Search Our Scientific Publications & Authors

AIChE J 2020 Mar 19;66(3). Epub 2019 Nov 19.

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.

We used the molecular modeling program Rosetta to identify clusters of amino acid substitutions in antibody fragments (scFvs and scAbs) that improve global protein stability and resistance to thermal deactivation. Using this methodology, we increased the melting temperature (T) and resistance to heat treatment of an antibody fragment that binds to the hemagglutinin protein (anti-HA33). Two designed antibody fragment variants with two amino acid replacement clusters, designed to stabilize local regions, were shown to have both higher T compared to the parental scFv and importantly, to retain full antigen binding activity after 2 hours of incubation at 70 °C. Read More

AIChE J 2018 Dec 11;64(12):4182-4186. Epub 2018 Jun 11.

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA90095, United States.

AIChE J 2018 Dec 8;64(12):4308-4318. Epub 2018 Sep 8.

Department of Chemistry, Haverford College, Haverford PA 19041, USA.

The successful engineering of biosynthetic pathways hinges on understanding the factors that influence acyl carrier protein (ACP) stability and function. The stability and structure of ACPs can be influenced by the presence of divalent cations, but how this relates to primary sequence remains poorly understood. As part of a course-based undergraduate research experience, we investigated the thermostability of type II polyketide synthase (PKS) ACPs. Read More

AIChE J 2019 Feb 5;65(2):629-639. Epub 2018 Oct 5.

Dept. of Chemical and Biological Engineering, Illinois Institute of Technology, Chicago, IL 60616.

Erroneous information from sensors affect process monitoring and control. An algorithm with multiple model identification methods will improve the sensitivity and accuracy of sensor fault detection and data reconciliation (SFD&DR). A novel SFD&DR algorithm with four types of models including outlier robust Kalman filter, locally weighted partial least squares, predictor-based subspace identification, and approximate linear dependency-based kernel recursive least squares is proposed. Read More

AIChE J 2018 Dec 12;64(12):4351-4360. Epub 2018 Oct 12.

Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.

The combination of cell culture models with microscale technology has fostered emergence of cell-based microphysiological models, also known as organ-on-a-chip systems. Body-on-a-chip systems, which are multi-organ systems on a chip to mimic physiological relations, enable recapitulation of organ-organ interactions and potentially whole-body response to drugs, as well as serve as models of diseases. Chemical reaction engineering principles can be applied to understanding complex reactions inside the cell or human body, which can be treated as a multi-reactor system. Read More

AIChE J 2019 Aug 9;65(8). Epub 2019 May 9.

Bioengineering Department, Northeastern University, Boston, Massachusetts.

While it is known that cancer cell interactions with vascular endothelial cells (ECs) drive metastatic cancer cell extravasation from blood vessels into secondary tumor sites, the mechanisms of action are still poorly understood. Here, we tested the hypothesis that neuraminidase-induced degradation of EC surface glycocalyx (GCX), particularly the sialic acid (SA) residue components of the GCX, will substantially increase metastatic cancer cell attachment to ECs. To our knowledge, our study is the first to isolate the role of GCX SA residues in cancer cell attachment to the endothelium, which were found to be differentially affected by the presence of neuraminidase and to indeed regulate metastatic cancer cell homing to ECs. Read More

AIChE J 2018 Dec 21;64(12):4319-4330. Epub 2018 Sep 21.

Chemistry, Engineering and Medicine for Human Health, Stanford University, Stanford CA 94305.

Plant natural products have served as a prominent source of medicines throughout human history, and are still used today as clinically-approved pharmaceuticals. However, many medicinal plants that produce useful compounds are slow-growing or recalcitrant to cultivation, making it difficult to investigate the underlying genetic/enzymatic machinery responsible for biosynthesis. To better understand the metabolism of bioactive natural products in slow-growing medicinal plants, we used DO labeling and LC-MS-based metabolomics to explore the biosynthesis of medically-relevant alkaloids in three plant species. Read More

AIChE J 2018 Nov 7;64(11):3803-3816. Epub 2018 Sep 7.

Wolfson School of Mechanical, Electrical and Manufacturing Engineering Loughborough University Loughborough Leicestershire, LE11 3TU U.K.

