Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 51, Issue 10 (Oct 2013)

Issues

Current and future use of “dried blood spot” analyses in clinical chemistry

Sylvain Lehmann
  • Corresponding author
  • CHU Montpellier, IRB, 80 Avenue Augustin Fliche, Montpellier 34295, France,
  • CHU Montpellier, Institut de Recherche en Biothérapie, Hôpital St Eloi, Laboratoire de Biochimie Protéomique Clinique et CCBHM, Montpellier, France
  • Université Montpellier 1, Montpellier, France
  • INSERM U1040, Montpellier, France
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Constance Delaby
  • CHU Montpellier, Institut de Recherche en Biothérapie, Hôpital St Eloi, Laboratoire de Biochimie Protéomique Clinique et CCBHM, Montpellier, France
  • Université Montpellier 1, Montpellier, France
  • INSERM U1040, Montpellier, France
  • Université Paris 7-Denis Diderot, Paris, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jérôme Vialaret
  • CHU Montpellier, Institut de Recherche en Biothérapie, Hôpital St Eloi, Laboratoire de Biochimie Protéomique Clinique et CCBHM, Montpellier, France
  • Université Montpellier 1, Montpellier, France
  • INSERM U1040, Montpellier, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jacques Ducos
  • CHU Montpellier, Unité de Virologie Lapeyronie, Montpellier, France
  • INSERM U1058, Montpellier, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Christophe Hirtz
  • CHU Montpellier, Institut de Recherche en Biothérapie, Hôpital St Eloi, Laboratoire de Biochimie Protéomique Clinique et CCBHM, Montpellier, France
  • Université Montpellier 1, Montpellier, France
  • INSERM U1040, Montpellier, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-06-01 | DOI: https://doi.org/10.1515/cclm-2013-0228

Abstract

The analysis of blood spotted and dried on a matrix (i.e., “dried blood spot” or DBS) has been used since the 1960s in clinical chemistry; mostly for neonatal screening. Since then, many clinical analytes, including nucleic acids, small molecules and lipids, have been successfully measured using DBS. Although this pre-analytical approach represents an interesting alternative to classical venous blood sampling, its routine use is limited. Here, we review the application of DBS technology in clinical chemistry, and evaluate its future role supported by new analytical methods such as mass spectrometry.

Keywords: dry blood spot; enzyme-linked immunosorbent assay (ELISA); mass spectrometry; polymerase chain reaction (PCR); pre-analytics

Introduction

Over a century since a new blood sampling method based on the use of a dry matrix was first described by Ivar Bang [1], the interest in dried blood spot technology has continuously evolved. This alternative approach, based on collecting blood spots on blotting paper and drying them, is called “dried blood spot” or DBS. In 1963, Robert Guthrie used this technique to develop systematic neonatal screening for the metabolic disease, phenylketonuria [2]. Set up for the first time in Scotland, this use of DBS spread to the UK in the 1970s, mainly to detect any innate errors in metabolism that were treatable. Of note, the use of DBS remains almost exclusively limited to this type of neonatal screening, even though many studies demonstrate its potential application in clinical biology, as well as in research. Indeed, classical clinical chemistry methods, small molecule and lipid analysis or molecular biology approaches, are all perfectly suited to the use of DBS. However, one limitation is represented by the small blood volumes associated with DBS sampling (5–10 µL) and therefore the need for very sensitive methods. Recent technological advances, in microfluidics, multiplex immunological/genomic detection systems, and mass spectrometry, could however settle most sensitivity problems. In this overview we will summarize the pros and cons of this particular biological sampling method and evaluate its future role in clinical biology.

General DBS procedure

Collection and sampling

The collection area (finger, heel) has to be first disinfected. The skin is then punctured with a sterile lancet (Figure 1). The first blood drop is dabbed and subsequent drops are placed on blotting paper marked with circles to be filled. Once all the required circles are filled, the blotting paper is left to dry for a few hours at room temperature on a non-absorbent surface. The drying time is very important as residual humidity favors bacterial development or molds and modifies the extraction stage [3].

DBS collection process. Peripheral blood is collected by the patient at home. He disinfects the area (finger) and pierces the skin using a sterile lancet before blotting the blood onto high quality filter paper. The DBS is dried for 1–3 h at room temperature and mailed using the classical envelope. At the laboratory, the DBS is stored at room temperature. The sample is punched (2–6 mm) and the analytes are extracted using an appropriate buffer before analysis.
Figure 1

DBS collection process.

Peripheral blood is collected by the patient at home. He disinfects the area (finger) and pierces the skin using a sterile lancet before blotting the blood onto high quality filter paper. The DBS is dried for 1–3 h at room temperature and mailed using the classical envelope. At the laboratory, the DBS is stored at room temperature. The sample is punched (2–6 mm) and the analytes are extracted using an appropriate buffer before analysis.

