Peter T. A. Reilly

Micro ion trap mass spectrometry

Experiments to perform mass spectrometry with ion traps of submillimeter dimension are described. Several trap geometries amenable to microfabrication have been explored. In these experiments, vapor-phase molecules were ionized by a pulse from a frequency-quadrupled Nd:YAG laser. The ions were trapped and mass analyzed by manipulating the radiofrequency voltages on the trap electrodes. Effects of trapping parameters on mass resolution and sensitivity are discussed.

The Elucidation of Charge-Transfer-Induced Matrix Effects in Environmental Aerosols Via Real-Time Aerosol Mass Spectral Analysis of Individual Airborne Particles

Matrix effects in real-time aerosol mass spectrometry (RTAMS) were investigated using Standard Reference Materials (SRMs) obtained from the National Institute of Standards and Technology (NIST). Suppression of major component ions by much less concentrated species was observed. Attempts were made to mimic the ion suppression using binary systems but were unsuccessful. Data are presented that suggest the origin of the matrix effect is charge transfer induced neutralization in the ablation plume.

Direct Observation of the Evolution of the Soot Carbonization Process in an Acetylene Diffusion Flame via Real-Time Aerosol Mass Spectrometry

Abstract Real-time aerosol mass spectrometry was used to measure the size and composition of individual soot particles in an acetylene diffusion flame. This on-line data analysis technique permits for the first time direct observation of the evolution of the carbonization process, determination of the degree of carbonization of each measured particle, and measurement of the size distribution of both polycyclic aromatic hydrocarbon (PAH)-containing and mature soot particles. The carbonization process is characterized by rapid exchange of hydrogen between the PAH and pyrolytic addition of small hydrocarbons to form larger PAH molecules. The hydrogen exchange rate builds until carbon–carbon bond rearrangement becomes facile. The structural rearrangement/dehydrogenation process is very rapid once started. Rapid carbonization permits unambiguous size measurement of both PAH-containing and mature soot particles. Rapid hydrogen exchange yields a low activation energy path for making radicals in the particle phase and permits the PAH-containing media to act as a hydrogen sink. The presence of substantial amounts of labile hydrogen in the PAH-containing particle is demonstrated by the presence of preferentially hydrogenated PAHs. The absence of ethynylated PAHs and the presence of the hydrogenated PAHs are the result of flame pyrolysis of the PAH-containing particles. Optical images of flame particles collected by an independent sampling method conclusively confirm the presence of the micron sized PAH-containing particles in the flame and strongly suggest that mature soot aggregates are formed directly from the micron-sized PAH-containing particles. The optical images and the size distribution data cast doubt on the currently accepted mechanisms for mature soot aggregate formation. A new mature soot aggregate formation mechanism found in the aerosol literature is presented. This mechanism readily explains our results and many of the universal characteristics of soot. The implications of these measurements are discussed.

Real-time detection of individual airborne bacteria

Airborne bacteria and bacterial spores were directly sampled by an ion trap mass spectrometer with an atmospheric pressure inlet system. Samples were aerosolized from suspensions of single species. The organisms were individually characterized in real time by laser ablation mass spectrometry. Either positive or negative ions could be studied. Ions of a particular value of m/z (mass to charge ratio) could be further characterized by tandem mass spectrometry in the ion trap.

Electron impact ionization in a microion trap mass spectrometer

A microscale ion trap mass spectrometer (r0=0.50 mm, z0=0.55 mm) with an electron gun for electron impact ionization of gaseous samples is described. Operated in the mass-instability mode, the trap had a m/z range from 40 to 400 Da. For single scans, peak widths of less than 0.2 Da were obtained.

Targeting prostate cancer cells with a multivalent PSMA inhibitor-guided streptavidin conjugate

Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, its high expression is associated with prostate cancer progression, and has been becoming an active target for imaging or therapeutic applications for prostate cancer. On the other hand, streptavidin-biotin system has been successfully employed in pretargeting therapy towards multiple cancers. Herein, we describe the synthesis of bifunctional ligands (biotin-CTT54, biotin-PEG(4)-CTT54, and biotin-PEG(12)-CTT54) possessing two functional motifs separated by a length-varied polyethylene glycol (PEG) spacer: one (CTT54) binds tumor-marker PSMA and the other (biotin) binds streptavidin or avidin. All three compounds exhibited high potencies (IC(50) values: 1.21, 2.53, and 10nM, respectively) and irreversibility; but only biotin-PEG(12)-CTT54 demonstrated specifically labeling PSMA-positive prostate cancer cells in a two-step pretargeting procedure. Additionally, the pre-formulated complex between biotin-PEG(12)-CTT54 and Cy5-streptavidin displayed the improved inhibitory potency (IC(50)=1.86 nM) and irreversibility against PSMA and rapid uptake of streptavidin conjugate into PSMA-positive prostate cancer cells through PSMA-associated internalization. Together, all these results supported a proof-concept that combination of streptavidin and PSMAs biotinylated inhibitor may lead to development of a novel strategy of tumor-targeting imaging or drug delivery towards prostate cancer.

