Research Projects in the SMART BioSyM IRG

(November 7, 2011)

1. Cellular Automata Models of Cell Migration The objective of this work is to develop cellular automata models of angiogenesis that incorporates experimentally verified knowledge about biological processes during angiogenesis and is capable of generating vessel networks that are visually similar to actual data from time-lapse images. These models are expected to be used to interpret and decode time-lapse images of cell migration as well as to be able to predict the effect of certain angiogenic factors and extra-cellular matrix properties. MIT Principal Investigator(s): Harry Asada (Mechanical Engineering) Singapore Collaborator(s): Justin Dauwels (NTU, School of Electrical and Electronics Engineering) 2. Unravelling The Molecular Mechanisms Of Endothelial Cell Behavior And Angiogenic Pattern Formation Using A Microfluidic In Vitro Angiogenesis System To investigate the molecular mechanisms that control endothelial cell behavior using a unique microfluidic in vitro angiogenesis system coupled with advanced technologies in bioimaging as well as molecular/cellular biology. The real-time dynamic observation and manipulation offered by this unique microfluidic angiogenesis system provide opportunities to unravel previously un-discovered fundamental mechanisms of angiogenesis. MIT Principal Investigator(s): Harry Asada (Mechanical Engineering) Singapore Collaborator(s): Ge Ruowen (NUS, Biological Sciences) 3. Spatio-Temporal Image Analysis of Cell Sprouting with Bayesian Estimation The aim of this work is to advance the understanding of cell behaviours and interactions with Bayesian estimation algorithms to provide more accurate interpretations of experimental data. The current focus is on analyzing the development of endothelial cell sprouts in in vitro experimentation. Results of this work would lead to closed-loop control of cell populations to a desired collective behaviour. MIT Principal Investigator(s): Harry Asada (Mechanical Engineering) Singapore Collaborator(s): Justin Dauwels (NTU, School of Electrical and Electronics Engineering Marcelo Ang (NUS, Mechanical Engineering) 4. Visualization of Angiogenic Pattern Formation Applying Hybrid Stochastic Dynamic Modeling to the Endothelial Cells Migration in the Microfluidic in vitro Environment The dynamics of the tip cell and stalk cells migration in the gel matrix field are computationally modeled as a 3-dimensional stochastic agent. The objective of this project is to develop a computational tool that can visualize spation-temporal distribution of the multiple cells in the event of the angiogenic sprouting formation governed by novel hybrid stochastic dynamics based experimental observations.

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MIT Principal Investigator(s): Harry Asada (Mechanical Engineering) Singapore Collaborator(s): Peter Chen (NUS, Mechanical Engineering) 5. Manipulation of Stiffness Gradients in Extracellular Microenvironment through Stochastic Control of Magnetic-Particle Ensemble The mechanical properties of microstructures that surround cells play an important role in determining the behavior of a cell population, including differentiation, proliferation, and apoptosis. The objective of this project is to develop engineering approaches to directly manipulate the extracellular microenvironment in order to produce desired changes in its stiffness. MIT Principal Investigator(s): Harry Asada (Mechanical Engineering) Singapore Collaborator(s): Peter Chen (NUS, Mechanical Engineering) 6. Real-time robust phase imaging for applications in biology Our objective is to develop novel optical systems for phase imaging, for a variety of applications in biology. When light propagates througha medium other than vacuum, the light amplitude and phase change as aresult of interaction with the medium. Those amplitude and phaseperturbations contain important information about the optical propertiesof that medium. However, only the intensity can be measured directly; the phase cannot be measured directly, but can be reconstructedcomputationally. We will derive novel statistical methods to estimate the phase from noisy intensity images. Those algorithms will then be implemented inhardware. Next we will use that system for studying cell migration, abnormal growth, and other phenomena in biology and beyond. MIT Principal Investigator(s): George Barbastathis (Mechanical Engineering) Singapore Collaborator(s): Justin Dauwels (NTU, School of Electrical & Electronic Engineering) 7. 3D in vivo Imaging to Understand How the Intestinal Epithelium Migrates Regeneration of intestinal epithelial tissue is a complex dynamic process that involves division and differentiation of stem cells. To understand intestinal epithelium migration and the interactions between molecular motors and structural proteins, this project targets to develop new 3D imaging techniques with improved spatio-temporal resolution. MIT Principal Investigator(s): George Barbastathis (Mechanical Engineering) Singapore Collaborator(s): Matsudaira (NUS, Biological Sciences) 8. Integrated Waveguide Based Particle Actuation and Imaging A new concept for simultaneous manipulation and imaging of particles in an opto-fluidic platform. The main motivation is to enable cell and tissue manipulation and measurement functions while avoiding the mechanical complication of free-space optics surrounding the fluidic channel that plague traditional optofluidic systems. Our concept replaces the free space optics with a multimode waveguide where light localization for trapping and imaging is achieved through interference between field modes including reflections.

