2003 — 2007 |
Lee, Cheng Devoe, Don Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nirt: Nanofluidic Networks For Single-Molecule Protein Analysis @ University of Maryland College Park
Project Abstract
The proposed research aims to develop novel approaches for realizing polymer-based nanofluidic networks, and apply these nanofabrication techniques to ultra-sensitive bioanalytical instrumentation for single-molecule protein separations. Complex biological samples such as tissues, tumors, serum, or cells can contain thousands of proteins ranging from highly abundant proteins which perform common housekeeping tasks, to extremely low abundance proteins which may be present in quantities as small as a single molecule per cell. This NIRT project addresses the need for high-resolution, high-sensitivity separation techniques which can sort ultra-low molarities, down to the individual protein or peptide level, for identification. successful completion of the project will result in new ultra-high-sensitivity screening strategies for applications ranging from fundamental biological studies to disease research and drug discovery. The proposed technology platform, coupling nanochannel-based single molecule detection with integrated sample manipulation, opens the potential for extraordinary reductions in sample consumption for broad-scale protein analysis where the quantity of protein is extremely limited, impacting industry-critical areas such as genomics, proteomics, and drug discovery.
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1 |
2004 — 2005 |
Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
'Control and System Integration of Micro- and Nano-Scale Systems' Panel and Workshop @ University of Maryland College Park
Intellectual Merit:
A workshop is planned to bring two disparate groups of researchers and educators together, those who deal with micro and nano systems issues and those who deal with control and system integrations design issues, specifically they each deal with:
- Extremely small length scales -- can pack lots of actuators and sensors into a tiny space.
- Distributed control and sensing techniques -- optimal placing of actuators/sensors, coordinated control, data extraction, etc.
- The interaction of many different physical phenomena across many different length and time scales -- complex phenomena, difficult to quantify.
- Systems analysis/design tools built to capture coupling across temporal and spatial scales -- tools may help understand physics.
- Large manufacturing variability, sensitive dependence on trace quantities of chemicals -- system uncertainty.
- Control theory tools have been built to address robustness -- quantify and design for uncertainty.
- Need dedicated, delicate and expensive equipment to measure basic quantities -- measurements are limited and may be noisy and it is hard to debug system errors.
- System identification tools, design of experiments, data mining -- mathematical tools may need help, research collaboration may be beneficial.
Support for a workshop is recommended to support the "Control and System Integration of Micro- and Nano-Scale Systems" Panel and Workshop. The funds are be used to provide support for approximately 80 US academic researchers and educators to meet and discuss the field of control and systems integration on the micro- and nano-length scales. Workshop participants will look at a number of areas including micro fabrication, nano fabrication, control optimization, bio-chem systems and modeling to see where collaborations could yield new developments and how the research can be integrated with education.
Broad Impact:
The purpose of the workshop is to foster collaboration between different disciplines to develop micro and nano scale integrated systems, as opposed to micro and nano components. The workshop is aimed at assessing the current state of this area and to look for future directions that could lead to new technology as well as develop new educational materials for use in academia and industry.
