Andrei Fedorov - US grants

0216368
Mizaikoff

The main thrust of this multi-disciplinary BE (IDEA) project is to develop and apply novel scanning probe microscopic (SPM) techniques for imaging chemical and biochemical processes at microbe-mineral interfaces. The ability to obtain chemical, topographical and ultimately optical information simultaneously at microbe-mineral interfaces has limited investigation of complex biological systems in previous research. Our project fosters interactions between experts in the fields of chemistry, biochemistry, geochemistry, microbiology, fluids and mass transport, microfabrication and spectroscopy. For the investigation of complex chemical and physical processes at microbe-mineral interfaces, correlation of in-situ obtained chemical, topographical and optical information is necessary, in order to understand microbial cell chemistry. Micro- and nanoelectrodes are integrated into atomic force microscopy (AFM) or scanning nearfield optical microscopy (SNOM) tips based on optimized microfabricated cantilevers. Besides mercury/gold amalgam electrodes for detecting Fe2+ production, nano-pH-electrodes will be integrated into scanning probe tips, mapping pH variations at the microbe-mineral interface. Such multifunctional SPM tips will provide simultaneous topographical, optical and (electro)chemical information correlated in space and time down to the nanoscale. Quantitative mathematical modeling and simulation of the electrochemical and physical processes taking place during the scanning process is essential for fundamental understanding and interpretation of obtained results. The developed multifunctional scanning nanoprobes will be used to determine the mechanism of reductive dissolution of Fe(III) minerals in the presence of FeRB and/or chemical reductants. Dissimilatory Fe(III) reduction is a relatively recent addition to the suite of anaerobic respiratory processes carried out by microorganisms and plays a significant role in global carbon cycling. Finally, this combined analytical technique can be extended to other environmental microbial processes involving minerals, such as the reductive dissolution of uranium, the precipitation of rhodochrosite and siderite, and the formation of manganese oxides. In addition, multifunctional scanning nanoprobes will be applicable to a wide variety of electrochemically active complex processes in a multitude of relevant fields, such as corrosion/biocorrosion, neurophysiology and cell signaling.

The goals of this Nanoscale Interdisciplinary Research Team (NIRT) research project are: 1) To develop a novel nanoscale manufacturing tool that utilizes EB-CVD, electron beam surface enhancement, or etching; 2) To obtain a fundamental understanding, via modeling and experimentation, of the physical, chemical, and materials phenomena that control deposition, surface enhancement, and etching; 3) To identify process-nanostructure-property relationships for a key set of materials that will permit fabrication of advanced nanoscale materials and devices, including integrating nanomaterials with microsystems. Nanoscale materials and devices offer great promise for many important civilian and military applications, but their fabrication often proves problematic. Similarly, integrating nanostructures with microsystems or other nano structures is one of the main roadblocks to transitioning from single structure fabrication to true nanomanufacturing. This research focuses on a technology that has an excellent potential for solving these problems -- Electron Beam Chemical Vapor Deposition or simply EB-CVD. Specifically, two electron beam processes will be developed. Both are capable of depositing metals and ceramics by EB-CVD and are complimentary in nature. The first process uses a tightly focused electron beam, i.e., beam diameters as small as 1 nm, to achieve high spatial resolution of the fabricated structures. The second process uses a broad beam and relies on constructive and destructive interference to permit patterning of large areas, leading to high throughput manufacturing. The judicious combination of these two processes offers a unique opportunity to manufacture very complex structures by computer-controlled concurrent movement of the narrowly focused and broad beams relative to the substrate.

Successful completion of this research will have significant broad impact. It will further the basic understanding of electron beam CVD and provide specifics for the deposition, surface enhancement, and etching of key materials permitting high volume fabrication of advanced nanoscale materials and devices, including microelectronics, photonics, sensors, nanocatalysts, and hybrid nano/micro systems. The EB-CVD systems will be centers for campus-wide nanomanufacturing research. Research methods and results will be transitioned to industry as well as incorporated into undergraduate and graduate courses. Effort will be made to ensure that female and underrepresented minority, K-12, REU, and graduate students are included.

