Microfluidic-Based Multi-Organ Platforms for Drug Discovery

Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of such platforms is still far from reality. Recent advances in physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling, micro- and nanotechnology, and in silico modeling have enabled single- and multi-organ platforms for investigation of new chemical agents and tissue-tissue interactions. This review provides an overview of the principles of designing microfluidic-based organ-on-chip models for drug testing and highlights current state-of-the-art in developing predictive multi-organ models for studying the cross-talk of interconnected organs. We further discuss the challenges associated with establishing a predictive body-on-chip (BOC) model such as the scaling, cell types, the common medium, and principles of the study design for characterizing the interaction of drugs with multiple targets.

[1]  I. Huang,et al.  Development of a FPW allergy biosensor for human IgE detection by MEMS and cystamine-based SAM technologies , 2008 .

[2]  N. Elvassore,et al.  Functional differentiation of human pluripotent stem cells on a chip , 2015, Nature Methods.

[3]  Gareth J Waldron,et al.  Reducing safety-related drug attrition: the use of in vitro pharmacological profiling , 2012, Nature Reviews Drug Discovery.

[4]  M. Brewster,et al.  Evaluation of gastrointestinal drug supersaturation and precipitation: strategies and issues. , 2013, International journal of pharmaceutics.

[5]  L. Shih,et al.  Histologic Types of Thymoma Associated with Pure Red Cell Aplasia: A Study of Five Cases Including a Composite Tumor of Organoid Thymoma Associated with an Unusual Lipofibroadenoma , 2001, International journal of surgical pathology.

[6]  Ethan Schonbrun,et al.  High-throughput fluorescence detection using an integrated zone-plate array. , 2010, Lab on a chip.

[7]  Kevin E. Healy,et al.  μOrgano: A Lego®-Like Plug & Play System for Modular Multi-Organ-Chips , 2015, PloS one.

[8]  Naomi J Halas,et al.  Observing metal-catalyzed chemical reactions in situ using surface-enhanced Raman spectroscopy on Pd-Au nanoshells. , 2008, Journal of the American Chemical Society.

[9]  Linfeng Xu,et al.  Various On-Chip Sensors with Microfluidics for Biological Applications , 2014, Sensors.

[10]  M Gibaldi,et al.  Influence of first-pass effect on availability of drugs on oral administration. , 1971, Journal of pharmaceutical sciences.

[11]  Alberto Rainer,et al.  Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering , 2015, Sensors.

[12]  A. Butte,et al.  Drug Discovery in a Multidimensional World: Systems, Patterns, and Networks , 2010, Journal of cardiovascular translational research.

[13]  Imran Shah,et al.  Systems toxicology from genes to organs. , 2013, Methods in molecular biology.

[14]  Mandy B. Esch,et al.  How multi-organ microdevices can help foster drug development. , 2014, Advanced drug delivery reviews.

[15]  Jong-Hoon Kim,et al.  Differentiation of Neural Progenitor Cells in a Microfluidic Chip‐Generated Cytokine Gradient , 2009, Stem cells.

[16]  Milica Radisic,et al.  Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers. , 2005, American journal of physiology. Heart and circulatory physiology.

[17]  Daniel C Leslie,et al.  A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice , 2012, Science Translational Medicine.

[18]  B. Chung,et al.  Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. , 2005, Lab on a chip.

[19]  Stephan Reichl,et al.  Organ on Chip , 2016 .

[20]  Ye Fang,et al.  A label-free optical biosensor with microfluidics identifies an intracellular signalling wave mediated through the β(2)-adrenergic receptor. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[21]  Elisa Cimetta,et al.  Microfluidic bioreactor for dynamic regulation of early mesodermal commitment in human pluripotent stem cells. , 2013, Lab on a chip.

[22]  Yael Zilberman,et al.  Microfluidic optoelectronic sensor for salivary diagnostics of stomach cancer. , 2015, Biosensors & bioelectronics.

[23]  J. F. Arenas,et al.  The role of charge-transfer states of the metal-adsorbate complex in surface-enhanced Raman scattering , 2002 .

[24]  Olivier Toussaint,et al.  Artefactual effects of oxygen on cell culture models of cellular senescence and stem cell biology , 2011, Journal of cellular physiology.

[25]  J. Yuhas,et al.  A simplified method for production and growth of multicellular tumor spheroids. , 1977, Cancer research.

[26]  Zeynep Altintas,et al.  Biomarkers and biosensors for the early diagnosis of lung cancer , 2013 .

[27]  K. Kneipp,et al.  SERS--a single-molecule and nanoscale tool for bioanalytics. , 2008, Chemical Society reviews.

[28]  Cécile Legallais,et al.  Metabolomics-on-a-chip of hepatotoxicity induced by anticancer drug flutamide and Its active metabolite hydroxyflutamide using HepG2/C3a microfluidic biochips. , 2013, Toxicological sciences : an official journal of the Society of Toxicology.

[29]  M. Yarmush,et al.  Evaluation of a microfluidic based cell culture platform with primary human hepatocytes for the prediction of hepatic clearance in human. , 2009, Biochemical pharmacology.

[30]  K. Rohr,et al.  Single‐cell‐based image analysis of high‐throughput cell array screens for quantification of viral infection , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[31]  Jerzy Leszczynski,et al.  Comprehension of drug toxicity: Software and databases , 2014, Comput. Biol. Medicine.

[32]  Zhongze Gu,et al.  Organ-on-a-Chip Systems: Microengineering to Biomimic Living Systems. , 2016, Small.

[33]  Roger D Kamm,et al.  A versatile assay for monitoring in vivo-like transendothelial migration of neutrophils. , 2012, Lab on a chip.

