08:00 | Conference Registration and Continental Breakfast in the Exhibit Hall |
| Session Title: Microfluidics/Lab-on-a-Chip as Biosensors for Disease Monitoring. |
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| Session Chairs: Joshua Edel, Ph.D. and Martyn Boutelle, Ph.D. |
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09:00 | | Keynote Presentation “Body-on-a-Chip”: A Microphysiological System for Drug Development Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University, President Hesperos, Inc., United States of America
Development of a human-based in vitro system has the potential to reduce dependency on animal testing and to make better predictions of human response to drugs. Also, there is the likelihood that by reducing the dependency on animals the process could be accelerated. In particular, in the event of pandemics or terrorism, the ability to use a human surrogate to rapidly screen possible drugs or candidate drug mixtures should be invaluable. Our efforts to construct human surrogates uses a combination of cell cultures and microfabrication. These devices have been referred to as "Body-On-a-Chip" systems. These devices are designed to be physical replicas of a physiologically based pharmacokinetic (PBPK) model where cell cultures or tissue engineered constructs are used to replace the differential equations for each organ compartment in the PBPK. A microfluidic system is used where each compartment is interconnect as they might be in a PBPK model. By using cell cultures in place of the equation, interactions of the drug with each tissue and communication between each tissue can be replicated even if the mechanisms are unknown and unexpected and would not be captured in the equation by themselves. Construction of a "pumpless" system is described and how might serve as a basis for a larger system (> 10 compartments) will be discussed. Such "chips" should be relatively low cost to construct and have the potential for broad application in drug development. I will discuss some of the issues in the design, construction and use of such devices. |
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09:45 | On-chip Phenotypic Analysis of Inflammatory Monocytes in Atherogenesis and Myocardial Infarction Scott Simon, Professor of Biomedical Engineering, University of California-Davis, United States of America
Acute myocardial infarction (MI) associated with coronary artery disease affects more than 2.5 million Americans annually and is a major cause of mortality worldwide. While stable coronary artery disease (CAD) can be promptly diagnosed through stress testing and angiography, plaque rupture due to atherosclerosis remains highly unpredictable. Furthermore, studies have shown that 50% of patients with MI lack the traditional risk factors for CAD, including elevated low-density lipoprotein cholesterol, fasting triglycerides, hypertension, and diabetes. Therefore, there is a clinical need for non-invasive assays of inflammatory cell activation to gauge its role in atherogenesis. Based upon relative expression of the monocyte markers CD14 and CD16 we assessed their numbers with the onset of CAD. These were identified by flow cytometry and their numbers in circulation increased in high risk subjects postprandial following a high fat meal, and in MI patients before treatment. In these high risk and CAD cohorts, we examined adhesion molecule expression on monocyte subsets and found that a member of the€ß2-integrin family associated with atherosclerosis, CD11c/CD18, was upregulated 60% on CD14++CD16+ inflammatory subset of monocytes. Furthermore, CD11c was upregulated 300% on patients undergoing an MI compared to healthy subjects. Since the integrins CD11c and VLA-4 support monocyte recruitment on VCAM-1, we sheared subject’s whole blood in our vascular mimetic microfluidic flow channels over recombinant VCAM-1. We detected a ~25% increase in enrichment of CD14++CD16+ monocytes postprandial and an ~80% increase for MI patients. There was no significant enrichment of the other monocyte subsets. This lecture will describe a lab on a chip approach to define the respective roles of CD11c as a biomarker of CAD and activator of VLA-4 dependent adhesion on VCAM-1 in high risk subjects and those experiencing MI. |
10:15 | High-Performance Biomarker Analysis Using Microfluidic Technology Yong Zeng, Associate Professor, University of Florida, United States of America
