Annual Review of Chemical and Biomolecular Engineering - Volume 3, 2012

Haldor Topsøe was born in Copenhagen, Denmark, in 1913. He studied chemical engineering at the Technical University of Denmark (DTU). In 1940, he founded the company Haldor Topsøe, which has become one of the most successful companies in the field of heterogeneous catalysis. The company develops and markets catalysts and processes for petroleum refining, air-pollution control, synthesis gas production, ammonia and methanol production and solid oxide fuel cells. The company Haldor Topsøe is also a leader in the production and state-of-the-art scientific characterization of new catalysts. Dr. Topsøe is currently the sole owner of the company. He has written numerous articles on ammonia synthesis, catalysis, and energy questions. He is the author of several books on economics. Dr. Topsøe has received numerous awards, including honorary doctorates from Aarhus University, DTU, and the Chalmers University in Sweden; the Gold Medal from the Royal Academy of Sciences; the Hoover Medal for his technical abilities and entrepreneurship; and the Grove Memorial Medal for Advances in Fuel Cell Technology. Topsøe is a member of the Danish and the Swedish Academies of Technical Sciences and of the U.S. National Academy of Engineering.

The following interview was conducted on August 16, 2010.

–Manos Mavrikakis

In recent years supported gold nanoparticles have emerged as efficient catalysts with considerable synthetic potential for liquid-phase oxidation reactions based on molecular oxygen as oxidant. Here we critically review the most attractive applications related to the selective oxidation of functional groups containing O, N, or Si heteroatoms. The reactions include the oxidation of alcohols, aldehydes, and organosilanes; the diverse transformations of amines; benzylic oxidations; and some one-pot multistep reactions starting with alcohol or amine oxidation. In complex liquid-phase transformations relying on bifunctional catalysis, appropriate choice of the support is frequently more important than the size of the gold particles. In some oxidation reactions gold nanoparticles outperform the traditional platinum-group metal catalysts, but the latest results indicate the superiority of bimetallic particles containing gold and platinum, palladium, or rhodium. The environmentally benign nature of the transformations is discussed.

Many natural and industrial processes involve a complex set of competing reactions that include several different species. Detailed kinetic modeling of such systems can shed light on the important pathways involved in various transformations and therefore can be used to optimize the process conditions for the desired product composition and properties. This review focuses on elucidating the various components involved in modeling the kinetics of pyrolysis and oxidation of polymers. The elementary free radical steps that constitute the chain reaction mechanism of gas-phase/nonpolar liquid-phase processes are outlined. Specification of the rate coefficients of the various reaction families, which is central to the theme of kinetics, is described. Construction of the reaction network on the basis of the types of end groups and reactive moieties in a polymer chain is discussed. Modeling frameworks based on the method of moments and kinetic Monte Carlo are evaluated using illustrations. Finally, the prospects and challenges in modeling biomass conversion are addressed.

The academic literature on and industrial practice of control of solution crystallization processes have seen major advances in the past 15 years that have been enabled by progress in in-situ real-time sensor technologies and driven primarily by needs in the pharmaceutical industry for improved and more consistent quality of drug crystals. These advances include the accurate measurement of solution concentrations and crystal characteristics as well as the first-principles modeling and robust model-based and model-free feedback control of crystal size and polymorphic identity. Research opportunities are described in model-free controller design, new crystallizer designs with enhanced control of crystal size distribution, strategies for the robust control of crystal shape, and interconnected crystallization systems for multicomponent crystallization.

Many industrial processes used to produce chemicals and pharmaceuticals would benefit from enzymes that function under extreme conditions. Enzymes from extremophilic microorganisms have evolved to function in a variety of extreme environments, and bioprospecting for these microorganisms has led to the discovery of new enzymes with high tolerance to nonnatural conditions. However, bioprospecting is inherently limited by the diversity of enzymes evolved by nature. Protein engineering has also been successful in generating extremophilic enzymes by both rational mutagenesis and directed evolution, but screening for activity under extreme conditions can be difficult. This review examines the emerging synergy between bioprospecting and protein engineering in developing extremophilic enzymes. Specific topics include unnatural industrial conditions relevant to biocatalysis, biophysical properties of extremophilic enzymes, and industrially relevant extremophilic enzymes found either in nature or through protein engineering.

Aerosol synthesis of materials is a vibrant field of particle technology and chemical reaction engineering. Examples include the manufacture of carbon blacks, fumed SiO2, pigmentary TiO2, ZnO vulcanizing catalysts, filamentary Ni, and optical fibers, materials that impact transportation, construction, pharmaceuticals, energy, and communications. Parallel to this, development of novel, scalable aerosol processes has enabled synthesis of new functional nanomaterials (e.g., catalysts, biomaterials, electroceramics) and devices (e.g., gas sensors). This review provides an access point for engineers to the multiscale design of aerosol reactors for the synthesis of nanomaterials using continuum, mesoscale, molecular dynamics, and quantum mechanics models spanning 10 and 15 orders of magnitude in length and time, respectively. Key design features are the rapid chemistry; the high particle concentrations but low volume fractions; the attainment of a self-preserving particle size distribution by coagulation; the ratio of the characteristic times of coagulation and sintering, which controls the extent of particle aggregation; and the narrowing of the aggregate primary particle size distribution by sintering.