[34]  Kedar Kulkarni,et al.  Assessing chronic liver toxicity based on relative gene expression data. , 2008, Journal of theoretical biology.

[35]  Wenxin Wang,et al.  Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. , 2013, Biomaterials.

[36]  Y. S. Zhang,et al.  Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers , 2016, Scientific Reports.

[37]  P. Bork,et al.  Large‐scale prediction of drug–target relationships , 2008, FEBS letters.

[38]  Donald Wlodkowic,et al.  Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells. , 2009, Lab on a chip.

[39]  Richard D Beger,et al.  Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity. , 2010, Toxicology and applied pharmacology.

[40]  Michael Chopp,et al.  Animal models of traumatic brain injury , 2013, Nature Reviews Neuroscience.

[41]  Milan Mrksich,et al.  Geometric cues for directing the differentiation of mesenchymal stem cells , 2010, Proceedings of the National Academy of Sciences.

[42]  Mandy B. Esch,et al.  Microfabricated mammalian organ systems and their integration into models of whole animals and humans. , 2013, Lab on a chip.

[43]  Leon Aarons,et al.  Combining the ‘bottom up’ and ‘top down’ approaches in pharmacokinetic modelling: fitting PBPK models to observed clinical data , 2015, British journal of clinical pharmacology.

[44]  H. Lang,et al.  A label-free immunosensor array using single-chain antibody fragments. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Andreas Hierlemann,et al.  96-Well Format-Based Microfluidic Platform for Parallel Interconnection of Multiple Multicellular Spheroids , 2015, Journal of laboratory automation.

[46]  K. Ren,et al.  Materials for microfluidic chip fabrication. , 2013, Accounts of chemical research.

[47]  C. Domingo,et al.  Importance of Metal–Adsorbate Interactions for the Surface-enhanced Raman Scattering of Molecules Adsorbed on Plasmonic Nanoparticles , 2007 .

[48]  Sukhdeep Singh,et al.  The future of the patient-specific Body-on-a-chip. , 2013, Lab on a chip.

[49]  Duc-Huy T Nguyen,et al.  Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro , 2013, Proceedings of the National Academy of Sciences.

[50]  William R. Mundy,et al.  Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: a case study of lindane-induced neurotoxicity. , 2015, Toxicology and applied pharmacology.

[51]  J. Zhang,et al.  Data mining reveals a network of early-response genes as a consensus signature of drug-induced in vitro and in vivo toxicity , 2013, The Pharmacogenomics Journal.

[52]  Michael PH Stumpf Biosimulation in Drug Development , 2008, Human Genomics.

[53]  Luis G Valerio,et al.  In silico toxicology for the pharmaceutical sciences. , 2009, Toxicology and applied pharmacology.

[54]  Vladimir B Bajic,et al.  In silico toxicology: computational methods for the prediction of chemical toxicity , 2016, Wiley interdisciplinary reviews. Computational molecular science.

[55]  Dae Hong Jeong,et al.  Effects of surface density and size of gold nanoparticles in a fiber-optic localized surface plasmon resonance sensor and its application to peptide detection , 2010 .

[56]  M. C. Newman,et al.  The practice of structure activity relationships (SAR) in toxicology. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[57]  Neil Kaplowitz,et al.  Idiosyncratic drug hepatotoxicity , 2005, Nature Reviews Drug Discovery.

[58]  Ali Khademhosseini,et al.  Dermal Patch with Integrated Flexible Heater for on Demand Drug Delivery , 2016, Advanced healthcare materials.

[59]  Martin Bergstrand,et al.  PBPK models for the prediction of in vivo performance of oral dosage forms. , 2014, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[60]  Chris Adami,et al.  On Modeling Life , 1994, Artificial Life.

[61]  D. Ingber,et al.  Reconstituting Organ-Level Lung Functions on a Chip , 2010, Science.

[62]  D. Ingber,et al.  Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. , 2012, Lab on a chip.

[63]  Ali Khademhosseini,et al.  Chip-Based Comparison of the Osteogenesis of Human Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells under Mechanical Stimulation , 2012, PloS one.

[64]  Dmitry A Markov,et al.  Thick-tissue bioreactor as a platform for long-term organotypic culture and drug delivery. , 2012, Lab on a chip.

[65]  T. Kennedy Managing the drug discovery/development interface , 1997 .

[66]  D. Ingber,et al.  Microfluidic organs-on-chips , 2014, Nature Biotechnology.

[67]  Janina Kneipp,et al.  Characterizing the kinetics of nanoparticle-catalyzed reactions by surface-enhanced Raman scattering. , 2012, Angewandte Chemie.

[68]  A. Orth,et al.  High-content analysis of three-dimensional tumor spheroids: investigating signaling pathways using small hairpin RNA , 2013, Nature Methods.

[69]  Thomas Hankemeier,et al.  Microfluidic 3D cell culture: from tools to tissue models. , 2015, Current opinion in biotechnology.

[70]  Bingcheng Lin,et al.  A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process , 2016, Scientific Reports.

[71]  Matthew A Cooper,et al.  A survey of the 2001 to 2005 quartz crystal microbalance biosensor literature: applications of acoustic physics to the analysis of biomolecular interactions , 2007, Journal of molecular recognition : JMR.

[72]  I Takeuchi,et al.  Sorting out behaviour of disaggregated cells in the absence of morphogenesis in Dictyostelium discoideum. , 1979, Journal of embryology and experimental morphology.

[73]  C. Cannizzaro,et al.  Microfluidic device generating stable concentration gradients for long term cell culture: application to Wnt3a regulation of β-catenin signaling. , 2010, Lab on a chip.

