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INDIANAPOLIS, IN, United States

Eberlin L.S.,Purdue University | Dill A.L.,Purdue University | Golby A.J.,Harvard University | Ligon K.L.,Harvard University | And 3 more authors.
Angewandte Chemie - International Edition | Year: 2010

Figure Presented Differentiation of human brain astrocytic tumor grades can be achieved by direct lipid analysis using desorption electrospray ionization mass spectrometry (DESI-MS). Distinctive lipid profiles are associated with the degree of malignancy, grades II, III, and IV (see picture). © 2010 wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Patent
Brigham, Women's Hospital and Prosolia, Inc. | Date: 2011-09-30

A system and sampling probe adaptable to an ultrasonic surgical instrument applies irrigation fluid and ultrasonic or vibrational energy to a target, and aspirates material desorbed from the target into a pick-up conduit. A suction source at the distal end of the conduit may aspirate the material released from the target with the irrigation fluid, thus efficiently sampling a broad range of materials from an arbitrary target to produce an analyzable effluent analyte stream which may be ionized and provided to the inlet of an ion-type analysis instrument, or may be fed directly to an instrument such as a flow cytometer, IR or fluorescence spectrophotometer, or other analyzer. Carrier gas may be provided to more effectively transport the desorbed material, and the probe may be incorporated into a robotic device to automatically carry out surface imaging or to effect sampling in hazardous environments.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 101.98K | Year: 2009

DESCRIPTION (provided by applicant): The overall objective of this Phase I STTR project is the commercialization of a new ionization source for ambient mass spectrometry based on the flowing afterglow of an atmospheric pressure glow discharge (APGD). This technology promises to have significant impact in pharmaceutical, clinical and biomedical research and its potential for enabling in vivo mass spectrometry detection in combination with existing technology is real. There is an acute need for the development of new technologies which enable rapid measurements with minimal sample pretreatment. Minimizing up-front sample preparation increases sample through-put by reducing the time required to go from raw material to a result. The recent development of ambient mass spectrometry methods has already resulted in the successful commercialization of just a few of these disruptive technologies. This project involves the fundamental characterization, optimization and development of a new direct sampling technology for mass spectrometry based on the flowing afterglow of an atmospheric pressure glow discharge developed at Indiana University by Prof. Gary Heiftje. Atmospheric pressure glow discharges have been extensively studied but not until very recently has it been attempted to use an atmospheric pressure glow discharge for direct sampling of surfaces in the open ambient air. We envision commercial ion sources that can be easily converted among several atmospheric pressure ionization techniques and can be retro-fitted to several different types of mass spectrometers or ion mobility spectrometers. The specific aims of this Phase I STTR proposal are: Aim 1: Investigate the APGD and flowing afterglow chemical environment using spectroscopic techniques. Aim 2: Identify electrode structures and materials for the anode and cathode in an attempt to optimize the atmospheric glow discharge characteristics using the information gained through completion of Aim 1. An optimized cell will be one which maximizes reagent ion density and controls their spatial distribution. Aim 3: Operate the APGD cell in combination with mass spectrometry and identify operating conditions for the cell geometries investigated in Aim 2. Aim 4: Assess the feasibility for coupling APGD to a commercial laser ablation mass spectrometry system. Phase II of this project will include the development of a commercial prototype of the APGD ion source based on the criteria defined in Phase I, further optimization of its performance and robustness, comparisons to other ambient ionization methods and applications development in the areas of pharmaceutical and biomedical research. Specifically, Phase II will focus in part on the development of the APGD cell in combination with commercially available laser ablation mass spectrometry systems, which will enable direct, 3D molecular imaging of biological tissues. Other application areas that will be explored with the same instrumentation include high throughput screening of combinatorial libraries and in vitro cytochrome P450 assays. PUBLIC HEALTH RELEVANCE: Prosolia's new and versatile ambient ionization source for mass spectrometry promises to enable high throughput chemical screening that will significantly impact pharmaceutical, clinical and biomedical research.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 161.71K | Year: 2015

