Houston, TX, United States
Houston, TX, United States

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The present invention relates to a method and apparatus for ionizing a neutral MALDI desorption plume, and in particular, for efficiently measuring the ionized MALDI desorption plume when post-ionization techniques are combined with a medium pressure MALDI-IM-oTOFMS instrument. Additionally, the present disclosure provides a method and apparatus that simultaneously separates tissue-sample MALDI ions by IM-oTOFMS according to their chemical family. After separation, the MALDI ions are directly compared to the ions created by post-ionizing the co-desorbed neutral molecules with a second laser wherein the second laser is delayed by a few hundred microseconds. The present disclosure further provides novel approaches that enhance the analysis of ions, including the use of giant fullerene internal standards to enhance mass accuracy, and ultraviolet (UV) declustering lasers to generate intact peptides and proteins, either of which may be followed by VUV post-ionization which generates identifiable structural fragments.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 2.39M | Year: 2011

DESCRIPTION (provided by applicant): Within the volume of a single cell, lines an extensive amount of information. The current scope of molecular imaging using mass spectrometry typically swamps the cell volume with organic acid matrix just to get observable signals. Herein lies the problem. Putting more matrix that there is analyte (i.e. cellular volume) inherently makes intracellular imaging via organic acids improbable. Therefore, Ionwerks has developed a comprehensive set of instrumentation, and nanoparticulate preparation techniques which combine two dimensional ion-mobility mass spectrometry and nanoparticulate tissue preparation which provide a means to analysis of tissues while preserving their histological attributes. Our research has demonstrated that sub-monolayers of nanoparticulates implanted into various depths within a tissue, provide agreeable signal levels. This means, the particulate to analyte ratio is much less that typical preparations: the chemical information is preserved and observable. The nanoparticulates will also be microfocused to allow for unique molecular secondary ion mass spectrometry (SIMS). Furthermore, we are developing small format oTOF MS detectors which can be combined with leading edge surface imaging techniques to create a one of a kind imaging platform from which surfaces / tissues can be morphologically imaged, and mass spectra of ejected ions can be recorded. PUBLIC HEALTH RELEVANCE: The goal of this project is implant histological prepared tissues with gold nanoparticulates, then to measure the ejected ions using a low profile oTOF-MS system from a microfocused nanoparticulate beam. This project will lay the groundwork for utilizing the helium ion-beam microprobe systems as a combined topographical imaging system, as well as molecular imaging systems.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 2.95M | Year: 2013

DESCRIPTION provided by applicant MALDI tissue imaging when enabled by Nanoparticulate NP Matrix implantation is maturing into a useful preclinical tool for biomarker and drug discovery in our laboratory and at NIDA IRP Quantitatively reproducible images from serial coronal sections suggest that relative quantitation is now possible in rodent models of disease and injury Nanoparticulate NP matrix implantation allows numerical quantitation of differences in biomarker levels in rodent disease and injury models No commercial instrument which performs mass spectral molecular imaging of tissues has software capable of analyzing and displaying these quality data sets Software and hardware developed under our antecedent phase II for analyzing the multidimensional data from our MALDI Ion Mobility MS imaging system will be expanded to serve this need and will also have dual use in correlating molecular image quality with the nano scale characterization of the NP matrices by advance materials analysis techniques such as the subnanometer resolution Zeiss Orion Helium Ion Microscope The continued growth of unique core shell NP matrices will continue to be aided by advanced materials analysis measurement of the NP structures and particle size distributions after implantation into the tissue Protocols for standards incorporation into and onto the tissue surface will attempt to prove the capability of relative and absolute quantitation in MALDI MS imaging PUBLIC HEALTH RELEVANCE Nanoparticulate NP matrix implantation numerical quantitation of differences in biomarker levels in rodent disease and injury models may be possible No commercial instrument which performs imaging has software capable of analyzing and displaying these data sets Software developed under a previous phase II for our Ion mobility system can be modified to fulfill these needs for other instruments Growth of new NPs advanced characterization and biological imaging will occur in parallel


