Annual Review of Chemical and Biomolecular Engineering - Volume 2, 2011

This paper is a short account, from a personal viewpoint, of the various contributions I have made to expand the academic basis of chemical engineering from its origin in the unifying concept of unit operations, focussed on process design, to encompassing all the professional activities of industrial chemical engineers. This includes all aspects of planning and scheduling the operations as well as designing and controlling the process plant. The span of my career also happens to include the birth of the age of computing, with all the consequential implications.

Solid oxide fuel cells (SOFCs) and solid oxide electrolyzers (SOEs) hold much promise as highly efficient devices for the direct interconversion of chemical and electrical energy. Commercial application of these devices, however, requires further improvements in their performance and stability. Because the performance of SOFC and SOE electrodes depends on their microstructures, electronic and ionic conductivities, and chemical reactivities, the needed improvements require the expertise of various disciplines, with catalytic science playing an important role. Highly active and thermally stable catalysts are required to limit the internal losses in the devices, increase the range of fuels they can use, and decrease the temperatures at which they operate. In this article we review some of the most important recent advances in catalysis for SOFC and SOE electrodes and highlight additional improvements that are needed.

The growing atmospheric CO2 concentration and its impact on climate have motivated widespread research and development aimed at slowing or stemming anthropogenic carbon emissions. Technologies for carbon capture and sequestration (CCS) employing mass separating agents that extract and purify CO2 from flue gas emanating from large point sources such as fossil fuel–fired electricity-generating power plants are under development. Recent advances in solvents, adsorbents, and membranes for postcombust- ion CO2 capture are described here. Specifically, room-temperature ionic liquids, supported amine materials, mixed matrix and facilitated transport membranes, and metal-organic framework materials are highlighted. In addition, the concept of extracting CO2 directly from ambient air (air capture) as a means of reducing the global atmospheric CO2 concentration is reviewed. For both conventional CCS from large point sources and air capture, critical research needs are identified and discussed.

The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

Since its inception more than a decade ago, the field of short interfering RNA (siRNA) therapeutics has demonstrated potential in the treatment of a wide variety of diseases. The power behind RNA interference (RNAi) therapy lies in its ability to specifically silence target genes of interest. As more biological data have become available, it has become evident that, in addition to mediating RNAi, siRNA molecules have the potential to potently induce the innate immune system. One of the significant challenges facing the field today is the differentiation between therapeutic effects caused by target-specific, RNAi-mediated gene silencing and those caused by nonspecific stimulation of the innate immune system. Unless appropriate experimental measures are taken to control for RNA-induced immunostimulation, genetic manipulation can be confused with immune activation. This review attempts to provide an accessible background in siRNA-relevant immunology and to highlight the ways in which siRNA can be engineered to avoid or provoke an innate immune response.

This review discusses a macroscopic thermodynamic procedure to calculate the solubility of gases, vapors, and liquids in glassy polymers that is based on the general procedure provided by the nonequilibrium thermodynamics for glassy polymers (NET-GP) method. Several examples are presented using various nonequilibrium (NE) models including lattice fluid (NELF), statistical associating fluid theory (NE-SAFT), and perturbed hard sphere chain (NE-PHSC). Particular applications illustrate the calculation of infinite-dilution solubility coefficients in different glassy polymers and the prediction of solubility isotherms for different gases and vapors in pure polymers as well as in polymer blends. The determination of model parameters is discussed, and the predictive abilities of the models are illustrated. Attention is also given to the solubility of gas mixtures and solubility isotherms in nanocomposite mixed matrices. The fractional free volume determined from solubility data can be used to correlate solute diffusivities in mixed matrices.

Plants represent a vast, renewable resource and are well suited to provide sustainably for humankind's transportation fuel needs. To produce infrastructure-compatible fuels from biomass, two challenges remain: overcoming plant cell wall recalcitrance to extract sugar and phenolic intermediates, and reduction of oxygenated intermediates to fuel molecules. To compete with fossil-based fuels, two primary routes to deconstruct cell walls are under development, namely biochemical and thermochemical conversion. Here, we focus on overcoming recalcitrance with biochemical conversion, which uses low-severity thermochemical pretreatment followed by enzymatic hydrolysis to produce soluble sugars. Many challenges remain, including understanding how pretreatments affect the physicochemical nature of heterogeneous cell walls; determination of how enzymes deconstruct the cell wall effectively with the aim of designing superior catalysts; and resolution of issues associated with the co-optimization of pretreatment, enzymatic hydrolysis, and fermentation. Here, we highlight some of the scientific challenges and open questions with a particular focus on problems across multiple length scales.