Abstract
CTS-0323564
A. Fedorov, Georgia Tech

Original research is proposed in several areas of fluid mechanics and mass/ion transport which are significant to data interpretation and instrument optimization of the atomic force microscopy (AFM) with application to in-situ, high spatial and temporal resolution imaging of biological cells. The series of increasingly complex models of the electrohydrodynamics of AFM tapping mode operation are proposed, which are based on the continuous transport theory and applicable for the AFM tip radius greater than 10nm and the sub-millisecond temporal resolution. Specifically, based on the first-principles, (1) the effect of the fluid mechanics of the inner and outer cellular fluids and the cell membrane deformation during an AFM tapping mode probing process will be quantified, (2) the effect of the charge double layer at the cell membrane surface on the AFM tip-biomembrane interactions will be assessed in a physiological system under conditions of local electrochemical equilibrium, (3) fundamentals of the ion transport across the flexible biological membrane will be investigated to establish the effect of electrochemical non-equilibrium on electrohydrodynamics of AFM tip-biomembrane interactions, and (4) the boundary integral solution methodology will be extended to simulation of a complex multiphysics problem such as AFM imaging of flexible biological specimens.

The scientific impact of the proposed research is beyond the realm of fluid dynamics and is expected in every field where atomic force microscopy is being used to investigate properties of soft samples in liquid environment. A success in the proposed theoretical analysis of electrohydrodynamics of AFM has a greatest potential to lead to almost immediate improvements in the fields of cellular biology, biomedical imaging, and scanning nanoprobe development. Specifically, this research will result in (1) quantitative
interpretation of the AFM imaging data in order to predict the cell morphology, membrane structure, surface charge, mechanical properties and molecular level interactions, (2) optimization of the AFM instrument operational characteristics (e.g., shape and size of the AFM tip and optimal tapping mode frequency and amplitude) that result in optimal functionality (i.e., highest spatial and temporal
resolution of imaging), and (3) development of new imaging modalities through "virtual" computer experiments for next generation of the integrated AFM-based multifunctional scanning probes.

An outreach program focused on demonstration and discussion of physical principles underlying the atomic force microscopy is also proposed in order to facilitate dissemination of research results and to promote understanding of latest advances in science and technology by pre-college students and general public. Owing to simplicity of physical principles underlying operation of the atomic force microscopy (i.e., an atomic-scale stylus working based on mass-and-spring physics), we will develop a set of internet-based
lectures describing fluid mechanics aspects of AFM tapping-mode imaging of soft membrane-bound samples for presentation to a wide audience, including students at Georgia Tech and high schools in the Atlanta area which are operated under the Georgia Tech academic mentorship. The lecture material will also be made available to general public by being videotaped and placed on the website of the Georgia Tech's Center for Enhancement of Teaching and Learning (CETL). Further, the computer visualization will be accompanied by a simple, "macroscale" experimental demonstration of the fluid motion induced in the liquid by tapping mode action of the cantilever when "a large AFM" tip probes the flexible, membrane-like surface of the balloon filled with a heavier liquid (e.g., water) and placed inside of a container filled with a transparent, lighter fluid (e.g., silicon oil) and seeded with tracer particles for flow visualization. Such an experimental demonstration would provide an opportunity to convey in a simple manner some of the most
fundamental concepts of fluid mechanics even beyond AFM applications such as, for example, the scaling of the flow phenomena and design of engineering experiments.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] We propose to develop a novel micromachined ultrasonic electrospray source which eliminates most, if not all, limitations of the conventional ESI technology, thereby providing scientists involved in biomedicine, functional proteomics and biomarker discovery with a unique MS interface for high throughput, ultrasensitive, and multiplexed analysis of proteins mixtures of biological significance. The proposed technology called AMUSE (Array of Micromachined UltraSonic Electrospray) ion source has potential for operation at low voltages with wide range of solvents, capable of minimizing the required sample size and improving sample utilization, and is inherently suitable for parallel, high throughput operation with multiplexing in the array format. Further, the ultrasonic electrospray source can be made inexpensive to be disposable since it is batch microfabricated using a simple process. We will design and fabricate the prototype(s) of the micromachined ultrasonic electrospray source array for use in mass spectrometric analysis of protein mixtures of biological relevance. We will test and optimize the performance of both ESI device concepts and to clearly quantify their potential advantages. We will evaluate the analytical performance of a time-of-flight mass spectrometer outfitted with the proposed micromachined ultrasonic electrospray source and compare it with existing commercial nanospray ion sources. Development of an improved electrospray source for protein mass spectrometry, as proposed here, would enable identification of new biomarkers of various human deceases, including various types of cancers. In addition, mass spectrometry is routinely used in drug development, and therefore the advancement of electrospray mass spectrometry will contribute directly to improvement in public health. [unreadable] [unreadable] [unreadable]

