Christopher J. Pulliam

Miniature and Fieldable Mass Spectrometers: Recent Advances

Dalton T. Snyder,† Christopher J. Pulliam,† Zheng Ouyang,‡ and R. Graham Cooks*,† †Department of Chemistry and Center for Analytical Instrumentation Development, Purdue University, West Lafayette, Indiana 47907, United States ‡Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States ■ CONTENTS Ambient Ionization and Sampling 2 Vacuum Systems 4 Analyzers and Configurations 6 MEMS and Other Alternative Fabrication Methods 8 Simulations 9 Electronics and Data Systems 12 Portable Systems 19 Mesoscale Systems 20 Planetary and Space Science Systems 21 Practical Applications 22 Expectations 23 Author Information 23 Corresponding Author 23 Notes 23 Biographies 23 Acknowledgments 24 References 24

Mass Spectrometry in the Home and Garden

AbstractIdentification of active components in a variety of chemical products used directly by consumers is described at both trace and bulk levels using mass spectrometry. The combination of external ambient ionization with a portable mass spectrometer capable of tandem mass spectrometry provides high chemical specificity and sensitivity as well as allowing on-site monitoring. These experiments were done using a custom-built portable ion trap mass spectrometer in combination with the ambient ionization methods of paper spray, leaf spray, and low temperature plasma ionization. Bactericides, garden chemicals, air fresheners, and other products were examined. Herbicide applied to suburban lawns was detected in situ on single leaves 5 d after application. Graphical Abstractᅟ

Experimental Characterization of Secular Frequency Scanning in Ion Trap Mass Spectrometers

AbstractSecular frequency scanning is implemented and characterized using both a benchtop linear ion trap and a miniature rectilinear ion trap mass spectrometer. Separation of tetraalkylammonium ions and those from a mass calibration mixture and from a pesticide mixture is demonstrated with peak widths approaching unit resolution for optimized conditions using the benchtop ion trap. The effects on the spectra of ion trap operating parameters, including waveform amplitude, scan direction, scan rate, and pressure are explored, and peaks at black holes corresponding to nonlinear (higher-order field) resonance points are investigated. Reverse frequency sweeps (increasing mass) on the Mini 12 are shown to result in significantly higher ion ejection efficiency and superior resolution than forward frequency sweeps that decrement mass. This result is accounted for by the asymmetry in ion energy absorption profiles as a function of AC frequency and the shift in ion secular frequency at higher amplitudes in the trap due to higher order fields. We also found that use of higher AC amplitudes in forward frequency sweeps biases ions toward ejection at points of higher order parametric resonance, despite using only dipolar excitation. Higher AC amplitudes also increase peak width and decrease sensitivity in both forward and reverse frequency sweeps. Higher sensitivity and resolution were obtained at higher trap pressures in the secular frequency scan, in contrast to conventional resonance ejection scans, which showed the opposite trend in resolution on the Mini 12. Mass range is shown to be naturally extended in secular frequency scanning when ejecting ions by sweeping the AC waveform through low frequencies, a method which is similar, but arguably superior, to the more usual method of mass range extension using low q resonance ejection. Graphical Abstractᅟ

Calibration procedure for secular frequency scanning in ion trap mass spectrometers

RATIONALE Mass spectra can be recorded using ion traps by scanning the frequency of an alternating current (ac) signal that corresponds to the secular frequency of a trapped ion. There is a considerable simplification in the instrumentation needed to perform such a scan compared with conventional scans of the radiofrequency (rf) amplitude. However, mass calibration is difficult. An algorithm that can be used to achieve mass calibration is investigated and the factors that affect ion mass assignments are discussed. METHODS Time domain data, recorded using a commercial benchtop linear ion trap mass spectrometer, are converted to the m/z domain using ion Mathieu parameter qu values which are derived from the dimensionless frequency parameter βu expressed as a continuing fraction in terms of qu . The relationship between the operating parameters of an ideal ion trap and the ion m/z ratio is derived from the Mathieu equations and expressed as an algorithm which through successive approximations yields the Mathieu qu value and hence m/z values and peak widths. The predictions of the algorithm are tested against experiment by sweeping the frequency of a small supplementary ac signal so as to cause mass-selective ejection of trapped ions. RESULTS Calibration accuracy is always better than 0.1%, often much better. Peak widths correspond to a mass resolution of 250 to 500 in the m/z 100-1800 range in secular frequency scans. CONCLUSIONS A simple, effective method of calibration of mass spectra recorded using secular frequency scans is achieved. The effects of rf amplitude, scan rate, and ac amplitude on calibration parameters are shown using LTQ linear ion trap data. Corrections for differences in ion mass must be made for accurate calibration, and this is easily incorporated into the calibration procedure. Copyright

Accelerated Chemical Reactions and Organic Synthesis in Leidenfrost Droplets

Leidenfrost levitated droplets can be used to accelerate chemical reactions in processes that appear similar to reaction acceleration in charged microdroplets produced by electrospray ionization. Reaction acceleration in Leidenfrost droplets is demonstrated for a base-catalyzed Claisen-Schmidt condensation, hydrazone formation from precharged and neutral ketones, and for the Katritzky pyrylium into pyridinium conversion under various reaction conditions. Comparisons with bulk reactions gave intermediate acceleration factors (2-50). By keeping the volume of the Leidenfrost droplets constant, it was shown that interfacial effects contribute to acceleration; this was confirmed by decreased reaction rates in the presence of a surfactant. The ability to multiplex Leidenfrost microreactors, to extract product into an immiscible solvent during reaction, and to use Leidenfrost droplets as reaction vessels to synthesize milligram quantities of product is also demonstrated.

