Next Generation Threat Detection
This project is jointly conducted by research groups at Purdue, Indiana University, and the University of Illinois-Urbana/Champaign. These groups, two of the three CAID partner institutions, are involved in the discovery, design, development and evaluation of instruments that can be used for the detection and characterization of chemical and biological warfare agents. This project focuses on determining whether cutting-edge analytical instrumentation and methods can be used for detecting CBA threats. The potential to miniaturize and combine several different instruments and approaches into a mobile platform is being assessed. Additionally, the project seeks to develop standard methods for performance evaluation across different instrument modalities.
Compact Mass Spectrometry Device for On-Site Clinical Diagnoses
A diagnostic system based on mass spectrometry technology (MS), Mini Bio, will be developed for on-site clinical diagnoses. It will have compact size (10 lb), low power consumption (<35W), capability of direct sampling and instantaneous reporting based on automatic spectral analysis. Direct sampling will allow the detection of metabolites, drug compounds, lipids, fatty acids, peptides and proteins directly from untreated samples such as breath, skin, tissue, urine and other body fluids. Mass spectrometry will provide highly specific molecular information on the sample. In comparison with the mass spectrometers used in the laboratory, the Mini Bio device will be specialized for individual targeted diagnosis so simple operation and direct reporting will be achievable for on-site diagnoses in the clinic.
Initial targeted diagnoses using the Mini Bio include the screening of inborn errors of metabolism (IEM) and identification of the extent of tumor tissue. Desorption electrospray ionization (DESI) or low temperature plasma (LTP) desorption will be used for direct sampling of metabolites from raw urine and phospholipids from untreated tissues. The signature urine metabolite patterns and tissue phospholipid profiles will be acquired by MS and used for diagnosis of these diseases states. Device development will be based on experience in the miniaturization of the mass spectrometers, the recent invention of ambient sampling methods and established uses of MS analysis in bioanalytical research.
Development of a High Efficiency Mass Spectrometry System
CAREER Award, National Science Foundation
In preliminary work, it is found that the sensitivity achieved using a miniature mass spectrometer with a discontinuous atmospheric pressure interface (DAPI) is comparable with those achieved using lab-scale instruments with hundreds-fold greater pumping capacity. A systematic study, including simulations, theoretical modeling, experimental characterizations and instrumentation development, is proposed to investigate the critical factors affecting efficiencies of ion focusing in air, ion loss and desolvation through an atmospheric pressure interface as well as the mass analysis at high pressure. New devices and methods will be developed based on these studies to allow a much improved efficiency for mass spectrometry analysis with simple instrumentation configurations.
An Analytical Instrumentation Development (AID) Training Program is proposed for the educational development based on instrumentation prototyping and research. Students with different backgrounds will work together and develop prototype instruments based on newly developed analytical technology and provide them for outside end-users to test and develop applications. The efficacy of integration of education with research and transition of learning to real problem solving will be explored. The model of training young instrumentalists for analytical instrumentation research development will be tested. The mechanisms of building a self-sustainable training program will be explored.
An important goal of this work is to explore an unusual approach to challenge the limitation of the sensitivity in MS analysis set by commercial instruments with standard instrumentation configurations. With the instrumentation improvements based on the proposed research, an immediate benefit will be made for miniaturization of mass spectrometry by allowing a transfer of MS methods developed on large laboratory instruments to the miniature MS devices. The validation of the technologies developed in this project on large scale instruments will potentially result in a significant increase in sensitivity of mass analysis and allow us to attack the most challenging problems in biological science where ultra high sensitivity is required to analyze samples available only in extremely small amounts.
Preparation of Chemically Functionalized Surfaces through Ion Soft Landing and their Utilization in Heterogeneous Reactions
Department of Energy
This proposal concerns polyatomic ion/surface interactions at low collision energy (low eV range), especially as related to the long-term objective of preparing reactive surfaces that might be prototypes of future catalytic materials. The overall aim is to broaden the applications of mass spectrometry through instrumentation and methods development and acquisition of chemical know-how relating to the preparation of specific and useful functionalized surfaces using ion soft landing (SL, including reactive soft landing) and associated ion/surface collision phenomena. Specific goals are: (i) Generation of functionalized surfaces through SL of molecular ions having appropriately arranged chemical functional groups in the gas phase and their gentle transfer onto a surface so as to prepare materials with controllable, and eventually catalytic, reactivity. (ii) Studies of the heterogeneous reactivity of particular modified surfaces at ambient pressure in the presence of vapor phase reagents through by of the gas-phase reaction products as well as examination of the post-exposure changes in surface chemistry. Polymerization of olefins, epoxidation and hydrogenation of small molecules, photo-enhanced reactions, and the preparation of organic inorganic hybrid materials will be of interest. (iii) Preparation of chemically modified high area surfaces (e.g. roughened silver and gold surfaces and nanostructured silicon) by and the development of methods for their chemical modification through the agency of ionic collisions. (iv) Improved understanding of charge neutralization/retention/build up phenomena at surfaces including methods of measuring charge build-up and its dependence on the nature of the ion/surface interactions occurring at hyperthermal energy. (v) Further modification of the completed SL instrument and reaction chamber to increase ion currents and allow the preparation and characterization of functionalized surfaces at greater rates. Increased throughput will be achieved using an array of ion sources and an array of ion traps for mass analysis. (vi) Characterization of modified surfaces will use secondary ion mass spectrometer (SIMS, new in situ capability), X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM) (external service facilities), and a proposed in-situ surface enhanced Raman spectroscopy (SERS) capability. Achievement of these objectives should increase the understanding of ion/surface collisions at hyperthermal energy, especially chemical transformations in the nature of the surface-bound products. The importance of the proposed experiments lies in the evaluation of mass spectrometry as a method for the preparation of high value products and in the continued acquisition of fundamental information on the collisions of ions with surfaces.