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1 |
2004 — 2009 |
Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Career: Feedback Control of Micro-Fluidic Systems and the Bio-Chemical Particles Inside Them @ University of Maryland College Park
Intellectual Merit Research will focus on feedback control of bio-molecules and of liquid packets inside micro-fluidic systems. The goal is to control the path and shape of micro-fluidic packets, and the trajectories and chemical reactions of bio/chem particles inside the packets. This will facilitate new micro-fluidic systems such as miniaturized drug delivery systems, and it will allow existing systems to function in noisy real world conditions. Specific control tasks will include: steering of many particles at once for targeted collisions between different cells, viruses, and bacteria; precision moving, splitting, and joining of droplets by electrically induced surface tension forces; and shape control of individual particles. For example, it is known that fluid flow can straighten DNA chains. Our grand challenge is to create a flow field that only unwraps a small portion of the DNA chain and makes a specific protein hit the start of that unwrapped section. Feedback control requires the integration of devices, sensing, control algorithms, and actuation. Such system integration raises fundamental research challenges. We will address four key areas that are open and which match our core expertise in fluid dynamics and control. 1) Real time sensor processing: Infer the position, type, shape, and properties of fluid packets and bio particles from the sensor data in real time. For example, we will infer the shape of cells down to tens of nanometers resolution by measuring the surrounding fluid flow using PIV (particle image velocimetry) and by efficiently solving an inverse inflow-to-shapel mathematics problem. 2) Control algorithm design: Based on the sensor data, compute the appropriate actuator response. For observed particle positions, find the electrode voltages to move the particles in the desired directions. 3) Control implementation: Our controllers must function in real time. This raises significant computational issues including controller reduction and state estimation from limited sensing. 4) Modeling: All three steps above rely on a quantifiable understanding of the systems at hand. These four steps will be implemented on micro fluidic systems in our lab and on systems in the labs of our collaborators. The research will focus primarily on topic two: control algorithm design. Broader Impact This proposal aims to unite research from different disciplines. The outreach plan reflects this aim: 1) Micro fluidics design competition supported by the Hinman undergraduate entrepreneurship CEO program: Each team in the competition will consist of students from engineering, physics, chemistry, biology, and the business school. Undergraduate teams will design and fabricate micro systems after taking pre-requisite micro fabrication courses. Successful teams will transition their ideas into business plans through the CEO program (the program provides undergraduates with the tools required to start and manage a business, see www.hinmanceos.umd.edu). In collaboration with the Women In Engineering (WIE) program, the competition will be used as a recruiting tool to attract women and under-represented minorities to science, systems research, and entrepreneurship. 2) Strong focus on multi-disciplinary undergraduate research: Undergraduate students will be involved in creating the experiments, developing the control algorithms, and testing the devices, and they will undertake internships at the companies and government labs with which my group collaborates. 3) Integrating the languages of control and micro/nano: The controls and micro/nano community speak different technical languages. For example, existing micro fluidic models are not suitable for control design. I will chair a micro fluidic ilmodeling versus designli workshop at the next AIAA Aerospace Sciences Meeting and Exhibit which will bring together researchers from these two communities. Future workshops will be organized at micro-systems and control conference. These workshops will focus on translating physical micro-systems control challenges into tractable control theory questions.
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1 |
2005 — 2015 |
Smela, Elisabeth (co-PI) [⬀] Smela, Elisabeth (co-PI) [⬀] Shapiro, Benjamin Abshire, Pamela [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Integrated Transduction, Actuation, and Control For Cell-Based Sensing [Uom_fy05_059] @ University of Maryland College Park
ABSTRACT IIS-0515873 Abshire, Pamela
The goal is to develop and demonstrate enabling technology for cell-based sensing. Cell clinics are microenvironments that enable the capture and characterization of cells. Each "clinic" is a micro-electro-mechanical system fabricated on a CMOS chip. Biological systems have high specificity, sensitivity, and adaptability that can be part of a highly integrated sensor. The first goals are sample preparation, cell loading, and system miniaturization using the tools of feedback control, integrated circuits, and microfluidics. Results will leveraged into two ongoing efforts in olfactory sensing and low-false-positive pathogen detection. Three aspects of the system will be demonstrated. (1) Electroosmotic flow control will remove all optically visible (>5 micron) particles from the sample. This will remove dirt, dust, and bacteria and leave behind odorants for presentation to the olfactory cell sensors. This system shall be capable of sufficiently high throughput to be used in real time. (2) Dielectrophoretic actuation for steering cells in three-dimensions will be used to position cells in the plane and to direct them into the cell clinic vials. (3)In order to develop field utility cell-based sensors, a vision system with the same dimensions as cell clinics for cell steering will be developed. The proposed technological advances will allow cell-based sensing to move toward actual implementation and use with real samples.
