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Clinical Chemistry 48: 947-949, 2002;
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(Clinical Chemistry. 2002;48:947-949.)
© 2002 American Association for Clinical Chemistry, Inc.

Technical Briefs

High-Throughput Analysis of Hemoglobin from Neonates Using Matrix-assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

Urban A. Kiernan1,2, Jeff A. Black3, Peter Williams2 and Randall W. Nelson1a

1 Intrinsic Bioprobes, Inc., 625 S. Smith Rd., Suite 22, Tempe, AZ 85281

2 Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85281

3 Perkin Elmer Life Sciences-Norton, 3985 Eastern Rd., Norton, OH 44203

aauthor for correspondence: fax 480-804-0778, e-mail rnelson@intrinsicbio.com

The risks associated with sickle cell and other untreated hemoglobinopathies have led to mandatory neonatal screenings in 41 of the 50 states in the US (1). Preliminary screenings are often performed by electrophoresis at alkaline pH on cellulose acetate, with follow-up analysis of abnormal samples by acid electrophoresis on citrate agar (2). Alternatively, isoelectric focusing (IEF) or HPLC can be used in the screenings (3), but other techniques offer advantages.

In the past decade, new mass spectrometry (MS) approaches, including matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS, have been applied to the study of proteins (4). MALDI-TOF MS offers a potent means of analyzing constituent chains of hemoglobin A (HbA) directly from samples as small as a single red blood cell (5). Mass accuracy and resolution are sufficient to determine the presence of point mutations within chains differing in mass by as little as ~20 Da. This ability allows detection of the ß6Glu->Val variant (~30 Da lower in molecular mass) during direct analysis of the intact chains. Moreover, the site of mutation can be determined by combining MALDI-TOF MS with specific enzymatic digestion, i.e., "mass mapping".

Thus, MALDI-TOF MS has the potential to be used in place of conventional approaches (6) for HbAS/HbS screening in the general population. To date, however, the mass spectrometric approaches have not been taken to the high-throughput mode necessary for efficient population screening, nor have they been applied to neonatal blood samples, which contain roughly equal portions of HbA and HbF. We report here progress in the development of a high-throughput mass spectrometric screening approach capable of screening the hemoglobin of neonates at rates of ~100 samples/h. In a blind analysis, 96 neonate blood samples were prepared for both intact protein . . . [Full Text of this Article]


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References




The following articles in journals at HighWire Press have cited this article:


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D. Nedelkov, D. A. Phillips, K. A. Tubbs, and R. W. Nelson
Investigation of Human Protein Variants and Their Frequency in the General Population
Mol. Cell. Proteomics, July 1, 2007; 6(7): 1183 - 1187.
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P. Lacan, M. Becchi, I. Zanella-Cleon, M. Aubry, D. Quinsat, N. Couprie, and A. Francina
Identification by Mass Spectrometry of a Hemoglobin Variant with an Elongated {beta}-Globin Chain
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