Microfluidics has emerged as a new paradigm in quantitative measurements of biomolecules and dynamic pathways across radically different spatiotemporal scales. In this presentation, I will share our research on developing microfluidics-based biotechnologies for quantitative analysis of cancer biomarkers, including bead-based digital PCR, actuatable microwell-patterned ELISA, and integrated microvesicle capture and analysis microsystem. Their applications to biomedical analyses of genetic mutations, protein biomarkers, and circulating exosomes derived from cancer patients will be discussed. |
10:45 | Coffee Break, Networking in the Exhibit Hall, and Meet the Exhibitors |
11:15 | Microfluidic Devices for Real-Time Clinical Monitoring of Microdialysis Streams Martyn Boutelle, Professor of Biomedical Sensors Engineering, Imperial College London, United Kingdom
Microdialysis probes are an FDA approved way of sampling the molecular composition of human tissue including the brain, the low volume flow rates (0.2 – 2 µL / min) of microdialysis probes are ideal for linking to microfluidic analysis devices. Concentrations of key biomarker molecules can then be determined continuously using either electrochemically (using amperometric, and potentiometic sensors) or optically. Droplet-based microfluidics, by digitizing the dialysis stream into discrete low volume samples, (a) allows rapid concentration change to be detected without the effects of the temporal smearing caused by dispersion, and (b) allows dialysate droplets to be quickly transported from the patient or surgical field to the analysis chip. This talk will describe the design, optimization, calibration and use of both droplet-based and continuous flow microfluidic analysis systems for clinical monitoring during reconstructive surgery and, for traumatic brain injury patients, extended monitoring of the brain in the intensive care unit. |
11:45 | | Keynote Presentation Novel Strategies in Single Molecule Sensing Joshua Edel, Professor, Imperial College London, United Kingdom
Analytical Sensors plays a crucial role in today’s highly demanding exploration and development of new detection strategies. Whether it be medicine, biochemistry, bioengineering, or analytical chemistry the goals are essentially the same: 1) improve sensitivity, 2) maximize throughput, 3) and reduce the instrumental footprint. In order to address these key challenges, the analytical community has borrowed technologies and design philosophies which has been used by the semiconductor industry over the past 20 years. By doing so, key technological advances have been made which include the miniaturization of sensors and signal processing components which allows for the efficient detection of nanoscale object. One can imagine that by decreasing the dimensions of a sensor to a scale similar to that of a nanoscale object, the ultimate in sensitivity can potentially be achieved - the detection of single molecules. This talk highlights novel strategies for the detection of single molecules using multiphase microfluidics. |
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12:30 | Networking Lunch in the Exhibit Hall, Meet the Exhibitors, View Posters |
13:30 | Technology Spotlight: Microfluidic Technologies for Point-of-Care Testing: Market & Technology Analysis Benjamin Roussel, Business Unit Manager of the Microfluidic & Medical Technologies (MedTech), Yole Développement
Microfluidics is an enabling technology allowing miniaturization and integration of laboratory protocols into portable devices. In the past few years, largest diagnostic companies worldwide have adopted microfluidic technology to commercialize innovative diagnostic tests. First, this paper presents our last researches on the market of point of care technologies, including market trends and forecasts. Then, the presentation will focus on Point of Care microfluidic devices material and manufacturing trends. Does a standardization is expected in the coming years? |
| Session Title: Microfluidics/LOAC for Research Applications. |
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| Session Chairs: Michael Shuler, Ph.D. and Carl Meinhart, Ph.D. |
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14:00 | Next-Generation Proteomics Tools Amy Herr, Professor, University Of California Berkeley, United States of America
