Open Access Publications
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Open access publications by faculty, postdocs, and graduate students in the Department of Chemical and Biomolecular Engineering
Now showing 1 - 5 of 54
- ItemScalable, process-oriented beam lattices: Generation, characterization, and compensation for open cellular structures(Additive Manufacturing, 2021-12-01) Woodward, Ian R.; Fromen, Catherine A.Additively manufactured lattices are emerging as promising candidates for structural, thermal, chemical, and biological applications. However, achieving a satisfactory prototype or final part with this level of complexity requires synthesis of disparate knowledge from the distinctly digital and physical processing stages. This work proposes an integrated framework for processing self-supporting, open lattice structures that do not require supports and facilitate material removal in post-processing steps. We describe a minimal yet comprehensive design strategy for generating uniform lattice structures with conformal open lattice skins for an arbitrary unit cell configuration. Using continuous liquid interface production (CLIP™) on a Carbon M1, printability is evaluated for five unique bending-dominated lattice structures at unit cell length scales from 0.5 to 3.5 mm and strut diameters ranging from 0.11 to 1.05 mm. Using a cubic lattice as a basis, we further examine dimensional fidelity with respect to 2D lattice void dimensions and part position, finding differences between length scales and within parts, due to physical processing artifacts. Finally, we demonstrate a functional grading strategy based on process control methods to compensate for dimensional deviations. Using an iterative approach based on a naïve process model, deviation of the planar strut radius in a cubic lattice was decreased by approximately 85% after two iterations. These insights and strategies can be readily applied to other structures, characterization techniques, and additive manufacturing processes, thereby improving the exchange of information between digital and physical processing and lowering the energy barriers to producing high-quality lattice parts.
- ItemAnodically-Generated Alkyl Radicals Derived from Carboxylic Acids as Reactive Intermediates for Addition to Alkenes(ChemElectroChem, 2023-05-12) Ding, Haoran; Orazov, MaratElectrochemically driven C−C coupling has the potential to reduce the cost and environmental impact of some organic syntheses currently accomplished through thermochemical methods. Here, we use electrochemical oxidation of carboxylic acids as a source of reactive carbon-centered radicals that enable radical addition to alkenes in the anode boundary layer. We demonstrate an optimization of reaction conditions to suppress the thermodynamically favored, but synthetically undesirable radical self-coupling in favor of radical addition to styrene. In methanol solvent, 88 % selectivity and 72 % Faradaic efficiency for targeted functionalized benzenes are achieved. For low current densities, iridium anodes outperform platinum, gold, palladium, and glassy carbon anodes. With constant potential or constant current electrolyses, the deposition of organic by-products on the catalyst surface leads to anode passivation. We show that periodic cathodic current pulses effectively regenerate the catalyst. Lastly, we confirm the role of free radicals in the reaction mechanism with a radical trap. Graphical Abstract available at: https://doi.org/10.1002/celc.202201099 Electrochemically driven C−C coupling: High anodic current density favors the formation of the undesirable radical self-coupling product. Low anodic current density favors the formation of the target product, but also leads to more solvent oxidation. Solvent oxidation at low current density can be suppressed by multiple methods to achieve high Faradaic efficiency of the target product at high selectivity.
