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Videos uploaded by user “ACEA Biosciences - A part of Agilent”
ACEA's xCELLigence System
 
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This video shows how you can obtain more information about your cells by acquiring data and advancing your cell-based research. Perform real-time, label-free cellular assays to: generate more physiologically relevant data, measure short-term and long-term cellular effects, continuously monitor cell responses without the use of exogenous labels, determine optimal time points for endpoint assays. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/
ACEA's xCELLigence DP Analyzer
 
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The xCELLigence systems provide a unique and powerful means to monitor cells in real-time without the potential artifacts generated through the use of labels. This non-invasive measurement allows detection of changes in adherence, morphology and viability without the need for over-expression of reporter and target proteins. This provides physiologically relevant data throughout the entire time course of the experiment. The RTCA DP Instrument expands the throughput and application options of the xCELLigence Real-Time Cell Analyzer (RTCA) portfolio. Featuring a dual-plate (DP) format, the instrument measures impedance-based signals in both cellular and cell invasion/migration (CIM) assays - without the use of exogenous labels. With outstanding application flexibility, the RTCA DP Instrument supports multiple users performing short-term and long-term experiments. For more information, please visit: http://www.aceabio.com/product/rtca-dp/
ACEA NovoCyte Flow Cytometer - Introduction
 
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Discover the intuitive features of using the NovoCyte Flow Cytometer and its NovoExpress Software. For more information, please visit: http://www.aceabio.com/products/novocyte/
xCELLigence Training
 
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Learn how to set up your xCELLigence system, run experiments, and some simple maintenance such as cleaning the instrument.
ACEA NovoCyte Flow Cytometer - Maintenance Overview
 
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Learn about the quick and simple maintenance of the NovoCyte Flow Cytometer. For more information, please visit: http://www.aceabio.com/products/novocyte/
Determining Optimal Cytotoxic Activity of Human Her2neu Specific CD8 T cells
 
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Erskine, C. L., Henle, A. M., Knutson, K. L. Determining Optimal Cytotoxic Activity of Human Her2neu Specific CD8 T cells by Comparing the Cr51 Release Assay to the xCELLigence System. J. Vis. Exp. (66), e3683, doi:10.3791/3683 (2012). The chromium release assay, a common assay for detecting cytotoxic T cell activity, has several limitations. Using antigen-specific CD8 T cells and the human breast cancer tumor line, SKBR3, in the present article, an impedance-based approach was examined for the capability of detecting cell killing. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/
Live Technical Webinar:  Measuring Calcium Flux by Flow Cytometry
 
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Presenter: Lauren Jachimowicz, Ph.D. Application Development Scientist, ACEA Biosciences, Inc. About this webinar: Accurate measurements of intracellular Ca2+ concentrations allows for a more comprehensive understanding of Ca2+ regulated cell functions and signaling pathways. Ca2+ is an important molecule that affects a wide range of physiological and pathological processes. Unlike other secondary messengers, Ca2+ is not synthesized or metabolized, but stored and rapidly released by channels/pumps that maintain Ca2+ concentrations in distinct cellular compartments. Flow cytometry allows real time measurement of a calcium flux response utilizing fluorescent Ca2+ indicators which exhibit an increase in fluorescence upon binding to Ca2+. In this webinar we will discuss the basics of calcium flux measurements by flow cytometry, providing specific details on experiment setup, acquisition, and analysis on the NovoCyte flow cytometer. Key topics to be covered: 1. Essentials of calcium measurements by flow cytometer 2. Calcium flux experimental setup and acquisition on the NovoCyte 3. Detailed analysis of calcium flux in a T cell line using calcium indicator dye Fluo-4/AM
A Real-time Technique to Measure Invasion of Endothelial Cell Monolayer by Cancer Cells
 
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Rahim, S., Üren, A. A Real-time Electrical Impedance Based Technique to Measure Invasion of Endothelial Cell Monolayer by Cancer Cells. J. Vis. Exp. (50), e2792, doi:10.3791/2792 (2011). This video demonstrates an in vitro technique for monitoring cancer cells invading through a monolayer of endothelial cells. The data is acquired in real-time as a function of changes in impedance on the surface of electrodes at the well bottom. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/
Derek Davies Testimonial - NovoCyte Flow Cytometer
 
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Derek Davies, Director at The Crick Research Institute, affirms NovoCyte is a staple in his role of managing flow core laboratory, with users of different level of flow experience. For more information, please visit: http://www.aceabio.com/products/novocyte/
RTCA Software Pro for Immunotherapy Applications
 
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RTCA Software Pro is an integrated software package for running and analyzing real time cell analysis data from xCELLigence RTCA DP, SP, and MP instruments. The powerful immunotherapy module is designed to measure cytolysis of target tumor cells by immune effector cells and other molecules. This software is ideal for analyzing various types of immunotherapy studies, including NK cells, CAR-T cells, bi-specific T cell Engagers (BiTEs), immune checkpoint inhibitors, or antibody dependent cell mediated cytotoxicity (ADCC). Benefits of RTCA Software Pro: -Simple Experimental Set Up -Easily Visualize Well Content -Generate Publication Ready Data -Easy Experimental Analysis -More Reproducible Cytolytic Data Visit aceabio.com to learn more.
Ryan Duggan Testimonial - NovoCyte Flow Cytometer
 
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Ryan Duggan, Technical Director at University of Chicago, attests to the unique usability of NovoCyte and its ‘cold-start to dots-on-the-plot’ capability, including the ability to analyze acquiring data at the same time. For more information, please visit: http://www.aceabio.com/products/novocyte/
Assessment of Ovarian Cancer Spheroid Attachment and Invasion of Mesothelial Cells in Real Time
 
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Bilandzic, M., Stenvers, K. L. Assessment of Ovarian Cancer Spheroid Attachment and Invasion of Mesothelial Cells in Real Time. J. Vis. Exp. (87), e51655, doi:10.3791/51655 (2014). Ovarian cancer cell invasion into the mesothelial lining of the peritoneum is a dynamic process over time. Utilizing a real time analyzer, the invasive capacity of ovarian cancer cells in a spheroid-mesothelial cell co-culture model can be quantified over prolonged time periods, providing insights into factors regulating the metastatic process. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/
Targeting the Reattachment of Circulating Breast Tumor Stem Cells to Reduce Metastasis
 
