cells from solid microcarriers. Data regarding the performance of this system for the culture of several different cell types is presented as part of other talks and posters at this conference. In summary, clear evidence will be presented on whether Vertical-Wheel technology provides the most ideal, versatile bioreactor for cell and gene therapy applications