Cell-based sensing has the potential for selectivity, sensitivity, and speed that far exceed today's chemical and biological sensors. Problems of olfactory sensing and pathogen detection are of immediate relevance to national security. This technology has clear applications in other diverse fields such as health care, pharmaceutical development, and environmental monitoring. The integrated transduction-actuation-control approach is expected to have an impact outside of cell-based sensing to labs-on-a-chip, microfluidics, and nanotechnology by developing basic technology and techniques for sophisticated manipulation of particles at the micro-scale. The PIs are engineers in several disciplines (fluids and controls, micro-fabrication and conjugated polymers, integrated circuits and biosensors) working closely with cell biologists, molecular pathologists, and experts in bio-functionalized surfaces and quantum dots. The PIs are pioneering the development of MEMS education kits that can be used outside of a clean room.
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1 |
2008 — 2012 |
Nochetto, Ricardo (co-PI) [⬀] Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Simulating the Dynamics of Electrowetting: Modeling, Numerics, and Validation @ University of Maryland College Park
0754983 Shapiro
Electrowetting is a technique for manipulating fluids on the micro-scale. By applying voltages at actuating electrodes, it is possible to (effectively) modify surface tension properties, and to move, split, merge, and mix liquid packets. Applications of electrowetting include re-programmable lab-on-a-chip systems, auto-focus cell phone lenses, and colored oil pixels for laptops and video-speed smart paper.
The PIs will develop experimentally validated models that will predict electrowetting dynamics first in two, then in three, spatial dimensions, which will enable next-generation system analysis, design, and control. The models will include the essential bulk-flow physics: surface tension, low-Reynolds fluid dynamics, electrostatics or electrodynamics, as well as critical loss-phenomena such as contact angle saturation and hysteresis. Moving liquid/gas or liquid/liquid interfaces, that can undergo split and merge topology changes, will be tracked by a combination of an implicit finite element (FEM) method, which will allow computation of interface curvature and the resulting surface tension forces naturally, easily, and accurately, and by the level-set method applied only locally at split/merge events, will naturally yield topology changes. This will combine the strengths of FEM (it handles curvature extremely accurately) and the level-set approach (it naturally captures topology changes). FEM will also be used to solve the low-Reynold's Navier Stokes equations, the electrostatic (or electrodynamic) part of Maxwell's equations, and to handle boundary conditions at the moving solid/liquid/gas triple line in a numerically sound manner. Triple line motion/pinning models will be evaluated and compared against electrowetting experiments - this will improve the initial hysteresis model and will incorporate a combined hydrodynamic and averaged molecular-kinetic description from the literature.
Intellectual Merit Currently, there are no modeling tools to understand and quantify the dynamic behavior of electrowetting systems. To build such models, the PIs will: 1) include the essential physical phenomena, 2) correctly state the bulk partial-differential-equations (especially the interplay between electrodynamic effects and the resulting fluid forces), 3) use the variational method to recast these equations and then create numerically viable FEM algorithms to solve them, 4) track moving interfaces, that can undergo topological changes, by a combination of the FEM and level-set methods, in a numerically sound manner, 4) include loss-phenomena such as saturation and hysteresis from first-principles and the literature (when possible) or from experimental data (when not), and 5) validate against electrowetting experiments, by isolating and confirming each new part. The merit is in achieving and combining these components.
Broader Impact The PIs collaborate with two leading electrowetting groups (at a university and a company), and are about to begin a collaboration with a third (a company). All three groups have expressed a strong need for such a physical-first-principles, experimentally informed, dynamic electrowetting modeling tool. If successful, the results will be used by the electrowetting community to understand, analyze, design, and control next-generation electrowetting systems. The methods developed for tracking 2-phase micro-flow topology changes will be of use in many other micro-fluidic applications.