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Breast tumor stem cells that are circulating in the bloodstream can invade distant tissues and lie dormant for long periods of time. Reemergence of these disseminated stem cells as metastatic tumors is a primary cause of patient death. In this webinar Dr. Stuart Martin from the University of Maryland School of Medicine (Baltimore, MD) discusses his utilization of multiple tools/techniques to discover microtentacles (McTNs) as novel cellular structures that promote the metastatic reattachment of circulating tumor cells in distant tissues. He specifically shows that: • Real-time electrical impedance assays with xCELLigence® demonstrate that McTNs influence tumor cell reattachment and migration efficiency, providing a platform for cancer stem cell identification and testing of new antimetastasis therapies • Live-cell confocal microscopy reveals that McTNs can penetrate blood vessel walls and also reinforce the multicellular spheres that are formed by many types of cancer stem cells After training as a Howard Hughes undergraduate research fellow at the University of Virginia, Dr. Stuart Martin received his Ph.D. from the University of California, San Diego. He then completed a Damon Runyon postdoctoral fellowship at Harvard Medical School where he combined functional genomic studies with mouse models of breast tumor metastasis under the mentorship of Dr. Phil Leder. In 2004, Dr. Martin joined the Marlene and Stewart Greenebaum Cancer Center (UMGCC) and the Department of Physiology at the University of Maryland School Of Medicine. He is currently working to apply physical science and engineering approaches to the study of cancer. In order to examine the mechanical properties of circulating tumor cells, Dr. Martin introduced the first optical cell stretcher in the United States. For his innovative research on breast cancer metastasis, in 2010 he was one of only three investigators in the United States recognized with an Era of Hope Scholar Award from the Congressionally-directed Medical Research Program. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/ REFERENCES: 1. Matrone, M.A., Whipple, R.A., Thompson, K., Cho, E.H., Vitolo, M.I., Balzer, E.M., Yoon, J.R., Ioffe, O.B., Tuttle, K.C., Tan, M. and Martin, S.S. Metastatic breast tumors express increased tau, which promotes microtentacle formation and the reattachment of detached breast tumor cells. Oncogene. 2010 Jun 3;29(22):3217-27. 2. Whipple, R.A., Cho, E.H., Balzer, E.M., Matrone, M.A., Vitolo, M.I., Yoon, J.R., Ioffe, O.B., Tuttle, K.C., Yang, J. and Martin, S.S. Epithelial-to-mesenchymal transition promotes tubulin detyrosination and microtentacles that enhance endothelial engagement. Cancer Res. 2010 Oct 15;70(20):8127-37. 3. Yoon, J.R., Whipple, R.A., Balzer, E.M., Cho, E.H., Matrone, M.A. and Martin, S.S. Local anesthetics inhibit kinesin motility and microtentacle protrusions of human epithelial and breast tumor cells. Breast Cancer Res. Treat. 2011 Oct;129(3):691-701. 4. Vitolo MI, Boggs AE, Whipple RA, Yoon JR, Thompson K, Matrone MA, Cho EH, Balzer EM, Martin SS. Loss of PTEN induces microtentacles through PI3K-independent activation of cofilin. Oncogene. 2013 Apr 25;32(17):2200-10. 5. Whipple RA, Vitolo MI, Boggs AE, Charpentier MS, Thompson K, Martin SS. Parthenolide and costunolide reduce microtentacles and tumor cell attachment by selectively targeting detyrosinated tubulin independent from NF-κB inhibition. Breast Cancer Res. 2013; 15(5):R83. 6. Charpentier MS, Whipple RA, Vitolo MI, Boggs AE, Slovic J, Thompson KN, Bhandary L, Martin SS. Curcumin targets breast cancer stem-like cells with microtentacles that persist in mammospheres and promote reattachment. Cancer Res. 2014 Feb 15;74(4):1250-60. 7. Perry NA, Vitolo MI, Martin SS, Kontrogianni-Konstantopoulos A. Loss of the obscurin-RhoGEF downregulates RhoA signaling and increases microtentacle formation and attachment of breast epithelial cells. Oncotarget. 2014 Sep 30;5(18):8558-68. 8. Boggs AE, Vitolo MI, Whipple RA, Charpentier MS, Goloubeva OG, Ioffe OB, Tuttle KC, Slovic J, Lu Y, Mills GB, Martin SS. α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration. Cancer Res. 2015 Jan 1;75(1):203-15. 9. Bhandary L, Whipple RA, Vitolo MI, Charpentier MS, Boggs AE, Chakrabarti KR, Thompson KN, Martin SS. ROCK inhibition promotes microtentacles that enhance reattachment of breast cancer cells. Oncotarget. 2015 Mar 20;6(8):6251-66.
Innovations Series with ACEA Bioscience's xCELLigence CardioECR System
 
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ACEA Bioscience's xCELLigence CardioECR System. For more information, please visit: http://www.aceabio.com/product/rtca-cardioecr/
Steve Offer on Characterizing Potential Biomarkers of Colorectal Cancer Using xCELLigence & NovoCyte
 
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CYTO 2016 Speaker: Steve Offer, Ph.D., Mayo Clinic School of Medicine Use of Real Time Cellular Analysis and Flow Cytometry to Characterize Potential Biomarkers of Aggressive Colorectal Cancer
A Flow Cytometry Method for Detecting Bacteria in Water
 
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About the Presenter Stephanie Ting, M. Eng Field Application Scientist – SE Asia, ANZ, HK&Macau, India, ACEA Biosciences Inc. Stephanie received her Masters in Mechanical Engineering from the University of Tokyo, Japan where she studied the effects of mechanobiological stimuli on the production of cartilage-like tissues using mesenchymal stem cells. Currently, she is the Field Application Scientist for SE Asia, ANZ, HK&Macau, and India.
Novocyte Webinar - CYTO Conference 2015
 
