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Houston, TX, United States

Dwivedi P.,Washington State University | Schultz A.J.,Ionwerks, Inc. | Hill Jr H.H.,Washington State University
International Journal of Mass Spectrometry | Year: 2010

A high-resolution ion mobility time-of-flight mass spectrometer with electrospray ionization source (ESI-IM-MS) was evaluated as an analytical method for rapid analysis of complex biological samples such as human blood metabolome. The hybrid instrument (IM-MS) provided an average ion mobility resolving power of ∼90 and a mass resolution of ∼1500 (at m/. z 100). A few μL of whole blood was extracted with methanol, centrifuged and infused into the IM-MS via an electrospray ionization source. Upon IM-MS profiling of the human blood metabolome approximately 1100 metabolite ions were detected and 300 isomeric metabolites separated in short analyses time (30. min). Estimated concentration of the metabolites ranged from the low micromolar to the low nanomolar level. Various classes of metabolites (amino acids, organic acids, fatty acids, carbohydrates, purines and pyrimidines, etc.) were found to form characteristic mobility-mass correlation curves (MMCCs) that aided in metabolite identification. Peaks corresponding to various sterol derivatives, estrogen derivatives, phosphocholines, prostaglandins, and cholesterol derivatives detected in the blood extract were found to occupy characteristic two-dimensional IM-MS space. Low abundance metabolite peaks that can be lost in MS random noise were resolved from noise peaks by differentiation in mobility space. In addition, the peak capacity of MS increased sixfold by coupling IMS prior to MS analysis. © 2010 Elsevier B.V. Source


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: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.95K | Year: 2009

This Small Business Innovation Research Phase I project is to develop a secondary electron detector which can be co-axially mounted with a micro-focused ion beam. Backscattered neutral atoms (and ions) and secondary electrons will be analyzed to give a measure both of surface element location and identity. This detector will enable unique types of secondary ion mass spectrometry. The electrons and negative backscattered ions can be energy and time analyzed to give a spatially resolved elemental image of the surface under examination. Beam damage is greatly reduced compared to secondary electron microscopy allowing its use on biological samples. This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).


Grant
Agency: Department of Defense | Branch: Air Force | Program: STTR | Phase: Phase I | Award Amount: 99.98K | Year: 2010

Surface analysis of many classes of large polymers (e.g. non-polar synthetic polymer) by laser desorption mass spectrometry (LDMS) is not possible using existing MALDI matrices. Here, we uniquely address this problem by combining two recent proprietary commercial products available exclusively from Ionwerks. 1) A nanoparticulate ion implanter decorates a surface with size selected metal or alloy nanoparticulates (NPs) yielding efficient LDMS (intact ions and neutrals). 2) Moreover, our LD ion mobility MS allows submicron spatial analysis of directly ejected ions liberated from these NP treated surfaces. Not only does the “gas phase electrophoresis” of the Ion Mobility sort molecular ions by chemical type, but predominantly desorbed neutrals are localized in space above the sample surface long enough to be ionized by additional laser pulses. Our nanoparticulate implanter is the ideal platform for determining the worth of plasmon resonances to LDMS. NP size, shape, and composition can be tailored to increase optical absorption. Are small NP (non plasmon) better matrices than larger NP (plasmon)? Our work shows small particles (1-10 nm gold) are needed for biomolecular tissue imaging. This may not be the general case—especially if the analysis can be accomplished by engineered NP neutral analyte desorption followed by post-ionization. BENEFIT: The anticipated benefit of this research is to provide a nanomatrix which can be utilized for low laser threshold, high spatial resolution surface analyis of large molecular compounds. MALDI analysis of solids as currently practiced requires dissolving the solid sample and combining matrix molecules in a solution which is subsequently dried and introduced into the LDMS for analysis. The analyte must be water soluble. In contrast, here we tackle the more general and pervasive problem of combining matrix with an intact molecular surface. Soft landing or implanting NP into a solid surface in principle (and so far in limited practice with biotissues) provides a universal means of incorporating matrix with any solid surface. Moreover, this approach retains the possibility to image the possible surface molecular heterogeneity (e.g. co-polymer segregation) at submicron spatial resolutions. Whether plasmon resonances turn out to be useful for these analyses can be uniquely and quickly determined for a broad range of nanoparticulates (our source can produce NP from any metal or metal alloy in size ranges from 1-30 nm). Moreover, as we find optimal matrices for soft landing or implantation into solids, it is but a simple matter to produce these same NP compositions and coverages onto a substrate (such as silicon) which can then serve as a MALDI matrix substrate to which analyte molecules in solution can be applied. Dual use applications for this technology include rapid screening of bacterial and virus populations, analysis of intact biofilms, synthetic polymer characterization, and biotissue analysis. Laser desorption MS has been historically dismissed as a surface analysis technique for inorganic surfaces such as semiconductors or strained layer superlattices. However plasmon resonance may provide controlled optical adsorption into the first nm of these solids opening the possibility for LDMS surface analysis of these important materials as well.


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.

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