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• W2012149695 abstract "The past two decades have witnessed impressive advances in the integration of microscale engineering with biology. The explosion of genomics and government support for biodefense research in the 1980s led to the inception of a new field now known as biological micro-electro-mechanical systems (bio-MEMS) that focuses on leveraging precision fabrication technologies developed in the microelectronics industry for the study of cells and biomolecules. Remarkable growth accomplished in this field has contributed to numerous conceptual and technological innovations in virtually all areas of life sciences. In particular, researchers have developed a wide variety of microengineered tools that provide unprecedented capabilities to control cultured living cells with high spatiotemporal precision and to present them with physiologically relevant microenvironmental cues.1Nam K.-H. Smith A. Lone S. et al.Biomimetic 3D Tissue Models for Advanced High-Throughput Drug Screening.J. Lab. Autom. 2015; 20: 201-215Google Scholar Recent progress in this microsystems approach for cell biology has also led to microengineered biomimetic models termed tissues- and organs-on-chips that reconstitute complex integrated physiological functions beyond cellular-level responses.2Tsui J.H. Lee W. Pun S.H. et al.Microfluidics-Assisted In Vitro Drug Screening and Carrier Production.Adv. Drug Deliv. Rev. 2013; 65: 1575-1588Google Scholar With the evolution and maturation of this field, we are now beginning to witness an exciting endeavor directed toward exploring the potential and real-world impact of these microengineered living systems for pharmaceutical and toxicological applications.3Sung J.H. Esch M.B. Prot J.M. et al.Microfabricated Mammalian Organ Systems and their Integration into Models of Whole Animals and Humans.Lab. Chip. 2013; 13: 1201-1212Google Scholar Fueled by recent escalating interest and support from both regulatory agencies and the pharmaceutical industry, microengineered cell- and tissue-based bioassays are emerging as an area of intense research investigation and technology commercialization.4Cavero I. Holzgrefe H. Comprehensive In Vitro Proarrhythmia Assay, a Novel In Vitro/In Silico Paradigm to Detect Ventricular Proarrhythmic Liability: A Visionary 21st Century Initiative.Expert Opin. Drug Saf. 2014; 13: 745-758Google Scholar This special issue of the Journal of Laboratory Automation offers an extensive survey of some of the most significant advances resulting from this recent trend that we believe are beneficial to a wide range of communities in pharmaceutical and toxicology research. Of particular interest in this special issue is the development of a combined contractility and electrophysiological assay for high-throughput cardiac safety screening. The inadequacies of current preclinical analysis methods for accurately predicting the arrhythmogenic potential of new drug candidates has garnered considerable attention in recent years. To that end, the current Cardiac In vitro Proarrhythmia Assay (CIPA) initiative has received support from both the U.S. Food and Drug Administration and pharmaceutical companies in the hope that it will lead to the development of more effective analytical methods for predicting the in vivo effects of new drugs.4Cavero I. Holzgrefe H. Comprehensive In Vitro Proarrhythmia Assay, a Novel In Vitro/In Silico Paradigm to Detect Ventricular Proarrhythmic Liability: A Visionary 21st Century Initiative.Expert Opin. Drug Saf. 2014; 13: 745-758Google Scholar,5Lee J. Razu M.E. Wang X. et al.Biomimetic Cardiac Microsystems for Pathophysiological Studies and Drug Screens.J. Lab. Autom. 2015; 20: 96-106Google Scholar Given this interest, platforms such as the one developed by Doerr and colleagues6Doerr L. Thomas U. Guinot D. et al.New Easy-to-Use Hybrid System for Extracellular Potential and Impedance Recordings.J. Lab. Autom. 2015; 20: 175-188Google Scholar are likely to come to the forefront of compound safety screening in the near future. In the presented study, the authors demonstrate how their 96-well plate assay can be used to record both field potential and contraction data, enabling multimodal analysis of cultured cardiomyocytes. Such a system provides more comprehensive information on the functional profiles of the cells, thereby enabling a more complete evaluation of compound action on the engineered cardiac monolayer. The results presented in this work demonstrate how multiple compounds can be assessed simultaneously to achieve higher-throughput analysis of drug action. Also of interest in this issue is the work of Kimura et al.7Kimura H. Ikeda T. Nakayama H. et al.An On-Chip Small Intestine–Liver Model for Pharmacokinetic Studies.J. Lab. Autom. 