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