High-throughput Research Research Articles

High Throughput Synthesis of Perovskite Oxides for Alkaline Oxygen Evolution Reaction Electrocatalysis: Nature of the a and B Sites

Electrochemical energy conversion technologies based on the oxygen evolution reaction (OER) are at the heart of many efforts to achieve a sustainable future, carbon-free fuel, and a circular economy. The sluggish kinetics of oxygen electrocatalysis, as well as the high overpotential required to attain practical current densities, limit the efficiency of several promising electrochemical technologies, including water and carbon dioxide electrolyzers, metal–oxygen batteries, and fuel cells. The most efficient OER catalysts are precious metals such as iridium- and ruthenium-based materials (i.e., IrO2 and RuO2). This fact represents a challenge against the cost-effective implementation of these electrolysis technologies.1-3 As a result, there is a necessity for the development of cost effective PGM-free OER catalysts, with equivalent or superior activity and durability to the PGM catalysts.This presentation will discuss the development and implementation of high-throughput synthesis methodology for PGM-free OER catalysts exploiting the rich chemistry of nanoporous materials4-7 and Argonne National Laboratory's High-Throughput Research Facility. The developed high-throughput methodology will expedite the assessment of the effect of composition and synthesis parameters on the activity of perovskite oxide alkaline electrolyte OER catalysts.AcknowledgementsThis work was supported by the U.S. Department of Energy, Advanced Research Projects Agency Energy (ARPA-E) under the DIFFERENTIATE program. This work was authored in part by Argonne National Laboratory, a U.S. Department of Energy (DOE) Office of Science laboratory operated for DOE by UChicago Argonne, LLC under contract no. DE-AC02-06CH11357.References Katsounaros, Ioannis, Serhiy Cherevko, Aleksandar R. Zeradjanin, and Karl JJ Mayrhofer. "Oxygen electrochemistry as a cornerstone for sustainable energy conversion." Angewandte Chemie International Edition53, no. 1 (2014): 102-121.Lee, Youngmin, Jin Suntivich, Kevin J. May, Erin E. Perry, and Yang Shao-Horn. "Synthesis and activities of rutile IrO2 and RuO2 nanoparticles for oxygen evolution in acid and alkaline solutions." The journal of physical chemistry letters3, no. 3 (2012): 399-404.Cherevko, S. et al. Oxygen and hydrogen evolution reactions on Ru, RuO2, Ir, and IrO2 thin film electrodes in acidic and alkaline electrolytes: A comparative study on activity and stability. Today 262, 170–180 (2016).Nahar, Lamia, Ahmed A. Farghaly, Richard J. Alan Esteves, and Indika U. Arachchige. "Shape controlled synthesis of Au/Ag/Pd nanoalloys and their oxidation-induced self-assembly into electrocatalytically active aerogel monoliths." Chemistry of Materials29, no. 18 (2017): 7704-7715.Farghaly, Ahmed A., Rezaul K. Khan, and Maryanne M. Collinson. "Biofouling-resistant platinum bimetallic alloys." ACS applied materials & interfaces10, no. 25 (2018): 21103-21112.Khan, Rezaul K., Ahmed A. Farghaly, Tiago A. Silva, Dexian Ye, and Maryanne M. Collinson. "Gold-Nanoparticle-Decorated Titanium Nitride Electrodes Prepared by Glancing-Angle Deposition for Sensing Applications." ACS Applied Nano Materials2, no. 3 (2019): 1562-1569.Farghaly, Ahmed A., Mai Lam, Christopher J. Freeman, Badharinadh Uppalapati, and Maryanne M. Collinson. "Potentiometric measurements in biofouling solutions: comparison of nanoporous gold to planar gold." Journal of The Electrochemical Society 163, no. 4 (2015): H3083.

(Invited) Machine Learning Driven Discovery and Optimization of Perovskite Alkaline Electrolyte Oxygen Evolution Reaction Electrocatalysts

