Enhancement of ion intensity in time-of-flight secondary-ionization mass spectrometry

Abstract

Enhancement of ion intensity in static secondary-ionization mass spectrometry (SIMS) has been achieved by using a matrix-assisted sample preparation technique. Previous investigations of polymers and biomolecules by SIMS indicated that secondary-ion (SI) yield is dependent on substrate coverage. Recently we discovered a sample preparation technique that enhanced the SI yield of cyclosporin A (CsA) in an allograft patient sample and neat samples of CsA (1202 u) and polystyrene (M w=2650 u). The preparation technique involves deposition of a submonolayer of cocaine hydrochloride (5 µL of a 20-µg/mL MeOH solution) on an etched silver substrate, solvent evaporation, and subsequent deposition of the analyte. This preparation method resulted in ∼300% increase in the SI yield of CsA and polystyrene when deposited from neat solutions. The original discovery was observed when a blood extract that contained CsA was deposited on an etched Ag substrate that had been soaking in a dilute cocaine solution for ∼2 months. In these initial experiments, the SI yield of CsA was enhanced by over 1 order of magnitude.

Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging

“…The central role of the sample surface has led to the development of several sample preparation techniques that have demonstrated increased molecular ion yields of high mass molecules. These are: (1) matrix-enhanced SIMS (ME-SIMS) [13][14][15][16][17][18][19][20]-uses the sample preparation protocols of MALDI to benefit from the detanglement [21] and chemical ionization aspects of MALDI [22][23][24]. Molecular ions of analytes as large as ubiquitin and lysozyme have been detected, and for lower mass analytes, Ͻ2 kDa, the ME-SIMS spectra frequently resemble those obtained using MALDI [17,19].…”

Using MESIMS to analyze polymer MALDI matrix solubility

“…In our experience, the MESIMS fragments have significantly higher mass resolution and mass accuracy than MALDI-PSD. While some polymers have been previously analyzed by MESIMS [2,3], these are the first examples that MESIMS can be successfully applied to a broad variety of oligomer samples.…”

“…MESIMS takes advantage of the surface sensitivity of SSIMS and incorporates the advantages available from appropriate sample preparation of MALDI. MESIMS has been shown to be effective for some biomolecules [1,2] and for a few low molecular weight polymers [2][3][4][5]. In these experiments, we test the effectiveness of MESIMS to probe solid-phase solubility issues for MALDI sample preparation.…”

“…M atrix-enhanced secondary ion mass spectrometry (MESIMS) is a relatively new analytical technique [1][2][3][4][5] developed as a cross between static secondary ion mass spectrometry (SSIMS) [6 -8] and matrix-assisted laser desorption ionization (MALDI) [9 -13] mass spectrometry. MESIMS takes advantage of the surface sensitivity of SSIMS and incorporates the advantages available from appropriate sample preparation of MALDI.…”

Improvement of signal intensities in static secondary-ion mass spectrometry using halide additives and substrate modification

“…Our group has recently reported the use of a submonolayer of cocaine hydrochloride on a silver substrate deposited prior to analyte deposition to promote analyte cationization. 13 Signal intensity improvement was demonstrated for several lipophilic compounds. The most signiÐcant e †ect was found for samples with large amounts of organic and inorganic contamination e.g.…”