Technology advances have driven a genomics revolution with sweeping impact on our understanding of life processes. Nevertheless, the arguably more important “proteomics revolution” remains unrealized. Proteins are complex; meaning that multiple physicochemical properties must be assayed. Consequently, proteomic studies are resource intensive and ‘data limited’. To drive a bold transformation of biomedicine, engineering innovation in proteomics instrumentation is needed. While microfluidic technology has advanced separations science, progress lags in the multi-stage separations that are a hallmark of proteomics. This talk will summarize new microengineering design strategies for critical multi-stage protein assays. Specifically, I will introduce our tunable photopatterned materials for switchable function, microfluidic architectures for seamless integration of discrete stages, and multiplexed readouts for quantitation. In a translational example, I will detail assay and design advances from our highly integrated Western blotting platforms. Discussion will span the spectrum of demonstrated assays: from diagnostics for HIV confirmation to biomarker validation of protein isoforms to single cell level Western blotting in the context of stem cell differentiation. Performance and operational gains will be discussed, including quantitation capability, total assay automation, integration of sample preparation, and workflows that require minutes not days. Ultimately, we aim to infuse engineering advances into the biological and biomedical sciences. |
14:30 | Digital Microfluidics and Magnetic Beads Alphonsus Ng, NSERC Canadian Graduate Scholar, University of Toronto, Canada
The marriage of magnetic beads and microfluidics systems is an emerging trend for many applications. In addition to being magnetically responsive, magnetic beads offer a dramatic increase in surface area to volume ratio, and can be functionalized with variety molecules such as antibodies and enzymes. This talk will focus on the manipulation of magnetic beads using a droplet-based fluid handling technique called Digital Microfluidics (DMF) and its applications in sample preparation, immunoassays, and catalysis. |
15:00 | Coffee Break and Networking with Exhibitors in the Exhibit Hall |
15:45 | Technology Spotlight: Commercialization Strategies for Emerging Technologies in Digital Biology and Diagnostics Ali Tinazli, Vice President – Head of Business Development & Sales, Sony DADC US Inc
This Presentation will Focus on the Following Topics:
[a]. Smart Consumables in Biomedical Device Markets [b]. Micro/Nano/Bio Technologies [c]. Single-Molecule Technologies [d]. Chip Technologies [e]. Integrated Cartridges [f]. Commercialization and Economy of Scale [g]. Economics for successful (Point-of-Care) in vitro Diagnostics Products [h]. Automation and Manufacturing Technologies [i]. Adoption of new Technologies in biomedical Markets [j]. Diagnostics and Digital Biology |
16:15 | Path to Low Cost Universal Microfluidic Platform Alexander Govyadinov, Senior Technologist, HP Incorporated, United States of America
A novel concept of low cost universal microfluidic platform utilizing materials and processes developed for low cost Thermal Inkjet business and repurposing jetting elements for pumps, mixers, valves etc is described. We believe that this low cost integrated microfluidic platform will promote a rapidly-growing microfluidic market.
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16:45 | Low-Cost Biochips with Membrane Microfluidic and Molecular Sensing Components Zdenek Slouka, Assistant professor, Dept. of Chemical Engineering, Institute of Chemical Technology Prague, Czech Republic, United States of America
A new low-cost (<$1) disposable polymer biochip platform, with 3-D architecture to allow easy fluid/electrical/optical connection and with integrated ion-selective membranes, will be reviewed. Electrically induced concentration and charge polarization across the ion-selective membrane is used to effect on-chip pumping, cell lysing, analyte concentration/separation, redox agent-insensitive electrical sensing , shear-enhanced selectivity, pH control, nanoparticle aggregation for colorimetric and plasmonic optical sensing etc. The modular designs of the membrane components allow dynamic large-volume manufacturing of different biochip designs. A large dynamic range(fM to mM), short assay time (30 min) and high selectivity (single mismatch) is reported for a particular turn-key nucleic acid sensing device for contagious diseases. |
17:15 | Technology Spotlight: Next Generation Multiplexed Subset Serology Screening for Auto-Immune Disorders using Grace Bio-Labs™ ArrayCAM™ Platform Daniel Schwartz, Commercial Project Manager, Grace Bio-Labs, Inc.