Electrochemical energy conversion technologies based on the oxygen evolution reaction (OER) are at the heart of many efforts to achieve a sustainable future, carbon-free fuel, and a circular economy. The sluggish kinetics of oxygen electrocatalysis, as well as the high overpotential required to attain practical current densities, limit the efficiency of several promising electrochemical technologies, including water and carbon dioxide electrolyzers, metal–oxygen batteries, and fuel cells. The most efficient OER catalysts are precious metals such as iridium- and ruthenium-based materials (i.e., IrO2 and RuO2). This fact represents a challenge against the cost-effective implementation of these electrolysis technologies.1-3 As a result, there is a necessity for the development of cost effective PGM-free OER catalysts, with equivalent or superior activity and durability to the PGM catalysts.This presentation will describe the application of machine learning (ML)-guided materials discovery and high-throughput synthesis to address these concerns, taking advantage of the intriguing properties and rich chemistry of nanoporous materials, the demonstrated capability of machine learning (ML)-guided materials discovery, and the high OER electrocatalytic activity of perovskites especially in alkaline media.4-10 Simulation of over 8,000 perovskites across a variety of cell sizes, space groups, and compositions using density functional theory (DFT) has been performed. Mining of the simulation data indicated that experimentally-known perovskites are characterized by low energy above the thermodynamic convex hull. Efficient search algorithms, deep learning-based models, and DFT calculations have been used to explore the space of perovskite oxides to produce novel compositions with tailored electronic descriptors. Promising compositions designed for high activity and stability are then selected for high throughput automated synthesis using the High-Throughput Research Facility at Argonne National Laboratory. A correlation between the phase purity, annealing temperature and OER activity has been identified.AcknowledgementsThis work was supported by the U.S. Department of Energy, Advanced Research Projects Agency-Energy (ARPA-E) under the DIFFERENTIATE program. This work was authored in part by Argonne National Laboratory, a U.S. Department of Energy (DOE) Office of Science laboratory operated for DOE by UChicago Argonne, LLC under contract no. DE-AC02-06CH11357.References Katsounaros, Ioannis, Serhiy Cherevko, Aleksandar R. Zeradjanin, and Karl JJ Mayrhofer. "Oxygen electrochemistry as a cornerstone for sustainable energy conversion." Angewandte Chemie International Edition53, no. 1 (2014): 102-121.Lee, Youngmin, Jin Suntivich, Kevin J. May, Erin E. Perry, and Yang Shao-Horn. "Synthesis and activities of rutile IrO2 and RuO2 nanoparticles for oxygen evolution in acid and alkaline solutions." The journal of physical chemistry letters3, no. 3 (2012): 399-404.Cherevko, S. et al. Oxygen and hydrogen evolution reactions on Ru, RuO2, Ir, and IrO2 thin film electrodes in acidic and alkaline electrolytes: A comparative study on activity and stability. Today 262, 170–180 (2016).Nahar, Lamia, Ahmed A. Farghaly, Richard J. Alan Esteves, and Indika U. Arachchige. "Shape controlled synthesis of Au/Ag/Pd nanoalloys and their oxidation-induced self-assembly into electrocatalytically active aerogel monoliths." Chemistry of Materials29, no. 18 (2017): 7704-7715.Farghaly, Ahmed A., Rezaul K. Khan, and Maryanne M. Collinson. "Biofouling-resistant platinum bimetallic alloys." ACS applied materials & interfaces10, no. 25 (2018): 21103-21112.Khan, Rezaul K., Ahmed A. Farghaly, Tiago A. Silva, Dexian Ye, and Maryanne M. Collinson. "Gold-Nanoparticle-Decorated Titanium Nitride Electrodes Prepared by Glancing-Angle Deposition for Sensing Applications." ACS Applied Nano Materials2, no. 3 (2019): 1562-1569.Farghaly, Ahmed A., Mai Lam, Christopher J. Freeman, Badharinadh Uppalapati, and Maryanne M. Collinson. "Potentiometric measurements in biofouling solutions: comparison of nanoporous gold to planar gold." Journal of The Electrochemical Society163, no. 4 (2015): H3083.Suntivich, Jin, Kevin J. May, Hubert A. Gasteiger, John B. Goodenough, and Yang Shao-Horn. "A perovskite oxide optimized for oxygen evolution catalysis from molecular orbital principles." Science334, no. 6061 (2011): 1383-1385.Hwang, Jonathan, Zhenxing Feng, Nenian Charles, Xiao Renshaw Wang, Dongkyu Lee, Kelsey A. Stoerzinger, Sokseiha Muy et al. "Tuning perovskite oxides by strain: electronic structure, properties, and functions in (electro) catalysis and ferroelectricity." Materials Today31 (2019): 100-118.Gómez-Bombarelli, Rafael, Jennifer N. Wei, David Duvenaud, José Miguel Hernández-Lobato, Benjamín Sánchez-Lengeling, Dennis Sheberla, Jorge Aguilera-Iparraguirre, Timothy D. Hirzel, Ryan P. Adams, and Alán Aspuru-Guzik. "Automatic chemical design using a data-driven continuous representation of molecules." ACS central science 4, no. 2 (2018): 268-276.

