Small molecule ambient mass spectrometry imaging by infrared laser ablation metastable-induced chemical ionization

A.S. Galhena, G.A. Harris, L. Nyadong, K.K. Murray, F.M. Fernandez, Small molecule ambient mass spectrometry imaging by infrared laser ablation metastable-induced chemical ionization, Anal. Chem. 82 (2010) 2178–2181. doi:10.1021/ac902905v.

Abstract

Presented here is a novel ambient ion source termed infrared laser ablation metastable-induced chemical ionization (IR-LAMICI). IR-LAMICI integrates IR laser ablation and direct analysis in real time (DART)-type metastable-induced chemical ionization for open air mass spectrometry (MS) ionization. The ion generation in the IR-LAMICI source is a two step process. First, IR laser pulses impinge the sample surface ablating surface material. Second, a portion of ablated material reacts with the metastable reactive plume facilitating gas-phase chemical ionization of analyte molecules generating protonated or deprotonated species in positive and negative ion modes, respectively. The successful coupling of IR-laser ablation with metastable-induced chemical ionization resulted in an ambient plasma-based spatially resolved small molecule imaging platform for mass spectrometry (MS). The analytical capabilities of IR-LAMICI are explored by imaging pharmaceutical tablets, screening counterfeit drugs, and probing algal tissue surfaces for natural products. The resolution of a chemical image is determined by the crater size produced with each laser pulse but not by the size of the metastable gas jet. The detection limits for an active pharmaceutical ingredient (acetaminophen) using the IR-LAMICI source is calculated to be low picograms. Furthermore, three-dimensional computational fluid dynamic simulations showed improvements in the IR-LAMICI ion source are possible.

Wavelength and time-resolved imaging of material ejection in infrared matrix-assisted laser desorption

X. Fan, K.K. Murray, “Wavelength and time-resolved imaging of material ejection in infrared matrix-assisted laser desorption,” J. Phys. Chem. A. 114 (2010) 1492–1497. doi:10.1021/jp9077163.

Abstract

Glycerol ablation at 2.94 μm and 3000 J/m2 fluence after (a) 10 ns, (b) 100 ns, (c) 1 μs, (d) 10 μs, (e) 24 μs, (f) 50 μs, (g) 100 μs, (h) 200 μs, (i) 500 μs, and (j) 1 ms.

The dynamics of glycerol ablation at atmospheric pressure was studied using fast photography. A mid-infrared optical parametric oscillator was used to irradiate a droplet of glycerol at normal incidence. The wavelength of the infrared source was tunable and was varied between 2.7 and 3.5 μm for the studies. After an adjustable delay, an excimer pumped dye laser was used to illuminate the expanding plume, and the 90° scattered light was imaged with a high-speed CMOS camera. The time delay between the IR and UV lasers was varied up to 1 ms with a particular emphasis in the early stages of plume evolution below 1 μs. The threshold fluence for plume formation varied between 1000 and 6000 J/m^2, and the minimum fluence corresponded to the OH stretch absorption of glycerol near 3.0 μm, which also corresponded to the greatest scattered light signal and duration of material emission. The velocity of the expanding plume was measured and ranged from >300 m/s near the OH stretch absorption to <100 m/s near the 3.4 μm CH stretch. Plume modeling calculations suggest that material removal is driven by phase explosion in the stress confinement regime that is at a maximum near the wavelength of the OH stretch absorption.

Fast photography setup from Fan & Murray, J. Phys. Chem. A. 114 (2010) 1492
Fast photography setup from Fan & Murray, J. Phys. Chem. A. 114 (2010) 1492
Fast photography setup (closeup) from Fan & Murray, J. Phys. Chem. A. 114 (2010) 1492
Fast photography setup (closeup) from Fan & Murray, J. Phys. Chem. A. 114 (2010) 1492
Instrument diagram from Fan & Murray, J. Phys. Chem. A. 114 (2010) 1492

Development of an efficient on-chip digestion system for protein analysis using MALDI-TOF MS

J. Lee, S.A. Soper, K.K. Murray, “Development of an efficient on-chip digestion system for protein analysis using MALDI-TOF MS,” Analyst. 134 (2009) 2426–2433. doi:10.1039/b916556h.

Abstract

(a) Assembled tryptic digestion microfluidic chip; chip components including PMMA substrate and cover slip, inlet and outlet connectors, capillary and stainless steel tubes. The sample solution was electrokinetically infused through the bioreactor and the matrix solution was loaded hydrodynamically with a syringe pump. Coaxial tubes mixed the bioreactor output with a matrix solution for deposition on a MALDI target. (b) Schematic top view of the fluid connection between the micropost bioreactor and the capillary tube interface to the deposition system. Two Pt electrodes were inserted into the sample inlet and the end of the bioreactor to electrokinetically drive the sample through the bioreactor.

