MALDI-TOF MS profiling as the first-tier screen for sickle cell disease in neonates: matching throughput to objectives.

Purpose: Universal newborn screening for sickle cell diseases (SCDs) is not currently performed in many countries concerned by this public health problem. Owing to the technical and financial limitations of standard profiling methods (IEF coupled to subsequent HPLC), ethnically targeted neonatal screening is often preferred. Here, we demonstrate that MALDI-MS-based SCD newborn screening could be considered as a potential method for a strategy to universal screening because of its high throughput, cost-effectiveness, sensitivity and ability to automatically discriminate sickle haemoglobin.

Experimental Design: We carried out a retrospective study of dried blood spots from 844 Guthrie cards. Four determinations of 1000 mass spectra were performed from each tested dried blood spot.

Results: The MALDI-MS-based screening was highly correlated with the reference method. Only 2.3% of the samples presented a poor spectral quality.

Conclusions And Clinical Relevance: Given that the overall acquisition, data reprocessing and software-assisted classification (ClinProTools™) time for processing four mass determinations (corresponding to one sample) was around 1 min, 1000 samples can be analysed per day. Rather than seeking to detect as many different haemoglobinopathies as possible, it would become possible to use MALDI-TOF-MS to screen (at a constant cost) as many samples as possible for sickle cell disease.