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.
Wiseman J.M.,Prosolia, Inc. |
Evans C.A.,Glaxosmithkline |
Bowen C.L.,Glaxosmithkline |
Kennedy J.H.,Prosolia, Inc.
Analyst | Year: 2010
A novel approach to the quantitative determination of xenobiotics in whole blood samples without sample preparation or chromatography is described. This method is based on direct analysis of microlitre volumes of blood which are spotted onto specialized paper cards and dried, with the resulting dried blood spots (DBS) analyzed directly via desorption electrospray ionization (DESI) mass spectrometry (MS). Using sitamaquine, terfenadine, and prazosin as model compounds with verapamil as a common internal standard, this methodology demonstrated detection of each compound down to 10 ng mL -1 from DBS where standard calibration curves show linearity from 10-10000 ng mL -1 with r 2 > 0.99. Three (3) different untreated types of filter papers (Whatman 903 and 31ETF as well as Ahlstrom 237) and two (2) treated types of filter paper (Whatman FTA and FTA Elute) were examined and the effect of each surface on the recovery of each analyte was evaluated. The results show that the untreated papers provide the best substrates for DBS analysis by DESI. A more in depth study of the quantitation of sitamaquine on 31ETF paper stock provided bias and error measurements of less than 20%. The promising results shown in this study may have important implications in the areas of therapeutic drug monitoring (TDM), clinical and forensic toxicology, and pharmacology. © 2010 The Royal Society of Chemistry.
Kennedy J.H.,Prosolia, Inc. |
Wiseman J.M.,Prosolia, Inc.
Rapid Communications in Mass Spectrometry | Year: 2010
The present work describes the methodology and investigates the performance of desorption electrospray ionization (DESI) combined with a triple quadrupole mass spectrometer for the quantitation of small drug molecules in human plasma. Amoxepine, atenolol, carbamazepine, clozapine, prazosin, propranolol and verapamil were selected as target analytes while terfenadine was selected as the internal standard common to each of the analytes. Protein precipitation of human plasma using acetonitrile was utilized for all samples. Limits of detection were determined for all analytes in plasma and shown to be in the range 0.2-40ng/mL. Quantitative analysis of amoxepine, prazosin and verapamil was performed over the range 20-7400ng/mL and shown to be linear in all cases with R 2 >0.99. In most cases, the precision (relative standard deviation) and accuracy (relative error) of each method were less than or equal to 20%, respectively. The performance of the combined techniques made it possible to analyze each sample in 15s illustrating DESI tandem mass spectrometry (MS/MS) as powerful tool for the quantitation of analytes in deproteinized human plasma. © 2010 John Wiley & Sons, Ltd.
Wiseman J.M.,Prosolia, Inc. |
Li J.B.,Prosolia, Inc.
Analytical Chemistry | Year: 2010
A method for the examination of intact tissue sections for gangliosides and other lipids using desorption electrospray ionization (DESI) mass spectrometry (MS) is presented. In the present work, thin tissue slices (16 μm) taken from the rat brain are thaw mounted onto planar chromatographic media and the lipids are eluted, partially separated, and analyzed directly from the plate by DESI-MS in the negative ion mode. With the lanes scanned parallel to the direction of the chromatographic separation in the full scan mode, the selected ion current associated with ions of separated lipid molecules is plotted in order of increasing Rf values. Distinctly different classes of lipids are detected using this method, including several ganglioside species (i.e., GQ1, GT1, GD1, and GM1) and sulfoglycosphingolipids. For the examination of gangliosides in the full scan negative ion mode from high-performance thin-layer chromatography (HPTLC) plates, the limit of detection (LOD) was determined to be approximately 3 pmol. Tandem mass spectrometry (MS/MS) using the linear ion trap was used to confirm the presence of selected gangliosides and other lipids directly from the HPTLC plate. DESI-MS/MS revealed the presence of both the GD1a and GD1b isomers. The simplicity of this approach where planar separations are relied upon for sample preparation and presentation to the MS should allow for the examination of a variety of complex samples including the rapid examination of foodstuffs, bacteria, whole blood, and needle biopsies for cancer diagnostics. © 2010 American Chemical Society.
Kennedy J.H.,Prosolia, Inc. |
Wiseman J.M.,Prosolia, Inc.