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Learn from the flow cytometry experts who presented their research studies and experiences in using the ACEA NovoCyte at the 2015 CYTO Conference.
Evaluation of ACEA's NovoCyte Flow Cytometer
 
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Dr. Garret Guenther, application development scientist at ACEA Biosciences, first provides an overview of the NovoCyte flow cytometer. Ryan Duggan, technical director of the Flow Cytometry Facility at the University of Chicago, then describes his lab's evaluation of multiple flow cytometers and explains how the usability of the NovoCyte sets it apart.
ACEA NovoCyte Cytometer Advantage
 
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The ACEA NovoCyte flow cytometer advantage as described and validated by key opinion leaders in the flow cytometry community including Derek Davies, Alan Saluk, and Ryan Duggan. For more information, please visit: http://www.aceabio.com/products/novocyte/
xCELLigence® RTCA CardioECR System
 
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Preclinical Safety Assessment, iPSC-cardiomyocytes Functional Maturation and Assessment of Inotropic Compounds
Innovations w/Ed Begley, Jr Featuring ACEA's RTCA xCELLigence CardioECR System- INTV1218
 
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As broadcast via Discovery Channel, Thursday, 12/18/2014. Innovations is dedicated to bringing viewers the most up-to-date, cutting edge information across a vast array of industries. From health and wellness to global business, renewable energy, and more, Innovations features practical solutions and important issues facing consumers and professionals alike. For more information visit InnovationsTelevision.com
Cell Cycle Analysis by Flow Cytometry (Webinar)
 
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DNA content analysis using flow cytometry is a powerful tool that can determine the effect of treatments on cell cycle and ploidy in particular relevance to tumours. However, how do you determine which DNA-binding dye to use? How do you accurately differentiate the different phases in the cell cycle in your population of cells? This webinar will teach the methods for cell cycle analysis with the following topics: During this webinar, we will cover: -Phases of a typical mammalian cell cycle -Characteristics of Nucleic Acid Stains -How to choose the right fluorochromes and properly prepare your cells -DNA ploidy & tumours Presenter: Stephanie Ting, M. Eng Field Application Scientist – SE Asia, ANZ, HK&Macau, India, ACEA Biosciences Inc.
Unraveling Kinase Inhibitor Cardiotoxicity with Cardiomyocyte Impedance Assays
 
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Cardiovascular (CV) toxicity is a leading cause of drug failure. Though implementing earlier testing has successfully reduced hERG-related arrhythmias, additional assays capable of identifying other functional CV effects remain elusive. There is a pressing need to address this gap for kinase inhibitors, which frequently display CV toxicity. In this webinar, Dr. Sarah K. Lamore of AstraZeneca Pharmaceuticals (Waltham, MA) presents her research utilizing cellular impedance measurement of beating cardiomyocytes to deconvolute kinase inhibitor cardiotoxicity. Specific topics covered include: • The principle behind cellular impedance assays • Translational predictivity for cardiac contractility assays (xCELLigence® vs. IonOptix) • CV toxicity assay development for kinase inhibitors (Chk & MARK) that have unresolved functional cardiotoxicity • Progress in Kinome-wide screening & deconvolution using cellular impedance assays Dr. Sarah K. Lamore is a discovery safety scientist at AstraZeneca Pharmaceuticals. Her current research focuses on combining cellular impedance and human iPSC-derived cardiomyocytes to deconvolute kinase inhibitor cardiotoxicity. Dr. Lamore received her Ph.D. in pharmacology and toxicology from the University of Arizona in 2012. Her doctoral work involved identifying cysteine cathepsins as novel targets of UVA-induced photooxidative stress. For more information, please visit: http://www.aceabio.com/product/rtca-cardio/ REFERENCES: 1. Lamore SD, Kamendi HW, Scott CW, Dragan YP, Peters MF. Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity. Toxicol Sci. 2013 Oct;135(2):402-13. 2. Scott CW, Zhang X, Abi-Gerges N, Lamore SD, Abassi YA, Peters MF. An impedance-based cellular assay using human iPSC-derived cardiomyocytes to quantify modulators of cardiac contractility. Toxicol Sci. 2014 Dec;142(2):331-8. 3. Peters MF, Lamore SD, Guo L, Scott CW, Kolaja KL. Human stem cell-derived cardiomyocytes in cellular impedance assays: bringing cardiotoxicity screening to the front line. Cardiovasc Toxicol. 2015 Apr;15(2):127-39.
Measuring the Growth of Microbial Biofilms in Real-Time: Evidence, Insights and Applications
 
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The xCELLigence instruments are revolutionizing pure and applied biofilm research. Beyond gains in efficiency, the real-time and label-free xCELLigence assay provides access to information that has been inaccessible using traditional methodologies. https://www.aceabio.com/video/new-era-biofilm-research/
Paul Wallace | AAI | Exosomes Present in Human Ovarian Tumor Microenvironment Rapidly Arrest T Cells
 
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AAI Annual Meeting 2017 Technology Seminar Sponsored by ACEA Biosciences Presented by Paul Wallace Exosomes Present in Human Ovarian Tumor Microenvironment Rapidly Arrest T Cells In this workshop Dr. Wallace will present a study on how membrane bound extracellular vesicles isolated from ovarian cancer patients have biophysical and compositional characteristics similar to vesicles called exosomes. The tumor-associated exosomes inhibit an early activation endpoint of a significant portion of virus (EBV and CMV) specific CD8+ T-cells that are stimulated with viral peptides presented in the context of Class I MHC. Early and late activation endpoints of peripheral blood CD4+ and CD8+ T-cells stimulated with immobilized antibodies to CD3 and CD28 are also significantly inhibited by the exosomes. The inhibition of the T-cells is induced directly and rapidly and occurs coincidentally with the exosomes binding to and internalization by the T-cells. The early arrest in the activation occurs without a loss of viability in the T-cells. The immune suppressive exosomes in the tumor microenvironment and the ability to block their T-cell inhibitory activity represent a potential therapeutic target to enhance the anti-tumor immunity of quiescent tumor-associated T cells, and to prevent the functional arrest
ACEA NovoCyte Video
 