[74]  Nancy A. Monteiro-Riviere,et al.  Characterization of microfluidic human epidermal keratinocyte culture , 2008, Cytotechnology.

[75]  Harish Shankaran,et al.  Physiologically-based pharmacokinetic model for Fentanyl in support of the development of Provisional Advisory Levels. , 2013, Toxicology and applied pharmacology.

[76]  S. Manalis,et al.  Micromechanical detection of proteins using aptamer-based receptor molecules. , 2004, Analytical chemistry.

[77]  P. Bork,et al.  Drug Target Identification Using Side-Effect Similarity , 2008, Science.

[78]  Varun Trivedi,et al.  A modular approach for the generation, storage, mixing, and detection of droplet libraries for high throughput screening. , 2010, Lab on a chip.

[79]  Uwe Marx,et al.  A multi-organ chip co-culture of neurospheres and liver equivalents for long-term substance testing. , 2015, Journal of biotechnology.

[80]  E. Seifried,et al.  Feasibility and efficacy of routine PCR screening of blood donations for hepatitis C virus, hepatitis B virus, and HIV-1 in a blood-bank setting , 1999, The Lancet.

[81]  Robert S. Balaban Allometry of brain metabolism , 2013, Proceedings of the National Academy of Sciences.

[82]  Tien Anh Nguyen,et al.  Microfluidic chip with integrated electrical cell-impedance sensing for monitoring single cancer cell migration in three-dimensional matrixes. , 2013, Analytical chemistry.

[83]  John P. Wikswo,et al.  Engineering Challenges for Instrumenting and Controlling Integrated Organ-on-Chip Systems , 2013, IEEE Transactions on Biomedical Engineering.

[84]  Arti Ahluwalia,et al.  Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism , 2014, Front. Bioeng. Biotechnol..

[85]  Megan L. McCain,et al.  Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. , 2011, Lab on a chip.

[86]  Hans Clevers,et al.  Modeling pancreatic cancer with organoids. , 2016, Trends in cancer.

[87]  David Beebe,et al.  Engineers are from PDMS-land, Biologists are from Polystyrenia. , 2012, Lab on a chip.

[88]  Jonathan D Posner,et al.  Simple replica micromolding of biocompatible styrenic elastomers. , 2013, Lab on a chip.

[89]  Jordi Mestres,et al.  Computational chemogenomics approaches to systematic knowledge-based drug discovery. , 2004, Current opinion in drug discovery & development.

[90]  T. Hartung,et al.  Electrophysiological recording of re-aggregating brain cell cultures on multi-electrode arrays to detect acute neurotoxic effects. , 2007, Neurotoxicology.

[91]  Lap Man Lee,et al.  The Application of Micropipette Aspiration in Molecular Mechanics of Single Cells. , 2014, Journal of nanotechnology in engineering and medicine.

[92]  F. Sonntag,et al.  A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. , 2015, Lab on a chip.

[93]  Hanseup Kim,et al.  Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB). , 2012, Lab on a chip.

[94]  Ivan Rusyn,et al.  Predicting drug-induced hepatotoxicity using QSAR and toxicogenomics approaches. , 2011, Chemical research in toxicology.

[95]  Arti Ahluwalia,et al.  Engineering Quasi-Vivo in vitro organ models. , 2012, Advances in experimental medicine and biology.

[96]  C. Larabell,et al.  Reciprocal interactions between beta1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[97]  María-Isabel Rocha-Gaso,et al.  Surface Generated Acoustic Wave Biosensors for the Detection of Pathogens: A Review , 2009, Sensors.

[98]  H. Clevers,et al.  Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications , 2013, Science.

[99]  S. Ekins,et al.  In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling , 2007, British journal of pharmacology.

[100]  Mark T. D. Cronin,et al.  Chapter 2:In Silico Tools for Toxicity Prediction , 2011 .

[101]  M. Yarmush,et al.  Emerging In Vitro Liver Technologies for Drug Metabolism and Inter-Organ Interactions. , 2016, Tissue engineering. Part B, Reviews.

[102]  M L Shuler,et al.  Combining Cell Culture Analogue Reactor Designs and PBPK Models to Probe Mechanisms of Naphthalene Toxicity , 2000, Biotechnology progress.

[103]  Chaenyung Cha,et al.  25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine , 2014, Advanced materials.

[104]  T. Ashburn,et al.  Drug repositioning: identifying and developing new uses for existing drugs , 2004, Nature Reviews Drug Discovery.

[105]  M. Yarmush,et al.  A microfluidic hepatic coculture platform for cell-based drug metabolism studies. , 2010, Biochemical pharmacology.

[106]  Pankaj Agarwal,et al.  A Pathway-Based View of Human Diseases and Disease Relationships , 2009, PloS one.

[107]  Rajarshi Guha,et al.  On exploring structure-activity relationships. , 2013, Methods in molecular biology.

[108]  Teck Chuan Lim,et al.  A microfluidic 3D hepatocyte chip for drug toxicity testing. , 2009, Lab on a chip.

[109]  R. Tagliaferri,et al.  Discovery of drug mode of action and drug repositioning from transcriptional responses , 2010, Proceedings of the National Academy of Sciences.

[110]  Hiroshi Yamada,et al.  Toxicogenomic multigene biomarker for predicting the future onset of proximal tubular injury in rats. , 2012, Toxicology.

[111]  Axel Scherer,et al.  A microfluidic processor for gene expression profiling of single human embryonic stem cells. , 2008, Lab on a chip.

[112]  Guoan Zheng,et al.  Optical imaging techniques in microfluidics and their applications. , 2012, Lab on a chip.

[113]  Jinwoo Kim,et al.  An integrative model of multi-organ drug-induced toxicity prediction using gene-expression data , 2014, BMC Bioinformatics.