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1 |
2009 — 2010 |
Luebbe, Andreas S. Shapiro, Benjamin |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Focusing of Drug-Coated Nano-Particles to Deep Tissue Tumors by Feedback Control @ Univ of Maryland, College Park
DESCRIPTION (provided by applicant): In chemotherapy treatment, the level of treatment is usually determined by the level of chemotherapy that the patient can withstand, not the amount that is necessary to kill all tumor cells. We will focus drug-coated magnetic nano-particles to tumors by dynamic control of external magnets, allowing focused (high-concentration) treatment at the tumor with low levels of chemotherapy in the rest of the body. Magnetic nano-particle drug delivery already exists but it is limited to tumors near the skin surface. In this R21 grant we aim to show that it is feasible to precisely control magnetic fields to focus chemotherapy nano-particles to tumors deep inside the body - our goal is to show proof-of-concept. Hence deep-focusing will be experimentally demonstrated in a simple vasculature phantom (as recommended by reviewer 1 in our first submission). PUBLIC HEALTH RELEVANCE: This research would allow targeted chemotherapy. It would allow confinement of drugs at deep tumors with a low concentration of drugs in the rest of the body, thus enabling more effective cancer treatment but reducing life-threatening chemotherapy side effects.
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0.987 |
2009 — 2012 |
Shapiro, Benjamin Smela, Elisabeth (co-PI) [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Spatial, High-Accuracy, Multiplexed Mapping of Genes in Human Tissue Sections @ Univ of Maryland, College Park
DESCRIPTION (provided by applicant): The aim of the proposed research is to demonstrate a technology to visualize the spatial distribution of genes and gene methylation in tissue sections. Our novel approach combines the key advantages of existing techniques: the amplification of in-situ PCR, the per-few-cells resolution of laser capture microdissection, and the multiplexing of FISH. We have already demonstrated that our technology can extract, amplify, and detect DNA in a spatially resolved manner using a substrate with mini-vials (so to a resolution of 1.6 millimeter per spot). Our aims now are to Aim 1 (achieve DNA methylation): Map GSTP1 promoter methylation over whole tissue sections from prostates with cancer. Aim 2 (achieve high spatial resolution): Miniaturize the technology to achieve a resolution of 100 ¿m. Aim 3 (multiplexing): Map multiple genetic alterations at once. We will demonstrate 3 but hundreds at once are possible in principle. It is also possible to spatially map gene expression (mRNA) by reverse-transcriptase PCR, and to quantify the amount of mRNA (by quantitative real-time PCR). Though we have initial results for both these directions and the path to them is open, we must meet aims 1 to 3 before we can move on to these more challenging areas. Consequently, multiplexed mRNA mapping and quantification will be done in future work. We will demonstrate a technology to spatially map genetic changes in tissue sections. Our method will allow the mapping of gene deletions, mutations, insertions, and methylations (silencing) in tumors, neighboring abnormal cells, and surrounding healthy tissue. The technology will be validated on frozen and paraffin fixed tissues supplied to us by Dr. Emmert- Buck at NCI and Dr. Olga Ioffe at UMB Medical School.
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0.987 |
2011 — 2015 |
Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Cdi-Type Ii: First-Principles Based Control of Multi-Scale Meta-Material Assembly Processes @ University of Maryland College Park
The assembly of colloidal nano- or micro-particles into perfectly ordered periodic structures provides a basis for manufacturing photonic band gap materials and other multi-scale meta-materials with unique electric, magnetic, and optical properties. Although proof-of-concept materials have been made in laboratories to verify their amazing properties, no existing process is yet sufficiently controllable, scalable, and robust for high-throughput manufacturing to enable commercial applications. The fundamental limitation to assembling colloidal components into ordered structures is the complex interplay of thermal motion, interparticle interactions, and external fields that lead to defect-rich and often arrested states. We propose a new approach to the meta-material assembly problem that combines expertise from four separate scientific fields that traditionally have had minimal interaction. Mathematical models of the colloidal systems, represented as free energy landscapes (FELs) in a few key variables that characterize the state of the assembly process, will be constructed using data from advanced microscopic imaging and analysis tools. The FELs will in turn be used as input to rigorous process control algorithms, developed for stochastic processes, that will navigate the landscapes to yield defect-free products. This strategy will be demonstrated and refined on prototype lab-scale reactors, using real-time digital microscopic imaging as the sensor and programmable particle-particle interaction potentials & electric fields as the actuators, to produce meta-materials.
