Tandem Mass Spectrometry in the Newborn Screening Laboratory

Abstract

A common definition of newborn screening is “the presumptive identification of unrecognized congenital disorders by the application of laboratory tests to an entire population.” Newborn screening began in the 1950s, when Robert Guthrie developed a screening test for the metabolic disorder phenylketonuria (PKU) based on measuring the level of the amino acid phenylalanine in dried, whole blood specimens collected on filter paper. The immediate success prompted similar, mandated “PKU Screening” in all states by the mid-1960s. Subsequently, test methods were developed for other congenital or metabolic disorders including hypothyroidism, maple syrup urine disease, galactosemia, and biotinidase. The paradigm involved a separate test procedure for each disorder. In the 1990s, that paradigm radically changed with the introduction of tandem mass spectrometry (MS/MS) into the newborn screening laboratory. Tandem mass spectrometry is a technique which uses 1 blood spot specimen to detect a multiple of potential disorders. MS/MS in the Laboratory The MS/MS technologies for routine use in high production laboratories (ie, newborn screening laboratories) have evolved from liquid chromatography/mass spectrometer (LCMS) systems. The 1970s and 1980s saw several advances in mass spectrometry instrumentation that included improved sample introduction techniques such as fast atom bombardment (FAB) and fast ion bombardment (FIB). Also the development in the 1980s of quadrupole (4 magnetic rods) units, linking them in series, and controlling the function (separation, fragmentation, and detection) of each unit led to today’s tandem mass spectrometry systems. Concurrently, experimentation with sample preparation techniques improved sensitivity and reproducibility by incorporating procedures based on the formation of