Thursday, 16 March 2017

08:00

Conference Registration, Conference Materials Pick-Up, Morning Coffee and Breakfast Pastries


Session Title: Conference Plenary Session -- Convergence of Technologies Constituting the BioEngineering Space

09:00

Martin YarmushKeynote Presentation

Hills and Valleys in the Landscape of Cell-Based BioMEMS and Tissue Engineering
Martin Yarmush, Founding Director of the Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, United States of America

This presentation will cover some interesting advances in the fields of cellular BioMEMS and tissue engineering with an eye towards identifying important considerations that may help spur future meaningful discoveries and products. Also some discussion will focus on government-mandated programs and choices, artifactual results, and misleading terminology that have not been helpful in moving these fields forward.

09:30

Gabor ForgacsKeynote Presentation

Monitoring Biological Processes In Situ: Lab-in-the-Tissue
Gabor Forgacs, Professor, University of Missouri-Columbia; Scientific Founder, Organovo; CSO, Modern Meadow, United States of America

Engineering of 3D tissues and organs has seen spectacular progress in recent years. The technologies of 3D-printing and organ-­on-the chip have provided invaluable tools and structures for basic research, drug toxicity assays or disease models. In the case of drug toxicity studies the engineered construct is typically subjected to either known drugs or to new candidate drugs and metabolic functions are measured by detection of metabolites in the culture medium in which the engineered construct resides. This type of monitoring however, reveals only limited information about how the internal structure (e.g. cell-­cell interactions) of the engineered construct is effected and thus about the suitability of the tissue for further applications, such as its use in disease studies or ultimately for implantation. Here we propose to combine 3D printing and BioMEMS and related technologies to build Lab-in-the-­tissue devices for the in situ monitoring of metabolic and functional properties of engineered tissues and organ structures.

10:00

Mehmet TonerKeynote Presentation

Microfluidics to Isolate Single and Clusters of Rare Circulating Tumor Cells to Manage Cancer Patients
Mehmet Toner, Helen Andrus Benedict Professor of Biomedical Engineering; Director, BioMEMS Center, Mass General Hospital and Harvard Medical School, United States of America

Viable tumor-derived circulating tumor cells (CTCs) have been identified in peripheral blood from cancer patients and are not only the origin of intractable metastatic disease but also marker for early cancer. However, the ability to isolate CTCs has proven to be difficult due to the exceedingly low frequency of CTCs in circulation. As a result their clinical use until recently has been limited to prognosis with limited clinical utility.  More recently, we introduced several microfluidic methods to improve the sensitivity of rare event CTC isolation, a strategy that is particularly attractive because it can lead to efficient purification of viable CTCs from unprocessed whole blood. The micropost CTC-Chip (µpCTC-Chip) relies on laminar flow of blood cells through anti-EpCAM antibody-coated microposts, whereas the herringbone CTC-Chip (HbCTC-Chip) uses micro-vortices generated by herringbone-shaped grooves to efficiently direct cells toward antibody-coated surfaces. These antigen-dependent CTC isolation approaches, also called “positive selection”, led to the development of a third technology, which is tumor marker free (or antigen-independent) sorting of CTCs. We call this integrated microfluidic system the CTC-iChip, based on the inertial focusing strategy, which allows positioning of cells in a near-single file line, such that they can be precisely deflected using minimal magnetic force.

10:30

Coffee Break and Networking

11:00

Joshua EdelKeynote Presentation

Novel Strategies in Single Molecule Sensing
Joshua Edel, Professor, Imperial College London, United Kingdom

Analytical Sensors play 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 nano-porous membranes.