[114]  R. Andrade,et al.  Drug-induced hepatotoxicity , 2003, The New England journal of medicine.

[115]  Philipp J. Keller,et al.  Fast, high-contrast imaging of animal development with scanned light sheet–based structured-illumination microscopy , 2010, Nature Methods.

[116]  James H Brown,et al.  Allometric scaling of metabolic rate from molecules and mitochondria to cells and mammals , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[117]  Lei Wang,et al.  Simultaneous generation of gradients with gradually changed slope in a microfluidic device for quantifying axon response. , 2013, Analytical chemistry.

[118]  A Sato,et al.  Development of a physiologically based pharmacokinetic model of organic solvent in rats. , 2000, Pharmacological research.

[119]  G. Whitesides,et al.  Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device , 2002, Nature Biotechnology.

[120]  Joel Dudley,et al.  Exploiting drug-disease relationships for computational drug repositioning , 2011, Briefings Bioinform..

[121]  Uwe Marx,et al.  Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[122]  Qing Yang,et al.  Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor. , 2015, Biomicrofluidics.

[123]  Richard S Paules,et al.  Use of transcriptomics in understanding mechanisms of drug-induced toxicity. , 2010, Pharmacogenomics.

[124]  Lior Gepstein,et al.  Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients. , 2013, European heart journal.

[125]  Shuichi Takayama,et al.  Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model. , 2011, Lab on a chip.

[126]  Emanuele Marconi,et al.  A microfluidic platform for chemoresistive testing of multicellular pleural cancer spheroids. , 2014, Lab on a chip.

[127]  Paul A Dayton,et al.  Functional ultrasound imaging for assessment of extracellular matrix scaffolds used for liver organoid formation. , 2013, Biomaterials.

[128]  Takao Hayakawa,et al.  Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4α transduction. , 2012, Molecular therapy : the journal of the American Society of Gene Therapy.

[129]  Bansi D Malhotra,et al.  Microfluidic‐integrated biosensors: Prospects for point‐of‐care diagnostics , 2013, Biotechnology journal.

[130]  Donald E Ingber,et al.  Mechanical control of tissue and organ development , 2010, Development.

[131]  Cécile Legallais,et al.  Metabolomics-on-a-chip and predictive systems toxicology in microfluidic bioartificial organs. , 2012, Analytical chemistry.

[132]  P. Clemons,et al.  Chemogenomic data analysis: prediction of small-molecule targets and the advent of biological fingerprint. , 2007, Combinatorial chemistry & high throughput screening.

[133]  Derek Tseng,et al.  Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications. , 2010, Lab on a chip.

[134]  G. Klebe,et al.  Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition. , 2004, Journal of medicinal chemistry.

[135]  Andrew G. Garrow,et al.  The value of in silico chemistry in the safety assessment of chemicals in the consumer goods and pharmaceutical industries. , 2012, Drug discovery today.

[136]  E. Jacoby Chemogenomics: drug discovery's panacea? , 2006, Molecular bioSystems.

[137]  Peter Molnar,et al.  Microphysiological systems and low-cost microfluidic platform with analytics , 2013, Stem Cell Research & Therapy.

[138]  Lixing Weng,et al.  Early Lung Cancer Diagnosis by Biosensors , 2013, International journal of molecular sciences.

[139]  Ivan Nestorov,et al.  Whole-body physiologically based pharmacokinetic models , 2007, Expert opinion on drug metabolism & toxicology.

[140]  Thomas Laurell,et al.  On-line monitoring of airborne chemistry in levitated nanodroplets: in situ synthesis and application of SERS-active Ag-Sols for trace analysis by FT-Raman spectroscopy. , 2003, Analytical chemistry.

[141]  Nam-Trung Nguyen,et al.  Towards Human on a Chip: Recent Progress and Future Perspective , 2014, Micro and Nanosystems.

[142]  A. Berg,et al.  BBB ON CHIP: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function , 2013, Biomedical microdevices.

[143]  Iain Gardner,et al.  Pharmacokinetics, Pharmacodynamics and Physiologically-Based Pharmacokinetic Modelling of Monoclonal Antibodies , 2013, Clinical Pharmacokinetics.

[144]  Michael L Shuler,et al.  A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers , 2009, Biotechnology and bioengineering.

[145]  Josue A. Goss,et al.  Microfluidic heart on a chip for higher throughput pharmacological studies. , 2013, Lab on a chip.

[146]  Gordana Vunjak-Novakovic,et al.  HeLiVa platform: integrated heart-liver-vascular systems for drug testing in human health and disease , 2013, Stem Cell Research & Therapy.

[147]  Lauren L Bischel,et al.  Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. , 2013, Biomaterials.

[148]  Andreas Hierlemann,et al.  Adding the 'heart' to hanging drop networks for microphysiological multi-tissue experiments. , 2015, Lab on a chip.

[149]  Michael J. Keiser,et al.  Predicting new molecular targets for known drugs , 2009, Nature.

[150]  Kevin Kit Parker,et al.  Functional Differences in Engineered Myocardium from Embryonic Stem Cell-Derived versus Neonatal Cardiomyocytes , 2013, Stem cell reports.

[151]  P. Welling,et al.  Influence of food and diet on gastrointestinal drug absorption: A review , 1977, Journal of Pharmacokinetics and Biopharmaceutics.

[152]  Bastian E. Rapp,et al.  Surface acoustic wave biosensors: a review , 2008, Analytical and bioanalytical chemistry.

[153]  J. Lippincott-Schwartz,et al.  Imaging Intracellular Fluorescent Proteins at Nanometer Resolution , 2006, Science.

