Jessica A. Stolee

Nanophotonic Ionization for Ultratrace and Single-Cell Analysis by Mass Spectrometry

Recent mechanistic studies have indicated that at subwavelength post diameters and selected aspect ratios nanopost arrays (NAPA) exhibit ion yield resonances ( Walker , B. N. , Stolee , J. A. , Pickel , D. L. , Retterer , S. T. , and Vertes , A. J. Phys. Chem. C 2010 , 114 , 4835 - 4840 ). In this contribution we explore the analytical utility of these optimized structures as matrix-free platforms for laser desorption ionization mass spectrometry (LDI-MS). Using NAPA, we show that high ionization efficiencies enable the detection of ultratrace amounts of analytes (e.g., ∼800 zmol of verapamil) with a dynamic range spanning up to 4 orders of magnitude. Due to the clean nanofabrication process and the lack of matrix material, minimal background interferences are present in the low-mass range. We demonstrate that LDI from NAPA ionizes a broad class of small molecules including pharmaceuticals, natural products, metabolites, and explosives. Quantitation of resveratrol in red wine samples shows that the analysis of targeted analytes in complex mixtures is feasible with minimal sample preparation using NAPA-based LDI. We also describe how multiple metabolite species can be directly detected in single yeast cells deposited on the NAPA chip. Twenty-four metabolites, or 4% of the yeast metabolome, were identified in the single-cell spectra.

Toward Single-Cell Analysis by Plume Collimation in Laser Ablation Electrospray Ionization Mass Spectrometry

Ambient ionization methods for mass spectrometry have enabled the in situ and in vivo analysis of biological tissues and cells. When an etched optical fiber is used to deliver laser energy to a sample in laser ablation electrospray ionization (LAESI) mass spectrometry, the analysis of large single cells becomes possible. However, because in this arrangement the ablation plume expands in three dimensions, only a small portion of it is ionized by the electrospray. Here we show that sample ablation within a capillary helps to confine the radial expansion of the plume. Plume collimation, due to the altered expansion dynamics, leads to greater interaction with the electrospray plume resulting in increased ionization efficiency, reduced limit of detection (by a factor of ~13, reaching 600 amol for verapamil), and extended dynamic range (6 orders of magnitude) compared to conventional LAESI. This enhanced sensitivity enables the analysis of a range of metabolites from small cell populations and single cells in the ambient environment. This technique has the potential to be integrated with flow cytometry for high-throughput metabolite analysis of sorted cells.

Polarization dependent fragmentation of ions produced by laser desorption from nanopost arrays

Tailored silicon nanopost arrays (NAPA) enable controlled and resonant ion production in laser desorption ionization experiments and have been termed nanophotonic ion sources (Walker et al., J. Phys. Chem. C, 2010, 114, 4835-4840). As the post dimensions are comparable to or smaller than the laser wavelength, near-field effects and localized electromagnetic fields are present in their vicinity. In this contribution, we explore the desorption and ionization mechanism by studying how surface derivatization affects ion yields and fragmentation. We demonstrate that by increasing the laser fluence on derivatized NAPA with less polar surfaces that have decreased interaction energy between the structured silicon substrate and the adsorbate, the spectrum changes from exhibiting primarily molecular ions to showing a growing variety and abundance of fragments. The polarization angle of the laser beam had been shown to dramatically affect the ion yields of adsorbates. For the first time, we report that by rotating the plane of polarization of the desorption laser, the internal energy of the adsorbate can also be modulated resulting in polarization dependent fragmentation. This polarization effect also resulted in selective fragmentation of vitamin B(12). To explore the internal energy of NAPA generated ions, the effect of the post aspect ratios on the laser desorption thresholds and on the internal energy of a preformed ion was studied. Elevated surface temperatures and enhanced near fields in the vicinity of high aspect ratio posts are thought to contribute to desorption and ionization from NAPA. Comparison of the fluence dependence of the internal energies of ions produced from nanoporous silicon and NAPA substrates indicates that surface restructuring or transient melting by the desorption laser is a prerequisite for the former but not for the latter.

Nanophotonic Ion Sources

Interactions between laser radiation and photonic structures at elevated laser intensities give rise to the production of positive and negative ions from adsorbates. These new types of ion sources exhibit properties that are significantly different from conventional laser desorption ionization sources. In this contribution comparisons are made between matrix‐assisted laser desorption ionization (MALDI) of biomolecules with ion production from laser‐induced silicon microcolumn arrays (LISMA) and nanopost arrays (NAPA). The sharp increase of ion yields from the nanophotonic ion sources follow a power law behavior with an exponent of up to n≈7, whereas in the case of MALDI n≈5. The strong field enhancement in the vicinity of the columns and posts scales with their aspect ratio. Slender high aspect ratio posts show reduced laser fluence threshold for ionization. Posts with diameters at or below the thermal diffusion length demonstrate high surface temperatures due to the radial confinement of the deposited en...