In terms of broader impact, successful development of fundamental tools for large-scale assembly of defect-free colloidal crystals has the potential to produce revolutionary technologies (e.g. optical computing, energy harvesting, sub-diffraction limit imaging, invisibility cloaking) not unlike the creation of single crystal silicon to enable integrated circuits and modern computing. No existing processes today are capable of producing such materials at a commercial scale despite 25 years of trial-and-error efforts. A strategy of rigorous real-time control using quantitatively accurate process models, like that proposed here, is required. The education and outreach activities will incorporate integrate concepts from modeling, control, simulations, and experiments, including rich visual data from colloid experiments (e.g. images, videos) and physics-based simulations (e.g. renderings, animations) to provide intuitive education/training for students at all levels.
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1 |
2012 — 2017 |
Montague, Enid (co-PI) [⬀] Mutlu, Bilge (co-PI) [⬀] Ferris, Michael (co-PI) [⬀] Squire, Kurt Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dip: Biosourcing: a Crowdsourcing Approach to Increasing Public Understanding in Computational Biosciences @ University of Wisconsin-Madison
This project explores the hypothesis that compelling learning games based on contemporary science that offer opportunities to contribute to scientific inquiry will lead to increased interest in science, increased career choice of science, increased conceptual understanding of science content, and better scientific literacy around what scientists do. The idea is to capitalize on crowd sourcing both to shed light on the answers to open scientific questions and to engage the public in authentic and needed scientific inquiry in meaningful ways. The PIs will extend four games that are already designed and built or that are under construction and develop a platform for supporting a broad range of participatory science games that offer the public opportunities to contribute to scientific inquiry. The chosen games all encourage sustained and deep participation, include apprenticeship opportunities and opportunities for practicing authentic science, promote reflection in and on action, and are designed to be emotionally compelling. Games come from four game genres: role-playing, strategy, action, and puzzle, as different people are drawn to different types of experiences. All are in the areas of bioscience and biotechnology, and each addresses some open question in bioscience or biotechnology that participants might shed light on. The broad range of games serves several purposes -- offering a substantial enough range of experiences that a broad range of participants can be expected to join in, offering enough diversity to know that the infrastructure tying the games together has all of the functionality required to support a broad range of such games, and offering enough diversity to answer targeted research questions. Research focuses on identifying the challenges in creating a broad and diverse public gaming community that interacts with more formal and established scientific and educational cultures, how learning occurs in such an environment and how to promote sustained engagement and deep learning, identifying core features and mechanisms of games that promote sustained engagement and science learning, and understanding the design features in the particular games being studied that contribute to sustained engagement and learning.
There is an increasing awareness among scientists that many contemporary science problems require (or could benefit tremendously from) an actively engaged public. Communicating the challenges and opportunities of science, and mobilizing the public to participate in and support scientific inquiry, requires shared understandings about the values, methods, and epistemologies of science (e.g., observation, data collection and analysis, reasoning from evidence, skepticism). This project focuses on design of learning opportunities that are both engaging and informative with respect to scientific literacy. The public is invited to participate in a variety of science-related "games," experiences with scientific inquiry that are engaging and exciting and that can contribute to scientific findings. Participants engage as scientists, carrying out the practices of scientists and reasoning about evidence to draw conclusions, in the process experiencing the thrills and frustrations involved in scientific discovery and inquiry. Investigators observe the participants in these games to draw out principles for designing additional learning experiences that can engage the public in science and promote scientific literacy and learning at the same time. What is learned in this analysis will also be applicable to designing engaging science experiences for use in schools.