Abstract

Proposal Title: NIRT: Active Nanoparticles in Nanostructured Materials Enabling Advances in Renewable Energy and Environmental Remediation

Proposal Number: CTS-0608896

Principal Investigator: David A. Dixon

Institution: University of Alabama Tuscaloosa

Analysis (rationale for decision):



This project will utilize new synthesis advances to develop catalytic materials for photo-electrochemical reactions with the aim of advancing renewable energy production and environmental remediation. Active nanostructured materials enable the development of new paradigms for the modification of interfaces which readily allow the generation of enhanced catalytic and sensing capabilities due to their uniquely confined structural and electronic properties. This integrated multidisciplinary program includes the synthesis of new nanomaterials that can undergo controllable changes, measurements of these changes, and the use of advanced computational methods to understand such changes in order to provide the most insight into how to control and utilize active nanostructured systems for practical technological applications. The overall approach is based on two recent synthetic advances by this team to generate nanoparticles and new nanostructures, which can be decorated by them. The first is the development of new compounds/materials for photo-electrochemical reactions. The second key advance has involved the development of porous silicon conductometric sensors. A key application area is the use of nanoparticles of TiO2, which have been modified by the addition of nitrogen to form the oxynitride, TiO2-xNx. This shifts the energy of the effective band gap of TiO2 so as to create a better photocatalytic absorber of photons in the visible part of the spectrum. In addition, these nanoparticles can be doped with metal ions to change how they interact with ligands such as water or organic molecules. A goal of the proposed effort is to use seeded nanostructured particles incorporated into hybrid micro/nano-structured environments as photocatalysts for: (1) the production of H2 from water splitting or from the gas-shift reaction and (2) the destruction of organic compounds in aqueous waste streams. A critical goal of the work is to utilize an integrated experimental and computational approach to understand the behavior of the catalytically active nanostructures, especially as they change structures and develop new properties in their active state.