2015; 20: 265-273Google Scholar to produce a functional liver-on-a-chip model for analyzing first-pass metabolism in vitro. Despite the current excitement surrounding the potential for organs-on-chips to revolutionize human tissue modeling, the ability to generate microfluidic models connecting multiple organ models perhaps holds even greater promise for driving forward the utility of bioengineered platforms. Platforms capable of effectively modeling tissue-tissue cross-talk may hold the key to accurately modeling compound absorption, distribution, metabolism, and excretion in human systems.8Esch M.B. Smith A.S. Prot J.M. et al.How Multi-Organ Microdevices Can Help Foster Drug Development.Adv. Drug Deliv. Rev. 2014; 69–70: 158-169Google Scholar In the presented study, the authors highlight that their model successfully links small intestine, liver, and lung organ models as a first step toward this goal. The developed system maintains physiological flow velocities to more closely mimic human blood flow and distributions. Importantly, treatment with cyclophosphamide was found to have an effect in the lung tissue only when cells were co-cultured with the liver mimic, indicating the ability for the system to mimic metabolism of the compound as is known to occur in vivo. Further development of systems such as this may lead to the development of complex multiorgan models that accurately model human systems, reducing reliance on animal models for system toxicity screening. In keeping with the movement toward high-throughput modalities, Kim et al.9Kim J.-Y. Fluri D. Kelm J. et al.96-Well Format-Based Microfluidic Platform for Parallel Interconnection of Multiple Multicellular Spheroids.J. Lab. Autom. 2015; 20: 274-282Google Scholar present a novel method for generating spheroid cultures in a 96-well plate interconnected through the use of microfluidic channels. Although less physiologically representative, this system could theoretically be used to generate a multiorgan platform linking 96 tissue compartments for complex intertissue communication analysis. The work of Kim et al. and Kimura et al. represent high-content and high-throughput multiorgan modeling, respectively, but both make use of microfluidic channels to transport medium. Ryu and colleagues10Ryu H. Oh S. Hyun J.L. et al.Engineering a Blood Vessel Network Module for Body-on-a-Chip Applications.J. Lab. Autom. 2015; 20: 296-301Google Scholar have sought to further improve the biomimicity of microfluidic technologies through the generation of transferrable cell-based blood vessel networks to create links between inlets, outlets, and cell chambers. The use of paracrine-secreting fibroblasts and endothelial cells in these units serves to improve the physiological accuracy of these modular systems and could help drive multiorgan models toward more accurate representations of human systems In addition to these exciting articles, this issue presents work on the development of an array of new technologies, including methods for achieving automated hanging drop culture production,11Aijian A.P. Garrell R.L. Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture.J. Lab. Autom. 2015; 20: 283-295Google Scholar novel viability assays that enable repeated assessment of a single sample,12Class B. Thorne N. Aguisanda F. et al.High-Throughput Viability Assay Using an Autonomously Bioluminescent Cell Line with a Bacterial Lux Reporter.J. Lab. Autom. 2015; 20: 164-174Google Scholar techniques for producing high-throughput 3D culture models,13Leung B.M. Moraes C. Cavnar S.P. et al.Microscale 3D Collagen Cell Culture Assays in Conventional Flat-Bottom 384-Well Plates.J. Lab. Autom. 2015; 20: 138-145Google Scholar and simplified methods for attaining reproducible high-throughput assays.14Guckenberger D.J. Berthier E. Beebe D. et al.High-Density Self-Contained Microfluidic KOALA Kits for Use by Everyone.J. Lab. Autom. 2015; 20: 146-153Google Scholar,15Schober L. Büttner E. Laske C. et al.Cell Dispensing in Low-Volume Range with the Immediate Drop-on-Demand Technology (I-DOT).J. Lab. Autom. 2015; 20: 154-163Google Scholar The collected primary research is supported by in a number of in-depth reviews detailing some of the most important standout technologies for advancing microengineered cell- and tissue-based assays for drug-screening applications.16Sun J. Yuan X. Wang S. et al.Advances in Techniques for Probing Mechanoregulation of Tissue Morphogenesis.J. Lab. Autom. 2015; 20: 127-137Google Scholar, 17Kim S.-H. Lee G.-H. Park J.Y. et al.Microplatforms for Gradient Field Generation of Various Properties and Biological Applications.J. Lab. Autom. 2015; 20: 82-95Google Scholar, 18Khetani S. Berger D. Ballinger K. et al.Microengineered Liver Tissues for Drug Testing.J. Lab. Autom. 2015; 20: 216-250Google Scholar, 19Hovell C. Sei Y.J. Kim Y. Microengineered Vascular Systems for Drug Development.J. Lab. Autom. 2015; 20: 251-258Google Scholar, 21Peris-Vicente J. Carda-Broch S. Esteve-Romero J. Validation of Rapid Microbiological Methods.J. Lab. Autom. 2015; 20: 259-264Google Scholar We have strived to collect and present a diverse array of articles in order to provide an inclusive overview of the field that emphasizes the importance of these new technologies for valuable real-world applications. We hope you enjoy this special issue from the Journal of Laboratory Automation! Dan Dongeun Huh, PhD Department of Bioengineering University of Pennsylvania Philadelphia, PA, USA Deok-Ho Kim, PhD Department of Bioengineering University of Washington Seattle, WA, USA The authors thank Alec Smith for critical reading and editing of this manuscript. The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article." @default.
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