Macroscopic characterizations of hydrophobicity (e.g., contact angle measurements) do not extend to the surfaces of proteins and nanoparticles. Molecular measures of hydrophobicity of such surfaces need to account for the behavior of hydration water. Theory and state-of-the-art simulations suggest that water density fluctuations provide such a measure; fluctuations are enhanced near hydrophobic surfaces and quenched with increasing surface hydrophilicity. Fluctuations affect conformational equilibria and dynamics of molecules at interfaces. Enhanced fluctuations are reflected in enhanced cavity formation, more favorable binding of hydrophobic solutes, increased compressibility of hydration water, and enhanced water-water correlations at hydrophobic surfaces. These density fluctuation–based measures can be used to develop practical methods to map the hydrophobicity/philicity of heterogeneous surfaces including those of proteins. They highlight that the hydrophobicity of a group is context dependent and is significantly affected by its environment (e.g., chemistry and topography) and especially by confinement. The ability to include information about hydration water in mapping hydrophobicity is expected to significantly impact our understanding of protein-protein interactions as well as improve drug design and discovery methods and bioseparation processes.

Several key strategies can be used to manage the risk associated with innovation to create maximum value. These include balancing the timing of investments versus cash flows, management of fads, prioritization across the company, savvy portfolio management, and a system of metrics that measure real success. Successful R&D managers will do whatever is necessary to manage the risks associated with an R&D program and stick to their long-term strategy.

We discuss novel solvents that improve the sustainability of various chemical reactions and processes. These alternative solvents include organic-aqueous tunable solvents; near-critical water; switchable piperylene sulfone, a volatile dimethylsulfoxide substitute; and reversible ionic liquids. These solvents are advantageous to a wide variety of reactions because they reduce waste and energy demand by coupling homogeneous reactions with heterogeneous separations, acting as in situ acid or base catalysts, and providing simple and efficient postreaction separations.

Natural products and their derivatives play an important role in modern healthcare as frontline treatments for many diseases and as inspiration for chemically synthesized therapeutics. With advances in sequencing and recombinant DNA technology, many of the biosynthetic pathways responsible for the production of these chemically complex yet valuable compounds have been elucidated. With an ever-expanding toolkit of biosynthetic components, metabolic engineering is an increasingly powerful method to improve natural product titers and generate novel compounds. Heterologous production platforms have enabled access to pathways from difficult to culture strains, systems biology and metabolic modeling tools have resulted in increasing predictive and analytic capabilities, advances in expression systems and regulation have enabled the fine-tuning of pathways for increased efficiency, and characterization of individual pathway components has facilitated the construction of hybrid pathways for the production of new compounds. These advances in the many aspects of metabolic engineering not only have yielded fascinating scientific discoveries but also make it an increasingly viable approach for the optimization of natural product biosynthesis.

Fundamental understanding of gas hydrate formation and decomposition processes is critical in many energy and environmental areas and has special importance in flow assurance for the oil and gas industry. These areas represent the core of gas hydrate applications, which, albeit widely studied, are still developing as growing fields of research. Discovering the molecular pathways and chemical and physical concepts underlying gas hydrate formation potentially can lead us beyond flowline blockage prevention strategies toward advancing new technological solutions for fuel storage and transportation, safely producing a new energy resource from natural deposits of gas hydrates in oceanic and arctic sediments, and potentially facilitating effective desalination of seawater. The state of the art in gas hydrate research is leading us to new understanding of formation and dissociation phenomena that focuses on measurement and modeling of time-dependent properties of gas hydrates on the basis of their well-established thermodynamic properties.

Polymorphism in molecular crystals is a prevalent phenomenon and is of great interest to the pharmaceutical community. The solid-state form is a key quality attribute of a crystalline product. Inconsistencies in the solid phase produced during the manufacturing and storage of drug substances and drug products may have severe consequences. It is essential to understand the solid-state behavior of the drug and to judiciously select the optimal solid form for development. This review highlights the pervasiveness and relevance of polymorphism and describes solid form screening and selection processes. Moreover, case studies on controlling polymorphs from a chemical development perspective are provided.

