Dried Blood Spot Analysis by Digital Microfluidics Coupled to Nanoelectrospray Ionization Mass Spectrometry

Citations Over TimeTop 1% of 2012 papers

Abstract

Dried blood spot (DBS) samples on filter paper are surging in popularity as a sampling and storage vehicle for a wide range of clinical and pharmaceutical applications. For example, a DBS sample is collected from every baby born in the province of Ontario, Canada, for quantification of approximately one hundred analytes that are used to screen for 28 conditions, including succinylacetone (SA), a marker for hepatorenal tyrosinemia. Unfortunately, the conventional methods used to evaluate DBS samples for newborn screening and other applications are tedious and slow, with limited options for automated analysis. In response to this challenge, we have developed a method to couple digital microfluidics (DMF) to nanoelectrospray ionization mass spectrometry (nESI-MS) for SA quantification in DBS samples. The new system is formed by sandwiching a pulled glass capillary emitter between the two DMF substrates such that the capillary emitter is immobilized without external seals or gaskets. Moreover, we introduce a new feedback control system that enables high-fidelity droplet manipulation across DBS samples without manual intervention. The system was validated by application to on-chip extraction, derivatization, and analysis of SA and other analytes from DBS samples, with comparable performance to gold-standard methods. We propose that the new methods described here can potentially contribute to a new generation of analytical techniques for quantifying analytes in DBS samples for a wide range of applications.

Related Papers

• → EBF Recommendation on the Validation of Bioanalytical Methods for Dried Blood Spots(2011)179 cited
• → Analyte and internal standard cross signal contributions and their impact on quantitation in LC–MS based bioanalysis(2011)50 cited
• → Impact of Sample Hemolysis on Drug Stability in Regulated Bioanalysis(2011)33 cited
• → Application of a design of experiment approach in the development of a sensitive bioanalytical assay in human plasma(2012)10 cited
• → Dried blood spots and their role in bioanalysis(2015)