Optimization of Synthesis Variables Towards Improved Activity and Stability of Fe-N-C PGM-Free Catalysts

Materials in the Fe-N-C family are the most promising platinum group metal-free (PGM-free) catalysts for the oxygen reduction reaction (ORR) in polymer electrolyte fuel cells (PEFCs).1-3 Although significant progress has been made in recent years in improving both the ORR activity and durability of the Fe-N-C catalysts, further improvements are needed, especially in long-term performance durability in hydrogen-air PEFCs, to enable their use in applications such as propulsion power for light-duty vehicles.3 The most active ORR catalysts in the Fe-N-C family were synthesized by heat treating iron salts or other iron-containing compounds with zinc-based zeolitic imidazolate frameworks (ZIFs) and/or phenanthroline (as carbon and nitrogen sources), or by heat treating iron-substituted ZIFs. For this family of PGM-free materials, it has been shown that many synthesis variables, such as the metal and carbon-nitrogen macrocycle content, the heat treatment temperature, atmosphere, and temperature profile all affect the activity and durability of the resulting catalysts.4-7 Optimization of these variables and testing the resulting catalyst properties is not a trivial task, and only a limited portion of the composite composition and temperature space has been explored for this family of catalysts.To accelerate optimization of the synthesis variables to obtain improved ORR activity and stability for the Fe-N-C catalysts, high-throughput synthesis and characterization methods were developed and utilized. An automation platform, a multi-port ball-mill, and parallel fixed bed reactors in Argonne’s High-throughput Research Laboratory were used to rapidly synthesize the PGM-free catalysts with systematically-varied synthesis conditions. A multi-channel flow double electrode (m-CFDE) cell and other cells were designed and constructed for the simultaneous testing the ORR activity and stability of the multiple catalysts synthesized. The ORR activity and stability of the catalysts were correlated with their Fe speciation, as determined using Fe K-edge X-ray absorption spectroscopy (XAFS), electrochemically-determined surface areas, and other variables, which is beneficial for the further improved catalyst activity and stability.References B. Pivovar, Nature Catalysis, 2 (2019) 562.S. Thompson and D. Papageorgopoulos, Nature Catalysis, 2 (2019) 558.L. Osmieri, J. Park, D.A. Cullen, P. Zelenay, D.J. Myers, and K.C. Neyerlin, Curr. Opin. Electrochem., 25 (2021) 100627.X. Wang, H. Zhang, H. Lin, S. Gupta, C. Wang, Z. Tao, H. Fu, T. Wang, J. Zheng, G. Wu, and X. Li, Nano Energy, 25 (2016) 110.H. Zhang, S. Hwang, M. Wang, Z. Feng, S. Karakalos, L. Luo, Z. Qiao, X. Xie, C. Wang, D. Su, Y. Shao, and G. Wu, J. Am. Chem. Soc., 139 (2017) 14143-14149.E. Proietti, F. Jaouen, M. Lefevre, N. Larouche, J. Tian, J. Herranz, and J.-P. Dodelet, Nature Comm. 2 (2011) 1.A. Zitolo, V. Goellner, V. Armel, M.-T. Sougrati, T. Mineva, L. Stievano, E. Fonda, and F. Jaouen, Nature Materials, 14 (2015) 937. This work was supported by the U.S. Department of Energy (DOE), Energy Efficiency and Renewable Energy, Hydrogen and Fuel Cell Technologies Office (HFTO) under the auspices of the Electrocatalysis Consortium (ElectroCat). This work utilized the resources of the Advanced Photon Source, a U.S. DOE Office of Science user facility operated by Argonne National Laboratory for DOE Office and was authored by Argonne, a U.S. Department of Energy (DOE) Office of Science laboratory operated for DOE by UChicago Argonne, LLC under contract no. DE-AC02-06CH11357.

Simultaneous High-Throughput Monitoring of Urethane Reactions Using Near-Infrared Hyperspectral Imaging.

High-throughput (HTP) research is becoming more widely utilized due to its advantages in rapid screening of large parameter space. When HTP is used for reaction screening, often only the end products are analyzed by off-line techniques, leaving behind valuable process information. Information-rich spectroscopy tools have remained under-utilized in HTP workflows. In this study, near-infrared (NIR) hyperspectral imaging (HSI) is demonstrated to be a versatile and accurate tool that can simultaneously monitor multiple reactions, opening up future opportunities to maximize information extraction from such HTP reaction screening experiments. Model urethane reactions are used here to demonstrate the concept, and the general approach can be widely applied to any reactions involving NIR-active functional groups. The fast speed and accurate chemical information made possible by NIR HSI are expected be another important addition to the toolkit of HTP research.

Abstract 42: High-throughput next-generation sequencing research solutions for detection of oncology variants, gene fusion events, and key oncology endpoints

