Direct Microextraction of Dried Blood Spots for Rapid, Multielement Quantification via ICP-MS

Dried blood spot (DBS) sampling, a technique that requires only a prick of the finger, has become a valuable method in clinical analysis due to its minimally invasive nature, reduced sample volume requirements, cost effectiveness, and simple storage conditions. Widely applied across healthcare and research domains, DBS analysis plays a critical role in disease diagnosis, newborn screening, therapeutic drug monitoring, and forensic investigations. DBS analysis is of specific interest in assessing exposure to medically relevant heavy metals, such as arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb). These metals can pose significant health risks due to their potential to bioaccumulate in tissues, leading to long-term adverse effects. The use of DBS sampling is particularly advantageous for populations where extensive blood collection is challenging such as with patients that are infants, children, elderly, etc. However, the limited sample volume presents analytical challenges, particularly for low-concentration analytes, necessitating a highly sensitive and selective detection method. Mass spectrometry (MS) is the predominant technique for DBS analysis, yet the complexity of the blood matrix often complicates direct analysis. Chromatographic separations and additional pre-treatment steps are frequently required before MS detection, resulting in time-consuming workflows. To address these issues, we present an alternative DBS analysis approach utilizing the Advion Plate Express microextraction device coupled with inductively coupled plasma (ICP)-MS. This direct sampling method enables rapid (< 3 min), highly sensitive (fg detection limits), and multi-element profiling of DBS substrates. In this approach, a ~2 x 4 mm region of the DBS sample is exposed to an extraction solvent, efficiently removing adsorbed species within 3 minutes with direct delivery to the ICP nebulizer. The use of aqueous calibrations standards for As, Cd, Hg, and Pb in a blood matrix is projected to provide accurate real-world quantifications. Additionally, case studies examining sample extraction reproducibility are presented. This method offers a streamlined, accessible approach for microextraction from DBS substrates and elemental detection in clinical analyses.