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0.939 |
2013 — 2016 |
Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Modeling and Control of Magnetic Chemotherapy @ University of Maryland College Park
The objective of this collaborative research award is to improve the delivery of chemotherapy drugs to its target tumors. With existing chemotherapy, it is estimated that less than 0.1 percent of the administered drugs are taken up by the tumor, the remaining 99.9 percent go to healthy tissue and cause severe and life-threatening side-effects. In magnetic drug targeting, chemotherapy can be attached to biocompatible magnetic particles. This allows magnetic control of the drugs - magnets placed outside the patient can potentially be used to focus the therapy to tumors. Doing so is difficult. The human body is complex and it is not yet understood how to actuate the magnets (when to turn them on and off) to best direct the drugs to the tumors. The goal of this project is to develop sophisticated and experimentally-validated tools to better understand how magnetized chemotherapy moves through the body, and based on these to develop methods to optimally actuate the magnets to better direct the chemotherapy to tumors.
If successful, the broader impact will be a suite of techniques to improve magnetic drug targeting - potentially moving it from a method that could only focus drugs to single shallow tumors, to one that could access deep tumors as well as small and poorly vascularized metastatic tumors spread throughout the body. This project is a collaborative effort between cancer clinicians, engineers, and mathematicians, and will also serve to bring these fields closer together in major part by training students to work effectively at the intersection of these three areas. High school, undergraduate, and graduate students will be involved in the research, and will interact with doctors, engineers, and mathematicians on a weekly basis.
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1 |
2014 — 2017 |
Waks, Edo [⬀] Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Brain Eager: Wireless Measurement of Neuronal Currents Using Spin-Torque Nano-Oscillators @ University of Maryland College Park
This award is jointly made by two programs the Instrument Development for Biological Research program (IDBR) and Emerging Frontiers (EF) in the Directorate of Biological Sciences (BIO).
The brain is a complex network of interconnected circuits that exchange signals in the form of action potentials. These action potentials hold the key to understanding cognition and complex thought. Currently available non-invasive methods for probing neuronal activity cannot achieve sufficient spatial or temporal resolution to observe individual action potentials from single neurons or small clusters, which is a major limitation. This principal investigator proposes to study a novel approach for non-invasive measurements that will be able to read out individual action potentials across the entire brain. This project will take advantage of recent advances in spintronic devices to create injectable nano-reporters that will detect weak electrical signals in the brain and convert them to microwave signals that can be detected wirelessly outside the body. The detection device to be used is the spin-torque nano-oscillator (STNO), which converts electrical signals into microwave field oscillations that can be detected wirelessly. This approach could ultimately lead to the first non-invasive technology capable of measuring activations of individual neurons and small-scale neuronal networks in live primates and humans. This capability would have a major impact on our understanding of the inner workings of the brain and cognition. It could also have important clinical applications, particularly in the areas of neurological disorders and brain machine interfaces.
The ability to monitor neuronal activity at the cellular level non-invasively is crucial for attaining a better understanding of cognition, as well as many clinical applications. Currently, all non-invasive methods for monitoring brain activity cannot simultaneously achieve the spatial and temporal resolution required to sense individual action potentials from a single neuron. This project is a novel approach for non-invasive measurements that will be able to read out individual action potentials across the whole brain from single neurons. To achieve the transduction of electrical activity to microwaves, a nano-sized device called a spin-torque nano-oscillator (STNO) will be used that converts steady electrical signals into microwave frequency magnetic field oscillations that can be detected wirelessly. The STNO responds in microseconds to electric signals, and thus can be directly used to measure individual neuronal action potentials. In addition, the STNO is a nano-scale device and can report on the firing and location of a single neuron. This project represents the first application to neurobiology of the exciting and rapidly evolving field of spintronics. A test system will be developed that includes a neuron simulator (a tunable circuit that simulates the voltages and impedance of a single neuron) and a high sensitivity microwave receiver to demonstrate the ability of these devices to report that activation state of a neuron wirelessly. this project also involves the design, fabrication, and test optimization of STNO devices for neurobiological applications. The ultimate and specific goal of this EAGER project is to perform a proof-of-concept demonstration of the proposed apparatus on a live squid axon.