Greater than 20 million Americans are afflicted by over 80 clinically distinct auto-immune diseases, an immune system dysfunction in which the body attacks its own organs, tissues and cells. Systemic autoimmune diseases such as Systemic lupus erythematosus, Sjorgren syndrome and others are a specific subset of diseases tested via immunofluorescence anti-nuclear antibody (ANA) screens followed by a cascade of reflex tests to identify multiple sub-set markers. Testing with numerous standard IF or EIA assays exhibit many issues including interpretation differences in techniques as well as the sensitivity and specificity across the myriad of different vendor platforms and methods causing variability. The microarray platform is particularly well suited to profiling multiple markers because the numerous analytes are measured on a fixed platform within a single sample thereby reducing ambiguous measurements or erroneous interpretations. Here we describe a robust, low cost, high throughput method for screening multiple ANA reflex markers within a single sample well. Our method consists of recombinant antigen arrays printed on Grace Bio-Labs ONCYTE® porous nitrocellulose film slides and employs multiple quantum nano-particle (QNP) detection probes imaged with the ArrayCAM™ instrument. This platform provides high signal to noise measurements driven by the native protein orientation and high binding capacity of the ONCYTE PNC film substrate coupled with the spectrally distinct wavelengths of the QNP detector dyes and ArrayCAM reader. The advantages of this system over IF or EIA for a clinical laboratory include significant laboratory time savings, internal sample normalization, low cost instrumentation, familiar and easy to use protocols while providing sensitivity/specificity capabilities commensurate with clinical lab standards.
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17:45 | Separation-based Sensors for Monitoring Drug Metabolism and Neurotransmitters in Freely Roaming Animals Susan Lunte, Professor, University of Kansas, United States of America
Most behavioral studies using microdialysis sampling require tethering of the animal to the microdialysis system so that the animal is freely moving but not freely roaming. In this paper, we describe an on-animal separation-based sensor that combines microdialysis sampling with microchip electrophoresis. The goal is to develop a miniaturized device that can be placed on-animal and is capable of continuous monitoring of drug and neurotransmitter concentrations in the brains of freely roaming sheep. Such a device, combined with video recording, will make it possible to directly correlate neurochemistry with animal behaviour. Microchip electrophoresis is employed for the analysis since it makes possible the separation and detection of several analytes simultaneously with good temporal resolution. Analytes are detected using electrochemical detection, a mode particularly well-suited to such portable analysis systems since the electrode and the potentiostat are easily miniaturized. The current on-animal system is about the size of a lunch box and is run by a laptop battery. The instrument is remotely controlled using telemetry. This system was first demonstrated by monitoring the generation of nitric oxide from subcutaneous infusions of nitroglycerin in freely roaming sheep. Recent progress in the development of an on-animal sensor for the continuous monitoring of biogenic amines in brain microdialysis samples will be presented. |
18:15 | Cocktail Reception in the Exhibit Hall: Visit the Exhibitors and Network with Your Peers |
| LATE-BREAKING SESSION: Emerging Technologies in Microfluidics, Lab-on-a-Chip, and Microarrays. |
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| Session Chair: Bertrand Jordan, Ph.D. |
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19:30 | Nanotextured Microfluidic Channels to Mimic Multiscale Architectures of Living Tissue Samir Iqbal, Associate Professor of Electrical Engineering and Bioengineering, University Of Texas At Arlington, United States of America
Recent advancements in chip-based probing, detection and characterization of diseased cells provides new insights about disease development and interactions of sub-cellular species with the physiological environment. Our work on using microfabrication and nanotechnology towards new modalities to examine the presence or absence of particular disease biomarkers at molecular and cellular scale will be discussed. Some work done in my lab on the integration of biomedical engineering, nanoscience and nanotechnology, with particular focus towards their application in diverse areas like nanomanufacturing, molecular diagnostics, chip-based recognition of cancer cells and site-specific controlled drug delivery systems will be presented. |
19:50 | Microfluidic Devices with Drops/Bubbles Sung Kwon Cho, Associate Professor, University Of Pittsburgh, United States of America