A novel lignocellulosic biomass pretreatment reactor has been designed and tested to investigate pretreatment efficacy of miscanthus grass. The reactor was designed to optimize the transfer of highly oxidative species produced by dielectric barrier discharge plasma to the liquid phase immediately after generation, by arranging close proximity of the plasma to the gas-liquid interface of microbubbles. The reactor produced a range of reactive oxygen species and reactive nitrogen species, and the rate of production depended on the power source duty cycle and the temperature of the plasma. Read More

AIChE J 2018 Dec 11;64(12):4255-4262. Epub 2018 Jul 11.

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, 2151 Berkeley Way, Berkeley, CA 94720.

The alkyne functionality has attracted much interest due to its diverse chemical and biological applications. We recently elucidated an acyl carrier protein (ACP)-dependent alkyne biosynthetic pathway, however, little is known about ACP interactions with the alkyne biosynthetic enzymes, an acyl-ACP ligase (JamA) and a membrane-bound bi-functional desaturase/acetylenase (JamB). Here, we showed that JamB has a more stringent interaction with ACP than JamA. Read More

AIChE J 2018 Dec 9;64(12):4247-4254. Epub 2018 Aug 9.

Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711.

Complete, accurate genome assemblies are necessary to design targets for genetic engineering strategies. Successful gene knockdowns and knockouts in Chinese hamster ovary (CHO) cells may prevent the expression of difficult-to-remove host cell proteins (HCPs). HCPs, if not removed, can cause problems in stability, safety, and efficacy of the biotherapeutic. Read More

AIChE J 2018 Dec 22;64(12):4229-4236. Epub 2018 Aug 22.

Dept. of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706.

Antibodies that target the blood-brain barrier (BBB) are of particular interest for the treatment of neurological diseases. Here, we screened a phage display single-chain antibody (scFv) library by brain perfusion in an attempt to isolate scFv that target the rat BBB. After four rounds of screening, the resulting antibody pool remained highly complex and discrete clonal sampling did not identify any scFvs capable of binding to the rat BBB. Read More

AIChE J 2019 Mar 18;65(3):992-1005. Epub 2018 Dec 18.

Artie McFerrin Dept. of Chemical Engineering, Texas A&M University, College Station, Texas 77843.

In this article, we present (1) a feature selection algorithm based on nonlinear support vector machine (SVM) for fault detection and diagnosis in continuous processes and (2) results for the Tennessee Eastman benchmark process. The presented feature selection algorithm is derived from the sensitivity analysis of the dual C-SVM objective function. This enables simultaneous modeling and feature selection paving the way for simultaneous fault detection and diagnosis, where feature ranking guides fault diagnosis. Read More

AIChE J 2018 Aug 23;64(8):2927-2933. Epub 2018 Feb 23.

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.

Ultrasound and hyperpolarized magnetic resonance imaging enable the visualization of biological processes in deep tissues. However, few molecular contrast agents are available to connect these modalities to specific aspects of biological function. We recently discovered that a unique class of gas-filled protein nanostructures known as gas vesicles could serve as nanoscale molecular reporters for these modalities. Read More

AIChE J 2018 Aug 7;64(8):3011-3022. Epub 2017 Dec 7.

Dept. of Haematology Imperial College London Harrow London HA1 3UJ U. K.

As breakthrough cellular therapy discoveries are translated into reliable, commercializable applications, effective stem cell biomanufacturing requires systematically developing and optimizing bioprocess design and operation. This article proposes a rigorous computational framework for stem cell biomanufacturing under uncertainty. Our mathematical tool kit incorporates: high-fidelity modeling, single variate and multivariate sensitivity analysis, global topological superstructure optimization, and robust optimization. Read More

AIChE J 2018 May 1;64(5):1859-1873. Epub 2018 Feb 1.

Shtern Research and Consulting Houston TX 77096.

The hydrodynamics of secondary flow phenomena in a disc-shaped gas vortex unit (GVU) is investigated using experimentally validated numerical simulations. The simulation using ANSYS FLUENT v.14a reveals the development of a backflow region along the core of the central gas exhaust, and of a counterflow multivortex region in the bulk of the disc part of the unit. Read More

AIChE J 2018 May 6;64(5):1573-1590. Epub 2018 Feb 6.