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MIT Principal Investigator(s): George Barbastathis (Mechanical Engineering) Singapore Collaborator(s): Collin Sheppard (NUS, Bioengineering) 9. Image processing for structured light imaging based microscopy and photon reassignment for deep tissue imaging The objective of the proposed works is to develop the novel algorithms for structured light imaging based microscopy, reject the out-of-focus information, for high speed 3D imaging applications in biological tissues. The methodologies are proposed to be developed for wide-field two-photon microscopy system based on temporal focusing to the study of how information about and contained within the recorded images is retrieved, analyzed, enhanced, and exchanged. The photon reassignment methodology is proposed to provide the capability to image deeper inside the tissues by numerical correction to the photons lost due to scattering and noise. MIT Principal Investigator(s): Peter So (Mechanical and Biological Engineering) Singapore Collaborator(s): Jagath C Rajapakse (NTU, Computer Engineering, Bioinformatics) 10. Super-resolution stimulated Raman scattering (SRS) microscopy Fluorescent imaging modalities, such as STED, PALM and STORM, has demonstrated the feasibility of super-resolution imaging. However, no comparable super-resolution imaging has been achieved based on non-fluorescent contrast mechanisms. We develop a novel super-resolution approach based on incorporating stimulated Raman scattering (SRS) contrast into a standing-wave (SW) total internal reflection microscope. SW-SRS microscopy has the potential to improve the lateral resolution of current SRS microscopy in total internal reflection geometry. MIT Principal Investigator(s): Peter So (Mechanical and Biological Engineering) Singapore Collaborator(s): Collin Sheppard (NUS, Bioengineering) 11. High throughput 3D imaging flow cytometer by HiLo The primary goal is to image live floating mammalian cells flowing in the microfluidic channel environment at the throughput of 1000 cells per second in three dimensions. This system has the potential to combine the function of the flow cytometer for statistical study of the large cell population and the confocal microscope for optically sectioned structure imaging, which currently are being performed separately. This can help screening of rare cells in flow or in culture such as locating fetal cells in maternal blood or detecting cancer cells in blood. In addition, this system would be useful for looking at pattern formation over large area. 3D high throughput imaging is made possible by employing wide field based structured light illumination for optical sectioning, and high speed, high sensitivity sCMOS camera for detecting the fluorescent signal from cells and the microfluidic control system for the transportation of the cells in the flow channel. In addition, Maximum Likelihood with Prior information based 3D reconstruction algorithm is developed to determine the 3D cell structure from the imaged 2D section data set. MIT Principal Investigator(s): Peter So (Mechanical and Biological Engineering) Singapore Collaborator(s): Jagath C Rajapakse (NTU, Computer Engineering, Bioinformatics)