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NovoCyte, the New Star of Benchtop Flow Cytometry Exceptional Performance at a Low Investment Cost Address the full range of current and future multi-parameter cellular analysis research needs with the NovoCyte flow cytometer. ACEA brings researchers high performance flow cytometry at a low investment cost with the NovoCyte platform. ACEA offers a system which is: Powerful - up to 15 parameter detection with enhanced sensitivity and resolution. Intuitive - automated instrument maintenance functions and advanced data analysis capabilities for greater usability. Customizable - 1 to 3 laser options, exchangeable filters, multiple sampling options and flexible analysis formats. Other important features enhance usability such as a fixed optical alignment, 7-log detection dynamic range with no need for PMT voltage adjustment, accurate volumetric-based cell counting, pressure sensors to monitor fluidic status in real-time, and automatic cleaning and de-contamination processes. ACEA also developed the NovoExpress™ software which is intuitive and easy to use. Flexible analysis templates and plotting tools offer enhanced data analysis efficiency.
Cardiotoxicity screening using hiPSC cardiomyocytes and ACEA's xCELLigence CardioECR sysem
 
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The “Innovations” TV program on the Discovery Channel recently featured the groundbreaking xCELLigence RTCA CardioECR system from ACEA Biosciences. In the clip shown here Dr. Blake Anson from Cellular Dynamics International describes the advantages of performing cardiotoxicity screening using hiPSC-derived cardiomyocytes and the xCELLigence CardioECR system. The complete program can be viewed here: https://www.youtube.com/watch?v=44bpQT3lCnk For more information, please visit: http://www.aceabio.com/product/rtca-cardioecr/
Compensation in Flow Cytometry Webinar
 
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Compensation in Flow Cytometry Webinar Speaker: Heather Paich
Combining RTCA With Flow Cytometry to Characterize BiTE/T Cell ...
 
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CYTO 2017 Workshop June 12, 2017 Workshop Title: Combining Real-Time Cell Analysis With Flow Cytometry to Characterize BiTE/T Cell-Mediated Cytolysis and Neutrophil Extracellular Traps Presenter: Brandon Lamarche, Ph.D., Sr. Scientist, ACEA Biosciences In this workshop you will learn about monitoring cellular impedance in real-time and without the use of labels. The xCELLigence instruments assess cell number, size, and attachment quality with unprecedented kinetic resolution and sensitivity. Herein we combine xCELLigence assays with NovoCyte flow cytometric analyses to characterize two key immunological prophylactic mechanisms. First, we track Bispecific T Cell Engager (BiTE)-mediated stimulation of cancer cell killing by T cells. Next, we shift our focus to NETosis, a cell death process that occurs when stimulated neutrophils cast an extracellular web containing DNA, histones, and anti-bacterial proteins that ensnare/neutralize invading organisms. Collectively, these talks will demonstrate how xCELLigence and flow assays can be run on the same sample to provide a wealth of information about cell health and behavior in diverse applications/contexts.
A Novel In Vitro Approach to Study Biocompatibility and Wound Healing
 
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Negative Pressure Wound Therapy (NPWT), where a vacuum is applied to an acute or chronic wound, has proven extremely effective for promoting would healing. The success of NPWT lies in its ability to draw the edges of a wound together, to promote granulation, and to remove infectious material. Critical to NPWT’s efficacy was the development of biocompatible materials capable of interfacing with the wound throughout the healing process. In this webinar Dr. Sandra N. Garcia from Kinetic Concepts Inc. (San Antonio, TX) describes the development of in vitro assays used to evaluate medical devices for toxicity/biocompatibility and efficacy in promoting wound healing. Specific topics addressed include: • Comparison of xCELLigence® real-time cellular analysis vs. conventional methods (visual assessment or WST-1 as described in ISO 10933-5) for assessing the cytotoxicity of medical devices in vitro • Advantages of the xCELLigence® cell invasion/migration (CIM) assay vs. a standard scratch assay for studying wound healing • Application of the xCELLigence® cell invasion/migration (CIM) device for evaluating the efficacy of Negative Pressure Wound Therapy (V.A.C.® NPWT) Dr. Sandra N. Garcia is a cell and tissue culture manager at Kinetic Concepts Inc. (KCI), a global medical device leader in transformational wound healing solutions headquartered in San Antonio TX. Dr. Garcia attended the University of Texas, San Antonio, and subsequently received her Ph.D. in cellular and molecular biology from the University of California, San Diego. She has over 20 years of experience as a research scientist, including two post-doctoral fellowships where she focused on cellular senescence and gene silencing at the Sam and Ann Barshop Institute and the University of Texas, San Antonio. More recently, Dr. Garcia has directed research elucidating the mechanisms of action for: CelluTome® (an automated epidermal micrografting tool), Grafjacket® (an acellular matrix), and V.A.C™ therapy on multiple patient stem cell populations. For more information about KCI or on-going studies, visit www.kci1.com or contact Dr. Garcia at sandra.garcia@kci1.com. For more information about xCELLigence, please visit: http://www.aceabio.com/products/xcelligence-rtca/ REFERENCES: Garcia SN, Gutierrez L, McNulty A. Real-time cellular analysis as a novel approach for in vitro cytotoxicity testing of medical device extracts. J Biomed Mater Res A. 2013 Jul;101(7):2097-106
WEBINAR: Exploring the Role of iPSC-Cardiomyocytes in Drug Discovery and Safety Assessment
 