11:30

Hsueh-Chia ChangKeynote Presentation

A Solid-State Nanopore microRNA Quantification Platform
Hsueh-Chia Chang, Bayer Professor of Engineering; Director, Center for Microfluidics and Medical Diagnostics, University of Notre Dame, United States of America

We report a new highly selective (PCR-free) solid-state nanopore miRNA quantification platform for liquid biopsy and single-cell assays. A single ion-track nanopore in a PET membrane is asymmetrically etched into a conic geometry and is coated with a high-permittivity dielectric layer by Atomic Layer Deposition.  The surface modified conic nanopore allows for high throughput molecular translocation (100 Hz vs 1 Hz for protein nanopores) and selective delay of single-stranded (ss) nucleic acids compared to their hybridized double-stranded (ds) duplex (mean translocation time of 100 ms vs 1 ms with 5% overlap in the two distributions). The delay is due to enhanced van der Waal attraction between exposed rings of the ss-nucleic acids, with delocalized electrons, with the high-permittivity coating. Individual translocation events can be recorded for a mixture of ss- and ds-nucleic acids numbering between 100 to 100,000.  Whether the translocating molecule of each event is an ss miRNA or its ds duplex can be discerned with 95% confidence.

12:00

Fiorenzo OmenettoDavid L. KaplanKeynote Presentation

Biomaterial Printing Frontiers
Fiorenzo Omenetto, Frank C. Doble Professor of Engineering, Associate Dean for Research, School of Engineering, Tufts University
David L. Kaplan, Stern Family Endowed Professor of Engineering, Professor & Chair -- Dept of Biomedical Engineering, Tufts University, United States of America

Biomaterials offer opportunities for devices that operate seamlessly at the interface of the biological and technological worlds.  Stringent requirements on material form and function are imposed when operating at the nanoscale or when interfacing such materials with microelectronic circuitry. Silk fibroin is a very attractive biopolymer for use as a polymorphic matrix for multiple material formats that are casted, printed, extruded, or molded. This opens opportunities for multi-functional, sustainable devices that leverage both the properties of the material and the  biological features that they can encompass.

12:30

Ron WeissKeynote Presentation

Synthetic Biology: From Parts to Modules to Therapeutic Systems
Ron Weiss, Director, MIT Synthetic Biology Center; Professor, Massachusetts Institute of Technology (MIT), United States of America

Synthetic biology is revolutionizing how we conceptualize and approach the engineering of biological systems. Recent advances in the field are allowing us to expand beyond the construction and analysis of small gene networks towards the implementation of complex multicellular systems with a variety of applications. In this talk I will describe our integrated computational / experimental approach to engineering complex behavior in a variety of cells, with a focus on mammalian cells. In our research, we appropriate design principles from electrical engineering and other established fields. These principles include abstraction, standardization, modularity, and computer aided design. But we also spend considerable effort towards understanding what makes synthetic biology different from all other existing engineering disciplines and discovering new design and construction rules that are effective for this unique discipline. We will briefly describe the implementation of genetic circuits and modules with finely-tuned digital and analog behavior and the use of artificial cell-cell communication to coordinate the behavior of cell populations. The first system to be presented is a genetic circuit that can detect and destroy specific cancer cells based on the presence or absence or specific biomarkers in the cell. We will also discuss preliminary experimental results for obtaining precise spatiotemporal control over stem cell differentiation for tissue engineering applications. We will conclude by discussing the design and preliminary results for creating an artificial tissue homeostasis system where genetically engineered stem cells maintain indefinitely a desired level of pancreatic beta cells despite attacks by the autoimmune response, relevant for diabetes.

13:00

Networking Lunch in the Exhibit Hall: Visit Exhibitors and Poster Viewing


Session Title: Microfluidics-based Approaches Drive Development of Applications in Tissue Chips and Bioprinting

14:00

Michael ShulerKeynote Presentation

Human “Body-on-a-Chip” Systems to Test Drug Efficacy and Toxicity
Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University; President & CEO, Hesperos, Inc., United States of America

Human microphysiological or “Body-on-a-Chip” systems are powerful tools to assess the potential efficacy and toxicity of drugs in pre-clinical studies.  Having a human based, multiorgan system, that emulates key aspects of human physiology can provide important insights to complement animal studies in the decision about which drugs to move into clinical trials.  Our human surrogates are constructed using a low cost, robust “pumpless” platform.  We use this platform in conjunction with “functional” measurements of electrical and mechanical activity of tissue constructs (in collaboration with J. Hickman, University of Central Florida). Using a system with four or more organs we can predict the exchange of metabolites between organ compartments in response to various drugs and dose levels.  We will provide examples of using the system to both predict the response of a target tissue as well as off-target responses in other tissues/organs.  We believe such models will allow improved predictors of human clinical response from preclinical studies.