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12. Sculpting Light: Single-shot 3D Multiphoton Microscopy The aim of this project is to develop a novel technique of acquiring multiple planes in a single exposure. Such an instrument will have a high throughput and have applications in various areas where spatial and temporal simultaneity is a concern. The challenges of the system include developing techniques of extracting individual images from a single exposure as well as the implementation of such a system. Unlike holography, there is no reference beam and the technique is based on manipulating light in both the spatial and temporal domains. MIT Principal Investigator(s): Peter So (Mechanical and Biological Engineering) Singapore Collaborator(s): Jagath C Rajapakse (NTU, Computer Engineering, Bioinformatics) Collin Sheppard (NUS, Bioengineering) 13. 3D Resolved Microrheology In this project we are developing the first axially resolved multiple particle tracking system for the purpose of 3D microrheology. The relevance of this project is varied and examples of application include the measurement of changes to the extra-cellular matrix in response to angiogenesis, the motility of bacteria in mucus, and to the differentiation of stem cells in response to changes in the local microenvironments. MIT Principal Investigator(s): Peter So (Mechanical and Biological Engineering) Roger Kamm (Mechanical and Biological Engineering) Singapore Collaborator(s): Lim Chwee Teck (NUS, Bioengineering and Mechanical Engineering) 14. High Throughput, High Content Multi-Focal Multi-Photon Microscopy Commercial high numerical aperture microscope objectives are typically of low throughput, limited by the object-side field of view (FOV) which is typically less than 1 mm in diameter only. This project targets to develop a novel adaptive optics based high-resolution, wide FOV objective for multiphoton microscopy with a FOV of 7 mm. This system has the potential to greatly increase the throughput for many applications, including high-speed image cytometry for drug discovery. MIT Principal Investigator(s): Peter So (Mechanical and Biological Engineering) Singapore Collaborator(s): Collin Sheppard (NUS, Bioengineering) 15. Cross-Scale Image Quantification and Informatics Analysis of Liver Diseases High throughput optical imaging capabilities will be developed to quantify molecular and cellular features in disease models in 3D tissue models, mice and rats; and correlate with data from clinical imaging modalities (MRI, ultrasound etc.) to establish the biological basis of the diagnostic imaging of liver diseases (cancer, cirrhosis and fatty liver). MIT Principal Investigator(s): Peter So (Mechanical and Biological Engineering) Singapore Collaborator(s): Jagath C Rajapakse (NTU, Computer Engineering , Bioinformatics) Hanry Yu (NUS, Physiology)

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16. 3D Microfluidics for stem cell therapy One of the major issue in stem cell therapies is the process by which stems cells, either adult or embryonic, are differentiated into different phenotypes. This project addresses that problem through the design and fabrication of novel microfluidic platforms and experimental methods to optimize the delivery of morphogens in a spatially- and time-dependent manner. MIT Principal Investigator(s): Roger Kamm (Mechanical and Biological Engineering) Singapore Collaborator(s): Mayasari Lim (NTU, Bioengineering) 17. Viscoelastic Behavior of Cytoskeletal Network To study experimentally and through theoretical modeling, the viscoelastic behavior of cytoskeletal networks. MIT Principal Investigator(s): Roger Kamm (Mechanical and Biological Engineering) Singapore Collaborator(s): Kin Liao (NTU, Bioengineering) 18. Simulating Injured Articular Cartilage Environment by Microfluidic Platform for cell based therapy Avascular nature of articular cartilage makes a limited capacity of self repairing. Cell based therapy is one of the promising approaches in treatment of the cartilage defects. Bone marrow derived mesenchymal stem cells (BMSC) have a significant potential for tissue repair. In this project, we use 3D microfluidic platform to simulate the injured tissue environment and find out the effective factors in homing of BMSCs. MIT Investigator(s): Roger Kamm (Mechanical and Biological Engineering) MIT Principal Investigator(s): James H. Hui (NUS, Orthopaedic Surgery) 19. Mesenchymal stem cells paracrine contributions on vascular formation and stabilization To elucidate and dissect the interactions between Endothelial Progenitor Cells (EPC) and human fetal Mesenchymal Stem Cell (hfMSC) types for regenerative therapy using 3D microfluidics co-culture platforms. MIT Principal Investigator(s): Roger Kamm (Mechanical and Biological Engineering) Singapore Collaborator(s): Jerry Chan (Duke-NUS Graduate Medical School) 20. 3D microfluidics for host-pathogen interactions Microfluidics now offers the opportunity to study the fundamental mechanisms by which pathogens interact with and invade host cells. These projects offer the opportunity for students to both work toward the optimization of microfluidic systems for the investigation of host-pathogen interactions as well as studies aimed at understanding the processes by which pathogens invade and cross an epithelial monolayer, simulating in vivo conditions. MIT Principal Investigator(s): Roger Kamm (Mechanical and Biological Engineering)

