Achieving High Detection Sensitivity (14 zmol) of Biomolecular Ions in Bioaerosol Mass Spectrometry

Bioaerosol mass spectrometry (BAMS) performs single-cell analysis in real time. However, the specificity of BAMS mass signatures has been limited by low sensitivity at high masses. To increase the mass range and sensitivity of BAMS, a novel design was developed that utilizes a linear flight tube with delayed extraction and an electrostatic ion guide. This study quantifies the sensitivity limits of the novel BAMS design and evaluates the feasibility of BAMS to detect higher mass biomarkers from single cells. All experiments were carried out using MALDI aerosol particles that were nebulized from solution. Sensitivity was assessed by generating particles with decreasing amounts of analyte via serial dilutions. The amount of analyte contained within each particle was calculated based on particle size, density, and molarity of the analyte within solution. A variety of biomolecular ions were studied and signals obtained from particles containing 300 zmol of maltopentaose, 132 zmol of α-cyclodextrin, and 14 zmol (∼8400 molecules) of gramicidin S are reported. The detection of 14 zmol of gramicidin S is to the best of our knowledge a record in sensitivity for MALDI TOF-MS.