Abstract Introduction: The Ion Torrent Genexus System has redefined the genomic profiling paradigm as the first fully-integrated, next-generation sequencing (NGS) research platform to provide an automated sample-to-report workflow with results in a single day. With a purification instrument, an enhanced chip architecture, and downstream reporting, the Genexus System provides a convenient solution to enable oncology research. Here we highlight the oncology research applications and high-throughput NGS capabilities of the Genexus System with Oncomine Comprehensive Assay Plus (OCA Plus), an oncology research panel that can detect variants, fusions, and evaluate key oncology research endpoints. We demonstrate the ability of OCA Plus on Genexus to evaluate tumor mutational burden (TMB), microsatellite instability (MSI), loss of heterozygosity (LOH), and homologous recombination repair deficiency (HRD). Methods: The high-throughput capabilities of the Genexus System enable it to support large oncology research panels such as OCA Plus, which comprises over 13,000 amplicons. The extensive per sample coverage allows for comprehensive DNA and RNA genomic profiling of relevant cancer biomarkers in over 500 genes including detection of over 1,300 fusion isoforms. We utilized high-molecular weight and FFPE samples, reference controls, and orthogonally tested research samples to evaluate DNA variant calling, RNA fusion calling, and key oncology research endpoints, including MSI, LOH, TMB, and HRD. Results: Commercially sourced reference control and research samples were sequenced using OCA Plus on the Genexus System. Sequencing data metrics showed ≥24 million reads per sample, with four samples supported per run. The high-throughput capacity of the Genexus chip architecture results in >95% of amplicons achieving a minimum of 500X coverage with an average coverage uniformity of ≥95% when evaluated across all >13,000 amplicons. Variant calling was assessed using the AcroMetrix Oncology Hotspot Control which has 328 hotspot variants covered by OCA Plus. Variant calling performance showed a hotspot and de novo variant sensitivity and PPV >95%. MSI score and status were assessed using known MSI-High and microsatellite stable (MSS) research samples and FFPE samples of interest. Results show high concordance with data from OCA Plus on GeneStudio. Conclusions: The increased throughput of the Genexus System combined with minimal touchpoints and a rapid turnaround time enables comprehensive genomic profiling for research assays such as OCA Plus where an increased number of sequencing reads leads to greater sensitivity for detecting rare variants and low-level fusion transcripts. Further, accurate characterization of key oncology research endpoints, such as TMB, MSI, LOH, and HRD, allow the Genexus System to accelerate research in the field of oncology. Citation Format: Kayla Zochowski, Dinesh Cyanam, Geoffrey Lowman, Jennifer Kilzer, Sameh El-Difrawy, Yan Zhu, Tanaya Puranik, Alex Phan, Derek Wong, Edith Kwong, Coleen Nemes, Iris Casuga, Frances Chan, Eun Ji Kim, Jianjun Guo, Vinay Mittal, Emily Norris, Shrutii Sarda, Mohit Gupta, Fan Shen, Steven Roman, Gabriel Vargas, Ying Jin, Annie Kraltcheva, Paul Williams, Amneet Gulati, Justin Rigby, Christopher Hoff, Richard Meade, Elaine Wong-Ho, Andrew Wong, Jamsheed Ghadiri, David Garcia-Viramontes, Scott Myrand, Seth Sadis. High-throughput next-generation sequencing research solutions for detection of oncology variants, gene fusion events, and key oncology endpoints [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 42.

A 3D Bioprinted in vitro Model of Neuroblastoma Recapitulates Dynamic Tumor-Endothelial Cell Interactions Contributing to Solid Tumor Aggressive Behavior.

Neuroblastoma (NB) is the most common extracranial tumor in children resulting in substantial morbidity and mortality. A deeper understanding of the NB tumor microenvironment (TME) remains an area of active research but there is a lack of reliable and biomimetic experimental models. This study utilizes a 3D bioprinting approach, in combination with NB spheroids, to create an in vitro vascular model of NB for exploring the tumor function within an endothelialized microenvironment. A gelatin methacryloyl (gelMA) bioink is used to create multi‐channel cubic tumor analogues with high printing fidelity and mechanical tunability. Human‐derived NB spheroids and human umbilical vein endothelial cells (HUVECs) are incorporated into the biomanufactured gelMA and cocultured under static versus dynamic conditions, demonstrating high levels of survival and growth. Quantification of NB‐EC integration and tumor cell migration suggested an increased aggressive behavior of NB when cultured in bioprinted endothelialized models, when cocultured with HUVECs, and also as a result of dynamic culture. This model also allowed for the assessment of metabolic, cytokine, and gene expression profiles of NB spheroids under varying TME conditions. These results establish a high throughput research enabling platform to study the TME‐mediated cellular‐molecular mechanisms of tumor growth, aggression, and response to therapy.

Biomimetic on-chip filtration enabled by direct micro-3D printing on membrane

Membrane-on-chip is of growing interest in a wide variety of high-throughput environmental and water research. Advances in membrane technology continuously provide novel materials and multi-functional structures. Yet, the incorporation of membrane into microfluidic devices remains challenging, thus limiting its versatile utilization. Herein, via micro-stereolithography 3D printing, we propose and fabricate a “fish gill” structure-integrated on-chip membrane device, which has the self-sealing attribute at structure-membrane interface without extra assembling. As a demonstration, metallic micromesh and polymeric membrane can also be easily embedded in 3D printed on-chip device to achieve anti-fouling and anti-clogging functionality for wastewater filtration. As evidenced from in-situ visualization of structure-fluid-foulant interactions during filtration process, the proposed approach successfully adopts the fish feeding mechanism, being able to “ricochet” foulant particles or droplets through hydrodynamic manipulation. When benchmarked with two common wastewater treatment scenarios, such as plastic micro-particles and emulsified oil droplets, our biomimetic filtration devices exhibit 2 ~ 3 times longer durability for high-flux filtration than devices with commercial membrane. This proposed 3D printing-on-membrane approach, elegantly bridging the fields of microfluidics and membrane science, is instrumental to many other applications in energy, sensing, analytical chemistry and biomedical engineering.