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1 |
2014 |
Shapiro, Benjamin |
R41Activity Code Description: To support cooperative R&D projects between small business concerns and research institutions, limited in time and amount, to establish the technical merit and feasibility of ideas that have potential for commercialization. Awards are made to small business concerns only. |
Drug Delivery Method For Sudden Sensorineural Hearing Loss @ Weinberg Medical Physics, Llc
DESCRIPTION (provided by applicant): The ultimate goal of the proposed project is to evaluate and commercialize a combination of proprietary magnet assemblies and magnetic nanoparticles (initially developed by our University STTR partner), that has been shown in preliminary animal studies to improve delivery of medications to the inner ear. Initial animal studies using the system (which uses magnetic forces to inject steroid-eluting magnetic nano-particles into the inner ear) have successfully reduced the degree of hearing loss and tinnitus in rats due to acoustic trauma. These initial studies suggest that the amount of steroids reaching the inner ear is increased ten-fold (compared to the current standard of trans-tympanic injection into the middle ear), without side effects. Our strategy is to demonstrate the utility of the magnetic injection system as a platform technology addressing the $4 billion hearing market, starting with a compelling clinical problem that currently is without a cure. Sudden Sensorineural Hearing Loss (SSHL) is an orphan disease without either a clear cause or a satisfactory therapy, and is considered to be an otologic emergency. Current therapies, which include oral and trans- tympanic steroid injection into the middle ear, are only partially effective. There is n widely-recognized animal model for SSHL, and as a result, we have been advised by regulatory experts that we would need to proceed directly to an investigational new drug (IND) application for human testing after showing improved drug delivery and safety in animals. We plan to advance in step-wise fashion by performing proof-of-principle and toxicity studies in the Phase I portion of the STTR project, and then conducting comprehensive pharmaco- kinetic studies in the STTR Phase II portion in preparation for the IND. The current standard of care in SSHL is to inject steroids into the middle ear. We expect that with preclinical demonstrations of low toxicity and high delivered more-uniform inner-ear concentrations using the magnetic injection system, the FDA would approve an IND augmenting trans-tympanic needle injections with magnetic injection of drug-eluting particles. Eventually we anticipate that the magnetic injection platform technology will be approved for other ear, nose and throat and CNS conditions. In Phase I, we will demonstrate the superiority of magnetic injection in attaining and maintaining physiologically-effective concentration of active ingredient in the inner ear (with low serum concentration). We will collect toxicity data for expected levels of steroid-loaded nanoparticles, quantifying levels of apoptotic and inflammatory responses in-vitro. With animal studies we will show significantly improved drug delivery and cochlear drug uniformity, and will demonstrate non-significant incidences of morbidity, mortality, and ototoxicity in-vivo. In Phase II, we will attempt to conduct rigorous pharmacokinetic studies and work with a strategic partner in the (fairly profitable) Orphan drug market, in preparation for IND submission.
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0.907 |
2015 — 2016 |
Weinberg, Irving Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Pfi:Air - Tt: Pulsed Shaped Magnetic Fields to Focus Therapy to Deep Tissue Targets @ University of Maryland College Park
This PFI: AIR Technology Translation (TT) project aims to enable a safe and effective magnetic focusing of magnetic particle therapies to address inoperable deep tissue tumors. The proposed technique of pulsed magnetic focusing will deliver nanotherapeutics to deep targets in order to direct chemotherapy to where it needs to go in the body. If successful, this technique would enable a technology that could improve treatment for a wide range of diseases. The project will result in a prototype device that will dynamically focus nanorods to deep targets in preclinical studies. In this research, biocompatible nanorods are first aligned in one direction by a fast magnetic pulse, and then before they can turn around a second shaped fast magnetic pulse applies forces on the rods that serve to focus them to a central target. Repeat magnetic pulsing brings all the rods to a central target between the magnets. These features provide the key advantage that therapy can now be focused to a deep target between magnets, for example to treat inoperable deep tissue tumors. Focusing of therapy to deep tissue targets has been a key goal in magnetic drug targeting, and prior efforts in this field have not yet been able to achieve this goal.