Graduate students, and undergraduate students participating in the program will acquire training on sophisticated instrumentation as they pursue new fundamental knowledge in complementary fields that will enable them to study the fundamental behavior of active nanostructures. They will leave with improved problem solving skills and greater scientific independence, and thus be better positioned to contribute to the national effort in science and technology. In addition, the student researchers will be exposed to a new interdisciplinary approach that will involve extensive collaboration with other universities and laboratories in the area of understanding the behavior of active nanoparticles. Undergraduates will be directly involved in the research program through the Honors College at The University of Alabama and the undergraduate programs at Case-Western and Georgia Tech. Involvement in the program of members of underrepresented groups will continue to be encouraged, and proactive efforts will be made to recruit members of these groups, particularly those early in their scientific careers. Minority students will be involved in the research through outreach programs at the participating institutions and through summer REU programs at the institutions. All participants in the project will be expected to contribute to the dissemination of research results in the scientific literature and at conferences.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] We propose to develop a novel micromachined ultrasonic electrospray source which eliminates most, if not all, limitations of the conventional ESI technology, thereby providing scientists involved in biomedicine, functional proteomics and biomarker discovery with a unique MS interface for high throughput, ultrasensitive, and multiplexed analysis of proteins mixtures of biological significance. The proposed technology called AMUSE (Array of Micromachined UltraSonic Electrospray) ion source has potential for operation at low voltages with wide range of solvents, capable of minimizing the required sample size and improving sample utilization, and is inherently suitable for parallel, high throughput operation with multiplexing in the array format. Further, the ultrasonic electrospray source can be made inexpensive to be disposable since it is batch microfabricated using a simple process. We will design and fabricate the prototype(s) of the micromachined ultrasonic electrospray source array for use in mass spectrometric analysis of protein mixtures of biological relevance. We will test and optimize the performance of both ESI device concepts and to clearly quantify their potential advantages. We will evaluate the analytical performance of a time-of-flight mass spectrometer outfitted with the proposed micromachined ultrasonic electrospray source and compare it with existing commercial nanospray ion sources. Development of an improved electrospray source for protein mass spectrometry, as proposed here, would enable identification of new biomarkers of various human deceases, including various types of cancers. In addition, mass spectrometry is routinely used in drug development, and therefore the advancement of electrospray mass spectrometry will contribute directly to improvement in public health. [unreadable] [unreadable] [unreadable]

CBET-0813986
Shi

Partial support is provided for the 3rd Energy Nanotechnology International Conference, which will be held in Jacksonville, Florida, on August 10 - 14, 2008. The purpose of this meeting is to engage a broad spectrum of the nanotechnology research community to address leading issues related to energy.

With respect to the intellectual merit of the conference, a significant component of the conference is the Workshop on Nanotechnologies for Solar and Thermal Energy Conversion and Storage. The invited participants to this workshop will address current barriers to solar and thermal energy conversion and storage, which are emerging as the most significant barriers to widespread application of renewable energy. The output of this workshop will be a roadmap describing future research directions in this vital area. The workshop report will be published as a journal article, allowing for broad dissemination of the findings.

The broader impacts of the conference include support for women and underrepresented minority participants. The conference, including the workshop discussed above, addresses crucial research needs inhibiting sustainable energy conversion and usage, and thus may lead to reduced consumption of fossil fuel resources.

This project is jointly funded by the Thermal Transport Processes (TTP) Program, of the Chemical, Bioengineering, Environmental, and Transport Systems (CBET) Division, by the Energy for Sustainability Program, also of CBET, and by the Nanoscale Science & Engineering Program, all within the Directorate for Engineering (ENG).

This "Small Grant for Exploratory Research" supports Prof. Andrei Fedorov for development and demonstration of a nanoscale chemical imaging device, the scanning mass spectrometer (SMS) probe, based on a novel approach to electrospray ionization (reverse-Taylor-cone electrospray). If successful, the device may extend the reach of imaging mass spectrometry, allowing, for the first time, in vitro transient imaging mass spectrometry of biomolecules under physiological conditions. Its value to biological and health related research activities is potentially especially significant, as biochemical imaging of live cells and tissues can be used to answer otherwise intractable questions of cell biology, and can lead to new diagnostic capabilities.

The research is important for advancement of both basic science and for new technology development. It will provide an improved understanding of transport phenomena for nanoelectrospray ionization from reverse Taylor cones. Due to the wide range of foreseeable uses, from forensics to manufacturing to biochemical imaging, the probe should rapidly find widespread utilization. Students and postdocs involved in the effort will be exposed to a broad, interdisciplinary program which will prepare them to contribute across a spectrum of important fundamental and applied research areas.