Integrated approach toward absorption, distribution, metabolism, and excretion of Xiaoke pills in zebrafish based on UPLC-HRMS and DESI-MS techniques

Traditional Chinese medicine (TCM) has been used in clinical settings for over 2000 years in China. The study of the absorption, distribution, metabolism, and excretion (ADME) of TCM in vivo could be beneficial for the discovery of the active components in TCM. However, the conventional strategies used for ADME research are based on rodent models and have the characteristics of lengthy experimental periods, complex processes, and extensive data processing, which make it difficult to perform rapid analyses and high-throughput ADME screening of the medicinal components of TCM. In this study, an integrated high-throughput research strategy for the in vivo ADME analysis of TCM was established based on a zebrafish model. Accordingly, a combination of ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS), desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, and in-house non-targeted precise-and-thorough background-subtraction (PATBS) data post-processing techniques were successfully applied for the analysis of the metabolism of zebrafish exposed to Xiaoke pills. A total of 49 compounds related to Xiaoke pills (including 13 prototypical components and 36 metabolites) were detected in zebrafish. In total, 32 of them, including puerarin, daidzein, deoxyschizandrin, formononetin, and glibenclamide, which have been identified to have hypoglycemic activity in our previous studies and are phase I and phase II metabolites resulting from the hydroxylation, demethylation, glucuronidation, sulfation, and glycosylation of the prototypical components in vivo, were found in rats treated with Xiaoke pills. Furthermore, the overall distribution of the known compounds in zebrafish exposed to Xiaoke pills was explored using DESI-MS. In summary, this study provides a practical approach for the high-throughput screening of the active components of TCM using a zebrafish model.

A Contemporary Insight of Metabolomics Approach for Type 1 Diabetes: Potential for Novel Diagnostic Targets.

High-throughput omics has been widely applied in metabolic disease, type 1 diabetes (T1D) was one of the most typical diseases. Effective prevention and early diagnosis are very important because of infancy and persistent characteristics of T1D. The occurrence and development of T1D is a chronic and continuous process, in which the production of autoantibodies (ie serum transformation) occupies the central position. Metabolomics can evaluate the metabolic characteristics of serum before seroconversion, the changes with age and T1D complications. And the addition of natural drug metabolomics is more conducive to the systematic and comprehensive diagnosis and treatment of T1D. This paper reviewed the metabolic changes and main pathogenesis from pre-diagnosis to treatment in T1D. The metabolic spectrum of significant abnormal energy and glucose-related metabolic pathway, down-regulation of lipid metabolism and up-regulation of some antioxidant pathways has appeared before seroconversion, indicating that the body has been in the dual state of disease progression and disease resistance before T1D onset. Some metabolites (such as methionine) are closely related to age, and the types of autoantibodies produced are age-specific. Some metabolites may jointly predict DN with eGFR, and metabolomics can further contribute to the pathogenesis based on the correlation between DN and DR. Many natural drug components have been proved to act on abnormal metabolic pathways of T1D and have a positive impact on some metabolic levels, which is very important for further finding therapeutic targets and developing new drugs with small side effects. Metabolomics can provide auxiliary value for the diagnosis of T1D and provide a new direction to reveal the pathogenesis of T1D and find new therapeutic targets. The development of T1D metabolomics shows that high-throughput research methods are expected to be introduced into clinical practice.

Advances Research in High-Throughput MgB2 Superconductivity

Superconducting materials find applications in a rapidly growing number of technological areas, and searching for novel superconductors continues to be a major scientific task. However, the steady increase in the complexity of candidate materials presents a big challenge to the researchers in the field. In particular, conventional experimental methods are not well suited to efficiently search for candidates in compositional space exponentially growing with the number of elements; neither do they permit quick extraction of reliable multidimensional phase diagrams delineating the physical parameters that control superconductivity. New research paradigms that can boost the speed and the efficiency of superconducting materials research are urgently needed. High-throughput methods for rapid screening and optimization of materials have demonstrated their utility for accelerating research in bioinformatics and pharmaceutical industry, yet remain rare in quantum materials research. In this paper, we will briefly review the history of high-throughput research paradigm and then focus on some recent applications of this paradigm in superconductivity research. We consider the role these methods can play in all stages of materials development, including high-throughput computation, synthesis, characterization, and the emerging field of machine learning for materials. The high-throughput paradigm will undoubtedly become an indispensable tool of superconductivity research in the near future.