Rapid Communications in Mass Spectrometry | Year: 2010
Salvia divinorum is widely cultivated in the US, Mexico, Central and South America and Europe and is consumed for its ability to produce hallucinogenic effects similar to those of other scheduled hallucinogenic drugs, such as LSD. Salvinorin A (SA), a kappa opiod receptor agonist and psychoactive constituent, is found primarily in the leaves and to a lesser extent in the stems of the plant. Herein, the analysis of intact S. divinorum leaves for SA and of acetone extracts separated using thin layer chromatography (TLC) is demonstrated using desorption electrospray ionization (DESI) mass spectrometry. The detection of SA using DESI in the positive ion mode is characterized by several ions associated with the compound - [M+H] +, [M+NH 4] +, [M+Na] +, [2M+NH 4] +, and [2M+Na] +. Confirmation of the identity of these ions is provided through exact mass measurements using a time-of-flight (ToF) mass spectrometer. The presence of SA in the leaves was confirmed by multi-stage tandem mass spectrometry (MS n) of the [M+H] + ion using a linear ion trap mass spectrometer. Direct analysis of the leaves revealed several species of salvinorin in addition to SA as confirmed by MS n, including salvinorin B, C, D/E, and divinatorin B. Further, the results from DESI imaging of a TLC separation of a commercial leaf extract and an acetone extract of S. divinorum leaves were in concordance with the TLC/DESI-MS results of an authentic salvinorin A standard. The present study provides an example of both the direct analysis of intact plant materials for screening illicit substances and the coupling of TLC and DESI-MS as a simple method for the examination of natural products. © 2010 John Wiley & Sons, Ltd.
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.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 350.00K | Year: 2013
DESCRIPTION: Development of an Intelligent Sample Introduction System for Mass Spectrometry There is a pressing need for new technologies that enable rapid measurements without significant compromise to the analytical data. Herein, we propose to develop arobust mass spectrometry (MS) based surface sampling device that enables direct analysis of a variety of materials including biological tissue and live microorganisms that promises to deliver on this objective. The basis for this device is the Liquid Micro junction Surface Sampling Probe (LMJSSP), a set of coaxial microfluidic capillaries that are pumped and aspirated to bring solvent to and away from a surface of interest, where micro extraction takes place at the interface between the probe and the sample. Prosolia has licensed the LMJSSP technology from AB Sciex and will partner with the original inventor at Oak Ridge National Laboratory via the NIH Lab to Marketplace program to create an advanced prototype towards a commercially viable product by makingthe technology more robust and user-friendly for applications in various bio analytical workflows. The tasks of this project can be divided into three Aims. The first and second Aims are to ensure that the hardware of the device is sufficiently easy to use for commercial viability. This includes characterization of the present prototype and exploration of a few promising methods for automatic control of matched liquid flows required for a continuous extractive junction to persist between probe and surface. Additionally, establishing a mechanism for maintaining an ideal distance between the probe and surface will be critical for successful implementation. Upon establishing methods for flow and height management with optimized control and reasonable potential for manufacture, these hardware modifications will be used to determine the analytical conditions for instrument operation. Specifically, standards will be created to determine the profile and efficiency of extraction under a variety of conditions (including within different laboratories). These will determine the expected limits for potential use, maintenance, and support to ensure robust operations calibrated for a variety of methodologies. During this section of work, investigations into potential increases in resolution from the standard probing arrangement via smaller variants will be performed to identify analytical metrics at histologically relevant sampling sizes of interest to diagnostic and biomarker researchers. Early experiments using another MS-based surface sampling technique, Desorption Electrospray Ionization, for direct bio analysis of live microorganisms were able to generate spectral profiles for bacterial colonies; however, the process to generate these results required frequent cleaningand exchanging of instrument capillaries due to fouling with bacteria that were blown off the surface and into the instrument inlet. Preliminary spectra obtained using our prototype LMJSSP system have been collected in a much more facile manner, and haveshown some particularly interesting features for distinguishing and characterizing different species and strains of bacteria. However, more fingerprints must be acquired in order to determine statistical significance and applicability of these data. In addition, we will establish he effects of sampling at various growth points and stress conditions in order to generate a potential library for automated classification. After implementing changes for automation and optimization, our prototype for direct analysis of surfaces, will be a simple sample introduction system transitioning from an academic prototype used by a few to a commercial prototype that can be deployed to many. By hewing to the milestones we propose: making appropriate hardware changes, determining analytical metrics corresponding to solvents and probe sizes, and gathering a statistically relevant number of profiles for bacterial analysis, the capacity for hands-off microorganism profiling will have been assessed. As such our phase II proposal will include further hardware refinements, a broader selection of samples, enhanced data integration, and processing software. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The proposed research promises to deliver a prototype device capableof autonomous analytical surface sampling in a high-throughput, high-resolution, and highly reproducible manner.
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
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.
Prosolia, Inc. | Date: 2017-01-12
Scientific equipment for testing, reading, and analyzing biological fluids.