The research objective of this award is to test the hypothesis that scaling laws can describe the physical phenomena governing droplet generation from ultrasonic actuation of complex fluids. The primary application of ultrasonic droplet generation and deposition in this project is for the development of a scalable additive manufacturing technology that allows three-dimensional structures to be printed from complex fluids, that is, fluids with non-Newtonian behavior or which have viscosities one to two orders of magnitude higher than that of typical printable fluids. Materials of interest include polyurethanes, conductive polymers, and ceramic pastes. As a result of this proposed work, the acoustics and droplet formation physical phenomena will be identified at multiple length and time scales. Computational fluid dynamics models will be developed that capture microscopic details of the ejection process. This knowledge will be used to create design guidelines for the new ultrasonic droplet deposition manufacturing technology.
If successful, this research could benefit society by enabling manufacturing technologies that can print a wide range of materials for applications ranging from complex, multi-material thermoplastic parts to photovoltaics, fuel injectors and vaccine delivery systems. Overcoming the limitations of current printing technologies will have a transformational effect on the additive manufacturing and potentially the ink-jet printing industries, since a much wider range of materials will be printable. Graduate and undergraduate students from under-represented groups will be recruited for this project. The proposed work will enhance the infrastructure for research and education by developing and maintaining facilities for atomization experiments and for part fabrication. Broad dissemination will be achieved through courses enhanced with research results, undergraduate research opportunities, active industry involvement, papers and presentations in engineering forums, and a web-site to report results and provide access to the developed additive manufacturing system.

0928716
Fedorov

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

Objectives and Methods to be Employed

Chemical processing frequently requires vaporizing liquid reagents, mixing, and heterogeneous reaction in the presence of a solid catalyst, followed by product separation. In traditional large scale chemical reactors each process is typically carried out in dedicated components, optimized for their given function, and linked together to form the overall system. Scaled down versions of these large-scale chemical plants have been considered for distributed applications, in particular hydrogen generation from hydrocarbon liquid feedstock, but the reactor design based on the individual unit operation approach has been shown to quickly become sub-optimal especially for space-constrained applications. To address this challenge of reactor scale-down, the concept of multifunctional reactors has emerged, in which synergistic combination of different unit operations is explored to achieve improved performance.

The Direct Droplet Impingement Reactor (DDIR) is a new concept for multifunctional chemical processing of high energy density liquid fuels at very high rate, enabling development of high density power conversion technologies. This project focuses on establishing fundamental understanding of the complex interplay between the fuel delivery, evaporation, and reaction in DDIR reactors, resulting in an experimentally-validated methodology for optimal design and operation of this new class of reactors.

Intellectual Merit

New theoretical and experimental tools will be developed to carry out a comprehensive study of the DDIR reactor concept. The following contributions are expected to result from the proposed investigation: (1) Theoretical analysis and simulations will yield the DDIR design map(s) that allow determination of optimal operating points using conversion rates and selectivity as performance metrics; (2) Theoretically-derived optimal design map(s) will be experimentally validated, demonstrating the predicted trends in DDIR reactor performance. The experimental validation will be instrumental in establishing a degree of confidence in extending the general theoretical framework developed to other reacting systems; and (3) Exploratory studies of the forced unsteady-state operation of the DDIR reactor will be undertaken, via experiments and simulations. It is conjectured that by changing these forcing time scales relative to the natural time scales of the system, improvements in time-averaged reactor performance may result.

Broader Impacts

If successful, this research could provide a significant benefit to society with potentially
transformational benefits to a wide range of engineering applications, including development of a new reactor technology for portable and distributed power generation and efficient chemical processing for a broad range of liquid fuels, including renewable energy sources. This research will advance discovery and understanding while promoting teaching, training, and learning by incorporating the research results into several academic courses and through undergraduate research opportunities. Broadening of participation by underrepresented groups will be achieved by engaging graduate and undergraduate students from under-represented groups, including graduates of HBMUs: Clark Atlanta, Spellman, and Morehouse Colleges. The work will enhance the infrastructure for research and education by developing and maintaining facilities for MEMS fabrication and characterization at the PI's institution. Broad dissemination to enhance scientific and technological understanding will be achieved through several activities. First, active industry involvement will be facilitated to enable the transfer of research results into industry practice. Second, research results will be disseminated through technical papers and presentations in engineering forums, as well as special events that the PI will organize for local high school students.

