Three nebulizer and four spray chamber configurations were evaluated to develop a selective and sensitive capillary interface to analyze phosphorothioate oligonucleotides by ICPMS. Nebulizers consisted of two of the most common low flow nebulizer designs, concentric and micro-concentric. Spray chambers utilized were a Scott chamber, a Cinnabar chamber, and two single pass configurations, all with different internal volumes. The influence of nebulizer designs and spray chamber volumes were determined by peak width measurements through flow injections made with and without the capillary column. This study capitalizes on the element specific detection abilities of ICPMS by elucidating phosphorus and sulfur in the phosphorothioate linkage of the 24 mer oligonucleotide by monitoring ³¹P⁺ and ³²S⁺. Comparisons of nebulizer/spray chamber responses were based upon absolute sensitivity for the 24 mer oligonucleotide. Micro-flow injection analysis generated absolute detection limits of ³¹P and ³²S of 0.17 pg and 0.16 pg, respectively, corresponding to 16 fmol of 24 mer oligonucleotide injected. This is the first record of a phosphorothioate oligonucleotide being quantitatively detected by ICPMS and the subsequent evaluation of low flow capillary nebulizer/spray chamber configurations optimized for its analysis.