[154]  Ron Shigeta,et al.  Statistical models for predicting liver toxicity from genomic data , 2013 .

[155]  Sejin Park,et al.  pH-sensitive solid-state electrode based on electrodeposited nanoporous platinum. , 2005, Analytical chemistry.

[156]  Donald E Ingber,et al.  Microengineered physiological biomimicry: organs-on-chips. , 2012, Lab on a chip.

[157]  Hui Zhao,et al.  Integrated microfluidic chip for endothelial cells culture and analysis exposed to a pulsatile and oscillatory shear stress. , 2009, Lab on a chip.

[158]  James P. Freyer,et al.  The Use of 3-D Cultures for High-Throughput Screening: The Multicellular Spheroid Model , 2004, Journal of biomolecular screening.

[159]  Eric K. Neumann,et al.  Inferring novel disease indications for known drugs by semantically linking drug action and disease mechanism relationships , 2009, BMC Bioinformatics.

[160]  Andrew P Worth,et al.  QSAR and metabolic assessment tools in the assessment of genotoxicity. , 2013, Methods in molecular biology.

[161]  Antje J Baeumner,et al.  Electrochemical microfluidic biosensor for the detection of nucleic acid sequences. , 2006, Lab on a chip.

[162]  Susan Z. Hua,et al.  On-chip microfluidic biosensor for bacterial detection and identification , 2007 .

[163]  P. Englebienne,et al.  Surface plasmon resonance: principles, methods and applications in biomedical sciences , 2003 .

[164]  Hisao Tajiri,et al.  The Functional Interrelationship between Gap Junctions and Fenestrae in Endothelial Cells of the Liver Organoid , 2007, Journal of Membrane Biology.

[165]  Alex J Walsh,et al.  Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. , 2014, Cancer research.

[166]  Martin Stelzle,et al.  Organ-Like Cell Cultures in Microfluidic Systems , 2013 .

[167]  Hans Clevers,et al.  Lgr5(+) liver stem cells, hepatic organoids and regenerative medicine. , 2013, Regenerative medicine.

[168]  Nikolay P Savchuk,et al.  Exploring the chemogenomic knowledge space with annotated chemical libraries. , 2004, Current opinion in chemical biology.

[169]  Linda G. Griffith,et al.  Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells , 2014, Stem Cell Reviews and Reports.

[170]  DA Lauffenburger,et al.  Physiome-on-a-Chip: The Challenge of “Scaling” in Design, Operation, and Translation of Microphysiological Systems , 2015, CPT: pharmacometrics & systems pharmacology.

[171]  Yi-Chung Tung,et al.  Optofluidic detection for cellular phenotyping. , 2012, Lab on a chip.

[172]  J. Carlsson,et al.  Proliferation and viability in cellular spheroids of human origin. , 1978, Cancer research.

[173]  K. Brouwer,et al.  In Vitro Methods to Support Transporter Evaluation in Drug Discovery and Development , 2013, Clinical pharmacology and therapeutics.

[174]  Mark W. Craven,et al.  Identification of toxicologically predictive gene sets using cDNA microarrays. , 2001, Molecular pharmacology.

[175]  Michael J. Keiser,et al.  Relating protein pharmacology by ligand chemistry , 2007, Nature Biotechnology.

[176]  J. DiMasi,et al.  Trends in Risks Associated With New Drug Development: Success Rates for Investigational Drugs , 2010, Clinical pharmacology and therapeutics.

[177]  Panos Macheras,et al.  Gastrointestinal Drug Absorption: Is It Time to Consider Heterogeneity as Well as Homogeneity? , 1997, Pharmaceutical Research.

[178]  Yeshaiahu Fainman,et al.  Optofluidic devices and applications in photonics, sensing and imaging. , 2012, Lab on a chip.

[179]  Harish Dureja,et al.  Classification models for safe drug molecules. , 2013, Methods in molecular biology.

[180]  Luke P. Lee,et al.  Microfluidic self-assembly of tumor spheroids for anticancer drug discovery , 2008, Biomedical microdevices.

[181]  Minoru Seki,et al.  Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions. , 2012, Biomaterials.

[182]  Uwe Marx,et al.  Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion. , 2013, Lab on a chip.

[183]  Stephanie Läer,et al.  A Physiologically Based Pharmacokinetic Drug–Disease Model to Predict Carvedilol Exposure in Adult and Paediatric Heart Failure Patients by Incorporating Pathophysiological Changes in Hepatic and Renal Blood Flows , 2015, Clinical Pharmacokinetics.

[184]  Josue A. Goss,et al.  Muscle on a chip: in vitro contractility assays for smooth and striated muscle. , 2012, Journal of pharmacological and toxicological methods.

[185]  James H. Brown,et al.  The origin of allometric scaling laws in biology from genomes to ecosystems: towards a quantitative unifying theory of biological structure and organization , 2005, Journal of Experimental Biology.

[186]  Olivier Bodenreider,et al.  The Unified Medical Language System (UMLS): integrating biomedical terminology , 2004, Nucleic Acids Res..

[187]  Yu Sun,et al.  (Micro)managing the mechanical microenvironment. , 2011, Integrative biology : quantitative biosciences from nano to macro.

[188]  Ali Khademhosseini,et al.  Elastomeric free-form blood vessels for interconnecting organs on chip systems. , 2016, Lab on a chip.

[189]  Ioanis Katakis,et al.  Design and testing of a packaged microfluidic cell for the multiplexed electrochemical detection of cancer markers , 2009, Electrophoresis.

[190]  Hee Chan Kim,et al.  Biosensors in microfluidic chips. , 2011, Topics in current chemistry.

[191]  J. Cairney,et al.  Rapid detection of bacterial spores using a quartz crystal microbalance (QCM) immunoassay , 2005, IEEE Sensors Journal.