DESCRIPTION (provided by applicant): Quite frequently in biomedical research there is a need to detect and monitor dynamic chemistries in solution in the vicinity of an interface. For instance, many studies focus on detection of chemical secretions from cultured tissues or cells into the surrounding medium. Often, such applications place specific demands on the required spatial and temporal resolution of the detection method. When monitoring secretions this would be due to heterogeneity in the cell types and behavior, and also variation in cellular activities with time. Labeling, with, for instance, a fluorescent marker, a radioactive marker, or using antigen/ antibody attachment, has been spectacularly successful as the foundation for imaging dynamic biochemistry, but concerns about the altering of labeled analyte behavior and non-specific binding cannot be eliminated. Furthermore, all targeted methods, including those based on labeling, are inherently limited in their discovery potential, as one cannot find what one is not looking for. The purpose of the proposed research is to overcome the inherent limitations of current biochemical imaging technologies. This will be done through the development of electrospray ion sources that can serve as mass spectrometry probes (MSP) for highly resolved biochemical detection from the microenvironment adjacent to biological interfaces. The research team has a demonstrated history of success inventing novel mass spectrometry ion sources, and proposes, for this project, to accomplish the ambitious task of combining all prerequisite capabilities for sample collection, processing, and ionization into a micro- sampling capillary. This "lab-on-a-tip" will include in-line microdialysis to remove salts and exchange solvent, as well as an integrated tryptic digestion micro-reactor. The research team will develop, optimize and demonstrate MSP through an established multifaceted approach combining experiment (including optical and mass spec characterization), analysis and simulation (first principles physical models and computational fluid dynamics), and state of the art manufacturing (microfabrication). MSP will assume an important role in biological research as a hypothesis generator, and will become a key tool in improving development of bioreactors for regenerative medicine applications. Successful results have potential for transformational benefits to a wide range of research applications, including biomarker discovery, improved understanding of healthy and diseased cell biology, biosensor development, and bio-manufacturing process analysis and control. In addition to presentation at conferences and publication in archival journals, the application of MSP technology to biological problems will be disseminated through an educational workshop hosted at Ga. Tech. Furthermore, the probe will be coupled to a TOF mass spectrometer that is part of the NSF supported National Nanotechnology Infrastructure Network (NNIN), and therefore available to users from industry and academic institutions alike. PUBLIC HEALTH RELEVANCE (provided by applicant): In this application, we propose to develop an ambient Mass Spectrometry Probe (MSP), which passively samples and softly ionizes large biomolecules directly from liquid at physiological conditions, and thus makes possible transient mass spectrometric monitoring at precisely controlled locations in a complex liquid environment, with MS spectra collected as a function of time. The resulting capability to directly monitor biochemistry in physiologically relevant solution conditions will enable biologists, biochemists, and bioengineers to spatially correlate chemical data with high precision, not only for the generation of clear chemical "images" of in vitro cultures, but also for the investigation of the role of heterogeneity and gradients in numerous important applications, including bio reactors for regenerative medicine, activity and behavior of bioengineered materials, and biosensor characterization. MSP will assume an important role in biological research as a hypothesis generator, and has the potential for transformational benefits to a wide range of research endeavors, including biomarker discovery, investigations of healthy and diseased cell biology, biosensor development, and bio-manufacturing process analysis and control.