- ItemReductive Enzyme Cascades for Valorization of Polyethylene Terephthalate Deconstruction Products(ACS Catalysis, 2023-04-07) Gopal, Madan R.; Dickey, Roman M.; Butler, Neil D.; Talley, Michael R.; Nakamura, Daniel T.; Mohapatra, Ashlesha; Watson, Mary P.; Chen, Wilfred; Kunjapur, Aditya M.To better incentivize the collection of plastic wastes, chemical transformations must be developed that add value to plastic deconstruction products. Polyethylene terephthalate (PET) is a common plastic whose deconstruction through chemical or biological means has received much attention. However, a limited number of alternative products have been formed from PET deconstruction, and only a small share could serve as building blocks for alternative materials or therapeutics. Here, we demonstrate the production of useful monoamine and diamine building blocks from known PET deconstruction products. We achieve this by designing one-pot biocatalytic transformations that are informed by the substrate specificity of an ω-transaminase and diverse carboxylic acid reductases (CAR) toward PET deconstruction products. We first establish that an ω-transaminase from Chromobacterium violaceum (cvTA) can efficiently catalyze amine transfer to potential PET-derived aldehydes to form monoamine para-(aminomethyl)benzoic acid (pAMBA) or diamine para-xylylenediamine (pXYL). We then identified CAR orthologs that could perform the bifunctional reduction of terephthalic acid (TPA) to terephthalaldehyde or the reduction of mono-(2-hydroxyethyl) terephthalic acid (MHET) to its corresponding aldehyde. After characterizing 17 CARs in vitro, we show that the CAR from Segniliparus rotundus (srCAR) had the highest observed activity on TPA. Given these elucidated substrate specificity results, we designed modular enzyme cascades based on coupling srCAR and cvTA in one pot with enzymatic cofactor regeneration. When we supply TPA, we achieve a 69 ± 1% yield of pXYL, which is useful as a building block for polymeric materials. When we instead supply MHET and subsequently perform base-catalyzed ester hydrolysis, we achieve 70 ± 8% yield of pAMBA, which is useful for therapeutic applications and as a pharmaceutical building block. This work expands the breadth of products derived from PET deconstruction and lays the groundwork for eventual valorization of waste PET to higher-value chemicals and materials.
- ItemNanoparticle pre-treatment for enhancing the survival and activation of pulmonary macrophage transplant(Drug Delivery and Translational Research, 2023-03-14) Jarai, Bader M.; Bomb, Kartik; Fromen, Catherine A.Despite recent clinical successes of chimeric antigen receptor T cell therapies in treating liquid cancers, many lingering challenges stand in the way of therapeutic translation to broader types of malignancies. Macrophages have been proposed as alternatives to T cells given macrophages’ advantages in promoting tumor infiltration, acquiring diverse antigens, and possessing the ability to continuously stimulate adaptive responses. However, the poor survival of macrophages upon transplantation in addition to transient anti-tumor phenotypical states have been major obstacles standing in the way of macrophage-based cell therapies. Given recent discoveries of nanoparticle strategies in improving macrophage survival and promoting phenotype retention, we herein report the ability to extend the survival and phenotype of macrophage transplants in murine lungs via pre-treatment with nanoparticles of varying degradation rates. Macrophages pre-treated with 100 µg/ml dose of poly(ethylene glycol) diacrylate nanoparticle formulations improve pulmonary macrophage transplant survival over untreated cells beyond 7 days, where degradable nanoparticle formulations result in over a 50% increase in retention of transplanted cell counts relative to untreated cells. Furthermore, pre-treated macrophages more efficiently retain an imposed pro-inflammatory-like polarization state following transplantation out to 7 days compared to macrophages pre-treated with a classical pro-inflammatory stimulus, interferon-gamma, where CD86 costimulatory molecule expression is greater than 150% higher in pre-treated macrophage transplants compared to untreated counterparts. These findings provide an avenue for a major improvement in the lifespan and efficacy of macrophage-based cell therapies and have broader implications to other phagocyte-based cellular therapeutics and administration routes. Graphical abstract available at: https://doi.org/10.1007/s13346-023-01319-6
- ItemA Genetic Engineering Toolbox for the Lignocellulolytic Anaerobic Gut Fungus Neocallimastix frontalis(ACS Synthetic Biology, 2023-04-21) Hooker, Casey, A.; Hanafy, Radwa; Hillman, Ethan T.; Muñoz Briones, Javier; Solomon, Kevin V.Anaerobic fungi are powerful platforms for biotechnology that remain unexploited due to a lack of genetic tools. These gut fungi encode the largest number of lignocellulolytic carbohydrate active enzymes (CAZymes) in the fungal kingdom, making them attractive for applications in renewable energy and sustainability. However, efforts to genetically modify anaerobic fungi have remained limited due to inefficient methods for DNA uptake and a lack of characterized genetic parts. We demonstrate that anaerobic fungi are naturally competent for DNA and leverage this to develop a nascent genetic toolbox informed by recently acquired genomes for transient transformation of anaerobic fungi. We validate multiple selectable markers (HygR and Neo), an anaerobic reporter protein (iRFP702), enolase and TEF1A promoters, TEF1A terminator, and a nuclear localization tag for protein compartmentalization. This work establishes novel methods to reliably transform the anaerobic fungus Neocallimastix frontalis, thereby paving the way for strain development and various synthetic biology applications.