14:30

Rong FanKeynote Presentation

Single-Cell Functional Proteomics: Small Devices for Big Impact
Rong Fan, Associate Professor of Biomedical Engineering; Director, Single-Cell Profiling Core, Yale University, United States of America

Dr. Fan will discuss novel technologies for single-cell proteomic profiling, in particular, a microchip technology for co-detection of 40+ functional proteins such as cytokines/chemokines at the level of single cells, representing the highest multiplexing recorded to date for a single-cell protein secretion function assay. This technology permits the full-spectrum dissection of anti-tumor T cell functions, correlating to clinical outcomes and potentially predicting therapeutic efficacy and toxicity.  Applying this technology to leukemic cells from patients identified the existence of polyfunctional cell populations associated with pathogenesis and therapeutic response. All these underscore the importance of measuring functional proteomic heterogeneity even in phenotypically identical cell populations in order to evaluate the quality of cell-based therapeutics or to monitor patient responses for precision medicine.

15:00

Veryst Engineering, LLCTechnology Spotlight:
Modeling and Simulation of Microfluidic Devices
Matthew Hancock, Senior Engineer, Veryst Engineering, LLC

Modeling and simulation are key components of the engineering development process, providing a rational, systematic method to engineer and optimize products and dramatically accelerate the development cycle over a pure intuition-driven, empirical testing approach. Modeling and simulation help to identify key parameters related to product performance (“what to try”) as well as insignificant parameters or conditions related to poor outcomes (“what not to try”). For microfluidic organ-on-chip devices, modeling and simulation can inform the design and integration of common components such as micropumps, manifolds, and channel networks. Modeling and simulation may also be used to estimate a range of processes occurring within the fluid bulk and near cells, including shear stresses, transport of nutrients and waste, chemical reactions, heat transfer, and surface tension & wetting effects. I will discuss how an array of modeling tools such as scaling arguments, analytical formulas, and finite element simulations may be leveraged to address these microfluidic device development issues. I will also work through a few examples in detail.

15:30

Coffee Break and Networking

16:00

Shannon StottKeynote Presentation

Exploring the Biophysics of Circulating Tumor Cell Clusters Using Microfluidics
Shannon Stott, Assistant Professor, Massachusetts General Hospital & Harvard Medical School, United States of America

Advances in microfluidic technologies, biomaterials and molecular profiling have propelled the rapid growth and interest in achieving a ‘liquid biopsy’ in cancer. As malignant tumors grow, they will aggressively invade surrounding tissue due to rapidly dividing cancer cells that are nourished by an ample blood supply. As these cancer cells are multiplying, individual circulating tumor cells (CTCs) are released into the blood stream at very low numbers (1 in a billion), but are highly desirable due to their molecular cargo.  In addition, thousands of tiny particles from the tumor will enter the blood stream, referred to as exosomes, which also contain genetic information about the tumor. Larger aggregates or clusters of tumor cells are thought to break off from the most aggressive cancers. Through a collaborative effort between bioengineers, biologists, and clinicians, my laboratory at Massachusetts General Hospital has developed microfluidic devices to isolate these rare circulating biomarkers from whole blood. Data from these devices will be presented with a focus on our recent effort to characterize the biophysics of clusters of CTCs and what the dynamics of their behavior might mean for understanding their role in metastasis.