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Featured Speaker: Armando Lagrutta, PhD, Merck & Co. Inc. Kristina Green, PhD, MyoKardia, Inc. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly utilized in basic biology research, drug discovery applications, and for studies of disease mechanisms. The opportunity to measure the contractility, viability, and electrophysiology of hiPSC-CMs in real time over extended periods can provide researchers unique mechanistic insights into the roles cardiomyocytes play in both normal development and cardiac disease. In this special webinar, scientists using hiPSC-CMs will describe new approaches aimed at enhancing assessment of hiPSC-CM functionality. The speakers will also discuss how these approaches can be used to explore compounds that modulate the force of cardiomyocyte contraction or to assess the safety and efficacy of drugs and drug combinations targeting cardiac tissue. In this webinar, you will gain insights on: New instrumentation to assess cardiomyocyte contractility, viability, and electrophysiology Label-free, real-time techniques to assess the “beating” of cardiomyocytes as a biologically-relevant measure of cardiomyocyte function Use of electrical pacing for further maturation of cardiomyocytes Techniques to detect functional cardiotoxicity In addition, you will also be able to ask your own specific questions of the speakers during a live question-and-answer session following the presentations.
ASCB 2016 Tech Seminar: Label-Free Real-Time Cell Analysis Technology for Cancer Immunotherapy
 
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Utilization of a Label-Free Real-Time Cell Analysis Technology for Cancer Immunotherapy Applications Speaker: Brandon Lamarche, Ph.D. Research Scientist at ACEA Biosciences, Inc.
Using Impedance-Based Approaches for Measuring Antigen-Specific Cytotoxic T cell Activity
 
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Immunotherapy, where the immune system is harnessed to treat and/or prevent disease, holds great promise in the fight against cancer. One noteworthy facet of cancer immunotherapy is the development of cancer-specific vaccines. In this webinar Dr. Keith L. Knutson from the Mayo Clinic (Jacksonville, FL) and VGTI discusses the use of ACEA’s xCELLigence® system in his efforts to discover a novel epitope for use in breast cancer vaccination. Specific topics covered include: • The concepts of cancer vaccine and immune therapy • Development of an impedance-based assay using the xCELLigence® system to monitor cytotoxic T-cell activity • The advantages of dynamic monitoring of cytotoxic T-cell activity using impedance-based assays vs. the traditional endpoint Chromium-51 Release Assay (CRA) Dr. Keith L. Knutson is currently the director of the Cancer Vaccine and Immune Therapies program at VGTI and is an affiliate associate professor in the Department of Immunology at the Mayo Clinic. He received his Ph.D. in physiology and pharmacology from the University of Georgia, Athens in 1995, and completed two postdoctoral fellowships in immunology at the University of British Columbia and the University of Washington. He was a 2004 recipient of the Howard Temin Award from the National Cancer Institute. Dr. Knutson’s current research focuses on the immunology and immunotherapy of breast and ovarian cancers. His interests are in both the basic immunobiology and clinical translation, including clinical trials. His laboratory is currently conducting research on cancer vaccines that augment CD4 helper T-cell immunity using peptide epitopes. These vaccine strategies are aimed at preventing patient relapse after conventional chemotherapies. Adoptive T-cell therapy, a strategy that involves infusing high numbers of T-cells into patients with active bulky malignancy, is also being examined in Knutson’s lab. Specific adoptive T-cell therapy projects include methods for T-cell expansion and in vitro generation of memory T-cells. Lastly, Dr. Knutson’s lab also seeks to understand how tumors evade the immune system and immune therapies. Several different mechanisms of immune escape are being investigated, including cellular reprogramming (e.g., epithelial to mesenchymal transition) and recruitment of regulatory T-cells and myeloid-derived suppressor cells into the tumor microenvironment. In addition to his research, Dr. Knutson participates in and chairs several study sections. He is currently a full member of the Department of Defense's Breast Cancer Research Program Integration Panel and a full member of the Tumor Microenvironment Study Section at the National Institutes of Health Center for Scientific Review. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/ REFERENCES: 1. Asiedu MK, Ingle JN, Behrens MD, Radisky DC, Knutson KL. TGFbeta/TNF(alpha)-mediated epithelial-mesenchymal transition generates breast cancer stem cells with a claudin-low phenotype. Cancer Res. 2011 Jul 1;71(13):4707-19. 2. Erskine CL, Henle AM, Knutson KL. Determining optimal cytotoxic activity of human Her2neu specific CD8 T cells by comparing the Cr51 release assay to the xCELLigence system. J Vis Exp. 2012 Aug 8;(66):e3683. 3. Henle AM, Erskine CL, Benson LM, Clynes R, Knutson KL. Enzymatic discovery of a HER-2/neu epitope that generates cross-reactive T cells. J Immunol. 2013 Jan 1;190(1):479-88. 4. Mader EK, Butler G, Dowdy SC, Mariani A, Knutson KL, Federspiel MJ, Russell SJ, Galanis E, Dietz AB, Peng KW. Optimizing patient derived mesenchymal stem cells as virus carriers for a phase I clinical trial in ovarian cancer. J Transl Med. 2013 Jan 24;11:20
Identifying Novel Combination Therapeutic Targets for Pancreatic Cancer
 
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Pancreatic cancer is presently a largely incurable disease. Increasing evidence suggests that effective treatment strategies will need to simultaneously target multiple molecular mediators of critical functions in pancreatic ductal adenocarcinoma cells (PDAC). In this webinar Dr. Melissa L. Fishel from the Indiana University School of Medicine (Indianapolis, IN) discusses the use of ACEA Bioscience’s xCELLigence® system, in conjunction with other cell/molecular biology tools, to elucidate the mechanism by which APE1 regulates STAT3 activity. The studies described in this webinar set a framework for future clinical studies on pancreatic cancer using dual-targeting APE1-STAT3 approaches. The webinar specifically addresses: • Dual-targeting of APE1 and STAT3 as a novel approach in pancreatic cancer chemotherapy • Advantages of monitoring the kinetic profiles of cell proliferation and migration • Benefits of integrating the xCELLigence® system with other cell/molecular biology tools Dr. Melissa L. Fishel is an assistant research professor of Pediatrics and Pharmacology & Toxicology at the Indiana University School of Medicine. Her research projects focus on novel combinations of therapeutics to enhance treatment of pediatric, pancreatic and ovarian cancers. In addition to testing these combinations in pediatric, pancreatic and brain cancer cell lines, she also uses ectopic and orthotopic mouse models to look at their efficacy in vivo. From 2001 to 2004 she was a postdoctoral fellow with M. Eileen Dolan at the University of Chicago, where she discovered connections between multiple DNA repair pathways/proteins in sensitizing cancer cells to chemotherapy. She obtained her Ph.D. in Biochemistry from Indiana University in 2001. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/ REFERENCES: Cardoso AA, Jiang Y, Luo M, Reed AM, Shahda S, He Y, Maitra A, Kelley MR, Fishel ML. APE1/Ref-1 regulates STAT3 transcriptional activity and APE1/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival. PLoS One. 2012;7(10):e47462.
Toxicity Bioassays: Unleashing the Power of Real-Time Cell Analysis for Health Risk  Assessment
 