Bioengineering Human Cartilage-Bone Tissues for Modeling of Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease worldwide, yet we continue to lack an understanding of disease etiology and pathology and effective treatment options. Essential to tissue homeostasis, disease pathogenesis, and therapeutic responses are the stratified organization of cartilage and cross talk at the osteochondral junction. Animal models may capture some of these features, but to establish clinically consistent therapeutics, there remains a need for high-fidelity models of OA that meet all the above requirements in a human patient-specific manner. In vitro bioengineered cartilage-bone tissue models could be developed to recapitulate physiological interactions with human cells and disease-initiating factors. In this study, we highlight human induced pluripotent stem cells (hiPSCs) as the advantageous cell source for these models and review approaches for chondrogenic fate specification from hiPSCs. To achieve native-like stratified cartilage organization with cartilage-bone interactions, spatiotemporal cues mimicking development can be delivered to engineered tissues by patterning of the cells, scaffold, and environment. Once healthy and native-like cartilage-bone tissues are established, an OA-like state can be induced through cytokine challenge or injurious loading. Bioengineered cartilage-bone tissues fall short of recapitulating the full complexity of native tissues, but have demonstrated utility in elucidating some mechanisms of OA progression and enabled screening of candidate therapeutics in patient-specific models. With rapid progress in stem cells, tissue engineering, imaging, and high-throughput omics research in recent years, we propose that advanced human tissue models will soon offer valuable contributions to our understanding and treatment of OA.

Modular multimodal platform for classical and high throughput light sheet microscopy

Light-sheet fluorescence microscopy (LSFM) has become an important tool for biological and biomedical research. Although several illumination and detection strategies have been developed, the sample mounting still represents a cumbersome procedure as this is highly dependent on the type of sample and often this might be time consuming. This prevents the use of LSFM in other promising applications in which a fast and straightforward sample-mounting procedure and imaging are essential. These include the high-throughput research fields, e.g. in drug screenings and toxicology studies. Here we present a new imaging paradigm for LSFM, which exploits modularity to offer multimodal imaging and straightforward sample mounting strategy, enhancing the flexibility and throughput of the system. We describe its implementation in which the sample can be imaged either as in any classical configuration, as it flows through the light-sheet using a fluidic approach, or a combination of both. We also evaluate its ability to image a variety of samples, from zebrafish embryos and larvae to 3D complex cell cultures.

Integrated high-throughput research in extreme environments targeted toward nuclear structural materials discovery

Arguably one of the most important factors in the fast deployment of advanced nuclear reactors, with major improvements in safety, is the development and qualification of radiation and corrosion tolerant materials, that serve as the structural components in reactor cores. However, the discovery, improvement, and assessment of materials resistant to radiation and corrosion in the advanced reactors’ extreme environments is quite demanding, time-consuming, and costly, which represents a significant barrier to materials innovation and qualification for nuclear energy. This short review highlights a novel, integrated, high-throughput (HTP) research framework to develop understanding and predictive models for irradiation at high doses and molten salt corrosion responses of structural Compositionally Complex Alloys (CCAs), with the objective to accelerate materials discovery for high-temperature nuclear structural applications. Using a novel in situ alloying technique, arrays of additively manufactured bulk CCAs are processed, heat-treated, and characterized, while still attached to the build plate. Leveraging recent development in automation of heavy-ion irradiation experiments at the University of Wisconsin Ion Beam Laboratory, arrays of CCAs can be rapidly irradiated to hundreds of dpa up to 800 °C. An innovative droplet corrosion method is also used to test molten salt corrosion behavior of CCAs arrays. Automated and rapid characterization methods are used to assess the irradiation and molten salt corrosion resistance of CCAs. Finally, a brief discussion of the results is presented considering future use of machine-learning-based methods to develop useful trends and highlight features of importance. Using this novel HTP approach, a robust and reliable database containing literally hundreds of data points for irradiation and corrosion responses of CCAs can be established within a year, which is considered a significant increase in the pace of nuclear structural materials research and discovery.

Structural Activity Relationship based Medicinal Perspectives of Pyrimidine Derivatives as Anti-Alzheimer’s Agents: A Comprehensive Review

Pyrimidine is an aromatic and heterocyclic organic compound containing a 6-membered ring consisting of four carbon and two nitrogen atoms on alternative positions. Pyrimidine scaffolds described theirexistence inthe medicinal chemist's cause for their synthesizing practicability and nonpoisonous nature. However, the reason behind neurological disorders is still an open challenge for scientific research and development organizations. Efficacy voids are widespread before researchers, despite high throughput research in the field of anti-Alzheimer's drugs.Researchers have constantly investigated all the probabilities for restraining the unwanted adverse effects of the anti-Alzheimer's agents and are focusing more extensively to rehabilitate neurological disorders. The scientific literature on drug development has been an aspiration to medicinal chemists and other researchers to facilitate further research. Therefore, this review emphasizes the structure-activity relationship (SAR) based approach and the pharmacological advancements of pyrimidine moiety in the new era of therapeutics as anti-Alzheimer's agents.