DESCRIPTION (provided by applicant): The overarching goal of this proposal is to develop a novel atmospheric pressure droplet desolvation/ ion collection interface for efficient delivery of softly ionized biomolecules to mass analyzers, which will dramatically improve sensitivity and dynamic range of mass spectrometry (MS) for complex biochemical samples. Such an interface is a critical enabling technology for raising MS capability to the next level, and to further advance this key tool in health related sciences, including applications to proteomics, metabolomics, biomarker discovery and drug development. An interdisciplinary research team comprised of a bioengineer, an analytical chemist, and a proteomics scientist will develop, demonstrate and optimize the novel interface system, DRILL (DRy Ion Localization and Locomotion), for ESI LC-MS workflows with a number of unique capabilities, using a multifaceted approach that combines innovative engineering design, supported by powerful electrohydrodynamics analysis, simulation and experiments, advanced DOE (design of experiment) analytical characterization methodology, and state-of-the-art applications to challenging proteomics problems. With an optimally-designed DRILL desolvation and ion transport interface, we aim to eliminate ion losses due to incomplete desolvation (including signal suppression) and inefficient ion collection, and to enable a dramatic improvement in sensitivity and dynamic range of detection as compared to the current state of the art. The research team members are well situated to meet the scientific and engineering challenges associated with addressing the need for an improved MS interface, with a track record of successful research on ion sources, bio-analytical devices and sensors, mass spectrometry, proteomics and interdisciplinary collaboration. As a result of this work, the research team will have completed all steps necessary to make the proposed DRILL system a widely applicable tool for biological and clinical researchers, aiming to improve current MS performance and to develop new MS applications for both top-down and bottom-up proteomics. Broad dissemination to enhance scientific and technological understanding will be achieved through several activities. In particular, the research results will be communicated through technical papers and presentations in scientific forums, developing an online resource summarizing the design and operation guidelines for DRILL device operation and enabled new LC-MS workflows, as well as special events (hands-on training workshops for clinical practitioners) that the research team plans to organize.

PROJECT SUMMARY The proposed project aims to develop a unique new instrument for multi-mode imaging of biological samples with sub-cellular spatial resolution. It is enabled by a synergistic combination of Scanning Electron Microscopy and a new mode of Desorption Electrospray Ionization (DESI) imaging mass spectrometry. The new technology is called BeamMap for Beam Enabled Accurate Mapping & Molecular Analyte Profiling ? where the enabling beams are the electron beam and the sprayed electrified liquid beam. BeamMap will provide untargeted characterization of protein, metabolite and lipid chemistry and correlation with topological features, yielding an order of magnitude improvement in the achievable resolution for electrospray based imaging, with chemical imaging resolution of ~ 250 nm and electron microscopy topological resolution of ~ 50 nm. Success in this high impact project has potential to bring about a transformative effect on many areas of biomedical sciences. The research team will develop, optimize and demonstrate BeamMap using a multifaceted approach that combines instrument design and simulation of critical components, state of the art micro/nanofabrication, and validation through carefully controlled experiments. As a result of this work, the research team will have be developed a fully functional, optimized, and well characterized prototype instrument, ready for application to challenging biomedical research questions. The PI and his research team are well situated for success, with a track record of high impact interdisciplinary research in mass spectrometry ion sources, bio-analytical devices, micro and nano-fabrication, and sensors development. This research will provide a new enabling technology for research endeavors in fundamental and clinical biology, medicine, analytical chemistry, and bioengineering. We expect that BeamMap will assume an important role in biological research as a hypothesis generator, and will become a key tool in molecular medicine applications. The proposed work will enhance the infrastructure for research and education by introducing a new powerful chemical imaging tool for use in high impact biological and therapeutic applications through the Marcus Center of Therapeutic Cell Characterization and Manufacturing (https://cellmanufacturing.gatech.edu/). Broad dissemination to enhance scientific and technological understanding will be achieved through technical papers and presentations in scientific forums and the use of the BeamMap by external scientists.