Nanofluidics-Based Mass Spectrometry. Applications for Biomarker Discovery in Lysosomal Storage Diseases

Abstract

Substantial efforts are currently invested in development of micro- and nanofluidics-based systems as front end technology for electrospray ionization (ESI) mass spectrometry (MS). Since its first introduction in biological MS chip-based ESI demonstrated a high potential to discover novel biopolymer species due to the efficient ionization properties, preferential formation of multiply charged ions and the elevated reproducibility and sensitivity. In combination with high-resolution mass spectrometers or instruments able to perform multistage fragmentation, chip-electrospray confirmed its unique ability to offer structural elucidation of minor species in complex mixtures, which often represent valuable biomarkers of severe diseases. This aspect is of particular importance for the applicability of chip MS in clinical investigation where only minute amounts of biological material are available. In view of these major advantages of nanofluidics in conjunction with modern MS, this chapter reviews the strategies, which allowed a successful application of chip technology for early diagnostic of lysosomal storage diseases. The first part is dedicated to the principles of ESI MS and to advanced nanochip systems for ESI MS. The second part highlights important achievements of nanochip ESI MS in biomarker discovery and diagnostic of LSDs such as Fabry and Schindler diseases. Finally, this chapter emphasizes that advanced chip ESI MS has real perspectives to become a routine method for early diagnosis and therapy of severe pathologies such as LSDs.