Dept. of Chemical Engineering & Chemistry, Multiphase Reactors Group Eindhoven University of Technology 5600 MB Eindhoven The Netherlands.

Fluidization is widely used in industries and has been extensively studied, both experimentally and theoretically, in the past. However, most of these studies focus on spherical particles while in practice granules are rarely spherical. Particle shape can have a significant effect on fluidization characteristics. Read More

AIChE J 2017 Dec 18;63(12):5335-5342. Epub 2017 Jul 18.

Process & Energy Dept., Intensified Reaction and Separation Systems group Delft University of Technology 2628 CB Delft The Netherlands.

In granular flow operations, often particles are nonspherical. This has inspired a vast amount of research in understanding the behavior of these particles. Various models are being developed to study the hydrodynamics involving nonspherical particles. Read More

AIChE J 2017 Apr 5;63(4):1263-1271. Epub 2016 Oct 5.

Dept. of Mechanical and Process Engineering ETH Zurich Zurich 8092 Switzerland.

Thermochemical splitting of CO via a ceria-based redox cycle was performed in a solar-driven thermogravimetric analyzer. Overall reaction rates, including heat and mass transport, were determined under concentrated irradiation mimicking realistic operation of solar reactors. Reticulated porous ceramic (RPC) structures and fibers made of undoped and Zr-doped CeO, were endothermally reduced under radiative fluxes of 1280 suns in the temperature range 1200-1950 K and subsequently re-oxidized with CO at 950-1400 K. Read More

AIChE J 2016 03 8;62(3):956-964. Epub 2016 Jan 8.

Dept. of Chemical Engineering, Center for Bioelectronics and Biosensors, Biodesign Institute and Fulton School of Engineering Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85287.

The development and performance characterization of a new differential pressure-based flow meter for human breath measurements is presented in this article. The device, called a "Confined Pitot Tube," is comprised of a pipe with an elliptically shaped expansion cavity located in the pipe center, and an elliptical disk inside the expansion cavity. The elliptical disk, named Pitot Tube, is exchangeable, and has different diameters, which are smaller than the diameter of the elliptical cavity. Read More

AIChE J 2016 Oct 6;62(10):3575-3584. Epub 2016 May 6.

Laboratory for Chemical Technology Faculty of Engineering and Architecture, Ghent University Ghent Belgium.

Coincident (simultaneous) three-component particle velocity measurements performed using two laser Doppler anemometry probes at the outlet section of a 9 m high cylindrical riser are for the first time presented for dilute flow conditions. Near the blinded extension of the T-outlet a solids vortex is formed. Particle downflow along the riser wall opposite the outlet tube is observed, which is restricted to higher riser heights at higher gas flow rates. Read More

AIChE J 2015 Dec 26;61(12):4114-4125. Epub 2015 Aug 26.

Shtern Research and Consulting Houston TX 77096 USA.

A unique normalized radial pressure profile characterizes the bed of a gas-solid vortex reactor over a range of particle densities and sizes, solid capacities, and gas flow rates: 950-1240 kg/m, 1-2 mm, 2 kg to maximum solids capacity, and 0.4-0.8 Nm/s (corresponding to gas injection velocities of 55-110 m/s), respectively. Read More

AIChE J 2016 Jun 17;62(6):2227-2233. Epub 2016 Feb 17.

Department of Chemical and Biological Engineering, Systems Biology Theme, Wisconsin Institute for Discovery, University of Wisconsin - Madison, 330 N Orchard Street, Madison, WI 53715, United States.

Liquid in a Petri dish spontaneously circulates in a radial pattern, even when the dish is at rest. These fluid flows have been observed and utilized for biological research, but their origins have not been well-studied. Here we used particle-tracking to measure velocities of radial fluid flows, which are shown to be linked to evaporation. Read More

AIChE J 2015 Dec;61(2):4502-4508

Department of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.

Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. Read More

AIChE J 2014 Apr;60(4):1236-1244

Dept. of Chemical and Biological Engineering, University of Wisconsin, Madison, WI 53706.