16:30

Daniel IrimiaKeynote Presentation

Accurate Sepsis Diagnostic in a Microfluidic Assay
Daniel Irimia, Associate Director, BioMEMS Resource Center, Harvard Medical School, United States of America

We identify sepsis in patients with higher precision than ever before, by measuring the motility phenotype of neutrophils, directly in a droplet of blood, using a novel microfluidic device.
 
Sepsis is a life-threatening condition when an abnormal response of the immune system injures one’s own body.  Early sepsis diagnostic could save lives; however, our current abilities for early diagnostic of sepsis early are limited.  In this presentation, we will discuss the design and validation of a novel microfluidic assay that significantly improves our abilities to diagnose and monitor sepsis in patients.  We focused on neutrophils, the white blood cells that are the earliest responders to tissue injury and microbial invasion.  We designed microfluidic devices that helped measure the motility phenotype of neutrophils with higher precision than ever before.  We simplified the logistics of neutrophil measurements by performing these measurements directly in one droplet of blood.  We optimized the assay on one cohort of 20 patients in the intensive care unit at the Massachusetts General Hospital and then validated the assay in a separate cohort of 20 patients.  Our results show that the new assay can help identify patients with sepsis and monitor the changes of their condition over time with significantly higher accuracy than current standards.

17:00

Sehyun ShinKeynote Presentation

Integrated Platelet Assays on a Microfluidic Platform
Sehyun Shin, Professor & Director, Korea University, Korea South

Aggregation and adhesion of platelets to the vascular wall are consequences of platelet activation and these cascade processes play critical roles in hemostasis and thrombosis at vascular injury sites. In this study, we designed a simple and rapid assay of platelet aggregation and adhesion in a microfluidic system. To activate platelets, either shear stress or agonists was selectively chosen for the required test. For shear-induced platelet activation (SIPA), a rotating stirrer in a circular chamber was designed with considering shear generation with secondary-flow-induced mixing. Agonists such ADP, epinephrine and arachidonic acid were carefully combined with collagen or fibrinogen. When platelets were activated in whole blood, they were driven through the microchannel under vacuum pressure. Activated platelets adhered to a collagen or fibrinogen-coated surfaces on microchannel, causing blood flow to significantly slow and eventually stop. In order to conduct the above whole test with quick and easy operation, a microfluidic chip was carefully designed with mimicking in vivo environment. To measure platelet adhesion and aggregation, the migration distance (MD) of blood through the microchannel was monitored. As degree of platelet activation increased, MD gradually decreased. For platelet-excluded blood samples, the blood flow did not stop even at the end of microchannel. These findings imply that either SIPA or agonist-induced platelet activation can be examined with the present proposed microfluidic system. Also, the MD is a potentially valuable index for measuring the degree of platelet activation and aggregation. The proposed microfluidic system can examine various anti-platelet drug tests with rapidity and simplicity, which is of potential to be used at any point-of-care.

17:30

MRD Biochip
Kutay Icoz, Assistant Professor, Abdullah Gul University Turkey, Turkey

MRD Biochip; immunomagnetic bead assisted microfluidics, may be an alternative to detect minimal residual disease (MRD). Current international treatment protocols aimed to monitor the MRD of the involved patients with Acute Lymphoid Leukemia on the 15th day of chemotherapy treatment. Since the resistant cancer cells (blast cells) can cause relapses and repeat the cancer, MRD monitoring is an important indicator for survival rate. In this project we are exploring several methods to capture, immobilize and quantify the target lymphoblast in a biochip.

18:00

Networking Reception with Beer, Wine and Appetizers. Engage with Fellow Delegates and Enjoy Views of the Charles River and the Boston Skyline

19:30

Clase of Day 1 of the Conference

19:45

Dinner Short Course on Biofabrication, 3D-Printing & Microfluidics [Separate Registration Required]

Friday, 17 March 2017

07:00

Morning Coffee, Breakfast Pastries and Networking in the Exhibit Hall


Session Title: Biofabrication Approaches and Applications

07:30

3-D Bio-Printed Glioblastoma-Vascular Niche
Guohao Dai, Associate Professor, Department of Bioengineering, Northeastern University, United States of America

In this talk, I will present the development of a 3-D bioprinting system to create functional perfused vasculature in thick tissue, and its application to construct a model to study glioblastoma vascular invasion.