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Singapore Collaborator(s): Ho Bow (NUS, Microbiology) 21. Molecular imaging of synaptic function in Alzheimer's disease Conventional fluorescence imaging approaches create contrast based only on the average intensity in a field of view. However, the intensity at each point contains much more information, and in particular it contains the information about the molecular dynamics of the labeled molecules. We have developed a light sheet based spectroscopy approach which is based on single plane illumination microscopy and fluorescence correlation spectroscopy (SPIM-FCS) which can access this information in a 3D sample and obtains at every point in an image plain the actual number of particles present and the diffusion coefficient or flow speed with which the particles move. In this project we aim to use SPIM-FCS to observe the molecular dynamics within the chemical synapses of neurons. The aim of this project is the imaging and the conduction of SPIM-FCS measurements on these cells and their synapses under different conditions and in particular under the influence amyloidogenic peptides. MIT Investigator(s): Roger Kamm (Mechanical and Biological Engineering) Singapore Collaborator(s): Thorsten Wohland (NUS, Chemistry) 22. Micropatterned Hydrogels for Systems Biology of Mesenchyaml Stem Cell (MSC) Growth and Differentiation Outstanding questions in the field of MSC biology revolve around the synergistic roles of autocrine and paracrine growth factors and extracellular matrix chemical composition and stiffness on growth, migration, and differentiation of stem cells. In this project, advanced 2D and 3D processing methods developed in the M.B.E.Chan/Hammond labs will be adapted to both existing hydrogel materials and new materials to create niches for MSC in the Griffith lab. An advantage of the approaches is the ability to pattern large areas with fidelity using robust processing methods. MIT Principal Investigator(s): Paula Hammond (Chemical Engineering) Linda Griffith (Biological Engineering) Singapore Collaborator(s): Mary Chan (NTU, Chemical and Biomolecular Engineering) 23. Endometriosis This project plans to integrate tissue engineering principles, novel biosensors, real time analysis and systems biology approaches in delineating the very early events leading to endometriosis. In addition, we will utilise advanced proteomic approaches to derive biomarkers of endometriosis activity which will be of relevance to the follow up of the disease course and its response to therapeutics. MIT Principal Investigator(s): Linda Griffith (Biological Engineering) Steven Tannebaum (Chemistry and Toxicology) Singapore Collaborator(s): Jerry Chan (Duke-NUS Graduate Medical School) 24. Mesenchymal Stem Cell Interactions with Endothelial Cells Endothelial cells require other cell types to develop into a mature and stable vascular network. In this study, microfluidic cell culture methods are used to examine these multi-cell type interactions. MIT Principal Investigator(s):
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Linda Griffith (Biological Engineering) Roger Kamm (Mechanical and Biological Enginnering) Singapore Collaborator(s): Jerry Chan (Duke-NUS Graduate Medical School) 25. Primary Human Neural Stem Cells To re-examine the role of FGF and EGF gradients in maintaining stemness and self-renewal, to examine the role of Notch in the same, and using lineage specific markers to track directed differentiation in real time. MIT Principal Investigator(s): Linda Griffith (Biological Engineering) Roger Kamm (Mechanical and Biological Enginnering) Singapore Collaborator(s): Jerry Chan (Duke-NUS Graduate Medical School) 26. Effects of Macromolecular Crowding on Mesenchymal stem cells (MSC) Structure & Function MSCs are a type of pluripotent precursor cell found in bone marrow, which can be coaxed in vitro to express certain characteristics of differentiated mesenchymal tissue lineages. Many therapeutic applications of MSCs require isolation from a given patient, expansion to useful cell numbers in culture, and reimplantation. This project attempts to understand several fundamental questions of MSC through in-vitro studies and in vivo applications which remain unanswered. MIT Principal Investigator(s): Krystyn Van Vliet (Material Science and Engineering & Biological Engineering) Singapore Collaborator(s): Michael Raghunath (NUS, Bioengineering & Biochemistry) 27. Mesenchymal Stem Cell Organization & Migration as a Function of Applied Stresses and Matrix Mechanics This project will focus on mulitscale analysis of bone marrow-derived mesenchymal stem cells as a function of externally applied stresses and matrix/substrata properties such as mechanical stiffness. MIT Principal Investigator(s): Krystyn Van Vliet (Material Science and Engineering & Biological Engineering) Singapore Collaborator(s): Mary Chan (NTU, Chemical and Biomolecular Engineering) Jerry Chan (Duke-NUS Graduate Medical School) 28. Mesenchymal Stem Cell Differentiation as a Function of Forced Ligand-Receptor Interactions This experiment-based project will focus on unique mechanical identification and sorting of stem cell state, particularly as a function of altered ligand-receptor binding kinetics. MIT Principal Investigator(s): Krystyn Van Vliet (Material Science and Engineering & Biological Engineering) Jongyoon Han (MElectrical Enginnering and Computer Science & Biological Engineering) Linda Griffith (Biological Engineering) Singapore Collaborator(s): Michael Raghunath (NUS, Bioengineering & Biochemistry) Lim Chwee Teck (NUS, Bioengineering and Mechanical Engineering)
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29. Kinetics of Adhesive Ligand-Receptor Interactions Under Force This project will use molecular-scale experiments and simulations to predict the lifetime of key ligandreceptor complexes between cells and between cells and extracellular matrices. MIT Principal Investigator(s): Krystyn Van Vliet (Material Science and Engineering & Biological Engineering) Roger Kamm (Mechanical and Biological Enginnering) Singapore Collaborator(s): Michael Raghunath (NUS, Bioengineering & Biochemistry), Lim Chwee Teck (NUS, Bioengineering and Mechanical Engineering) Jean Paul Thiery (A*STAR-IMCB) 30. Pericyte-Endothelial Cell Interactions This project will conduct experiments and simulations to quantify the chemomechanical effects of pericyte-endothelial cell interactions on angiogenesis. MIT Principal Investigator(s): Krystyn Van Vliet (Material Science and Engineering & Biological Engineering) Singapore Investigator(s): Mayasari Lim (NTU, Bioengineering) 31. Effects of Acidic pH on Cell Behavior This project will conduct experiments and simulations to quantify the effects of acidic pH typical of tumors and wounds on molecular and cell adhesion MIT Principal Investigator(s): Krystyn Van Vliet (Material Science and Engineering & Biological Engineering) Singapore Collaborator(s): Mayasari Lim (NTU, Bioengineering) 32. Single-Strand Binding Protein Binding to Single Stranded DNA Such proteins are involved DNA replication and in DNA damage repairing process. This research aims to study the mechanical properties of DNA-SSB complexes. Two major experimental methods will be involved: (1).Magnetic tweezer manipulation of DNA-SSB co-polymer, (2) AFM imaging of DNA-SSB copolymers. MIT Principal Investigator(s): Matthew Lang (Biological and Mechanical Engineering) Patrick Doyle (Chemical Engineering) Singapore Collaborator(s): Jie (NUS, Physics) 33. Single Molecule Microscopy of the Biophysics of DNA The goal of this project is to understand single DNA physics in confinement and subject to electric fields. Recently, we have found that a moderate electric field strongly compresses isolated DNA polymer coils into isolated globules. Insight into the nature of these compressed states is gained by the expansion of the molecules back to equilibrium after halting the electric field. Additionally we have demonstrated that large DNA molecules and low ionic strength favor such compression. MIT Principal Investigator(s):
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Patrick Doyle (Chemical Engineering) Singapore Collaborator(s): Jie Yan (NUS, Physics) Johan van der Maarel (NUS, Physics) 34. Single-Molecule Studies of DNA Intercalators Many ligands bind to DNA by intercalation. Famous examples are some commonly used DNA dyes and anti cancer compounds. This research investigates the interaction between DNA and DNA intercalators using a magnetic tweezer. Applying tensile force to the DNA enhances intercalation that results in DNA elongation. By monitoring the real time elongation of a single DNA, the kinetics and equilibrium properties of the interactions can be obtained with high accuracy.