Drops/bubbles provides unique functionalities in small scales and have spawn many novel microfluidic technologies, especially in digital microfluidics. In this talk, I will present and discuss a wide range of drop/bubble applications to microfluidic devices. The subtopics may include droplet-based particle sampling/concetrating/separating, bubble-based micro manipulators, and bubble-based micro propulsion for micro scale swimming robots. For these applications, the major actuating principles are electrowetting-on-dielectrics (EWOD) and acoustic excitation. Detailed mechanisms of these principles in the above applications will be also discussed in the talk. |
20:10 | Feedback System Control (FSC): An Effective and Rapid Screening Platform for Combinatorial Drugs Xianting Ding, Professor, Shanghai Jiao Tong University, China, China
Drug combinations have been increasingly applied in clinical treatments towards various types of lethal diseases, including HIV, TB and cancers, due to the superior advantages of high efficacy, low toxicity and low occurrence of drug resistance. The death rate of HIV patients was dropped by 60% in two years after drug cocktails were introduced. While the drug combinations are in generally effective, optimizing drug combinations remains challenging. M drugs with N dose levels lead to NM total possibilities. For instance, 6 drugs with 10 dose levels ends up 1 million combinations, a prohibitive searching space for conventional trial-by-error type of drug optimization approaches. Furthermore, drug-drug interactions and drug-system interactions can be extremely complicated. Therefore, the information acquired from individual cellular molecules could hardly assess the accumulative response at the bio-system level. Herein, we introduce a Feedback System Control (FSC) approach, aiming to rapidly optimize drug combinations out of millions of possibilities. The FSC approach combines biological experimental tests and engineering feedback control algorithms, avoids the high-throughput examination on large dataset, optimizes a few combinations iteratively, bypasses the complicated intracellular molecular interactions, and is able to identify the optimal solution with only several rounds of experiments by testing less than 0.1% of the total searching space. The FSC platform technology has been successfully applied for optimizing drug combinations for 3 types of viral infections, 6 types of cancers, and other biological scenarios such as paradise control, stem cell maintenance and optimization of traditional Chinese medicine (TCM). |
20:30 | Impedance Spectroscopy Tools for Quantifying Transport Phenomena in Nanochannels and Tissues Shaurya Prakash, Associate Professor, Department of Mechanical and Aerospace Engineering, The Ohio State University, United States of America
Over the past century, electrical or electrochemical impedance spectroscopy (EIS) has been used by chemists and biologists to study reaction rate kinetics, corrosion phenomena, battery aging, and tissue characteristics to name a few applications. EIS measures a current or voltage response of a system to an alternating voltage or current signal and records the response as complex impedance. The key idea is that the input is a small amplitude signal and therefore permits use of small-signal theory and linearization to analyze system response through data containing both magnitude and phase information. |
20:50 | Requirements for Clinical Utility of Expression Signatures and SNP Profiles based on Microarray Data Bertrand Jordan, Emeritus Research Director, National Centre for Scientific Research, France
DNA microarrays have allowed extensive expression profiling of normal and pathological samples as well as whole-genome association studies aimed at finding the genes involved in frequent, multigenic diseases. While this has provided much new knowledge, the transition to actual clinical applications has been limited. Expression profiles have been applied for prognostic and predictive purposes, particularly in oncology and for breast cancer. Many tests (>50) have been proposed and published, but only a few are actually used and only one or two can be considered commercially successful. This is due to the need for a very robust implementation, to the required demonstration of analytical validity, clinical validity and above all clinical utility, in addition to regulatory requirements and cost/reimbursement issues. Whole-genome SNP profiling has revolutionised the genetics of complex diseases, with the successful implementation of GWAS studies that have at last provided solid identification of loci and genes influencing common, multigenic diseases. However the relative risks associated with the deleterious alleles identified are generally small, of the order of 1.2 to 1.5, and their predictive value at the level of an individual is accordingly very limited. Profiles marketed direct to consumers have met with regulatory problems. As additional knowledge accumulates in the future, these analyses will acquire more definite medical value. |
21:10 | Close of LATE-BREAKING SESSION. |