08:00

Michael GelinskyKeynote Presentation

Strategies for Bioprinting of Macroscopic Tissue Constructs
Michael Gelinsky, Professor and Head, Center for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine, Technische Universität Dresden, Germany

Bioprinting has developed very fast in the last couple of years and several additive manufacturing technologies as well as biomaterials, suitable for fabrication of cell containing constructs are available today. But one major problem still limits manufacturing of mechanically stable and macroscopic tissue equivalents: bioprinting with live cells requires soft and low concentrated hydrogels (‘bioinks’) whereas for construction purposes stiff, high concentrated and/or highly crosslinked materials are needed. Several and very different strategies have been proposed to overcome this problem, e. g. combining highly viscous cell-free materials like PCL as mechanically stable framework with less viscous, cell-laden hydrogels; increasing the viscosity of bioinks by blending with other (bio)polymers or short fibers – or stabilizing the constructs during fabrication with inert supportive materials. The lecture will give an overview about some of the current developments and novel strategies for bioprinting of macroscopic tissue constructs.

08:30

Novel Composite Bioinks For 3D Bioprinting
Wojciech Swieszkowski, Professor in Materials Design Division, Faculty of Materials Science and Engineering, Warsaw University of Technology, Poland

3D bioprinting is a fast-emerging technique in tissue engineering which allows for the controlled and simultaneous 3D deposition of living cells and supporting biomaterials. This technique combines the features of 3D printing of the patient-specific scaffolds with the possibility of precisely depositing living cells in the 3D space. Many synthetic and natural polymeric inks have been applied in bioprinting. The goal is to develop ink which possesses properties of native extracellular matrix. Inspiration from the reinforcing fibres occurring in articular cartilage or ceramic particles in bone tissue prompted us to use these reinforcements to enhance stability and mechanical properties of the hydrogel based bioink. The objective of this work was to show the reinforcing effect of short sub-micron fibres (SF) or micro-particles in 3D printed cells-hydrogel constructs. The biodegradable polymeric SF and TCP ceramic particles were embedded in alginate/gelatin hydrogels matrix and printed with different types of cells. Preliminary results revealed a beneficial influence of additional reinforcements on stability and mechanical properties of the tissue engineered hybrid construct and cell growth in vitro.

09:00

3D Multimodal Bioprinter Capable of Multiscale Deposition to Deal with Tissue Complexity
Fabien Guillemot, CEO, Poietis, France

Dealing with tissue complexity and reproducing the functional anisotropy of human tissues remain a puzzling challenge for tissue engineers. Emergence of the biological functions results from dynamic interactions between cells, and with extracellular matrix. Experimental data showing that cell fate (migration, polarization, proliferation…) is triggered by biochemical and/or mechanical cues arising from cell micro-environment suggests that tissue formation obeys to short range orders without reference to a macroscopic or global pattern. In that context, the winning tissue engineering strategy might rely on guiding tissue morphogenesis from the cell to the tissue level.  From a technological point of view, the Laser-Assisted Bioprinting (LAB) technology has emerged as an alternative method to inkjet and bioextrusion methods, thereby overcoming some of their limitations (namely clogging of print heads or capillaries) to pattern living cells and biomaterials with a micron-scale resolution and high cell viability. LAB applications has been limited so far to biofabrication of thin constructs.  In this work, we present an original 3D multimodal and modular bioprinter which combines LAB with microvalve bioprinting. Thanks to this system, cells can be printed at cell resolution using LAB while biomaterials are printed with a coarser resolution (100 µm) using microvalve bioprinting. Interestingly, we show that 1 mm thick 3D constructs can be printed with different biomaterial layer thicknesses (eg made of collagen, agarose) and with multiple cell micropatterns across tissue constructs.  In conclusion, combining technologies featured by different resolution opens new horizons for controlling micro and macro organization of tissue components, and hence for guiding  cellular morphogenesis within thick 3D tissues.

