Mass spectrometry is now widely used in newborn screening laboratories. This technology is proving to be cost-effective and competitive for the detection of sickle cell disease and other hemoglobinopathies in newborns. Here are 4 reasons to adopt this technique.
Targeted, mass spectrometry selects only certain peptides of interest in hemoglobin. It therefore addresses hemoglobinopathies such as sickle cell disease (SCD), other variants of hemoglobin or thalassemia. Here are 4 reasons to use mass spectrometry for newborn screening for sickle cell disease.
1) A specific and sensitive methodology for newborn screening for sickle cell disease and other hemoglobin disorders
Newborn screening for sickle cell disease and hemoglobinopathies by mass spectrometry is primarily based on the hemoglobin extraction. The samples come as dried blood spots (DBS). The hemoglobin is then digested into peptides by a protease such as trypsin. Tandem mass spectrometry (MS/MS) allows to analyze the mixture of peptides generated, using an electrospray ionization source (ESI). The first advantage of MS/MS lies in the sensitivity of this technique. The second advantage consists in its specificity: the selection of a parent ion and one or two daughter ions allows the identification of each peptide with two or three levels of analytical confidence .
2) Rationalizing the costs of newborn screening
ESI-MS/MS-based screening also rationalizes newborn screening laboratory resources: laboratory equipment can be more fully used and applied to newborn screening for sickle cell disease.
For example :
- This implementation makes the purchase of a mass spectrometer, typically used for metabolic diseases screening, more cost-effective: costs and maintenance fees can be divided over several applications.
- The punchers produce standard punch size (3.0/3.2 mm), sufficient for the detection of hemoglobin variants (HbS, HbC, HbE, HbD or HbO) and thalassemia by MS/MS .
3. Hemoglobinopathies: simplified and personalized analytical interpretation of results
Software integration reduces time and facilitates data interpretation compared to high-performance liquid chromatography (HPLC) and isoelectric focusing (IEF) . In addition, the ability to target only certain peptides allows each laboratory to focus on the hemoglobinopathies of interest: screening may be limited to SCD (HbS) or may include other hemoglobin disorders. Thus, newborn screening for sickle cell disease by MS/MS can be adapted to local practices and requirements.
4. Samples stability
In contrast to IEF, HPLC and capillary electrophoresis, the MS/MS analysis relies on the peptides of the hemoglobin molecule. This makes sample storage less restrictive: high humidity and/or high temperature have little effect on peptide analyses. This is not the case for the analysis of the whole hemoglobin molecule. Indeed, under these conditions, half of hemoglobin A and S degrade after 10 days. 
Similarly, Barts hemoglobin (indicative of α-thalassemia) possesses limited stability on filter paper. Analysis of the corresponding peptides would remove the time constraint conditioned by this stability.
Newborn screening for sickle cell disease using mass spectrometry combines undeniable technical and economic qualities:
- Use of existing equipment
- Ease of interpretation of results
- Simplified sample logistics
- Adaptability to local requirements
These qualities are the major assets of this technique.
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 CLSI. Newborn Screening for Hemoglobinopathies. 1st ed. CLSI guideline NBS08; 2019.
 Adam, B. W. et al. (2014) ‘Stabilities of intact hemoglobin molecules and hemoglobin peptides in dried blood samples’, Clinica Chimica Acta, 429, pp. 59–60.
 Daniel, Y. and Tuner, C. (2018) ‘Newborn Sickle Cell Disease Screening Using Electrospray Tandem Mass Spectrometry’, Int. J. Neonatal Screen., 4, 35.
By Madeleine Boulanger, PhD - R&D Scientist