DESCRIPTION provided by applicant Most samples of chemical interest are complex mixtures making the usual combination of chromatography with mass spectrometry MS a natural choice However the increased demand for chemical analysis by mass spectrometry in many areas of science makes it imperative to increase efficiency of analysis by minimizing sample workup and overall analysis time which makes direct mixture analysis highly desirable These demands were in many ways solved in with the development of ambient mass spectrometry a branch of mass spectrometry which allows spectra to be recorded on samples in their native state with minimal or no sample preparation Ambient ionization provides the speed needed for in situ experiments by recording mass spectra instantaneously on unmodified samples in their native state and in the ambient environment Sample analytes are loaded onto a substrate material for sampling and supporting the analytes to be studied Nonpolar substrate surfaces currently used in ambient MS offer an advantage over other existing materials in the analysis of a variety of analytes but have limited utility in that they often are impure mechanically weak single use offer poor sample loading have decreased signal intensity and stability and are not easy to modify making them useful for only a particular class of analytes As an alternative to the more widely used sampling materials such as paper and glass we have developed novel organosiloxane OSX polymer materials that have the potential to be used as sampling substrates in ambient ionization methods Our materials can be chemically tuned to increase signal intensity molecule selectivity signal stability and can also be chemically modified by covalent attachment of molecules to serve different analytical purposes within many other possibilities In Aim we will investigate and optimize the synthetic parameters that affect the polymer features such as its porosity polarity hydrophobicity hydrophilicity and its surface features and chemistry In Aim we will use the OSX polymer as a sampling material in spray ionization and desorption electrospray ionization DESI MS to evaluate the performance of the polymer and to identify the optimal operating conditions signal intensity and stability for the polymers investigated and designed in Aim In Aim we will evaluate the feasibility of coupling the polymers to as commercial ambient MS using Prosoliaandapos s commercial robotic sources To assess the utility of these OSX polymers as sampling materials we will analyze drugs in blood serum and study in situ digestion of proteins on polymer surfaces grafted with an enzyme Given the many advantages of OSX polymers they will make excellent commercial products that can widen the application of ambient ionization MS in many different areas including clinical medical diagnostics and proteomics PUBLIC HEALTH RELEVANCE Ambient mass spectrometry has been increasingly used in many areas of science such as forensics clinical diagnostics and drug analysis as it allows for direct and fast detection of samples However there are limitations in the sampling materials currently used for ambient mass spectrometry We propose to develop and test novel improved sampling materials that can be chemically modified for improving the performance of ambient mass spectrometry analysis and expanding its use


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 740.79K | Year: 2011

DESCRIPTION (provided by applicant): The overall objective of this Phase II STTR project is the commercialization of a new ionization source for ambient mass spectrometry based on the flowing afterglow of an atmospheric pressure glow discharge. This technology promises to have significant impact in pharmaceutical, clinical and biomedical research. Ultimately, we envision commercial ion sources that can be easily switched among several atmospheric pressure ionization techniques and can be retro-fitted to several different types of mass spectrometers or ion mobility spectrometers. Phase I of this project was highly successful. Alpha prototypes were developed, tested and feasibility proven. Optical spectroscopy measurement revealed novel species (He2+), whichare implicated in the ionization mechanism. Further, the plume temperature measurements revealed hot spots' within the afterglow where thermal desorption is most efficient and results in higher sensitivity. We demonstrated that the ion source could directly desorb and ionize a variety of chemical species and further tested the method in the direct analysis of mycobacterium smegmatis cells. Finally, the coupling of the ion source to a laser ablation cavity proved to yield molecular information with high spatial resolution. The phase II specific aims are as follows: 1. Prototype Development. Beta prototypes of the FAPA ion source will be designed and built based on the criteria defined at the conclusion of the Phase I grant. The sources will include the development of an optimized FAPA discharge cell and a mass spectrometer mounting system with computer controlled sample positioning system. Additionally, prototype support electronics, including the constant current, high voltage DC power supply, a discharge gas temperature controller, and a discharge gas flow controller. Finally, software will be developed to control these elements and automate sample collection. There will be a minimum two beta prototypes built for testing and validation simultaneously at Indiana University and Prosolia. 2. Characterization and Optimization of the sampling process at atmospheric pressure: We will use schlieren photography in combination with mass spectrometry and computer simulations to provide the ideal sampling environment at the interface between the reagent ion gas plume and the vacuum inlet to the mass spectrometer. 3. Source Characterization and applications development: Our approach is three-fold: 1) to test and characterize the beta prototype FAPA source developed in Aim 1 by examining neat samples while varying the gas flow, heater temperature, and device impact angle and assessing the usual figures of merit, detection limits, precision, accuracy, carry-over, and throughput; 2) examining the effects of modifying gas phase chemistries to effect atmospheric pressure fragmentation reactions for generating NIST searchable spectra; and 3) to apply the optimal device parameters, gas-phase chemistry and sampling conditions to a combinatorial study of one hundred drug-like molecules of various properties and compare the results to the same study by DESI. We believe it is important to show our customers a range of molecules in size and hydrophobicity to make it easier for them to assess the likelihood their proposed applicationwill be successful. Upon successful completion of the proposed aims, Prosolia will proceed into phase III commercialization where FAPA ion source products (hardware and software) and services will be commercialized. Further, strategic licensing and partnerships will be secured to commercialize the technology as an add-on accessory to laser ablation cavities, gas chromatographs and/or liquid chromatographs. PUBLIC HEALTH RELEVANCE: Prosolia's new and versatile ambient ionization source for mass spectrometry promises to enable high throughput chemical screening that will significantly impact pharmaceutical, clinical and biomedical research.

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