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 350.50K | Year: 2014

DESCRIPTION (provided by applicant): A new thin film approach to increasing the gain and sensitivity of current and future fast particle detectors is hypothesized. An increased ion induced secondary electron yield at the first surface of the detector while retaining high timing accuracy will make such detectors suitable replacement for MCP detectors in biological applications such as electron or ion microscopies and time of flight mass spectrometers. Moreover, the detector may be sensitive to the energy ormomentum of the incoming ion. Such information could simplify MALDI or electrospray MS spectra containing highly charged molecular ions. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: A new type of ion detector will enhance secondary electrongains compared to standard multi-channelplate detectors. Direct replacement sale of detectors or sale of ion detectors and electronics are both commercial options. This will greatly improve mass spectra of systems in use.


Grant
Agency: Department of Defense | Branch: Air Force | Program: SBIR | Phase: Phase I | Award Amount: 149.91K | Year: 2013

ABSTRACT: Core-shell Metastable Intermolecular Compounds (CS-MICs) will be examined utilizing gas-phase nanocluster production, formed into an atomic beam, accelerated and implanted into polymers of interest for air stability studies as well as preliminary exothermic properties. This will include depth profiling via ESCA, XPS, determination of chemistry state at depth, coupled with long term studies at controlled humidity environments followed by ESCA, XPS. SEM-EDS of individual particles will also be undertaken to compare to the average XPS profiles. Surface passivation chemistries will be examined with regard to the coating chemistry, implantation depth, and polymer composition, and from this, air stability factors for a given condition can be provided which is of great use at a chemical level considering the exothermic properties of nanothermite. The goal of this Phase I is to provide well controlled production routes for Core-Shell MICs along with implanted substrates for further energetic studies and plans for scale-up productions can be designed. BENEFIT: Providing a route to air-stable core-shell metastable intermolecular compounds as well as the corresponding energetic studies has the potential to open up several new avenues for commercial success including but not limited to sales of core-shell cluster beamlines, R & D services for customers with specific chemistry desires, and delivery of processes which generate scaled up amounts of core-shell thermites at a level applicable to use within the propulsion and energy delivery needs of the military. Furthermore, the use within microdevices at small scales is also an avenue for a successful core-shell chemistry immediately as the current coating levels may provide a means for initial microdevice tests. Our current work has focused upon the control of the chemistry of the nanoparticle, and implanting this into the sample of interest. The analysis and demonstration of nanothermites implanted below the surface of a polymer, resulting in passivation of the bare-metal or layered surface, and creation of a long-duration air stable thermite would be directly applicable to the field of directed energy and would be an immediately desired product.


Methods and devices for mass spectrometry are described, specifically the use of nanoparticulate implantation as a matrix for secondary ion and more generally secondary particles. A photon beam source or a nanoparticulate beam source can be used a desorption source or a primary ion/primary particle source.


Patent
Ionwerks, Inc. | Date: 2010-11-30

Described is an analytical method and apparatus for counting and measuring the flight time of secondary electrons, secondary ions and neutrals, scattered ions and/or neutrals and for correlating coincidences between these while maintaining a continuous un-pulsed, micro-focused, primary particle beam for impinging a surface for purposes of microprobe imaging and microanalysis.


Methods and devices for mass spectrometry are described, specifically the use of nanoparticulate implantation as a matrix for secondary ion and more generally secondary particles. A photon beam source or a nanoparticulate beam source can be used a desorption source or a primary ion/primary particle source.


Time-of-flight mass spectrometer instruments are disclosed for monitoring fast processes with large dynamic range using a multi-threshold TDC data acquisition method or a threshold ADC data acquisition method. Embodiments using a combination of both methods are also disclosed.


Methods and devices for mass spectrometry are described, specifically the use of nanoparticulate implantation as a matrix for secondary ion and more generally secondary particles. A photon beam source or a nanoparticulate beam source can be used a desorption source or a primary ion/primary particle source.

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