Low Temperature Plasma Coupled to Portable Mass Spectrometry
Department of Homeland Security
Chemical analysis of surfaces in the ordinary ambient environment is the subject of this proposal. A new molecular analysis method, based on rf discharges in air, will be evaluated. A low temperature plasma (LTP) probe will be used with the possibility to provide very fast, chemically-specific data on organic compounds present on surfaces. A better understanding of the method will be sought through experiments and dynamical simulations, which will be used to optimize operating conditions. The LTP ion source will also be implemented on a miniature mass spectrometer (Mini 10). Performance testing of the system will include speed, sensitivity, specificity, precision, applicability to a wide range of organic and inorganic compounds, and spatial area of analysis, as well as evaluation of reliability, operating costs, and quality of data obtained using tandem mass spectrometry to interrogate complex mixtures.
The fundamental knowledge derived from the simulations and physico-chemical studies of mechanism should contribute directly to improving the LTP probe. If successful, the work will result in an extremely simple, low-power device that generates ions from virtually any organic compound on a surface or in solution. It will be coupled to a handheld mass spectrometer and this will allow tandem mass spectrometry experiments in which complex mixtures are characterized rapidly for their constituents without prior sample preparation. The ability to perform high throughput yet chemically highly specific measurements will have many implications, including those aimed at rapid and reliable detection of chemical agents in homeland security, forensics, and in drug abuse situations.
Ion Reaction, Ion Dissociation and Ion Collection in the Open Laboratory Environment
National Science Foundation
The Analytical and Surface Chemistry Program of NSF supports this work to devise means of performing significant parts of the mass spectrometric experiment outside the mass spectrometer, in the open laboratory environment. In this way, it is hoped to achieve gains in speed and performance, while minimizing the inefficiencies associated with transferring ions into vacuum. Working with ions in the ambient environment also enables fuller exploration of the fundamental chemical relationships between the reactions of ions in solution and those of ions in the mass spectrometer. These studies gain broad impact because mass spectrometry is an analytical tool used widely in science and industry for chemical analysis; it has special roles in pharmaceutical discovery, environmental monitoring, food safety, forensics and biomedical research. Its high sensitivity, chemical specificity (low false positives), and the diversity of applications have elevated it to an outstanding position among methods of chemical analysis. Work in the Cooks laboratory also addresses the urgent national need to improve the infrastructure of science by contributing to the training of instrumentation scientists.
Development of a Biofluid Transport, Separation and Molecular Analysis System Using Microfluidics and a Miniature Mass Spectrometer
The central objective of this proposal is to develop an integrated instrument that detects and correctly identifies biomarkers. This will be done by acquiring small-volume fluid samples, subjecting them to on-line separation and preconcentration in a nanofluidic-microfluidic emitter chip and then characterizing them using on-line mass spectrometry in a miniature mass spectrometer. Critical performance tests of the analysis system will target the molecular markers of oxidative stress using biofluids which mimic cerebrospinal fluid (CSF) with special emphasis on developing procedures for identifying and quantifying steroids, triglycerides, and phospholipids and their oxidized forms. The proposed instrumental approach offers much of value to the biological sciences, for example making it possible to realize real-time functional assays of changes in fundamental metabolic, regulatory and signaling processes in response to environmental factors. Fundamental improvements in the performance of mass spectrometers (such as greater ionization efficiency in electrospray) and in microfluidic devices will result from the synergy of this project, making possible future generations of biological instruments of even greater power and utility. Successful instrumentation development will impact medical diagnostics. The same markers relevant to biological oxidation processes of primary importance are germane to the early detection and development of prognosis in a host of diseases, including multiple sclerosis, Alzheimerâ€™s disease, Niemann-Pick C, amyotrophic lateral sclerosis, heart disease, Parkinson’s disease and ischemic stroke. Thus, the development of the instrument described here is readily translatable from the world of fundamental biological investigations into human health.
Tissue Imaging Using Desorption Electrospray Ionization Mass Spectrometry
It is proposed to develop new imaging methods which can be used to identify lipids and other chemicals that might serve as biomarkers to follow the fundamental processes occurring in the course of neural diseases like multiple sclerosis. Specific information on the chemical changes in the nerve sheath will be sought in order to allow future diagnosis and prognosis of neural diseases. Ongoing efforts at diagnosis of cancer through MS imaging of tissue sections is included.
Research in Mass Spectrometry
Research will be conducted into the fundamentals of ion motion in mass analyzers and ion optical systems. Reactions and other applications useful in mass spectrometry will also be studied.
Professor Graham Cooks
560 Oval Drive
Department of Chemistry, Purdue University,
West Lafayette, IN 47907-1393
Phone: 765-494- 5263
Professor Fred Regnier
560 Oval Drive
Department of Chemistry, Purdue University,
West Lafayette, IN 47907-1393
Bindley Bioscience Building
1203 W State Street
West Lafayette, IN 47907-2057