Mass spectrometry in newborn and metabolic screening: historical perspective and future directions

Abstract

The growth of mass spectrometry (MS) in clinical chemistry has primarily occurred in two areas: the traditional clinical chemistry areas of toxicology and therapeutic drug monitoring and more recent, human genetics and metabolism, specifically inherited disorders of intermediary metabolism and newborn screening. Capillary gas chromatography and electrospray tandem MS are the two most common applications used to detect metabolic disease in screening, diagnostics and disease monitoring of treated patients. A few drops of blood from several million newborn infants are screened annually throughout the world making this the largest application of MS in medicine. Understanding the technique, how it grew from a few dozen samples per week in the early 1990s to increasing daily volume today will provide important information for new tests that either expand newborn screening or screening in other areas of metabolism and endocrinology. There are numerous challenges to the further expansion of MS in clinical chemistry but also many new opportunities in closely related applications. The model of newborn screening and MS in medicine may be useful in developing other applications that go beyond newborns and inherited metabolic disease. As MS continues to expand in clinical chemistry, it is clear that two features will drive its success. These features are excellent selectivity and multiple analyte or profile analysis; features recognized in the 1950s and remain true today.