Tumors are similar to organs, with unique physiology giving rise to an unusual set of transport barriers to drug delivery. Cancer therapy is limited by nonuniform drug delivery via blood vessels, inhomogeneous drug transport into tumor interstitium from the vascular compartment, and hindered transport through tumor interstitium to the target cells. Four major abnormal physical and physiological properties contribute to these transport barriers. Accumulated solid stress compresses blood vessels to diminish the drug supply to many tumor regions. Immature vasculature with high viscous and geometric resistances and reduced pressure gradients leads to sluggish and heterogeneous blood flow in tumors to further limit drug supply. Nonfunctional lymphatics coupled with highly permeable blood vessels result in elevated hydrostatic pressure in tumors to abrogate convective drug transport from blood vessels into and throughout most of the tumor tissue. Finally, a dense structure of interstitial matrix and cells serves as a tortuous, viscous, and steric barrier to diffusion of therapeutic agents. In this review, we discuss the origins and implications of these barriers. We then highlight strategies for overcoming these barriers by modulating either drug properties or the tumor microenvironment itself to enhance the delivery and effectiveness of drugs in tumors.

Current integrated circuit (IC) manufacturing consists of more than 800 process steps, nearly all of which involve reactions at surfaces that significantly impact device yield and performance. From initial surface preparation through film deposition, patterning, etching, residue removal, and metallization, an understanding of surface reactions and interactions is critical to the successful continuous scaling, yield, and reliability of electronic devices. In this review, some of the most important surface reactions that drive the development of microelectronic device fabrication are described. The reactions discussed do not constitute comprehensive coverage of this topic in IC manufacture but have been selected to demonstrate the importance of surface/interface reactions and interactions in the development of new materials, processing sequences, and process integration challenges. Specifically, the review focuses on surface reactions related to surface cleaning/preparation, semiconductor film growth, dielectric film growth, metallization, and etching (dry and wet).

The field of microfluidics has exploded in the past decade, particularly in the area of chemical and biochemical analysis systems. Borrowing technology from the solid-state electronics industry and the production of microprocessor chips, researchers working with glass, silicon, and polymer substrates have fabricated macroscale laboratory components in miniaturized formats. These devices pump nanoliter volumes of liquid through micrometer-scale channels and perform complex chemical reactions and separations. The detection of reaction products is typically done fluorescently with off-chip optical components, and the analysis time from start to finish can be significantly shorter than that of conventional techniques. In this review we describe these microfluidic analysis systems, from the original continuous flow systems relying on electroosmotic pumping for liquid motion to the large diversity of microarray chips currently in use to the newer droplet-based devices and segmented flow systems. Although not currently widespread, microfluidic systems have the potential to become ubiquitous.

Medical technologies are evolving at a very rapid pace. Portable communication devices and other handheld electronics are influencing our expectations of future medical tools. The advanced medical technologies of our future will not necessarily be large expensive systems. They are just as likely to be small and disposable. This paper reviews how microsystems are already impacting health care as commercial products or in clinical development. Example systems for point-of-care testing (POCT), patient monitoring tools, systemic drug delivery, local drug delivery, and surgical tools are described. These technologies are moving care from hospitals to outpatient settings, physicians' offices, community health centers, nursing homes, and the patients' homes. Microsystems that are rapidly adopted fulfill significant medical needs and are compatible with existing clinical practice.

Future integrated circuits and packages will require extraordinary dielectric materials for interconnects to allow transistor advances to be translated into system-level advances. Exceedingly low-permittivity and low-loss materials are required at every level of the electronic system, from chip-level insulators to packages and printed wiring boards. In this review, the requirements and goals for future insulators are discussed followed by a summary of current state-of-the-art materials and technical approaches. Much work needs to be done for insulating materials and structures to meet future needs.

The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this effort has been translated to actual therapies, especially in the areas of skin replacement and, to a lesser extent, cartilage repair. A good amount of thoughtful work has also yielded prototypes of other tissue substitutes such as nerve conduits, blood vessels, liver, and even heart. Forward movement to clinical product, however, has been slow. Another offshoot of these efforts has been the incorporation of some new exciting technologies (e.g., microfabrication, 3D printing) that may enable future breakthroughs. In this review we highlight the modest beginnings of the field and then describe three application examples that are in various stages of development, ranging from relatively mature (skin) to ongoing proof-of-concept (cartilage) to early stage (liver). We then discuss some of the major issues that limit the development of complex tissues, some of which are fundamentals-based, whereas others stem from the needs of the end users.