Magnesium alloy design: Examples from the Materials in Extreme Dynamic Environments Metals Collaborative Research Group

Designing metallic materials for resistance to ballistic penetration is challenging because mechanical behavior under dynamic loading involves multiple possible mechanisms of deformation and failure which are sensitive to details of structure on scales ranging from atomic to macroscopic. In this overview we use the example of magnesium alloys, which have promise as lightweight protective materials, to illustrate some of the key scientific and technical challenges in this area. Using a system design chart for magnesium alloys as a focal point, we describe three particular sets of processing-structure-properties connections: (i) The role of second-phase particles in spall failure, (ii) microstructural control through equal-channel angular extrusion (ECAE) to improve dynamic strength, and (iii) controlling crystallographic texture and plastic anisotropy for improved ballistic performance. We discuss implications of the multi-scale nature of behavior in structural metals – considering both performance in applications as well as thermomechanical processing – for potential high-throughput research and development of structural alloys and processes. We conclude with some thoughts about using system design charts to help set direction and establish priorities in large materials development projects.

Transposon sequencing: A powerful tool for the functional genomic study of food-borne pathogens

Genome-wide functional genetic studies of food-borne pathogens could provide a comprehensive understanding of the mechanisms underline their survival and pathogenesis in the harsh environments during food processing and infections. Traditional methods such as physical mutagenesis, chemical mutagenesis, and labeled DNA fragment insertion mutation techniques are time-consuming, labor-intensive and low precision. Although RNA-Seq and other omics methods enable high-throughput research on a genome-wide scale, the obtained results of gene transcription or expression cannot establish direct causal connection between the genetic determinants and particular functions. Transposon sequencing (Tn-seq) is an emerging microbial functional genomic technology based on transposon mutagenesis and high-throughput sequencing technologies, which is able to quantitatively track millions of independent mutants in a single experiment, and therefore efficiently map the “genotype-phenotype” relationship and the genetic interaction networks of a bacterium. This article summarizes the common types and hazards of food-borne pathogens, the development of Tn-seq technology, and its applications in studying the physiology, pathogenesis, and environmental survival of food-borne pathogens. • Food-borne pathogens are a common concern of food safety worldwide. • Transposon sequencing (Tn-seq) is an emerging microbial functional genomics technology. • Tn-seq can efficiently establish “genotype-phenotype” correspondence. • The development and applications of Tn-seq are reviewed.

Reimagining the future of African brain health: Perspectives for basic research on the pathogenesis of cryptococcal meningitis

Cryptococcal meningitis is a fatal opportunistic infection of the brain and a leading cause of neurological damage and death in immunocompromised individuals. This neglected fungal disease of the brain is a huge burden on the health systems of developing countries, especially in Sub-Saharan Africa, where up to 25% of people living with HIV/AIDS succumb to it. Cryptococcal fungal cells have a predilection for the brain and they are capable of traversing the blood brain barrier and invade the brain where they cause infection, inflammation and a disruption of normal brain function. A robust host neuroimmune response is critical for pathogen clearance and survival, and a good understanding of the mechanisms underlying its development in the host is critical for the development of effective treatments. However, past basic research studies have been focussed on the characteristics of the fungus and its effect on the peripheral immune system; with little attention paid to how it interacts with brain immune cells. This mini review briefly discusses the paucity of basic research data on the neuroimmune response to cryptococcal infection, raises pertinent questions on how the brain cells respond to the fungal infection, and thereafter discusses models, techniques and advanced technologies that could be useful for carrying out high-throughput research on the pathogenesis of cryptococcal meningitis.

Mobile electrophoresis kit for high school students: Scientific practices with innovation.

Gel electrophoresis (GE) is the most preferred and adapted technique for the separation and identification of biological molecules like proteins/peptides and nucleic acids from diverse types of organisms. All over the world, researchers, educators, and students aspiring to work in biochemistry and molecular biology disciplines use the polyacrylamide gel electrophoresis (PAGE) technique for resolving proteins/nucleic acids for understanding the structure and function of any cell. A simple PAGE technique requires a wide range of chemicals/reagents along with a well-equipped and well-spaced laboratory. We have developed a compact and impeccable mobile electrophoresis kit suitable for any vertically oriented PAGE technique. This comprehensive and portable laboratory set-up provides the complete advantages of safety, cost-efficiency, space management, and utility to the researchers for high-throughput research. All new equipment of the mobile electrophoresis kit is fabricated using inexpensive and off-the-rack components. Overall performance of the mobile kit was verified through a practical exercises executed by high school students with positive outcomes.

