Jeremy A. Barry

MSiReader: An Open-Source Interface to View and Analyze High Resolving Power MS Imaging Files on Matlab Platform

AbstractDuring the past decade, the field of mass spectrometry imaging (MSI) has greatly evolved, to a point where it has now been fully integrated by most vendors as an optional or dedicated platform that can be purchased with their instruments. However, the technology is not mature and multiple research groups in both academia and industry are still very actively studying the fundamentals of imaging techniques, adapting the technology to new ionization sources, and developing new applications. As a result, there important varieties of data file formats used to store mass spectrometry imaging data and, concurrent to the development of MSi, collaborative efforts have been undertaken to introduce common imaging data file formats. However, few free software packages to read and analyze files of these different formats are readily available. We introduce here MSiReader, a free open source application to read and analyze high resolution MSI data from the most common MSi data formats. The application is built on the Matlab platform (Mathworks, Natick, MA, USA) and includes a large selection of data analysis tools and features. People who are unfamiliar with the Matlab language will have little difficult navigating the user-friendly interface, and users with Matlab programming experience can adapt and customize MSiReader for their own needs.

Direct analysis of textile fabrics and dyes using infrared matrix-assisted laser desorption electrospray ionization mass spectrometry.

The forensic analysis of textile fibers uses a variety of techniques from microscopy to spectroscopy. One such technique that is often used to identify the dye(s) within the fiber is mass spectrometry (MS). In the traditional MS method, the dye must be extracted from the fabric and the dye components are separated by chromatography prior to mass spectrometric analysis. Direct analysis of the dye from the fabric allows the omission of the lengthy sample preparation involved in extraction, thereby significantly reducing the overall analysis time. Herein, a direct analysis of dyed textile fabric was performed using the infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source for MS. In MALDESI, an IR laser with wavelength tuned to 2.94 μm is used to desorb the dye from the fabric sample with the aid of water as the matrix. The desorbed dye molecules are then postionized by electrospray ionization (ESI). A variety of dye classes were analyzed from various fabrics with little to no sample preparation allowing for the identification of the dye mass and in some cases the fiber polymer. Those dyes that were not detected using MALDESI were also not observed by direct infusion ESI of the dye standard.

Global optimization of the infrared matrix-assisted laser desorption electrospray ionization (IR MALDESI) source for mass spectrometry using statistical design of experiments.

Design of experiments (DOE) is a systematic and cost-effective approach to system optimization by which the effects of multiple parameters and parameter interactions on a given response can be measured in few experiments. Herein, we describe the use of statistical DOE to improve a few of the analytical figures of merit of the infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source for mass spectrometry. In a typical experiment, bovine cytochrome c was ionized via electrospray, and equine cytochrome c was desorbed and ionized by IR-MALDESI such that the ratio of equine:bovine was used as a measure of the ionization efficiency of IR-MALDESI. This response was used to rank the importance of seven source parameters including flow rate, laser fluence, laser repetition rate, ESI emitter to mass spectrometer inlet distance, sample stage height, sample plate voltage, and the sample to mass spectrometer inlet distance. A screening fractional factorial DOE was conducted to designate which of the seven parameters induced the greatest amount of change in the response. These important parameters (flow rate, stage height, sample to mass spectrometer inlet distance, and laser fluence) were then studied at higher resolution using a full factorial DOE to obtain the globally optimized combination of parameter settings. The optimum combination of settings was then compared with our previously determined settings to quantify the degree of improvement in detection limit. The limit of detection for the optimized conditions was approximately 10 attomoles compared with 100 femtomoles for the previous settings, which corresponds to a four orders of magnitude improvement in the detection limit of equine cytochrome c.