Amyloidogenesis is the process of formation of protein aggregates with fibrillar morphology. Because amyloidogenesis is linked to neurodegenerative disease, there is interest in understanding the mechanism of fibril growth. Kinetic models of amyloidogenesis require data on the number concentration and size distribution of aggregates, but this information is difficult to obtain using conventional methods. Read More

AIChE J 2014 Apr;60(4):1225-1235

Department of Chemical & Biological Engineering, University of Wisconsin - Madison, Madison, WI 53706, USA.

Several studies have demonstrated that 3D culture systems influence human embryonic stem cell (hESC) phenotypes and fate choices. However, the effect that these microenvironmental changes have on signaling pathways governing hESC behaviors is not well understood. Here, we have used a 3D microwell array to investigate differences in activation of developmental pathways between 2D and 3D cultures of both undifferentiated hESCs and hESCs undergoing initial differentiation in embryoid bodies (EBs). Read More

AIChE J 2014 Apr;60(4):1381-1392

Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison WI, 53706-1607, United States.

Self-assembling redox mediators have the potential to be broadly useful in a range of interfacial electrochemical contexts because the oxidation state and state of assembly of the mediator are closely coupled. In this paper, we report an investigation of the self-assembly of single- and double-tailed ferrocenyl amphiphiles (FTMA and BFDMA, respectively) at the surfaces of Pt electrodes and the impact of the dynamic assembled state of the amphiphiles on their rate of oxidation. We conclude that frozen aggregates of BFDMA adsorb to the surfaces of the Pt electrodes, and that slow dynamics of reorganization BFDMA within these aggregates limits the rate of electrooxidation of BFDMA. Read More

AIChE J 2014 Apr 5;60(4):1253-1268. Epub 2014 Mar 5.

Dept. of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, WI 53705.

Stochastic chemical kinetics has become a staple for mechanistically modeling various phenomena in systems biology. These models, even more so than their deterministic counterparts, pose a challenging problem in the estimation of kinetic parameters from experimental data. As a result of the inherent randomness involved in stochastic chemical kinetic models, the estimation methods tend to be statistical in nature. Read More

AIChE J 2014 Apr;60(4):1245-1252

Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Antibodies that target and internalize into blood-brain barrier (BBB) endothelial cells offer promise as drug delivery agents. Previously, we identified a single-chain antibody (scFvA) capable of binding to the BBB. In an attempt to improve the binding and internalization properties of the single chain antibody (scFvA), a biotinylation tag (Avitag) was fused to scFvA and the protein secreted by yeast. Read More

AIChE J 2013 Oct;59(10):3578-3585

Dept. of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712.

Novel glucose-sensitive systems for the release of insulin from poly(diethylaminoethyl methacrylate) (PDEAEM) micro-particles and nanoparticles decorated with glucose oxidase and catalase enzymes have been developed. The effect of polymer composition and loading conditions on the insulin loading efficiency and release was studied. The optimal conditions for loading insulin into PDEAEM microparticles were found to be at a loading pH of 5. Read More

AIChE J 2013 Feb;59(2):346-354

Department of Chemical Engineering and Materials Science, University of Minnesota - Twin Cities, 421 Washington Ave. SE, Minneapolis, MN 55455, .

AIChE J 2013 May;59(5):1432-1440

Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801 ; Departments of Chemistry, Biochemistry, and Bioengineering, and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801.

Directed evolution, the laboratory process by which biological entities with desired traits are created through iterative rounds of genetic diversification and library screening or selection, has become one of the most useful and widespread tools in basic and applied biology. From its roots in classical strain engineering and adaptive evolution, modern directed evolution came of age twenty years ago with the demonstration of repeated rounds of PCR-driven random mutagenesis and activity screening to improve protein properties. Since then, numerous techniques have been developed that have enabled the evolution of virtually any protein, pathway, network or entire organism of interest. Read More

AIChE J 2011 Dec 31;57(12):3249-3258. Epub 2011 Oct 31.

Dept. of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139.

AIChE J 2012 May 31;58(5):1619-1637. Epub 2011 May 31.

Dept. of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544.

