Dr. Liz Dhummakupt discussed the implications of utilizing PaperSpray ionization mass spectrometry as a rapid alternative platform to analyze aerosolized chemical warfare agents (CWAs) requiring no sample prep with benefits including improved resolution and sensitivity.
There is a growing need for improved analysis of aerosolized chemical warfare agents (CWAs). Current detection methods (ion mobility spectrometry, colorimetric paper, etc.) suffer from poor resolution, detector saturation and sensitivity to temperature and humidity. Paper spray ionization mass spectrometry (PS-MS) offers a rapid alternative platform that requires no sample preparation. Aerosolized CWA simulants, trimethyl phosphate (TMP), dimethyl methylphosphonate (DMMP), and diisopropyl methylphosphate (DIMP), were captured in the traditional manner (‘gold-standard’) by passing the air through a glass fiber filter disk or by capturing it directly onto Prosolia’s paper spray cartridge consumable. Both approaches were performed in tandem and rigorously compared.
CWA simulants at varying concentrations were prepared and aerosolized using an in-house built aerosol chamber. To facilitate the aerosol capture onto the paper spray cartridges a custom 3D printed holder was designed and built. The air flow through each of the collection devices (PS-MS vs. Gold-Standard) was maintained at 1.5 L per minute to assure the same volume of air sampled across methods. After collection, the PS cartridges were analyzed using the Prosolia Velox 360 on a Thermo Fisher Orbitrap Elite MS; the filtration disks were extracted and analyzed on an Agilent 6490 Triple Quad MS.
The results from each capture and detection strategy were compared. In both instances, each approach yielded linear calibration curves with R2-values between 0.98-0.99 for each compound and similar limits of detection (LOD) in terms of disbursed aerosol concentration. Therefore, the paper spray method generates comparable results to the gold-standard extraction method, but the PS analysis does not require the extraction step. Based off these results, the sampling efficiency for each technique was calculated. While the glass fiber filter disk has a higher sampling efficiency (~40%), the paper spray method produces analogous results even with a lower sampling efficiency (~1%).
Dr. Elizabeth S Dhummakupt received her bachelor’s degree in chemistry and biology from Vanderbilt University in 2010. She attended graduate school at the University of Florida in the Department of Chemistry. While there, she worked under the direction of Dr. Richard Yost, and her Ph.D. research focused on analysis of illicit drugs in dried blood spots using MALDI and paper spray ionization mass spectrometry. After graduating in 2015, she was a post-doctoral researcher at UF for Dr. Timothy Garrett with projects focusing on development of uHPLC-HRMS methods for metabolomics. Dr. Dhummakupt is currently a National Research Council post-doctoral researcher at Edgewood Chemical Biological Center in Maryland where she is developing methods for analysis of chemical warfare agents via paper spray ionization MS.
The ECBC mass spectrometry facility is led by Dr. Trevor Glaros and is comprised of a multidisciplinary team of scientists whose core competencies range widely encompassing proteomics, metabolomics, molecular biology, and instrument development. Chemical and biological agents pose a serious challenge to public health as well as to military personnel worldwide. As such, our primary mission, using mass spectrometry as a tool, is to aid in the development of novel of therapeutics and detection strategies to protect our warfighters.
Learn how PaperSpray® technology has enabled targeted quantitative analysis of drugs within a single cartridge from Nick Manicke as he discusses this and other emerging applications improved through mass spectrometry.
Recent applications of paper spray MS will be described, including therapeutic drug monitoring and drug screening. The therapeutic drug monitoring application consists of targeted quantitative analysis on a triple quad mass spectrometer. The drug screening work involves screening for over 100 different drug targets from a single paper spray cartridge on a Q Exactive mass spectrometer. Results for paper spray screening of post-mortem blood samples will be included. Emerging applications performed using novel paper spray cartridges will also be presented. This will include analyzing designer drugs such as fentanyl analogs and spice cannabinoids on a paper spray cartridge with built-in solid phase extraction. Another new area to be presented will be targeted detection of plasma proteins from an all-in-one cartridge.
Manicke joined the faculty of the Department of Chemistry and Chemical Biology at Indiana University-Purdue University Indianapolis (IUPUI) in August of 2013 after spending the previous two years as the principal scientist for a Purdue University spin-out company founded on technology Manicke co-invented as a post-doctoral researcher at Purdue. Manicke earned his Ph.D. in analytical chemistry at Purdue University in 2009 under the supervision of R. Graham Cooks. He earned his undergraduate degree in biochemistry from the University of Evansville (Indiana). Manicke has authored or co-authored over 30 peer-reviewed scientific papers on mass spectrometry including recent papers in Analytical Chemistry, Clinical Chemistry, and JASMS. He has also delivered podium presentations at the ASMS Conference on Mass Spectrometry and at the Mass Spectrometry: Applications to the Clinical Laboratory (MSACL) conference.