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MIT Principal Investigator(s): Patrick Doyle (Chemical Engineering) Singapore Collaborator(s): Jie Yan (NUS, Physics) 35. Magnetic Tweezing of Single DNA The goal of this project is to develop magnetic tweezers for studying DNA-protein and DNA-crowder interactions. A magnetic-tweezer setup with ingenious temperature controller has been built. The DNA overstretching transition through both of the B-to-S" transition pathway and the strand-unpeeling pathway has been studied with the tweezers. The entropy change and enthalpy change during both transition pathways are determined. Based on these experiments, we have revealed for the first time that the DNA overstretching transition through the B-to-S transition pathway leads to a highly ordered double-stranded structure without melting of DNA base pairs. MIT Principal Investigator(s): Patrick S Doyle (Chemical Engineering) Singapore Collaborator(s): Jie Yan (NUS, Physics) Johan van der Maarel (NUS, Physics) 36. Single DNA Physics in Crowded Nanofluidic Devices To perform single molecule experiments and modeling to understand DNA physics in highly confined nanofluidic devices and in the prescence of cell-mimicing crowding agents. MIT Principal Investigator(s): Patrick Doyle (Chemical Engineering) Singapore Collaborator(s): Johan Vander Maarel (NUS, Physics) Jeroen A. van Kan (NUS, Physics) Yan Jie (NUS, Physics) 37. Nanofluidic Separation Chips for Large DNA Molecules To design, construct and experimentally evaluate new nanofluidic ratchets and sieves for large DNA separations. MIT Principal Investigator(s): Patrick Doyle (Chemical Engineering) Singapore Collaborator(s): Vander Maarel (NUS, Physics) Jeroen A. van Kan (NUS, Physics) 38. Microrheology to Study DNA-Topoisomerase Interaction and the role of Anti-cancer Drugs Topoisomerases are of special interest due to their involvement in a large number of biological activities including unlinking DNA catenates, resolving intertwined chromosomes etc. Topoisomerases are also the target of some anti-cancer drugs, because its inhibition impedes the division of cells. This can be due to the blocking of the double strand passage reaction and/or the formation of cross-linking protein clamps between different DNA segments. We specifically wanted to understand how anticancer drugs affect this process. We employ multiple particle tracking microrheology for this effort. The technique allows us to follow in real-time the change in the structure and rheology of these small, precious samples.