09:30

Joyce WongKeynote Presentation

Microfabricated Systems to Study Cancer Metastasis
Joyce Wong, Professor, Boston University, United States of America

In this talk, I will describe our recent work in which we have developed simple microfabricated systems in which cancer cells interact with niche cells and other models of microenvironments that can be easily microfabricated. More complex systems can be developed to look at isolated steps in the metastasis process. Finally, I will describe our work that integrates simple tissues on a chip with optimization of drug delivery carriers and imaging contrast agents.

10:00

BioSpherix, Ltd.Technology Spotlight:
BioSafety in the Age of BioManufacturing
Alicia Henn, Chief Scientific Officer, BioSpherix, Ltd.

It is a tough topic to confront, but as BioManufacturing advances through its formative years, biosafety has often been disregarded. It is not unusual to see laboratory workers operating bioprinters on an open bench. Recently, bioprinting manufacturers have pushed to make bioprinters enclosable by standard room air BSCs, however there are many drawbacks to this approach. We will discuss laboratory acquired infections, accessible biosafety technology, and the importance of protecting the students and workers under our supervision.

10:30

Coffee Break and Networking in the Exhibit Hall: Visit Exhibitors and Poster Viewing

11:00

Digital Biomanufacturing and Advanced Bioinks Enable 3D/4D Bioprinting
William G Whitford, Strategic Solutions Leader Bioprocess, GE Healthcare Life Sciences, United States of America

Synergies in bioprinting are appearing from individual researchers focusing on divergent aspects of the technology.  Many are now evolving from simple mono-dimensional operations to model-controlled multi-material, interpenetrating networks using multi-modal deposition techniques.  Bioinks are being designed to address numerous critical process parameters.  These bioink parameters include such structural material characteristics as supramolecular chemistries, biological considerations as cell nutritional requirements and physical properties as plastic flow and hydrodynamic force.  These factors, combined with advances in artificial intelligence, automation and robotics, are evolving our concept of bioprinting in general.  Such digital biomanufacturing concepts as increased monitoring, data handling, connectivity, computer power, control algorithms and automation promise new advances including real-time optimization of the printing process.  The IIoT, Big Data and the Cloud complement such initiatives as Lean PPD, SCADA and DCS to advance our process control capabilities.  In digitally biomanufactured tissue constructs both the cellular constructs and architectural design for any necessary vascular component in is being addressed.  More and higher quality data are being collected and analysis is becoming richer.  This information management and model generation is now describing a “process network” promising more efficient use of both locally and imported raw data and supporting accelerated decision making.  Soon we will see real-time optimization of the immediate bioprinting bioprocess based on such high value criteria as instantaneous progress assessment and comparison to previous activities.

11:30

Capillary Forces and Bone Regeneration in Bone Scaffolds
Amy J. Wagoner Johnson, Associate Professor, Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, United States of America

More than 1.5 million people undergo bone graft procedures annually in the US to repair defects that will not heal spontaneously. These defects severely decrease quality of life and are an economic burden to those affected and to the health care system. The already considerable demand is growing rapidly as the population ages and life expectancy increases. The biggest technical and scientific challenge to treating these defects is in achieving complete osteointegration. There are promising approaches that combine scaffolds with exogenous cells and growth factors; however, these approaches are complex, expensive, and are still often considered to be too risky to the patient. Our approach is to use capillary action to impregnate biphasic calcium phosphate (BCP) scaffolds that have macro and microporosity, with cells at the time of implantation. Three groups of samples, DRY, WET, and samples without micropores (NMP), were implanted for 3 weeks and then imaged using microcomputed tomography and assessed by histology. WET samples had microporosity, but were infiltrated with PBS prior to implantation.  After three weeks, the average bone volume fraction was the same for DRY versus WET, and both were greater than NMP. However, the distribution of bone and the depth of bone growth was significantly enhanced for DRY samples compared to WET and NMP. The results have important implications in scaffold design and use of this mechanism will help to address the challenge of incomplete osteointegration in scaffold-based bone repair. Further, it will do so without the use of growth factors or exogenous cells.