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Modern public health protection requires ongoing surveillance of environmental media (water, air, food and soil) for potentially harmful chemicals. There is currently an unmet need for in vitro toxicity assays with higher sensitivity, lower interference, and better predictive value than what is possible using animal studies. Dr. Stephan Gabos at the University of Alberta in Canada has been developing such assays for the detection and evaluation of environmental chemicals using the xCELLigence® Real-Time Cell Analysis (RTCA) technology. During this webinar, Dr. Gabos addresses: • The health risk assessment paradigm of the 21st century • Current public/environmental toxicology applications including: classification of chemicals into the Globally Harmonized System (GHS) categories, prediction of a compound’s mode of action (MOA), water toxicity testing, assays for nanoparticles and air particulate matter, and identification of mutagenic substances • Future trends in public health toxicology and health risk assessment Dr. Stephan Gabos is currently a research scientist within the Division of Analytical and Environmental Toxicology in the Department of Laboratory Medicine and Pathology at the University of Alberta. Prior to this, he was the senior science advisor within the Office of the Chief Medical Officer of Health (Alberta, Canada). Dr. Gabos received his M.D. from the University of Medicine and Pharmacy, Tirgu Mures, Romania in 1976, and research training in pathology and epidemiology at the University of Medicine and Pharmacy, Tirgu Mures, Tufts University, and the John Hopkins Hospital. He has a broad range of research interests including environmental toxicology and epidemiology, cytotoxicity, exposure assessment, biomonitoring, and health risk assessment. He has published over 50 papers in peer reviewed journals, and has authored several cytology and histology manuals and book chapters. He has been employed in a variety of research, administrative, and executive management positions within the Cancer Board and the Ministry of Health in Alberta, Canada. His former positions include Head of Environmental Epidemiology and Director of Health Surveillance, Alberta Health, Edmonton. For his service to the government of Alberta and his contributions in the field of environmental health, Dr. Gabos received the Premier’s Award of Excellence four separate times. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/ REFERENCES: 1. Xing JZ, Zhu L, Jackson JA, Gabos S, Sun XJ, Wang XB, Xu X. Dynamic monitoring of cytotoxicity on microelectronic sensors. Chem Res Toxicol. 2005 Feb;18(2):154-61. 2. Moe, B., McGuigan, C. F., Li, X.-F., Dabek-Zlotorzynska, E. and Gabos, S. 2014. Cell-Electronic Sensing of Cellular Responses to Micro- and Nanoparticles for Environmental Applications. Encyclopedia of Analytical Chemistry. 1–28. 3. Ibrahim F, Huang B, Xing J, Gabos S. Early determination of toxicant concentration in water supply using MHE. Water Res. 2010 May;44(10):3252-60. 4. Pan T, Huang B, Zhang W, Gabos S, Huang DY, Devendran V. Cytotoxicity assessment based on the AUC50 using multi-concentration time-dependent cellular response curves. Anal Chim Acta. 2013 Feb 18;764:44-52. 5. Pan T, Khare S, Ackah F, Huang B, Zhang W, Gabos S, Jin C, Stampfl M. In vitro cytotoxicity assessment based on KC(50) with real-time cell analyzer (RTCA) assay. Comput Biol Chem. 2013 Dec;47:113-20. 6. Pan TH, Huang B, Xing JZ, Zhang WP, Gabos S, Chen J. Recognition of chemical compounds in contaminated water using time-dependent multiple dose cellular responses. Anal Chim Acta. 2012 Apr 29;724:30-9. 7. Huang DY, Mock M, Hagenbuch B, Chan S, Dmitrovic J, Gabos S, Kinniburgh D. Dynamic cytotoxic response to microcystins using microelectronic sensor arrays. Environ Sci Technol. 2009 Oct 15;43(20):7803-9.. 8. Boyd JM, Huang L, Xie L, Moe B, Gabos S, Li XF. A cell-microelectronic sensing technique for profiling cytotoxicity of chemicals. Anal Chim Acta. 2008 May 12;615(1):80-7. 9. Moe B, Gabos S, Li XF. Real-time cell-microelectronic sensing of nanoparticle-induced cytotoxic effects. Anal Chim Acta. 2013 Jul 30;789:83-90. 10. Xing JZ, Gabos S, Huang B, Pan T, Huang M, Chen J. High-throughput quantitative analysis with cell growth kinetic curves for low copy number mutant cells. Anal Bioanal Chem. 2012 Oct;404(6-7):2033-41. 11. Pan T, Li H, Khare S, Huang B, Yu Huang D, Zhang W, Gabos S. High-throughput screening assay for the environmental water samples using cellular response profiles. Ecotoxicol Environ Saf. 2015 Apr;114:134-42.
Flow Cytometry Simplifying Assay Panel Design and WorkFLOW (ACEA Bio + FluoroFinder)
 