Single-cell analysis (SCA) has been increasingly recognized as the key technology for the elucidation of cellular functions, which are not accessible from bulk measurements on the population level. Thus far, SCA has been achieved by miniaturization of established engineering concepts to match the dimensions of a single cell. However, SCA requires procedures beyond the classical approach of upstream processing, fermentation, and downstream processing because the biological system itself defines the technical demands. This review characterizes currently available microfluidics and microreactors for invasive (i.e., chemical) and noninvasive (i.e., biological) SCA. We describe the recent SCA omics approaches as tools for systems biology and discuss the role of SCA in genomics, transcriptomics, proteomics, metabolomics, and fluxomics. Furthermore, we discuss applications of SCA for biocatalysis and metabolic engineering as well as its potential for bioprocess optimization. Finally, we define present and future challenges for SCA and propose strategies to overcome current limitations.

We review the molecular principles underlying the homogeneous nucleation of a crystal phase from the melt phase, as elucidated by molecular simulation methods. Classical nucleation theory serves as the starting point for describing the nature of nucleation processes, but it does not derive from molecular principles itself. Density functional theory and molecular simulations offer tools for delving into the molecular origins of nucleation. Here, we emphasize the rapid development of molecular simulation methodologies for studying crystal nucleation from the melt. These methodologies are broadly categorized as free energy sampling methods, dynamical or mean first-passage time methods, and composite approaches that take advantage of both. The crucial selection of order parameters to distinguish the crystal phase from the liquid phase and important features of the reaction coordinate are emphasized. The system size dependence of the nucleation free energy barrier is also examined.

In the current climate of several interrelated impending global crises, namely, climate change, chemicals, energy, and oil, the impact of green chemistry with respect to chemicals and biofuels generated from within a holistic concept of a biorefinery is discussed. Green chemistry provides unique opportunities for innovation via product substitution, new feedstock generation, catalysis in aqueous media, utilization of microwaves, and scope for alternative or natural solvents. The potential of utilizing waste as a new resource and the development of integrated facilities producing multiple products from biomass is discussed under the guise of biorefineries. Biofuels are discussed in depth, as they not only provide fuel (energy) but are also a source of feedstock chemicals. In the future, the commercial success of biofuels commensurate with consumer demand will depend on the availability of new green (bio)chemical technologies capable of converting waste biomass to fuel in a context of a biorefinery.

Synthetic biology has made significant leaps over the past decade, and it now enables rational and predictable reprogramming of cells to conduct complex physiological activities. The bases for cellular reprogramming are mainly genetic control components affecting gene expression. A huge variety of these modules, ranging from engineered fusion proteins regulating transcription to artificial RNA devices affecting translation, is available, and they often feature a highly modular scaffold. First endeavors to combine these modules have led to autoregulated expression systems and genetic cascades. Analogous to the rational engineering of electronic circuits, the existing repertoire of artificial regulatory elements has further enabled the ambitious reprogramming of cells to perform Boolean calculations or to mimic the oscillation of circadian clocks. Cells harboring synthetic gene circuits are not limited to cell culture, as they have been successfully implanted in animals to obtain tailor-made therapeutics that have made it possible to restore urea or glucose homeostasis as well as to offer an innovative approach to artificial insemination.

The invention of the transistor followed by more than 60 years of aggressive device scaling and process integration has enabled the global information web and subsequently transformed how people communicate and interact. The principles and practices built upon chemical processing of materials on silicon have been widely adapted and applied to other equally important areas, such as microfluidic systems for chemical and biological analysis and microscale energy storage solutions. The challenge of continuing these technological advances hinges on further improving the performance of individual devices and their interconnectivity while making the manufacturing processes economical, which is dictated by the materials' innate functionality and how they are chemically processed. In this review, we highlight challenges in scaling up the silicon wafers and scaling down the individual devices as well as focus on needs and challenges in the synthesis and integration of multifunctional materials.

The ability of antibodies to bind to target molecules with high affinity and specificity has led to their widespread use in diagnostic and therapeutic applications. Nevertheless, a limitation of antibodies is their propensity to self-associate and aggregate at high concentrations and elevated temperatures. The large size and multidomain architecture of full-length monoclonal antibodies have frustrated systematic analysis of how antibody sequence and structure regulate antibody solubility. In contrast, analysis of single and multidomain antibody fragments that retain the binding activity of mono-clonal antibodies has provided valuable insights into the determinants of antibody aggregation. Here we review advances in engineering antibody frameworks, domain interfaces, and antigen-binding loops to prevent aggregation of natively and nonnatively folded antibody fragments. We also highlight advances and unmet challenges in developing robust strategies for engineering large, multidomain antibodies to resist aggregation.