Conservation

Once dry, the DBS cards are moved into a waterproof plastic bag, possibly along with a desiccant and a humidity indicator [4]. The purpose of the desiccant is to finalize the drying process, which also minimizes any risk of infection associated with sampling. Periods of storage at room temperature vary according to the biological factor, from 1 week for proteins [5], to 1 year or more for nucleic acids [6]. As far as serology is concerned, the blotting papers are usually kept at –20°C upon receipt [7]. For long-term preservation (up to several years) the blotting papers are stored either at −20°C or –80°C [8, 9].

Extraction

Extraction of the analytes from DBS specimens needs to be achieved using a standard procedure. One or more 2–8 mm diameter discs are then created with a specific punch. These small “spots” are placed in an elution buffer for variable time spans according to the procedure. The DBS extraction is then treated as a hemolyzed whole blood sample, and tested with methods often intended for plasma or serum. The elution buffer plays a major role in re-solubilizing the analytes to be tested. A wide variety of buffers are described in the literature. The most common are saline/phosphate buffers, often with added detergents (Tween, Triton…), carrier proteins and chelators [ethylene diamine tetra acetic acid (EDTA)], as well as organic buffers with methanol, acetonitrile or ethanol. For nucleic acids, standard commercial kits exist which are compatible with molecular biology tests, from polymerase chain reaction (PCR) to genomic chips [10].

Pros and cons of DBS

One of the main advantages of using DBS technology is that it allows access to samples in pre-analytical situations were standard blood collection is challenging (problem with sampling, storage). The typical DBS contains approximately 50 µL of whole blood on an average surface of 12 mm2 (Figure 2). It enables the testing of various analytes such as nucleic acids, proteins, lipids, or small organic and non-organic molecules (Table 1). Two types of DBS are mostly available: cotton paper filters of different qualities (Whatmann 903 Protein Saver Cards Whatmann, Springfield Mill, UK; Perkin Elmer 226 Spot Saver Card, Perkin Elmer, Waltham, USA) and glass microfiber filter papers (Agilent Bond Elut DMS, Santa Clara, CA, USA; Sartorius Glass Microfiber Filters, Goettingen, Germany). The main difference between the two supports is that the glass fiber does not soak up reagents, which diminishes non-specific analyte adsorption on the membrane.

Comparison of the use of classical blood sampling versus DBS sampling resulting in a 100-fold reduction in blood volume and an ease of storage.
Figure 2

Comparison of the use of classical blood sampling versus DBS sampling resulting in a 100-fold reduction in blood volume and an ease of storage.

Table 1

Overview of DBS card usage in clinical chemistry other than its use for neonatal screening.

In comparison to conventional blood testing, DBS offers practical, clinical and financial advantages. Firstly, DBS collection is easy to perform and relatively painless (Figure 1). It can be carried out by the patient at home, without the need for specialized structures such as medical laboratories. This sampling procedure is far less invasive than venipuncture, therefore is better suited for patients requiring numerous blood tests, such as those with damaged/altered veins, the elderly or infants. The use of DBS also minimizes the volume of blood taken from patients. It has been shown that drying the blood spot on blotting paper damages the capsid of viruses [HIV, Cytomegalovirus (CMV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV)] [108] reducing any possible risk of contamination for medical or paramedical staff [4]. In addition, it enables the shipping of samples by regular mail with no particular risk of contamination. This represents a valuable asset for sampling in remote communities either located far away from a testing laboratory or with limited technical infrastructure available, therefore provides added value compared to standard blood sampling [59]. Through its small size and stacking capacity, DBS is also a valuable solution for reducing and facilitating storage in clinical laboratories and biobanks [109]. It is noteworthy that in case of storage, an individual bagging or a separation using a sturdy paper will be important to avoid the possibility of cross-contamination between cards [3]. These properties of DBS have been utilized in experimental research, by facilitating pharmacological studies and pharmacokinetics on small animals with very limited volumes of biological liquids. This follows the regulations aimed at protecting small animals (decreasing sample volume and sophistication of sampling methods) during pre-clinical studies [110]. Concerning sample stability, many studies have shown that most analytes from whole blood are stable at room temperature for at least 7 days. In some cases such as opiates, DBS even increases stability during storage [111], and nucleic acids are a major tool for short- and long-term preservation, as they can be isolated after several months at room temperature and several years at −20°C. [112]. From a medico-economical point of view, it is interesting to note that the use of DBS allows a significant cost reduction due to decreased requirements in trained staff, facilitated transportation, storage, and processing.

A major drawback of DBS technology resides in the nature of the biological sample itself (Figure 2). In a standard sampling procedure, either serum or plasma is analyzed, whereas DBS samples are composed of hemolyzed whole blood. Hence, interferences due to hemoglobin and the release of intracellular content could occur. The blood cells (erythrocytes, leukocytes, platelets etc.) are altered by the drying process, thus cellular hematological testing is impossible. Drying can also denature proteins and alters the enzymatic activity of blood proteins (aspartate transaminase). Any remaining cells in the samples can also change the global protein composition and therefore modify the concentration of some analytes. In some cases, clinical thresholds set up using standard blood samples need to be adapted. Hematocrit that affects blood dispersal on the blotting paper also needs to be taken into account [113]. The small volume of samples resulting from the DBS can be a disadvantage for low sensitivity assays [4] and for running multiple tests.