A solid-phase trypsin microreactor was constructed and operated with electrokinetically-driven flow for the digestion of proteins and coupled off-line with MALDI-TOF MS. The bioreactor was fabricated from poly(methyl methacrylate), PMMA, by hot embossing using a mold master prepared by micro-milling. The solid-phase bioreactor consisted of a 4 cm long, 200 microm wide, and 50 µm deep microfluidic channel that was populated with an array of 50 µm diameter micropost structures with a 50 µm inter-post spacing. The bioreactor was prepared by covalently attaching the proteolytic enzyme, trypsin, to the UV-modified surface of the PMMA microstructures using the appropriate coupling reagents. The performance of the system was evaluated using a set of proteins. The bioreactor provided efficient digestion of cytochrome c at a field strength of 375 V/cm, producing a reaction time of approximately 20 s to produce 97% sequence coverage for protein identification. Bovine serum albumin (BSA), phosphorylase b, and beta-casein were also assessed and the sequence coverages were 46, 63, and 79%, respectively, using the same reactor residence time. Furthermore, Escherichia coli was used as a model to demonstrate the feasibility of fingerprint analysis for intact cells using this solid-phase bioreactor.

Microfluidics with MALDI analysis for proteomics

J. Lee, S.A. Soper, K.K. Murray, “Microfluidics with MALDI analysis for proteomics–a review,” Anal. Chim. Acta. 649 (2009) 180–190. doi:10.1016/j.aca.2009.07.037.

Abstract

MALDI target deposition from a microfluidic chip

Various microfluidic devices have been developed for proteomic analyses and many of these have been designed specifically for mass spectrometry detection. In this review, we present an overview of chip fabrication, microfluidic components, and the interfacing of these devices to matrix-assisted laser desorption ionization (MALDI) mass spectrometry. These devices can be directly coupled to the mass spectrometer for on-line analysis in real-time, or samples can be analyzed on-chip or deposited onto targets for off-line readout. Several approaches for combining microfluidic devices with analytical functions such as sample cleanup, digestion, and separations with MALDI mass spectrometry are discussed.

Matrix-assisted laser desorption/ionization with untreated silicon targets

J.-K. Kim, K.K. Murray, “Matrix-assisted laser desorption/ionization with untreated silicon targets,” Rapid Commun Mass Spectrom, 23 (2009) 203–205. doi:10.1002/rcm.3842.

Abstract: Untreated silicon targets compared to conventional stainless steel targets were used for MALDI analysis of small and large molecules. Samples and matrices were deposited on silicon wafers and commercial stainless targets and irradiated with a 337 nm N2 laser. The resulting ions were accelerated and mass separated in a time-of-flight mass spectrometer. The silicon target resulted in intense and reproducible signals. Peak resolution and S/N were not significantly affected by the substrate, but detection limit was approximately ten times better with silicon substrate. The most notable observations on silicon substrate were shot-to-shot and spot-to-spot reproducibility. The RSD of peak height and area for the silicon substrate is approximately 1.5 times better for shot-to-shot and 3 to 10 times better for spot-to-spot reproducibility compared to the stainless steel substrate.

SEM images of MALDI sample spots on a silicon target
SEM images of MALDI sample spots on a silicon target.

Is Wikipedia the Public Face of Mass Spectrometry?

Presented at the 57th ASMS Conference on Mass Spectrometry, Philadelphia, Pennsylvania, May 31th to June 4th 2009

Is Wikipedia the Public Face of Mass Spectrometry? 57th ASMS Conference on Mass Spectrometry, Philadelphia, Pennsylvania, May 31th to June 4th 2009

Introduction

Wikipedia is a web resource that is described as “the free encyclopedia that anyone can edit.” The low barrier for participation is both one of the best and worst features of the site. The drawbacks of easy participation are the sometimes opinionated, uninformed or simply malicious editors whereas the advantages are fast content creation that is easily accessible and often self-correcting.

Hypothesis: Wikipedia is the most popular source of on-line mass spectrometry information and has the potential to be a source of good information if a sufficiently large number of mass spectromerists become editors.

What is Wikipedia?

Founded less than a decade ago, Wikipedia is now one of the most popular websites and the most popular reference site.