[192]  J Wang,et al.  Microfabricated electrophoresis chips for simultaneous bioassays of glucose, uric acid, ascorbic acid, and acetaminophen. , 2000, Analytical chemistry.

[193]  Kee Suk Ryu,et al.  A modular microfluidic architecture for integrated biochemical analysis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[194]  Seung-Woo Cho,et al.  A microfluidic array for quantitative analysis of human neural stem cell self-renewal and differentiation in three-dimensional hypoxic microenvironment. , 2013, Biomaterials.

[195]  Olga Tcheremenskaia,et al.  Mutagenicity, carcinogenicity, and other end points. , 2013, Methods in molecular biology.

[196]  Jiajie Yu,et al.  On chip porous polymer membranes for integration of gastrointestinal tract epithelium with microfluidic ‘body-on-a-chip’ devices , 2012, Biomedical microdevices.

[197]  Philip E. Bourne,et al.  Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors , 2009, PLoS Comput. Biol..

[198]  Michael L Shuler,et al.  Murine in vitro model of the blood-brain barrier for evaluating drug transport. , 2011, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[199]  Aydogan Ozcan,et al.  Wide-field optical detection of nanoparticles using on-chip microscopy and self-assembled nanolenses , 2013, Nature Photonics.

[200]  Eli J. Weinberg,et al.  In vitro analysis of a hepatic device with intrinsic microvascular-based channels , 2008, Biomedical microdevices.

[201]  John P. Puccinelli,et al.  Thermal aging and reduced hydrophobic recovery of polydimethylsiloxane , 2006 .

[202]  Yi-Chung Tung,et al.  Electrofluidic pressure sensor embedded microfluidic device: a study of endothelial cells under hydrostatic pressure and shear stress combinations. , 2013, Lab on a chip.

[203]  Robert Langer,et al.  High throughput methods applied in biomaterial development and discovery. , 2010, Biomaterials.

[204]  Luke P. Lee,et al.  An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. , 2007, Biotechnology and bioengineering.

[205]  M. Ghert,et al.  Lost in translation: animal models and clinical trials in cancer treatment. , 2014, American journal of translational research.

[206]  D. Rognan Chemogenomic approaches to rational drug design , 2007, British journal of pharmacology.

[207]  Zhao-Bang Zeng,et al.  Genes related to apoptosis predict necrosis of the liver as a phenotype observed in rats exposed to a compendium of hepatotoxicants , 2008, BMC Genomics.

[208]  L. Samson,et al.  A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction. , 2005, Current drug metabolism.

[209]  Rohit N Kulkarni,et al.  Derivation of Human Induced Pluripotent Stem Cells from Patients with Maturity Onset Diabetes of the Young* , 2013, The Journal of Biological Chemistry.

[210]  Guanghui Hu,et al.  Human Disease-Drug Network Based on Genomic Expression Profiles , 2009, PloS one.

[211]  Ali Khademhosseini,et al.  Engineering microscale topographies to control the cell-substrate interface. , 2012, Biomaterials.

[212]  Lider S. Leon,et al.  Development of a human physiologically based pharmacokinetic (PBPK) model for dermal permeability for lindane. , 2016, Toxicology letters.

[213]  F. Sonntag,et al.  A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. , 2013, Lab on a chip.

[214]  M. Spector,et al.  Organoid Models of Human and Mouse Ductal Pancreatic Cancer , 2015, Cell.

[215]  W. Tassaneeyakul,et al.  Formation of omeprazole sulphone but not 5-hydroxyomeprazole is inhibited by grapefruit juice. , 2000, British journal of clinical pharmacology.

[216]  Cheng-Hsien Liu,et al.  Rapid heterogeneous liver-cell on-chip patterning via the enhanced field-induced dielectrophoresis trap. , 2006, Lab on a chip.

[217]  A. Ozcan,et al.  High-throughput screening of large volumes of whole blood using structured illumination and fluorescent on-chip imaging. , 2012, Lab on a chip.

[218]  Brendon M. Baker,et al.  Microfluidics embedded within extracellular matrix to define vascular architectures and pattern diffusive gradients. , 2013, Lab on a chip.

[219]  Joseph Wang Electrochemical glucose biosensors. , 2008, Chemical reviews.

[220]  Delbert Dueck,et al.  Clustering by Passing Messages Between Data Points , 2007, Science.

[221]  Andreas Hierlemann,et al.  Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis , 2014, Nature Communications.

[222]  Eric Leclerc,et al.  Investigation of omeprazole and phenacetin first‐pass metabolism in humans using a microscale bioreactor and pharmacokinetic models , 2015, Biopharmaceutics & drug disposition.

[223]  Aydogan Ozcan,et al.  Toward giga-pixel nanoscopy on a chip: a computational wide-field look at the nano-scale without the use of lenses. , 2013, Lab on a chip.

[224]  Peng Huang,et al.  Drug-induced nephrotoxicity: clinical impact and preclinical in vitro models. , 2014, Molecular pharmaceutics.

[225]  I. Ges,et al.  A microfluidic platform for chemical stimulation and real time analysis of catecholamine secretion from neuroendocrine cells. , 2013, Lab on a chip.

[226]  S. Lindstedt,et al.  Use of allometry in predicting anatomical and physiological parameters of mammals , 2002, Laboratory animals.

[227]  D. Gerhold,et al.  Monitoring expression of genes involved in drug metabolism and toxicology using DNA microarrays. , 2001, Physiological genomics.

[228]  Lucas H. Hofmeister,et al.  Scaling and systems biology for integrating multiple organs-on-a-chip. , 2013, Lab on a chip.