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About this Webinar Researchers and flow cytometry users spend a significant amount of time designing flow assay panels and analyzing their samples. In this webinar, viewers will have the chance to learn about tools and recent developments in flow cytometry that simplify assay design and workflow. Our speakers will explore the capabilities of benchtop and cost-effective flow cytometry systems and the easiest way to design flow panels. Webinar Features - Design and capabilities of a NovoCyte flow cytometer - New features that simplify setup, acquisition, and analysis - How to design multicolor fluorescent panels using FluoroFinder’s experiment design platform - Tips for building better panels in less time
Bispecific Antibody Constructs Mediate Immunotherapeutic Retargeting
 
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Chronic viral hepatitis is a major public health threat. Current strategies for eradicating the virus and treating virus-induced liver disease and hepatocellular carcinoma are very limited. Novel therapeutic strategies are in urgent need. Immunotherapeutic retargeting of effector cells is a promising approach to circumvent the immunotolerant state found in malignancies and chronic viral infections. In this webinar Dr. Bohne from the German Research Center for Environmental Health (Helmholtz Zentrum München) will discuss using xCELLigence® RTCA technology in conjunction with other cellular/molecular tools to identify bispecific antibody constructs as a promising new immunetherapeutic approach against chronic hepatitis B. Specific topics covered include: • An overview of the molecular biology of hepatitis B virus (HBV) infection and strategies for developing T-cell based therapeutics for viral hepatitis and hepatocellular carcinoma • The design of tetravalent bispecific antibody constructs • Use of xCELLigence® RTCA in quantitative assessment of T-cell and antibody-dependent T-cell mediated cytotoxic elimination of HBV-infected target cells Dr. Felix Bohne is a group leader within the Institute of Virology at the German Research Center for Environmental Health (Helmholtz Zentrum München). His current research focuses on better understanding the interaction of the hepatitis B (HBV) and C (HCV) viruses with their host, as well as developing new therapeutic strategies to treat chronic viral hepatitis and hepatocellular carcinoma. Dr. Bohne received his Ph.D. in Genetics from the University of Cologne. He then conducted postdoctoral research on the immunology of liver transplantation at the Hospital Clinic of Barcelona. Dr. Bohne subsequently completed a prestigious personal postdoctoral fellowship granted by the Deutsche Forschungsgemeinschaft (DFG) at the Technical University of Munich and at the German Research Center for Environmental Health. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/
ASCB 2016 Tech Seminar: A Novel Flow Cytometry-Based Technology for mRNA Detection
 
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A Novel Flow Cytometry-Based Technology for mRNA Detection Speaker: Wini Luty Senior Product Manager, Enzo Life Sciences, Inc.
Identifying a Novel Diagnostic and Therapeutic Target for Metastatic Breast Cancer
 
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With metastasis posing the primary challenge in the clinical management of breast cancer, there is high demand for effective diagnostic and therapeutic strategies focused on this facet of the disease. In this webinar, Dr. Michele Vitolo from the University of Maryland discusses the multi-pronged approach her lab has used to identify a tight correlation between acetylated alpha-tubulin levels and aggressive metastatic behavior in breast cancer. The implications for defining a simple prognostic biomarker in patients with breast cancer is presented. Other topics covered include: • An overview of microtentacles and their function in promoting metastatic reattachment of circulating tumor cells in distant tissues. • Using impedance-based label-free real-time xCELLigence® technology to quantitatively access the role of alpha-tubulin acetylation on breast cancer cell adhesion, invasion and migration properties • The correlation between increased alpha-tubulin acetylation and lymph node metastases, increased risk of disease progression, and death in patients Dr. Michele I. Vitolo obtained her B.S. at Franklin and Marshall College and her Ph.D. at the University of Maryland, Baltimore where she is currently an assistant professor of physiology in the School of Medicine. Dr. Vitolo has a long-standing interest in the molecular genetics of cancer. Her work has focused on PTEN loss and the progression of breast cancer. PTEN loss and the acquisition of PIK3CA activating mutations are often assumed to be reciprocal and mutually exclusive mutations, each resulting in the unregulated activation of the PI3K/Akt signaling pathway. However, she and her colleagues have recently reported differences in cytoskeletal structure and signaling between PTEN loss and PI3K activation. This finding could have new implications for patients with PTEN loss that are on current PI3K inhibitor therapies, possibly resulting in reduced drug efficacy. Currently, her research interests are focused on: 1) how the loss of PTEN promotes apoptosis-resistant cells which continue to respond cytoskeletally to the challenging environment of the bloodstream during metastasis, and 2) elucidating the cytoskeletal structural and signaling differences in cells with PTEN loss and PI3K activation. For more information, please visit: http://www.aceabio.com/products/xcelligence-rtca/ REFERENCES: 1. Matrone, M.A., Whipple, R.A., Thompson, K., Cho, E.H., Vitolo, M.I., Balzer, E.M., Yoon, J.R., Ioffe, O.B., Tuttle, K.C., Tan, M. and Martin, S.S. Metastatic breast tumors express increased tau, which promotes microtentacle formation and the reattachment of detached breast tumor cells. Oncogene. 2010 Jun 3;29(22):3217-27. 2. Whipple, R.A., Cho, E.H., Balzer, E.M., Matrone, M.A., Vitolo, M.I., Yoon, J.R., Ioffe, O.B., Tuttle, K.C., Yang, J. and Martin, S.S. Epithelial-to-mesenchymal transition promotes tubulin detyrosination and microtentacles that enhance endothelial engagement. Cancer Res. 2010 Oct 15;70(20):8127-37. 3. Yoon, J.R., Whipple, R.A., Balzer, E.M., Cho, E.H., Matrone, M.A. and Martin, S.S. Local anesthetics inhibit kinesin motility and microtentacle protrusions of human epithelial and breast tumor cells. Breast Cancer Res. Treat. 2011 Oct;129(3):691-701. 4. Vitolo MI, Boggs AE, Whipple RA, Yoon JR, Thompson K, Matrone MA, Cho EH, Balzer EM, Martin SS. Loss of PTEN induces microtentacles through PI3K-independent activation of cofilin. Oncogene. 2013 Apr 25;32(17):2200-10. 5. Whipple RA, Vitolo MI, Boggs AE, Charpentier MS, Thompson K, Martin SS. Parthenolide and costunolide reduce microtentacles and tumor cell attachment by selectively targeting detyrosinated tubulin independent from NF-κB inhibition. Breast Cancer Res. 2013; 15(5):R83. 6. Charpentier MS, Whipple RA, Vitolo MI, Boggs AE, Slovic J, Thompson KN, Bhandary L, Martin SS. Curcumin targets breast cancer stem-like cells with microtentacles that persist in mammospheres and promote reattachment. Cancer Res. 2014 Feb 15;74(4):1250-60. 7. Perry NA, Vitolo MI, Martin SS, Kontrogianni-Konstantopoulos A. Loss of the obscurin-RhoGEF downregulates RhoA signaling and increases microtentacle formation and attachment of breast epithelial cells. Oncotarget. 2014 Sep 30;5(18):8558-68. 8. Boggs AE, Vitolo MI, Whipple RA, Charpentier MS, Goloubeva OG, Ioffe OB, Tuttle KC, Slovic J, Lu Y, Mills GB, Martin SS. α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration. Cancer Res. 2015 Jan 1;75(1):203-15. 9. Bhandary L, Whipple RA, Vitolo MI, Charpentier MS, Boggs AE, Chakrabarti KR, Thompson KN, Martin SS. ROCK inhibition promotes microtentacles that enhance reattachment of breast cancer cells. Oncotarget. 2015 Mar 20;6(8):6251-66.
Evaluating Drug Induced Proarrhythmic Risk Using the CardioECR System
 