Founded in 20011
2.9 M English language articles (13 M total)2
7th most popular website (#1 Reference)3
Used by 9% of global Internet users3
684 M visits annually4

Wikipedia Growth Plot

The growth of the English Wikipedia was exponential between 2003 and 2006 with a doubling time of one year. Growth is now linear.

Mass Spectrometry on Wikipedia

~ 200 pages in the category “Mass Spectrometry”
WikiProject Mass spectrometry
Wikimedia Commons category “Mass Spectrometry”

Top 10 Google Hits for the term Mass Spectrometry:

Wikipedia
Michigan State University
American Society for Mass Spectrometry
University of Arizona
Scripps Research Institute
Colby College
Wikimedia Commons
SpectroscopyNow
iMass.com
Virginia Tech

The Wikipedia entry is hit #1 and Wikimedia Commons (diagrams and photographs) is hit #7. ASMS is hit #3 with university courses filling most of the other top spots.

The Wikipedia page Mass Spectrometry had 517,000 views in 2008, more than 1400 hits per day. The dip in the summer and peaks at mid-semester suggests educational use.

Becoming a Wikipedia Editor

Because Wikipedia is such an important source of mass spectrometry information, participation by the mass spectrometry community should by encouraged both in an organized and ad hoc manner. It should be noted that there are significant barriers to scientists desiring to become Wikipedia editors, but there are also many useful resources.

Barriers
Wiki document markup
Wikipedia protocols
Article layout
Interacting with non-science editors
Reconciling scientific and Wikipedia review

Resources
Tutorials and documentation on Wikipedia
WikiProjects
WikiProject Mass Spectrometry
WIkiProject Chemistry
WikiProject Physics
WikiProject Molecular and Cellular Biology
Portals
Chemistry Portal
Physics Portal
Molecular and Cellular Biology Portal
Reference markup tools
Current Wikipedia Editors

Recommendations

Develop a formal policy on Wikipedia content
National organizations (ASMS, BSMS, ANZSMS, etc.)
International Mass Spectrometry Foundation
Coordinate with relevant committees
Education, History, Standards, etc.
Encourage participation
Evaluate content

References

Microfluidic chips for mass spectrometry-based proteomics

Lee, J., Soper, S. A., & Murray, K. K. (2009). Microfluidic chips for mass spectrometry-based proteomics. Journal of Mass Spectrometry, 44(5), 579–593. doi:10.1002/jms.1585

Abstract

Lee, Soper, & Murray, Microfluidic chips for mass spectrometry-based proteomics. J Mass Spectrom, 44, 579 (2009); doi:10.1002/jms.1585

Microfluidic devices coupled to mass spectrometers have emerged as excellent tools for solving the complex analytical challenges associated with the field of proteomics. Current proteome identification procedures are accomplished through a series of steps that require many hours of labor‐intensive work. Microfluidics can play an important role in proteomic sample preparation steps prior to mass spectral identification such as sample cleanup, digestion, and separations due to its ability to handle small sample quantities with the potential for high‐throughput parallel analysis. To utilize microfluidic devices for proteomic analysis, an efficient interface between the microchip and the mass spectrometer is required. This tutorial provides an overview of the technologies and applications of microfluidic chips coupled to mass spectrometry for proteome analysis. Various approaches for combining microfluidic devices with electrospray ionization (ESI) and matrix‐assisted laser desorption/ionization (MALDI) are summarized and applications of chip‐based separations and digestion technologies to proteomic analysis are presented.

McNeese March 2009

In March of 2009, I visited McNeese State University in Lake Charles, Louisiana to give a talk and visit my collaborator Prof. Mark Merchant, “the alligator man”. Mark gave me a tour of his alligator holding facilities on campus.

Alligator in pen at McNeese State University, March 2009

Mark wanted to get this alligator to open its mouth so that I could get a good photo.

Prof. Mark Merchant with an alligator at McNeese State University March 2009
Prof. Mark Merchant with an alligator at McNeese State University March 2009

Sure enough, the alligator did open his mouth. Note Chemistry Department Head Ron Darbeau who was on the proper side of the fence during all of this. I was 15 feet away and the gate was open.

Prof. Mark Merchant testing alligator stimulus and response at McNeese State University March 2009.

Alligator at McNeese State University March 2009

In the next cage over, Mark scooped out a handful of baby alligators.

Prof. Mark Merchant with baby alligators at McNeese State University March 2009

I call the one on the right “Bitey” – he clamped down on my knuckle when I unwisely offered it to him.

Baby Alligators at McNeese State University March 2009