Membrane Pretreatment and Cell Conditioning for Proton Exchange Membrane Water Electrolysis

As the research community studying proton exchange membrane water electrolysis (PEMWE) grows, it is important to develop methods that achieve transparent, reproducible research. Reproducibility of performance and durability is a challenge facing the PEMWE field, as the published literature includes a wide spread of results obtained with nominally similar materials. [1] Prior round-robin performance benchmarking efforts [1] have identified inadequate cell conditioning as a major source of variation in apparent cell performance. Inadequate pre-treatment and conditioning can lead to instability in initial performance and adds ambiguity to durability measurements. However, excessively prolonged conditioning procedures limit the throughput of testing and the pace of research. Pretreatment and conditioning methods vary significantly across the research literature, but little systematic investigation is available into the mechanisms of these procedures or how procedural differences may impact results.This presentation will discuss investigations into the effects of membrane pre-treatment and operating procedures during cell conditioning on initial performance and catalyst-specific accelerated stress tests, with the aim of recommending procedures to enable clear, reproducible, and high-throughput research. Methods investigated include the use of hydrogen peroxide, acids, and hydration at elevated temperature for membrane pretreatment, and conditioning procedures such as current or voltage holds and cycling. The investigations cover both the impacts of these procedures on cell performance and stability as well as underlying mechanisms and processes taking place in the cell materials. [1] G. Bender et al., International Journal of Hydrogen Energy, 44, 9174–9187 (2019).

High Throughput Synthesis and Characterization of Multi-Metallic PGM-Free Aerogels for Catalyzing the Oxygen Evolution Reaction

Electrochemical energy conversion and storage technologies are at the heart of the societal pursuit towards circular economy, greenhouse gas emission-free fuel and sustainable energy future. The oxygen evolution reaction (OER) plays a central role in many of these electrochemical technologies, such as electrolyzers and metal-air batteries. The sluggish kinetics of the 4-electron oxidation of water to O2 and the resulting large overpotential limit the efficiency of these devices. The low abundance, prohibitive cost, and moderate stability of state-of-the-art OER catalysts, iridium- and ruthenium-based materials (i.e., IrO2 and RuO2) are obstacles against the cost-effective implementation of electrolysis technologies.1-3 To address these concerns and take the advantage of the intriguing properties and rich chemistry of nanoporous materials,4-7 we have developed a high throughput synthesis route for multi-metallic PGM-free aerogels for catalyzing the OER. The synthesis route is capable of producing 100 samples per batch using the High-Throughput Research Facility at Argonne National Laboratory. The effect of electrocatalyst composition (metal ion ratio) as well as the nature of the metal centers on the OER electrocatalytic activity have been evaluated.AcknowledgementsThis work was supported by the U.S. Department of Energy, Advanced Research Projects Agency Energy (ARPA-E) under the DIFFERENTIATE program. This work was authored in part by Argonne National Laboratory, a U.S. Department of Energy (DOE) Office of Science laboratory operated for DOE by UChicago Argonne, LLC under contract no. DE-AC02-06CH11357.References Katsounaros, Ioannis, Serhiy Cherevko, Aleksandar R. Zeradjanin, and Karl JJ Mayrhofer. "Oxygen electrochemistry as a cornerstone for sustainable energy conversion." Angewandte Chemie International Edition53, no. 1 (2014): 102-121.Lee, Youngmin, Jin Suntivich, Kevin J. May, Erin E. Perry, and Yang Shao-Horn. "Synthesis and activities of rutile IrO2 and RuO2 nanoparticles for oxygen evolution in acid and alkaline solutions." The journal of physical chemistry letters3, no. 3 (2012): 399-404.Cherevko, S. et al. Oxygen and hydrogen evolution reactions on Ru, RuO2, Ir, and IrO2 thin film electrodes in acidic and alkaline electrolytes: A comparative study on activity and stability. Today 262, 170–180 (2016).Nahar, Lamia, Ahmed A. Farghaly, Richard J. Alan Esteves, and Indika U. Arachchige. "Shape controlled synthesis of Au/Ag/Pd nanoalloys and their oxidation-induced self-assembly into electrocatalytically active aerogel monoliths." Chemistry of Materials29, no. 18 (2017): 7704-7715.Farghaly, Ahmed A., Rezaul K. Khan, and Maryanne M. Collinson. "Biofouling-resistant platinum bimetallic alloys." ACS applied materials & interfaces10, no. 25 (2018): 21103-21112.Khan, Rezaul K., Ahmed A. Farghaly, Tiago A. Silva, Dexian Ye, and Maryanne M. Collinson. "Gold-Nanoparticle-Decorated Titanium Nitride Electrodes Prepared by Glancing-Angle Deposition for Sensing Applications." ACS Applied Nano Materials2, no. 3 (2019): 1562-1569.Farghaly, Ahmed A., Mai Lam, Christopher J. Freeman, Badharinadh Uppalapati, and Maryanne M. Collinson. "Potentiometric measurements in biofouling solutions: comparison of nanoporous gold to planar gold." Journal of The Electrochemical Society163, no. 4 (2015): H3083.