[229]  Luke P. Lee,et al.  Human iPSC-based Cardiac Microphysiological System For Drug Screening Applications , 2015, Scientific Reports.

[230]  Frank Caruso,et al.  Engineering and evaluating drug delivery particles in microfluidic devices. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[231]  Jan Böttger,et al.  “Artificial micro organs”—a microfluidic device for dielectrophoretic assembly of liver sinusoids , 2011, Biomedical microdevices.

[232]  Jong Hwan Sung,et al.  A micro cell culture analog (microCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. , 2009, Lab on a chip.

[233]  Kapil Pant,et al.  SyM-BBB: a microfluidic Blood Brain Barrier model. , 2013, Lab on a chip.

[234]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[235]  D. Grainger,et al.  A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity. , 2012, Pharmacology & therapeutics.

[236]  Marc P Y Desmulliez,et al.  Lab-on-a-chip based immunosensor principles and technologies for the detection of cardiac biomarkers: a review. , 2011, Lab on a chip.

[237]  Mandy B. Esch,et al.  The role of body-on-a-chip devices in drug and toxicity studies. , 2011, Annual review of biomedical engineering.

[238]  D. Kohn,et al.  Hematopoietic stem cells for cancer immunotherapy , 2014, Immunological reviews.

[239]  Emilio Benfenati,et al.  Comparison and Possible Use of In Silico Tools for Carcinogenicity Within REACH Legislation , 2011, Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews.

[240]  J. Lehár,et al.  Multi-target therapeutics: when the whole is greater than the sum of the parts. , 2007, Drug discovery today.

[241]  John P Wikswo,et al.  Biology coming full circle: Joining the whole and the parts , 2015, Experimental biology and medicine.

[242]  H. Byrne,et al.  Cell viability assessment using the Alamar blue assay: a comparison of 2D and 3D cell culture models. , 2015, Toxicology in vitro : an international journal published in association with BIBRA.

[243]  Vivienne Wee,et al.  Patriarchy in Secular and Religious Varieties , 2006 .

[244]  Laura M Ensign,et al.  Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. , 2012, Advanced drug delivery reviews.

[245]  B. J. Kane,et al.  Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes. , 2006, Analytical chemistry.

[246]  Hélder A Santos,et al.  Simple Microfluidic Approach to Fabricate Monodisperse Hollow Microparticles for Multidrug Delivery. , 2015, ACS applied materials & interfaces.

[247]  Fahmeed Hyder,et al.  Cortical energy demands of signaling and nonsignaling components in brain are conserved across mammalian species and activity levels , 2013, Proceedings of the National Academy of Sciences.

[248]  Jong Hwan Sung,et al.  A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. , 2010, Lab on a chip.

[249]  Harvey J Clewell,et al.  Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results , 2012, Critical reviews in toxicology.

[250]  Jamie A Davies,et al.  In vivo maturation of functional renal organoids formed from embryonic cell suspensions. , 2012, Journal of the American Society of Nephrology : JASN.

[251]  Jonathan D Posner,et al.  Simple, low-cost styrene-ethylene/butylene-styrene microdevices for electrokinetic applications. , 2013, Analytical chemistry.

[252]  Yu Ri An,et al.  Construction of a predictive model for evaluating multiple organ toxicity , 2016, Molecular & Cellular Toxicology.

[253]  Ali Khademhosseini,et al.  A microfluidic optical platform for real-time monitoring of pH and oxygen in microfluidic bioreactors and organ-on-chip devices. , 2016, Biomicrofluidics.

[254]  Chunsheng Wu,et al.  Cell-based biosensors and their application in biomedicine. , 2014, Chemical reviews.

[255]  Uwe Marx,et al.  The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture , 2015, Journal of visualized experiments : JoVE.

[256]  John P Wikswo,et al.  The relevance and potential roles of microphysiological systems in biology and medicine , 2014, Experimental biology and medicine.

[257]  Wolfgang Friess,et al.  Reconstructed skin models as emerging tools for drug absorption studies , 2013, Expert opinion on drug metabolism & toxicology.

[258]  C. London,et al.  Dogs as a Model for Cancer. , 2016, Annual review of animal biosciences.

[259]  Joel Dudley,et al.  Network-Based Elucidation of Human Disease Similarities Reveals Common Functional Modules Enriched for Pluripotent Drug Targets , 2010, PLoS Comput. Biol..

[260]  D. Beebe,et al.  PDMS absorption of small molecules and consequences in microfluidic applications. , 2006, Lab on a chip.

[261]  J Y Kresh,et al.  Real-time monitoring of adhesion and aggregation of platelets using thickness shear mode (TSM) sensor. , 2007, Biosensors & bioelectronics.

[262]  B. Ruggeri,et al.  Animal models of human disease: challenges in enabling translation. , 2014, Biochemical pharmacology.

[263]  Aydogan Ozcan,et al.  Field-portable lensfree tomographic microscope. , 2011, Lab on a Chip.

[264]  Jian Wang,et al.  In Silico Elucidation of the Molecular Mechanism Defining the Adverse Effect of Selective Estrogen Receptor Modulators , 2007, PLoS Comput. Biol..

[265]  Albert van den Berg Quantitative biosciences from nano to macro Indexed in MEDLINE ! , 2012 .

[266]  Aydogan Ozcan,et al.  Lensless wide-field fluorescent imaging on a chip using compressive decoding of sparse objects , 2010, Optics express.

[267]  G. Vunjak‐Novakovic,et al.  Engineered microenvironments for controlled stem cell differentiation. , 2009, Tissue engineering. Part A.

[268]  Roger D. Kamm,et al.  Differentiation of Embryonic Stem Cells into Cardiomyocytes in a Compliant Microfluidic System , 2011, Annals of Biomedical Engineering.

