Pamela A. Abshire - US grants

0225489
Smela

The PIs will develop integrated microstructures and circuitry for single cell
capture and characterization. Each of these "clinics" will consist of a
cell-sized cavity, or microvial, and a lid. The lid can be opened and
closed by hinges constructed from polypyrrole microactuators which link
rigid plates to the substrate. These clinics will be fabricated on
conventional bulk silicon as well as on ultra-thin silicon-on-sapphire
(SOS) substrates. Integration of the microstructures with CMOS
electronics allows integrating sensors, detection, and stimulation
circuitry together, while SOS provides a transparent substrate which
allows optical measurements of cell activity within the chamber. Sensing
modalities will be tailored for specific applications and include:
impedance measurements, extracellular recording and stimulation of
electrically active cells, optical measurements, and current or voltage
clamp measurements using microfabricated needles within the chamber.
The potential applications are numerous, spanning a spectrum from detailed
physiological studies of specific mechanisms to whole cell studies of
ecology or developmental biology to collecting concentrated cell
secretions to statistical studies of assayed cell properties.

EIA-0238061 Pamela A. Abshire University of Maryland College-Park CAREER: Physical Information Efficiency for Sensing, Communicating, and Computing

In physical computational efficiency, there is no free lunch. Tradeoffs of performance versus resources are everywhere, placing limits on performance and efficiency. To streamline technological processes, we may study and even mimic biology's highly efficient integrated systems that get the most bang for their resource bucks - the ultimate small smart systems that will revolutionize application design microelectronics, bioengineering, nanoscience and other fields. This line of intellectual inquiry opens up vistas to engage the minds of scientist and lay people alike. Consider a miniaturize autonomous cell clinic able to navigate your bloodstream and deliver therapy directly to damaged cells. Or environmental micro bots for security, monitoring and situation awareness. All are possible once we pinpoint ways to boost communication and computation to use resources in the most efficient ways. This research is laying critical groundwork for comparative analysis and application across biological and technological systems. Lunch may never be free-but it can become much cheaper and more nutritious.

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.

The objective of this research project is to develop a miniaturized system for detecting explosives based on odorant sensing using mammalian olfactory sensory neurons (OSNs). This will be achieved by fabricating an integrated microsystem on which OSNs are cultured and monitored. By detecting the electrical signals produced by OSNs, it would be possible to achieve high-sensitivity, high-specificity, high-speed, stand-off detection of trace amounts of compounds present in explosives.

Intellectual Merit
The research is expected to add biological components to traditional sensor microsystems, which will be transformative for many applications. This research will identify and develop means for solving the technical challenges facing the realization of cell-based sensors. In addition, it will provide a scientific tool to answer a number of outstanding questions about mammalian olfaction.

Broader Impacts
One of the broader impacts is that cell-based chemical sensors would have diverse applications, outside of IED detection: monitoring food and air, odor-based medical diagnosis, drug detection in airports, and screening of pharmaceuticals. Other broader impacts will be the education of students in this area through new courses, and raising awareness about the cutting edge in the nano-micro-info-bio fields through workshops for middle-school teachers in a range of disciplines, including science, history, and art.

The gold standard against which chemical sensors are compared is the dog?s nose. However, dogs are expensive to train and can only be used a few hours per day. By detecting the electrical signals produced by olfactory sensory neurons (OSNs), it should be possible to achieve high-sensitivity, high-specificity, high-speed, stand-off detection of trace amounts of compounds associated with volatile human compounds characteristic of gender, stress, individual ?fingerprint?, and various medical conditions. The team plans to develop a miniaturized system for human biometric characterization using, initially immortalized cell lines for detection of human compounds and then developing techniques for direct detection of airborne odorants using artificial mucous, thin membranes, continuous perfusion with water or a combination. Cell-based chemical sensors will have broad societal benefits through diverse applications, outside of biometric detection: explosives detection, monitoring food and air, odor-based medical diagnosis, drug detection in airports, and screening of pharmaceuticals, to name a few. This project will support two full time graduate research assistants. The PIs are actively engaged in educating graduate and undergraduate students and interdisciplinary curricular development. The PIs have demonstrated strong track records of mentoring and supporting students from underrepresented groups and of developing and supporting programs that train and promote these students.

The REU Site Program BIEN "Biosystems Internships for ENgineers" will
provide summer research opportunities in the Department of Electrical
and Computer Engineering (ECE) at the University of Maryland, College
Park (UMCP) for 10 undergraduate students per year in the applications
of electrical engineering (EE) to biosystems. Many breakthroughs in
modern medicine and science have been built on EE foundations, notably
in the technical areas of medical devices, nanotechnology and information
technology. The BIEN program builds upon a solid track record of research
innovation at the interface between electrical engineering and biology.
Examples of research topics reflect the breadth and depth of biosystems
applications in electrical engineering, ranging from nanotechnology and
microelectronic devices to autonomous control, information security,
system modeling, speech recognition, and neuromorphic signal processing.
Targeted students will be talented undergraduates who have completed
their sophomore year in electrical engineering and related programs.
Significant emphasis will be placed on recruiting students from under
represented groups and students from schools lacking similar research
opportunities. BIEN students will spend ten weeks in the summer on
campus involved in research in small teams consisting of undergraduates,
graduate students and faculty advisors. A program of seminars, workshops,
and field trips will complement and reinforce the learning experience.