12:00

Development of a Magnetic Levitation Platform for Rapid and On-Site Medical Diagnostics
Savas Tasoglu, Assistant Professor, University of Connecticut, United States of America

Currently, many medical diagnostic procedures are inefficient and inaccessible to a large population in the world because these procedures require advanced and expensive testing equipment as well as labor-intensive protocols to be carried out by a trained technician. Here, we present a versatile platform technology designed for point-of-care diagnostics which uses magnetic levitation to separate cells on the basis of their densities and measure the density distribution of the cells in a patient sample. We have demonstrated its versatility in the ability to measure density change in cells for a range of diagnostic applications including sickle cell disease diagnosis, white blood cell cytometry, and rare object detection in biological samples.

12:30

Spatiotemporally Modifiable Hydrogels from Cellulose
William Gramlich, Assistant Professor, Department of Chemistry, University of Maine, United States of America

Cellulose derivatives have long been used as hydrogel biomaterials due to their biocompatibility and wide availability, but these materials have traditionally had low modulus as the hydrogels are formed through physical entanglement. The limitations of physically crosslinked cellulose biomaterials have stymied their use in areas such as regenerative medicine and stem cell differentiation. Chemically crosslinked cellulose hydrogels alleviate these limitations, but require pendent reactive groups off cellulose, which typically necessitates using organic solvents to functionalize these molecules. In this work, cellulose derivatives such as carboxymethyl cellulose (CMC) and cellulose nanofibrils (CNF) have been functionalized with pendent groups that allow for spatiotemporal modification of the hydrogel properties.  Norbornene-functionalized CMC and CNF have been crosslinked through radical initiated thiol-ene click chemistry with a variety of dithiol crosslinkers. By selecting crosslinkers that are stimuli responsive, stimuli responsive cellulose hydrogels can be created. Using photopatterning and these stimuli responsive crosslinkers, hydrogels can be spatiotemporally modified in three-dimensions to introduce stimuli response in specific areas, affecting cell behavior.

13:00

Networking Lunch in the Exhibit Hall: Visit Exhibitors and Engage with Your Fellow Delegates

13:30

Luncheon Presentation: A Vascularized Endocrine Pancreas Microphysiological System
Timothy Kassis, Researcher, DARPA-PhysioMimetics Program, Massachusetts Institute of Technology (MIT), United States of America

Diabetes has reached epidemic proportions and is on a steep rise globally. A hallmark of diabetes is characterized by dysfunctional pancreatic islets. These pancreatic islets are a spherical aggregate of around 20 different cell types with the beta cells being the main type of cell implicated in the disease. Islets are highly vascularized and it has been shown that both the blood flow through this vasculature as well as endothelial cell-signaling are critical components in regulating beta cells and how they produce insulin in response to glucose. The authors developed a vascularized pancreas microphysiological system (MPS) that can potentially be used to study human islet physiology and pathophysiology within a relevant 3D physiological microenvironment, with the ability to connect the MPS to a 7-organ interaction platform to build a ‘human-on-a-chip’ for diabetes research. The authors believe that their platform will provide researchers with an invaluable tool to study pancreatic islets in both health and disease.


Session Title: Innovation & Emerging Themes in the Use and Deployment of MEMS, Microfluidics and Biofabrication Technologies

14:00

Tracheal Tissue Engineering Using 3D Bioprinting
Todd Goldstein, Researcher, Northwell Health, United States of America

Utilizing various techniques and novel materials we 3D Bioprinted tracheal cartilage with the end goal to tissue engineer a tracheal segment.