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Cardiovascular toxicity is a leading cause of drug attrition. There is an urgent need for more predictive and higher throughput assays capable of providing mechanistic toxicity information earlier in the drug discovery and development process. In this webinar Dr. Haoyu Zeng of Merck Research Laboratories (West Point, PA) discusses his work using the new xCELLigence® RTCA CardioECR system in conjunction with iPSC cardiomyocytes to assess the cardiotoxic liability of compounds. He describes his experience using the CardioECR system to screen drugs as part of the FDA CiPA (Comprehensive in vitro Proarrhythmia Assay) initiative. Specific topics covered include: • An overview of in vitro cardiotoxicity screening • The unique features of the CardioECR system – simultaneous monitoring of cardiomyocyte contractility and field potential • Results from the CiPA validation study at Merck using the CardioECR system Dr. Haoyu Zeng received his B.S. in biology from the University of Science and Technology of China, and his Ph.D. in molecular pharmacology from Brown University, studying the nicotinic acetylcholine receptor with Dr. Edward Hawrot. Following his graduate work, he did postdoctoral training with Dr. Irwin Levitan at the University of Pennsylvania where he focused on calcium-activated potassium channels. Dr. Zeng was a senior scientist at SK Bioscience before joining Merck Safety Assessment as a senior pharmacologist in 2007. He is currently a principal scientist in Merck’s Department of Safety and Exploratory Pharmacology. He is the author/co-author of more than 12 manuscripts/book chapters and has presented at more than 10 scientific conferences. For more information, please visit: http://www.aceabio.com/product/rtca-cardioecr/
Cardiac Toxicity Assessment Using Stem Cell Derived Cardiomyocytes
 
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Cardiac toxicity is a major hurdle in drug development. In this webinar Dr. Matthew F. Peters of AstraZeneca Pharmaceuticals (Boston, MA) discusses the utility of combining ACEA Bioscience’s xCELLigence® Cardio system with stem cell-derived cardiomyocytes for evaluating the cardiac risk of compounds. The xCELLigence® Cardio system is shown to provide a high throughput, quantitative and predictive assay that can be used early in the drug discovery process. Dr. Peters specifically addresses: • Advancements in cellular impedance assays • Drug screening applications utilizing cardiomyocyte cultures • Cardiosafety attrition in comparison to other disease areas Dr. Matthew F. Peters is a principal scientist at AstraZeneca Pharmaceuticals in Boston, MA. He has a long-standing interest in harnessing the sensitivity and versatility of label-free technology to address gaps in in vitro drug discovery screening. His initial work sought to develop assays capable of characterizing GPCR ligands with functional selectivity. More recently, he has focused on developing label-free impedance-based assays to address the dearth of early phase, high-throughput screens for cardiovascular function/toxicity. He was awarded his Ph.D. in physiology from the University of North Carolina for work developing a new model of the molecular organization of dystrophin complexes. Dr. Peters’ postdoctoral fellowship at Johns Hopkins University focused on elucidating the pathogenic mechanisms involved in Huntington’s disease. For more information, please visit: http://www.aceabio.com/product/rtca-cardio/ REFERENCES: 1. Peters MF, Scott CW, Ochalski R, Dragan YP. Evaluation of cellular impedance measures of cardiomyocyte cultures for drug screening applications. Assay Drug Dev Technol. 2012 Dec;10(6):525-32. 2. Lamore SD, Kamendi HW, Scott CW, Dragan YP, Peters MF. Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity. Toxicol Sci. 2013 Oct;135(2):402-13. 3. Scott CW, Zhang X, Abi-Gerges N, Lamore SD, Abassi YA, Peters MF. An impedance-based cellular assay using human iPSC-derived cardiomyocytes to quantify modulators of cardiac contractility. Toxicol Sci. 2014 Dec;142(2):331-8. 4. Peters MF, Lamore SD, Guo L, Scott CW, Kolaja KL. Human stem cell-derived cardiomyocytes in cellular impedance assays: bringing cardiotoxicity screening to the front line. Cardiovasc Toxicol. 2015 Apr;15(2):127-39.
Alan Saluk Testimonial - NovoCyte Flow Cytometer
 
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Alan Saluk, Director at Scripps Research Institute, attests to ACEA's emergence as a key player in the Flow Cytometry market. For more information, please visit: http://www.aceabio.com/products/novocyte/
ASCB 2016 Tech Seminar: Simplifying your WorkFLOW
 
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Simplifying your WorkFLOW Speaker: Garret Guenther, Ph.D. Application Scientist at ACEA Biosciences, Inc.