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MIT Principal Investigator(s): Patrick S Doyle (Chemical Engineering) Singapore Collaborator(s): Johan van der Maarel (NUS, Physics) 39. Combining Microfluidics and Active Microrheology to Study Mucus Bodily fluids commonly change their rheology in response to infection, disease states or even hormonal cues. A common example is the change in saliva stringy-ness with the common cold. Experimental challenges exist to quantify the rheology of a small quantity of these relatively elastic fluidic. In this project we are intersted in leveraging our expertise in magnetic tweezing and microfluidics to build new devices to study mucus properties MIT Principal Investigator(s): Patrick S Doyle (Chemical Engineering) Singapore Collaborator(s): Jie Yan (NUS, Physics) Johan van der Maarel (NUS, Physics) 40. Microfluidics Based Cell Sorting The goal of this project it to develop and apply microfluidic tools for sorting cells based on their mechanical properties (size/deformability). Changes in the physical properties of cells are typically characteristic of many diseases as well as indicative of varying phenotypic functions within the same population. MIT Principal Investigator(s): Jongyoon Han (Electrical Enginnering and Computer Science & Biological Engineering) Singapore Collaborator(s): Lim Chwee Teck (NUS, Bioengineering and Mechanical Engineering) Peter Chen (NUS, Mechanical Engineering) 41. High-Speed Imaging of Cilia Motion from Nasal Biopsy Samples Cilia motion of nasal epithelial cells will be imaged using a high speed camera and high resolution microscopy technique. The scientific goal is to develop and validate a multi-scale computational model for predicting cilia motion, as well as correlate the cilia motion parameters (beating frequencies etc.) to physiological/pathophysiological variables, in order to gain understanding and potentially identify physical biomarkers from the measurement. MIT Principal Investigator(s): Jongyoon Han (Electrical Enginnering and Computer Science & Biological Engineering) Singapore Collaborator(s): Lee Heow Pueh (NUS, Mechanical Engineering) Khoo Boo Cheong (NUS, Mechanical Engineering) De Yun Wang (NUH) 42. Biomechanical Study of Biofluids Using Micro/Nanofluidic Channels To explore and study the rheological properties of various biofluids (e.g. mucus), especially within/around micro/nanofilter systems. The goal here is to identify useful physical biomarkers that can be correlated with the physiological/biochemical properties of these fluids.

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MIT Principal Investigator(s): Jongyoon Han (Electrical Enginnering and Computer Science & Biological Engineering) Singapore Collaborator(s): Yee Cheong Lam (NTU, Mechanical & Aerospace Engineering) 43. On-Chip Magnetic Resonance Device for single cell and molecular-level detection In this pilot project, we will design, fabricate and test such a microfluidic magnetic resonance spectroscopy system, with the intention of applying the tool to the magnetic, non-invasive cell monitoring and profiling. The two potential application modes are suggested, but more diverse applications are possible once the system feature is firmly identified. MIT Principal Investigator(s): Jongyoon Han (Electrical Enginnering and Computer Science & Biological Engineering) Singapore Collaborator(s): Nguyen Nam Trung (NTU, Mechanical & Aerospace Engineering) 44. Electrochemical Sensors for Biocatalysis Transition metal complexes and electroactive proteins can be combined with electrodes for detection of short-lived free radicals such as nitric oxide (NO) and peroxynitrite. The project goal is to develop biosensor systems that monitor the electrochemistry of spatially resolved radical analysis for physiological and biomedical applications. MIT Investigator(s): Jongyoon Han (Electrical Enginnering and Computer Science & Biological Engineering) Singapore Collaborator(s): Sangho Kim (NUS, Bioengineering)

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