14:30

Correlating Single Cell Interactions to Collective Cellular Responses in 3D Tumor Spheroids Using Droplet Microfluidics
Tali Konry, Associate Professor, Northeastern University, United States of America
Seamus McKenney, Research Scientist, Northeastern University, United States of America

15:00

Application of a Graphene Oxide Chip for Circulating Tumor Cell Isolation and Transcriptome Analysis in Prostate Cancer
Molly Kozminsky, Researcher, University of Michigan, United States of America

Circulating tumor cells were isolated from 42 whole blood samples from prostate cancer patients using a sensitive graphene oxide based microfluidic device. Immunofluorescence staining and RNA extraction were performed on parallel chips for enumeration (range: 3-166 cells/mL) and transcriptome analysis.

15:30

Expansion of Circulating Tumor Cells in Pancreatic Cancer using a High Throughput Microfluidic Labyrinth
Lianette Rivera, Researcher, University of Michigan, United States of America

Using a label free microfluidic technology, the Labyrinth, the first ever pancreatic CTC culture was achieved. Multiple characterization studies proved that these patient derived CTC cultures could be used for investigating personalized therapy avenues for cancer patients.

16:00

In vitro Adipogenic and Osteogenic Differentiation of Bone-Marrow Derived Mesenchymal Stem Cells Using a Chitosan/Dextran-based Hydrogel
Jaydee Cabral, Research Fellow, Department of Chemistry, University of Otago, New Zealand

A chitosan/dextran-based (CD) injectable, nontoxic, surgical hydrogel has been developed and shown to be an effective post-operative aid in prevention of scar tissue formation in vivo. CD hydrogel’s effectiveness in a surgical setting prompted an investigation into its capacity as a potential bone marrow derived mesenchymal stem cell (BM-MSC) delivery vehicle for regenerative wound healing applications. By housing BM-MSCs within a biocompatible hydrogel matrix, viability and protection in cultivation, as well as direct delivery to the damaged site in the host tissue may be achieved. BM-MSC growth and proliferation in the presence of CD hydrogel were determined by Calcein-AM/Ethidium homodimer-1 fluorescence staining; and by nuclear staining with Hoechst 33342, followed by automated counting of micrographs using ImageJ. Flow cytometry studies revealed expression of a conventional BM-MSC surface marker profile. In addition, BM-MSCs in the CD hydrogel were able to successfully differentiate into adipocytes and osteocytes. In summary, the CD hydrogel supports MSC growth and differentiation; and therefore, may be used as a potential stem cell delivery vehicle for regenerative medicine and tissue engineering applications.

16:30

Ultra-High Throughput Detection (> 1 million droplets / sec) of Fluorescent Droplets Using a Cell Phone Camera and Time Domain Encoded Optofluidics
Ravi Yelleswarapu, Research Scientist, University of Pennsylvania, United States of America

We have developed the microdroplet Megascale Detector (microMD) which can generate and detect the fluorescence of millions of droplets per second (1000x faster than conventional approaches) using only a conventional cell-phone camera to overcome the bottleneck of expensive, low-throughput detection.

17:00

Characterization and Separation of U937 Monocytes and U937-Differentiated Macrophages Using 3D Carbon Electrode Dielectrophoresis
Yagmur Yildizhan, Faculty of Engineering and Natural Sciences, Sabanci University Turkey, Turkey

Tumor-associated macrophages (TAM), one of the key players in tumor microenvironment, are involved in tumor development and progression in many cancers. Here, we will present carbon electrode dielectrophoresis (carbon-DEP) as a characterization tool to identify and separate U937 monocytes and U937-differentiated macrophages. First, we will differentiate monocytes to obtain macrophages. Next, we will apply carbon-DEP to determine specific crossover frequencies as signatures. Since DEP does not require any pre-labeling for the cells, it will allow direct characterization of cells based on their physical intrinsic properties without altering their genetic and phenotypic properties. Finally, we will verify our results using traditional assays. When we obtain their dielectrophoretic signatures, we will isolate and enrich them for high-throughput biochemical analysis.

17:30

Close of Day 2 of the Conference