The objective of this research is to discover new fundamental principles, design methods, and technologies for realizing distributed networks of sub-cm3, ant-sized mobile micro-robots that self-organize into cooperative configurations. The approach is intrinsically interdisciplinary and organized along four main thrusts: (1) Algorithms for distributed coordination and control under severe power, communication, and mobility constraints. (2) Electronics for robot control using event-based communication and computation, ultra-low-power radio, and adaptive analog-digital integrated circuits. (3) Locomotion devices and efficient actuators using rapid-prototyping and MEMS technologies that can operate robustly under real-world conditions. (4) Integration of the algorithms, electronics, and actuators into a fleet of ant-size micro-robots.

No robots at the sub-cm3 scale exist because their development faces a number of open challenges. This research will identify and determine means for solving these challenges. In addition, it will provide new solutions to outstanding questions about resource-constrained algorithms, architectures, and actuators that can be widely leveraged in other applications. The PIs will adopt a co-design philosophy that promotes cross-disciplinary research and tight collaboration.

Networks of ant-sized robots are expected to be useful in disaster relief, manufacturing, warehouse management, and ecological monitoring, as well as in new unforeseen applications. In addition, the new methods and principles proposed here can be transitioned to other highly-distributed and resource-constrained engineering problems, such as air-traffic control systems. This research program will train Ph.D. students with unique skills in the design of hybrid distributed networks and it will involve undergraduate students, particularly underrepresented minorities and women.

Chemical detection using biological cells that live on the surface of an integrated circuit chip is a promising approach to identifying odors, disease, and pathogens. For example, the principal investigators have previously demonstrated that a chip can be used to detect electrical signals generated by odor-sensing cells taken from the nose when those cells are exposed to particular odors. Despite decades of research into olfactory sensors, we are still using animals, primarily dogs for odor detection; a cell-phone like device for odor detection would have widespread applications throughout society. This project aims to develop technology that overcomes the main practical challenge for devices based on cell-based sensing: the need to supply cells to these devices. Storage or supply of cells prior to device use has been challenging: shipping cells to the device location so that they can be loaded into it just prior to use is infeasible in many scenarios, as is keeping the cells alive for long periods of time during which power may be unavailable and environmental temperatures are varying. A dryable animal cell line that can be cultured in the lab and methods for genetically engineering these cells has recently been developed by others. The proposed research will lay the necessary groundwork for using such cells on chip for cell-based sensing, so that the cells can be stored in stasis on chip and later re-animated by the addition of water. The long term goal of the research is to develop a bionose-on-a-chip that can be used in a hand-held device for odor identification, replacing dogs in applications such as security, explosives detection, and search and rescue, and opening new possibilities for monitoring food safety and origin, controlling industrial processes, and even diagnosing disease.

The proposed work comprises three efforts to demonstrate the feasibility of using dryable cell lines on chip. First, a gel system will be established that is compatible with cell patterning and subsequent dessication. In the bionose application, cells expressing distinct olfactory receptors will be patterned onto particular sensing electrodes within a hydrogel host matrix, then dried in situ. The host hydrogel should be compatible with culture of cells, maintain mechanical integrity during and after drying, and support rapid exchange of ions and small molecules. A range of gel systems that can be patterned using a bioplotter will be studied. Second, the integrated circuit sensing chip will be packaged and integrated with microfluidics. This will facilitate the dehydration-rehydration process and promote testing of the system with odorants. Both conventional micro-molding and 3-dimensional printing will be evaluated. Third, the design of the on-chip micro-electrodes that monitor the electrical activity of the odorant cells will be optimized through modeling and simulation to maximize detection of the signals and to minimize anticipated crosstalk between different cell populations on the same chip. These developments will lay the groundwork not only for the bionose-on-a-chip application, but also other cell-based bioelectronic sensing devices. The proposed work is challenging because microfluidics and other organ on a chip approaches must be coupled with state of the art circuit technologies and cutting edge biology.

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.

The Planning Grants for Engineering Research Centers competition was run as a pilot solicitation within the ERC program. Planning grants are not required as part of the full ERC competition, but intended to build capacity among teams to plan for convergent, center-scale engineering research.

The National Academy of Medicine's Institute of Medicine (IOM) estimates that 116 million people in the United States are impacted by pain every year, at an annual cost to the country in the hundreds of billion dollars. Chronic pain conditions are particularly difficult to treat, since pain is a complex experience that is not the result of a single factor. The key to better understand the complexity of pain conditions is to identify the biological changes it creates. The Engineering Research Center for Adaptive Small-systems for data Analytic Pain management (ERC-ASAP) proposes to place miniaturized autonomous sensing systems in several areas of the body. This will allow simultaneous monitoring of biological activities across multiple organs, providing insight into the causes of chronic pain and its onset. This grant enables planning activities to establish the proposed Center, potentially leading to new breakthrough technologies for diagnosis and monitoring that could alter the national pain management landscape.

The activities of the NSF ERC-ASAP Planning Grant will allow for the development of the management structures and multi-disciplinary team formation. Planning grant activities will also include a diverse set of stakeholder community members, necessary for effective convergent engineering practices. The center goals are to engage representatives from the main stakeholder community for constructive dialogues to identify challenges and solutions. One major outcome will be to co-develop the center mission and goals with active, continuous user community collaboration and investment. Expert-guided stakeholder engagement workshops will build and establish a strong partnership with institutional and industrial collaborators, as well as medical experts, systems engineers and data scientists, health professionals, decision and social behavior scientists, and federal regulators. In addition, a state-wide online survey and questionnaire will be conducted within the health service community to identify specific challenges, delivery, treatment options, and payer models for a device-driven engineering approach.

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.