Semiconductor nanocrystals are promising materials for low-cost large-area electronic device fabrication. They can be synthesized with a wide variety of chemical compositions and size-tunable optical and electronic properties as well as dispersed in solvents for room-temperature deposition using various types of printing processes. This review addresses research progress in large-area electronic device applications using nanocrystal-based electrically active thin films, including thin-film transistors, light-emitting diodes, photovoltaics, and thermoelectrics.

Mixed ion and electron conductors (MIECs) have garnered increased attention as active components in the electrodes of solid oxide electrolyzers (for electricity to fuel conversion) and especially of solid oxide fuel cells (for fuel to electricity conversion). Although much of the work in the literature is directed toward the understanding of oxygen electroreduction on the surfaces of MIECs, more recent studies also explore the role of these materials in fuel electrooxidation. In both cases, the rich chemical and electronic behaviors of MIECs imply a broad range of possible reaction pathways. We highlight the significant progress that has been made in elucidating these pathways through well-designed experimental and computational studies. At the macroscopic level, patterned electrode studies enable identification of active sites, whereas at the microscopic level, surface-sensitive techniques in combination with atomistic-level simulations are beginning to reveal the nature of the rate-determining step(s) and enable rational design of materials with enhanced activity.

Knowledge of high-pressure phase equilibria is crucial in many fields, e.g., for the design and optimization of high-pressure chemical and separation processes, carbon capture and storage, hydrate formation, applications of ionic liquids, and geological processes. This review presents the variety of methods to measure phase equilibria at high pressures and, following a classification, discusses the measurement principles, advantages, challenges, and error sources. Examples of application areas are given. A detailed knowledge and understanding of the different methods is fundamental not only for choosing the most suitable method for a certain task but also for the evaluation of experimental data. The discrepancy between the (sometimes low) true accuracy of published experimental data and the (high) accuracy claimed by authors is addressed. Some essential requirements for the generation of valuable experimental results are summarized.

One of the central problems in statistical mechanics is that of finding the density of states of a system. Knowledge of the density of states of a system is equivalent to knowledge of its fundamental equation, from which all thermodynamic quantities can be obtained. Over the past several years molecular simulations have made considerable strides in their ability to determine the density of states of complex fluids and materials. In this review we discuss some of the more promising approaches proposed in the recent literature along with their advantages and limitations.

Our modern society must solve various severe problems to maintain and increase our quality of life: from water stress to global warming, to fossil fuel depletion, to environmental pollution. The process intensification (PI) strategy is expected to contribute to overcoming many of these issues by facilitating the transition from a resource-intensive to a knowledge-intensive industrial system that will guarantee sustainable growth. Membrane operations, which respond efficiently to the requirements of the PI strategy, have the potential to replace conventional energy-intensive separation techniques, which will boost the efficiency and reduce the environmental impact of separations as well as conversion processes. This work critically reviews the current status and emerging applications of (integrated) membrane operations with a special focus on energy and environmental applications.

Advanced cell culture techniques are increasingly needed to better understand basic cell physiology, predict in vivo response, and engineer de novo functional tissue substitutes. Toward this concept, hydrogels have emerged as biomimetic in vitro culture systems that allow cells to be grown in or on user-defined microenvironments that recapitulate many critical aspects of native tissue. Hydrogel biofunctionality can be engineered predictably and precisely via the tailorability of the hydrogel's chemical and mechanical properties, each of which directly influences cell fate. In this review, we highlight state-of-the-art hydrogel platforms that have been used to assay and define cell behavior, placing an emphasis on recent directions in systems that offer dynamic control of material properties in time and space. We review current understanding of cell-material interactions in 2D and discuss recent and future efforts, as well as challenges, in extending this work to 3D. Ultimately, advances in hydrogel culture systems, synthetic approaches, and biological assays that can be performed in 3D are providing new opportunities to recapitulate fully the native cell niche.

The lithium-ion battery is the most promising battery candidate to power battery-electric vehicles. For these vehicles to be competitive with those powered by conventional internal combustion engines, significant improvements in battery performance are needed, especially in the energy density and power delivery capabilities. Recent discoveries and advances in the development of electrode materials to improve battery performance are summarized. Promising substitutes for graphite as the anode material include silicon, tin, germanium, their alloys, and various metal oxides that have much higher theoretical storage capacities and operate at slightly higher and safer potentials. Designs that attempt to accommodate strain owing to volumetric changes upon lithiation and delithiation are presented. All known cathode materials have storage capacities inferior to those of anode materials. In addition to variations on known transition metal oxides and phosphates, other potential materials, such as metal fluorides, are discussed as well as the effects of particle size and electrode architecture. New electrolyte systems and additives as well as their effects on battery performance, especially with regard to safety, are described.