Mapping Antiretroviral Drugs in Tissue by IR-MALDESI MSI Coupled to the Q Exactive and Comparison with LC-MS/MS SRM Assay

AbstractThis work describes the coupling of the IR-MALDESI imaging source with the Q Exactive mass spectrometer. IR-MALDESI MSI was used to elucidate the spatial distribution of several HIV drugs in cervical tissues that had been incubated in either a low or high concentration. Serial sections of those analyzed by IR-MALDESI MSI were homogenized and analyzed by LC-MS/MS to quantify the amount of each drug present in the tissue. By comparing the two techniques, an agreement between the average intensities from the imaging experiment and the absolute quantities for each drug was observed. This correlation between these two techniques serves as a prerequisite to quantitative IR-MALDESI MSI. In addition, a targeted MS2 imaging experiment was also conducted to demonstrate the capabilities of the Q Exactive and to highlight the added selectivity that can be obtained with SRM or MRM imaging experiments. Fig. aᅟ

Mass Recalibration of FT-ICR Mass Spectrometry Imaging Data Using the Average Frequency Shift of Ambient Ions

AbstractAchieving and maintaining high mass measurement accuracy (MMA) throughout a mass spectrometry imaging (MSI) experiment is vital to the identification of the observed ions. However, when using FTMS instruments, fluctuations in the total ion abundance at each pixel due to inherent biological variation in the tissue section can introduce space charge effects that systematically shift the observed mass. Herein we apply a recalibration based on the observed cyclotron frequency shift of ions found in the ambient laboratory environment, polydimethylcyclosiloxanes (PDMS). This calibration method is capable of achieving part per billion (ppb) mass accuracy with relatively high precision for an infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI dataset. Comparisons with previously published mass calibration approaches are also presented. Figureᅟ

Global Optimization of the IR Matrix-Assisted Laser Desorption Ionization (IR MALDESI) Source for Mass Spectrometry Using Statistical Design of Experiments

Design of experiments (DOE) is a systematic and cost-effective approach to system optimization by which the effects of multiple parameters and parameter interactions on a given response can be measured in few experiments. Herein, we describe the use of statistical DOE to improve a few of the analytical figures of merit of the infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source for mass spectrometry. In a typical experiment, bovine cytochrome c was ionized via electrospray, and equine cytochrome c was desorbed and ionized by IR-MALDESI such that the ratio of equine:bovine was used as a measure of the ionization efficiency of IR-MALDESI. This response was used to rank the importance of seven source parameters including flow rate, laser fluence, laser repetition rate, ESI emitter to mass spectrometer inlet distance, sample stage height, sample plate voltage, and the sample to mass spectrometer inlet distance. A screening fractional factorial DOE was conducted to designate which of the seven parameters induced the greatest amount of change in the response. These important parameters (flow rate, stage height, sample to mass spectrometer inlet distance, and laser fluence) were then studied at higher resolution using a full factorial DOE to obtain the globally optimized combination of parameter settings. The optimum combination of settings was then compared with our previously determined settings to quantify the degree of improvement in detection limit. The limit of detection for the optimized conditions was approximately 10 attomoles compared with 100 femtomoles for the previous settings, which corresponds to a four orders of magnitude improvement in the detection limit of equine cytochrome c.

Global optimization of the infrared matrix-assisted laser desorption electrospray ionization (IR MALDESI) source for mass spectrometry using statistical design of experiments: DOE optimization of IR MALDESI source

Design of experiments (DOE) is a systematic and cost-effective approach to system optimization by which the effects of multiple parameters and parameter interactions on a given response can be measured in few experiments. Herein, we describe the use of statistical DOE to improve a few of the analytical figures of merit of the infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source for mass spectrometry. In a typical experiment, bovine cytochrome c was ionized via electrospray, and equine cytochrome c was desorbed and ionized by IR-MALDESI such that the ratio of equine:bovine was used as a measure of the ionization efficiency of IR-MALDESI. This response was used to rank the importance of seven source parameters including flow rate, laser fluence, laser repetition rate, ESI emitter to mass spectrometer inlet distance, sample stage height, sample plate voltage, and the sample to mass spectrometer inlet distance. A screening fractional factorial DOE was conducted to designate which of the seven parameters induced the greatest amount of change in the response. These important parameters (flow rate, stage height, sample to mass spectrometer inlet distance, and laser fluence) were then studied at higher resolution using a full factorial DOE to obtain the globally optimized combination of parameter settings. The optimum combination of settings was then compared with our previously determined settings to quantify the degree of improvement in detection limit. The limit of detection for the optimized conditions was approximately 10 attomoles compared with 100 femtomoles for the previous settings, which corresponds to a four orders of magnitude improvement in the detection limit of equine cytochrome c.