The three-dimensional (3-D) structure prediction of proteins, given their amino acid sequence, is addressed using the first principles-based approach ASTRO-FOLD 2.0. The key features presented are: (1) Secondary structure prediction using a novel optimization-based consensus approach, (2) β-sheet topology prediction using mixed-integer linear optimization (MILP), (3) Residue-to-residue contact prediction using a high-resolution distance-dependent force field and MILP formulation, (4) Tight dihedral angle and distance bound generation for loop residues using dihedral angle clustering and non-linear optimization (NLP), (5) 3-D structure prediction using deterministic global optimization, stochastic conformational space annealing, and the full-atomistic ECEPP/3 potential, (6) Near-native structure selection using a traveling salesman problem-based clustering approach, ICON, and (7) Improved bound generation using chemical shifts of subsets of heavy atoms, generated by SPARTA and CS23D. Read More

AIChE J 2011 Nov;57(11):3132-3142

Particle Technology Laboratory, Institute of Process Engineering, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zürich, Switzerland.

Core-shell particles preserve the bulk properties (e.g. magnetic, optical) of the core while its surface is modified by a shell material. Read More

AIChE J 2011 Jun;57(6):1638-1645

Dept. of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 119260, Singapore.

Superparamagnetic magnetic nanoparticles were successfully functionalized with poly(methacrylic acid) via atom transfer radical polymerization, followed by conjugation to doxorubicin (Dox). Because of pH-sensitive hydrazone linkages, the rate and extent of Dox release from the particles was higher at a lower pH and/or a higher temperature than at physiological conditions. Appropriate changes to the pH and temperature can increase the drug release from the particles. Read More

AIChE J 2008 Oct;54(12):3048-3067

Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, TX 77251-1892.

The need for techniques to facilitate the regeneration of failing or destroyed tissues remains great with the aging of the worldwide population and the continued incidence of trauma and diseases such as cancer. A 16-year history in biomaterial scaffold development and tissue engineering is examined, beginning with the synthesis of novel materials and fabrication of 3D porous scaffolds. Exploring cell-scaffold interactions and subsequently cellular delivery using biomaterial carriers, we have developed a variety of techniques for bone and cartilage engineering. Read More

AIChE J 2009 06 30;55(6):1311-1324. Epub 2009 Apr 30.

Dept. of Chemical Engineering and Dept. of Biomedical Engineering, The University of Texas at Austin, Cockrell School of Engineering, Austin, TX 78712 Dept. of Pharmaceutics, The University of Texas at Austin, College of Pharmacy, Austin, TX 78712.

Intelligent drug delivery systems (DDS) are able to rapidly detect a biological event and respond appropriately by releasing a therapeutic agent; thus, they are advantageous over their conventional counterparts. Molecular imprinting is a promising area that generates a polymeric network which can selectively recognize a desired analyte. This field has been studied for a variety of applications over a long period of time, but only recently has it been investigated for biomedical and pharmaceutical applications. Read More

AIChE J 2007 Jan;53(1):160-173

Dept. of Chemical Engineering, Princeton University, Princeton, NJ 08544.

A novel methodology for the de novo identification of peptides by mixed-integer optimization and tandem mass spectrometry is presented in this article. The various features of the mathematical model are presented and examples are used to illustrate the key concepts of the proposed approach. Several problems are examined to illustrate the proposed method's ability to address (1) residue-dependent fragmentation properties and (2) the variability of resolution in different mass analyzers. Read More

AIChE J 1996 Jul;42(7):2069-79

Laboratoire de Genie Chimique, Universite Paul Sabatier, Toulouse, France.

During the IML-2 space shuttle mission, the RAMSES instrument was operated in the Spacelab module. This continuous-flow electrophoresis device performs separation and purification of protein solutions on a preparative scale. Samples containing artificial mixtures of pure proteins were used to test the capabilities of the device, and useful separations were obtained for proteins having a mobility difference of only 3 x 10(-9) m2 V-1 s-1. Read More

AIChE J 1995 May;41(5):1184-93

Laboratory of Renewable Resources Engineering, Purdue University, West Lafayette, IN 47907, USA.

Mobile-phase additives, commonly used to modulate absorbate retention in gradient elution chromatography, are usually assumed to be either linearly retained or unretained. Previous theoretical work from our laboratory has shown that these modulators, such as salts in ion-exchange and hydrophobic interaction chromatography and organic modifiers in reversed-phase chromatography, can absorb nonlinearly, giving rise to gradient deformation. Consequently, adsorbate peaks that elute in the vicinity of the head of the deformed gradient may exhibit unusual shapes, form shoulders, and/or be concentrated. Read More