Detection and classification of individual airborne microparticles using laser ablation mass spectroscopy and multivariate analysis

We are developing a method for the real-time analysis of airborne microparticles based on laser-ablation mass spectroscopy. Airborne particles enter an ion trap mass spectrometer through a differentially pumped inlet, are detected by light scattered from two continuous-wave (CW) laser beams, and sampled by a 10-ns excimer laser pulse at 308 nm as they pass through the center of the ion trap electrodes. Following the laser pulse the stored ions are mass analyzed with the use of conventional ion trap methods. In this work thousands of positive and negative ion spectra were collected for 18 different samples: six species of bacteria, six types of pollen, and six types of particulate matter. The data were averaged and analyzed with the use of the multivariate patch algorithm (MPA), a variant of traditional multivariate analysis. The MPA successfully differentiated between all of the average positive ion spectra and 17 of the 18 average negative ion spectra. In addition, when the average positive and negative spectra were combined the MPA correctly identified all 18 types of particles. Finally, the MPA is also able to identify the components of computer-synthesized mixtures of spectra from the samples studied. These results demonstrate the feasibility of using a less-specific real-time analytical monitoring technique to detect substantial changes in the background concentration of environmental organisms, indicating that a more selective assay should be initiated.

Trapping of intact, singly-charged, bovine serum albumin ions injected from the atmosphere with a 10-cm diameter, frequency-adjusted linear quadrupole ion trap.

High-resolution real-time particle mass measurements have not been achievable because the enormous amount of kinetic energy imparted to the particles upon expansion into vacuum competes with and overwhelms the forces applied to the charged particles within the mass spectrometer. It is possible to reduce the kinetic energy of a collimated particulate ion beam through collisions with a buffer gas while radially constraining their motion using a quadrupole guide or trap over a limited mass range. Controlling the pressure drop of the final expansion into a quadrupole trap permits a much broader mass range at the cost of sacrificing collimation. To achieve high-resolution mass analysis of massive particulate ions, an efficient trap with a large tolerance for radial divergence of the injected ions was developed that permits trapping a large range of ions for on-demand injection into an awaiting mass analyzer. The design specifications required that frequency of the trapping potential be adjustable to cover a large mass range and the trap radius be increased to increase the tolerance to divergent ion injection. The large-radius linear quadrupole ion trap was demonstrated by trapping singly-charged bovine serum albumin ions for on-demand injection into a mass analyzer. Additionally, this work demonstrates the ability to measure an electrophoretic mobility cross section (or ion mobility) of singly-charged intact proteins in the low-pressure regime. This work represents a large step toward the goal of high-resolution analysis of intact proteins, RNA, DNA, and viruses.

Tandem mass spectrometry of uranium and uranium oxides in airborne particulates.

A method for detection of uranium in airborne microparticles in real time has been developed. Positive identification of uranium is achieved by isolating UO(2+) ions and following their reaction with residual oxygen molecules to yield UO(2)(+).

Transportable real-time single-particle ion trap mass spectrometer

A transportable ion trap mass spectrometer for real-time detection and characterization of individual airborne particles was constructed by minimal modification of a commercial ion trap mass spectrometer. A blank flange was replaced with a flange containing an aerodynamic lens based inlet, light scattering detection optics and ablation/ionization laser optics. Four holes were drilled into the ring electrode. Timing electronics boards running off of in-place power systems were added and integrated with the existing software. The modified mass spectrometer and laser system was packaged in a rugged wheeled frame for easy transport. Particles entered the instrument through a 100μm orifice and were passed through an aerodynamic lens system that produced a well-collimated particle beam over a wide range of sizes. The particle beam passed through a skimmer into the main chamber where individual particles were optically detected and sized with two focused 532nm diode lasers on their way to the ion trap. When the ...