Single analyzer precursor scans using an ion trap

RATIONALE Precursor ion and neutral loss scans are general survey methods of tandem mass spectrometry (MS/MS) used for detecting structurally related compounds. Until now they have been performed in multiple analyzer instruments, e.g. triple quadrupoles and hybrid MS/MS instruments. Implementation of precursor ion scans in single mass analyzers would be advantageous in reducing instrument complexity. METHODS Adoption of secular frequency scanning as a method of mass-selective excitation is shown to enable precursor scans in a single ion trap in a miniature mass spectrometer. A small supplementary alternating current (ac) signal is swept in frequency so as to cause mass-selective excitation of trapped ions. Simultaneously, a higher fixed amplitude ac signal is applied at the fixed secular frequency of a product ion, ejecting the mass-selected product ion and providing temporal data corresponding to a precursor ion spectrum. RESULTS Precursor scanning in a single ion trap is demonstrated using a mixture of three illicit drugs: cocaine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA). Acquisition of the spectra as a function of the frequency of the product ejection waveform demonstrates that the signals acquired represent precursor ion scans. CONCLUSIONS Secular frequency scanning is a nonconventional method of mass scanning that in combination with product ion ejection enables precursor scans in single ion traps. This phenomenon is demonstrated here for a miniature linear ion trap, but the concepts described also apply to quadrupole mass filters. Copyright

Accelerated hydrazone formation in charged microdroplets.

RATIONALE Electrospray ionization-mass spectrometry (ESI-MS) is an emerging tool for reaction monitoring. It can be accompanied by reaction acceleration in charged droplets. METHODS The time course of the bulk reaction of indoline-2,3-dione with phenylhydrazine in methanol to produce 3-(2- phenylhydrazono)indolin-2-one was monitored by ESI. Both nanoESI and electrosonic spray ionization (ESSI) were used for this study as representing two common forms of ionization for reaction monitoring. The effect on product yield of the distance the droplets travel between the source and the MS inlet was varied and product/starting material ratios were examined. RESULTS Product yield is dramatically increased by increasing the distance. At short distances reaction monitoring can be performed without acceleration and at greater distances reaction acceleration occurs. This distance effect over the course of the reaction roughly parallels the time dependence of the bulk-phase reaction. CONCLUSIONS Reaction acceleration in droplets is attributed to solvent evaporation leading to increased surface to volume ratios. An acceleration factor of 10(4) , measured relative to the bulk reaction at short times, is readily achieved by simply increasing the droplet distance of flight showing that the same ionization source can be used to monitor reactions with or without acceleration. Copyright

Analysis of bacteria using zero volt paper spray

The application of zero volt paper spray to the discrimination between species of bacteria is demonstrated here. While absolute signal intensities of representative lipids from bacterial membranes were three orders of magnitude lower than for conventional paper spray performed at high potential (kilovolts), the significant reduction in noise offset this disadvantage, resulting in clear separation in principal component analysis space between Gram positive and Gram negative bacteria as well as excellent separation between bacteria species.

Electrophoretic Desalting To Improve Performance in Electrospray Ionization Mass Spectrometry

Mass spectrometers are sensitive tools used to identify and quantify both small and large analytes using the mass-to-charge ratios ( m/ z) of ions generated by electrospray ionization (ESI) or other methods. Ionization typically generates protonated or deprotonated forms of the analytes or adducts with adventitious metal ions derived from the spray solvent. The formation of a variety of ionized forms of the analyte as well as the presence of cluster ions complicates the data and can have deleterious effects on the performance of the mass spectrometer, especially under high salt or buffer conditions. To address this, a method involving a dual-electrode nano-electrospray source has been implemented to rapidly and temporarily desalt the spray solution of interfering cationic and anionic species using electrophoretic transport from the spray tip. Peptides, proteins, and pharmaceutical drugs all showed improved results after the desalting process as measured by the quality of the mass spectra and the limits of detection achieved. Importantly ordinary phosphate buffers could be used to record protein mass spectra by nano-ESI.

Simultaneous Online Monitoring of Multiple Reactions Using a Miniature Mass Spectrometer

Advances in chemical sampling using miniature mass spectrometer technology are used to monitor slow reactions at a frequency of ca. 180 h-1 (on the Mini 12) with no sample carryover and with inline derivatization in the case of poorly ionizing compounds. Moreover, we demonstrate high reproducibility with a relative error of less than 10% for major components. Monitoring is enabled using a continuous-flow nanoelectrospray (CF-nESI) probe contained in a custom-built 3D-printed rotary holder. The holder position is automatically set using a stepper motor controlled by a microcontroller. Reaction progress of up to six reactions, including hydrazone formation and Katritzky transamination, can be monitored simultaneously without carryover for several hours.