This project addresses the following technology gap(s) as it translates from research discovery toward commercial application. Dynamic magnetic focusing of nanorods to a target between magnets was shown in benchtop experiments. In this NSF AIR TT research, the technology will be tested in tissue samples, scaled up to an in-vivo system, and its safety and utility shall be optimized and verified. In addition, personnel involved in this project will receive innovation, entrepreneurship, and technology translation experiences through developing and helping commercialize this technology.
The project engages Weinberg Medical Physics who will act as an industry liaison and supply the effort with equipment, expertise, and with connections to strategic partners and future investors in this technology translation effort from research discovery toward commercial reality.
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1 |
2021 — 2025 |
Yong, Darryl Horn, Ilana Garner, Brette Shapiro, Benjamin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Teaching Amidst Uncertainty: Developing Mathematics Teachers' Groupwork Monitoring Practices
Decades of research shows that students learn best and instruction is more inclusive when students have opportunities to talk about mathematics. For this reason, many conceptually-oriented mathematics instructional approaches emphasize peer-to-peer discussion. Yet research diverges around questions of how teachers should manage such discussions, an instructional practice referred to as groupwork monitoring. There is contradictory guidance on issues of teacher involvement: should teachers stand back to support student autonomy or involve themselves frequently to support productive sensemaking? This study addresses two open questions in mathematics education and teacher learning research related to groupwork monitoring. The first question centers on groupwork monitoring itself: How can teachers foster productive mathematical talk among students? The second question touches on an underdeveloped topic in teacher education: in what ways can teacher preparation and professional development support teachers in learning effective group work monitoring. Many teacher education strategies –– such as rehearsing routines or learning curriculum –– aim for teachers to learn well-structured, predictable aspects of instruction, yet there are not clear approaches in helping teachers learn to support more interactive and emergent aspects of mathematics teaching. This Design and Development project addresses these challenges by studying experienced and accomplished secondary mathematics teachers’ learning about groupwork monitoring in a large urban school district. Using contemporary information visualization techniques and open-source tools , alongside a video-based coaching activity, teachers will a) analyze classroom video records featuring group math discussions and b) uncover and investigate their specific interactions with student groups as well as their overall approach to this important phase of their lessons. Through these tools, teachers will develop strategic and integrated understandings of effective groupwork monitoring strategies. As a result of this work, teachers and researchers will be able to better connect teachers’ monitoring choices to students’ peer-to-peer math talk.
To investigate how experienced secondary mathematics teachers learn about groupwork monitoring, the project will develop rich visualization tools to analyze classroom discussions, engage teachers in analytical activities, and study resultant teacher and student learning. In Phase 1, the project team will build on existing visualization tools to develop efficient processes for producing interactive visualizations of monitoring that provide new ways to link classroom video to teachers’ overall interactional patterns. In Phase 2, 12-16 experienced secondary mathematics teachers in six school-based teams will engage over a two-year period with teacher professional development designed to enhance their sensemaking about monitoring, both individually and in teams. The enhanced video feedback system will allow teachers to guide, document, and investigate their evolving sensemaking. In Phase 3, individual and team learning portraits of productive math talk will be developed from the rich corpus of classroom and teacher sensemaking data. At the same time, the corpus will be analyzed using quantitative methods to investigate the conditions under which different teacher monitoring moves support or impede students’ productive math talk. The primary research products will be: 1) novel, open-source tools that dynamically visualize teachers’ monitoring work over a lesson, coordinated with specific teacher-group interaction; 2) a framework for mathematics teachers’ monitoring; 3) a theory about teachers’ learning of responsive and situated practices, of which monitoring is an example; and 4) stronger empirical evidence to guide mathematics teachers’ monitoring practices.
The Discovery Research preK-12 program (DRK-12) seeks to significantly enhance the learning and teaching of science, technology, engineering and mathematics (STEM) by preK-12 students and teachers, through research and development of innovative resources, models and tools. Projects in the DRK-12 program build on fundamental research in STEM education and prior research and development efforts that provide theoretical and empirical justification for proposed projects.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.948 |