[269]  C. Erlichman,et al.  Cytotoxicity of adriamycin in MGH-U1 cells grown as monolayer cultures, spheroids, and xenografts in immune-deprived mice. , 1984, Cancer research.

[270]  R. Kamm,et al.  In Vitro Model of Tumor Cell Extravasation , 2013, PloS one.

[271]  Hartmut Derendorf,et al.  Pharmacokinetic/Pharmacodynamic Modeling in Drug Research and Development , 2000, Journal of clinical pharmacology.

[272]  S. Clissold,et al.  Paracetamol and Phenacetin , 2012, Drugs.

[273]  Sebastian Schlücker,et al.  Synthesis of bifunctional Au/Pt/Au Core/shell nanoraspberries for in situ SERS monitoring of platinum-catalyzed reactions. , 2011, Journal of the American Chemical Society.

[274]  E. Leclerc,et al.  Liver and kidney cells cultures in a new perfluoropolyether biochip , 2016 .

[275]  Samir Sarikouch,et al.  Successful matrix guided tissue regeneration of decellularized pulmonary heart valve allografts in elderly sheep. , 2015, Biomaterials.

[276]  A. Khademhosseini,et al.  Microscale technologies for tissue engineering and biology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[277]  D. Ingber,et al.  Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[278]  Rameen Beroukhim,et al.  Molecular characterization of the tumor microenvironment in breast cancer. , 2004, Cancer cell.

[279]  Paul A Clemons,et al.  The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease , 2006, Science.

[280]  Yu-Hsiang Hsu,et al.  In vitro perfused human capillary networks. , 2013, Tissue engineering. Part C, Methods.

[281]  E. Leclerc,et al.  Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines. , 2014, Toxicology in vitro : an international journal published in association with BIBRA.

[282]  Albert J. Keung,et al.  Soft microenvironments promote the early neurogenic differentiation but not self-renewal of human pluripotent stem cells. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[283]  M. D. Davidson,et al.  Microengineered Liver Tissues for Drug Testing , 2015, Journal of laboratory automation.

[284]  Johannes D. Seelig,et al.  Label-free protein assay based on a nanomechanical cantilever array , 2002 .

[285]  Liping Du,et al.  Microfabricated Electrochemical Cell-Based Biosensors for Analysis of Living Cells In Vitro , 2012, Biosensors.

[286]  Hao Zhu,et al.  From QSAR to QSIIR: searching for enhanced computational toxicology models. , 2013, Methods in molecular biology.

[287]  Tony Jun Huang,et al.  Optofluidic imaging: now and beyond. , 2013, Lab on a chip.

[288]  Gwo-Bin Lee,et al.  Microfluidic cell culture systems for drug research. , 2010, Lab on a chip.

[289]  Bryan L. Roth,et al.  Finding New Tricks For Old Drugs: An Efficient Route For Public-Sector Drug Discovery , 2005, Nature Reviews Drug Discovery.

[290]  Yanqiu Yu,et al.  A Review of the Application of Body-on-a-Chip for Drug Test and Its Latest Trend of Incorporating Barrier Tissue , 2016, Journal of laboratory automation.

[291]  D. Beebe,et al.  Human Embryonic Stem Cells and Microfluidics , 2004 .

[292]  Jinyi Wang,et al.  On-Chip Construction of Liver Lobule-like Microtissue and Its Application for Adverse Drug Reaction Assay. , 2016, Analytical chemistry.

[293]  Cynthia A Afshari,et al.  Prediction of Nephrotoxicant Action and Identification of Candidate Toxicity-Related Biomarkers , 2005, Toxicologic pathology.

[294]  Jing Liu,et al.  Perfused drop microfluidic device for brain slice culture-based drug discovery , 2016, Biomedical microdevices.

[295]  Emanuela Merelli,et al.  Agent-based models of cellular systems. , 2013, Methods in molecular biology.

[296]  Mark A Burns,et al.  Microfluidic assembly blocks. , 2008, Lab on a chip.

[297]  Anthony Atala,et al.  Liver-Tumor Hybrid Organoids for Modeling Tumor Growth and Drug Response In Vitro , 2015, Annals of Biomedical Engineering.

[298]  Albert P. Li,et al.  Accurate prediction of human drug toxicity: a major challenge in drug development. , 2004, Chemico-biological interactions.

[299]  G. Schneider,et al.  Predicting Compound Selectivity by Self‐Organizing Maps: Cross‐Activities of Metabotropic Glutamate Receptor Antagonists , 2006, ChemMedChem.

[300]  Raghuraman Venkatapathy,et al.  Developmental toxicity prediction. , 2013, Methods in molecular biology.

[301]  Martin Fussenegger,et al.  Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. , 2003, Biotechnology and bioengineering.

[302]  Shuichi Takayama,et al.  Fabrication of two-layered channel system with embedded electrodes to measure resistance across epithelial and endothelial barriers. , 2010, Analytical chemistry.

[303]  Jae Young Lee,et al.  Human induced pluripotent stem cell-based microphysiological tissue models of myocardium and liver for drug development , 2013, Stem Cell Research & Therapy.

[304]  Qasem Ramadan,et al.  In vitro micro-physiological models for translational immunology. , 2015, Lab on a chip.

[305]  Ruth E. Cameron,et al.  A Multifunctional 3D Co-Culture System for Studies of Mammary Tissue Morphogenesis and Stem Cell Biology , 2011, PloS one.

[306]  Christopher Moraes,et al.  On being the right size: scaling effects in designing a human-on-a-chip. , 2013, Integrative biology : quantitative biosciences from nano to macro.