The U.S. Department of Energy (DOE) is promoting the development of ethanol from lignocellulosic feedstocks as an alternative to conventional petroleum-based transportation fuels. DOE funds both fundamental and applied research in this area and needs a method for predicting cost benefits of many research proposals. To that end, the National Renewable Energy Laboratory (NREL) has modeled many potential process designs and estimated the economics of each process during the last 20 years.This report is an update of the ongoing process design and economic analyses at NREL. We envision updating this process design report at regular intervals; the purpose being to ensure that the process design incorporates all new data from NREL research, DOE funded research and other sources, and that the equipment costs are reasonable and consistent with good engineering practice for plants of this type. For the non-research areas this means using equipment and process approaches as they are currently used in industrial applications.For the last report 1 , published in 1999, NREL performed a complete review and update of the process design and economic model for the biomass-to-ethanol process utilizing co-current dilute acid prehydrolysis with simultaneous saccharification (enzymatic) and co-fermentation. The process design included the core technologies being researched by the DOE: prehydrolysis, simultaneous saccharification and co-fermentation, and cellulase enzyme production. In addition, all ancillary areas-feed handling, product recovery and purification, wastewater treatment (WWT), lignin combustor and boiler-turbogenerator, and utilities-were included. NREL engaged Delta-T Corporation (Delta-T) to assist in the process design evaluation, the process equipment costing, and overall plant integration. The process design and costing for the lignin combustor and boiler turbogenerator was reviewed by Reaction Engineering Inc. (REI) and Merrick & Company reviewed the wastewater treatment.Since then, NREL has engaged Harris Group (Harris) to perform vendor testing, process design, and costing of critical equipment identified during earlier work. This included solid/liquid separation and pretreatment reactor design and costing. Corn stover handling was also investigated to support DOE's decision to focus on corn stover as a feedstock for lignocellulosic ethanol. Working with Harris, process design and costing for these areas were improved through vendor designs, costing, and vendor testing in some cases. In addition to this work, enzyme costs were adjusted to reflect collaborative work between NREL and enzyme manufacturers (Genencor International and Novozymes Biotech) to provide a delivered enzyme for lignocellulosic feedstocks. This report is the culmination of our work and represents an updated process design and cost basis for the process using a corn stover feedstock.The process design and economic model are useful for predicting the cost benefits of proposed research. Proposed research results can be translated into mo...

The National Renewable Energy Laboratory (NREL) has undertaken a complete review and update of the process design and economic model for the biomass-to-ethanol process based on co-current dilute acid prehydrolysis, along with simultaneous saccharification (enzymatic) and co-fermentation. The process design includes the core technologies being researched by the U.S. Department of Energy (DOE): prehydrolysis, simultaneous saccharification and co-fermentation, and cellulase enzyme production. In addition, all ancillary areas-feed handling, product recovery and purification, wastewater treatment lignin burner and boiler-turbogenerator, and utilities-are included. NREL engaged Delta-T Corporation to assist in the process design evaluation, the process equipment costing, and overall plant integration. The process design and costing for the lignin burner and boiler turbogenerator has been reviewed by Reaction Engineering Inc. and the wastewater treatment by Merrick & Company. An overview of both reviews is included here. The purpose of this update was to ensure that the process design and equipment costs were reasonable and consistent with good engineering practice for plants of this type using available technical data. For the non-research areas this means using equipment and process approaches as they are currently being used in industrial applications. For areas currently being researched by NREL, we used the best research estimates of near-term data to develop a process design and equipment specifications consistent with existing similar commercial operations. This work has resulted in an economic model that can be used to predict the cost of producing ethanol from cellulosic biomass using this technology if a plant were to be built in the next few years. The model was also extended using technology improvements that are expected to be developed based on the current DOE research plan. Future process designs and cost estimates are given for the years 2005, 2010, and 2015. The process design and economic model will also be useful for predicting the cost benefits of proposed research. Proposed research results can be translated into modifications of the process design and the economic impact assessed. This will allow DOE, NREL, and other researchers to set priorities on future research based on its potential to reduce the cost of producing ethanol.

With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3-10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.

Transdermal delivery of peptides and other biological macromolecules is limited due to skin's inherent low permeability. Here, the authors report the use of a deep eutectic solvent, choline and geranate (CAGE), to enhance topical delivery of proteins such as bovine serum albumin (BSA, molecular weight: ≈66 kDa), ovalbumin (OVA, molecular weight: ≈45 kDa) and insulin (INS, molecular weight: 5.8 kDa). CAGE enhances permeation of BSA, OVA, and insulin into porcine skin ex vivo, penetrating deep into the epidermis and dermis. Studies using tritium-labeled BSA and fluorescein isothiocyanate labeled insulin show significantly enhanced delivery of proteins into and across porcine skin, penetrating the skin in a time-dependent manner. Fourier transform IR spectra of porcine stratum corneum (SC) samples before and after incubation in CAGE show a reduction in peak area attributed to SC lipid content, suggesting lipid extraction from the SC. Circular dichroism confirms that CAGE does not affect insulin's secondary conformation. In vivo studies in rats show that topical application of 10 U insulin dispersed in CAGE (25 U kg −1 insulin dose) leads to a highly significant 40% drop in blood glucose levels in 4 h that is relatively sustained for 12 h. Taken together, these studies demonstrate that CAGE is a promising vehicle for transdermal delivery of therapeutic proteins; specifically, as a noninvasive delivery alternative to injectable insulin for the treatment of diabetes.