Use of DBS in clinical chemistry

The primary use of DBS in France is systematic neonatal screening. As blood sampling in newborns is difficult, DBS technology represents a viable alternative. DBS testing was set up in 1978 by the French Association for screening and preventing disabilities in children (http://www.afdphe.org/). Sampling of newborns enables the detection of phenylketonuria, hypothyroidism, adrenal hyperplasia, cystic fibrosis and sickle cell disease (in some areas). The extension of these tests to cover a wider number of diseases, similar as in to USA, is currently under consideration [28]. A positive result will always be confirmed or denied by further specific tests. Beyond its use for neonatal screening, many clinical analytes can be measured using DBS. These analytes are divided into four major categories as follows (see also Table 1):

Exogenous nucleic acids

The measurement of nucleic acids is typically required in the virology field. There is a growing interest in viral screening through nucleic acid detection (RNA, DNA) using DBS, as current molecular biology technologies [quantitative polymerase chain reaction (Q-PCR), reverse transcription polymerase chain reaction (RT-PCR)] are very sensitive and require only a small sample amount (<20 µL). Nevertheless, it is important to note that the amount of material available from a DBS sample is between 1 and 2 logs lower compared to a standard serum or plasma sample. The preservation of nucleic acids on blotting paper is stable for long periods [3], providing it is dried and stored away from humidity in a suitable plastic bag containing a desiccant. DBS nucleic acid detection is mainly used in screening for viral diseases such as cytomegalovirus [15], herpes simplex virus [11], hepatitis A [55], hepatitis C [13] and HIV [114].

Peptides – proteins

Concerning proteins and peptides one caveat is represented by the relative difficulty of their extraction from DBS samples, as well as the low sensitivity of certain protein dosage. The main proteins measured from DBS can be classified into two groups: standard serum proteins and antibodies. The most widely used analytical techniques are immunological assays which measure clinical analytes with good specificities and sensitivities. An example is represented by the immunoturbidimetric assay for glycated hemoglobin (to monitor glycemic balance in diabetic patients). Glycated hemoglobin measured from DBS samples correlate well with standard tests. In addition, this analyte remains stable for over 15 days on DBS [30]. DBS is also well adapted for the enzyme-linked immunosorbent assay (ELISA) detection of specific antibodies against Epstein-Barr virus [50], Rubella virus [74], dengue virus [75] or hepatitis C [7, 59] and HIV virus [13].

An interesting evolution of liquid chromatography/mass spectrometry (LC/MS) is represented by quantitative techniques for measuring peptides and proteins [115]. This approach was adapted on DBS to measure ceruloplasmin for the neonatal screening of Wilson’s disease [28] and for peptide C quantification [116]. When used in multiplex mode (multiple reaction monitoring) this mass spectrometry method has the potential to measure many analytes within only a few microliters [115]. For instance, Chambers et al. [117] have succeeded in quantifying a panel of 40 serum proteins from DBS, using this approach.

Lipids, sugars and small molecules

Phenylalanine, an amino acid measured in phenylketonuria screening of newborns, exemplifies the dosage of small molecules using DBS [2]. Small organic molecules are significantly less sensitive than proteins to the drying process which characterizes DBS samples. In addition, the major progress of liquid chromatography/mass spectrometry (LC/MS) in this field has allowed the quantification of many small molecules such as vitamin D [118] or lipids [79]. For instance, high levels of triglycerides, representing an important risk for cardiovascular and coronary diseases, can be quantified using DBS. These analytes remain stable on DBS for 30 days at room temperature and up to 90 days at 4°C. The profiling of glycans on DBS was also recently achieved using mass spectrometry [119].

Xenobiotics

In 1993, Henderson et al. [120] demonstrated the use of DBS for detecting narcotics, such as cocaine, through modification of a radioimmunoassay (RIA) commercial kit. Xenobiotic testing using DBS has since played an important role, mainly by the screening of antimalarial and antiretroviral drugs by LC/MS in isolated populations [95]. Another example is represented by the quantification of nine antiretroviral molecules in HIV using DBS. This detection method has been validated by the Food and Drug Administration (FDA) with sample stability ranging from 12 to over 90 days at room temperature [92]. In the field of toxicology, which is a major application of DBS [121], Saussereau et al. [122] have, for example, developed a new drug screening method based on LC/MS using on-line extraction for the quantification of opiates, cocainics or amphetamines. The development of these new measurement techniques, based on LC/MS for xenobiotics, will greatly increase the interest of using DBS in clinical chemistry.

Genomics

The clinical potential of DBS for genomics has been demonstrated as early as 1987 [123]. DNA micro-extraction from dried blood has allowed the detection of mutations responsible for diseases such as cystic fibrosis [124], X fragile syndrome [107], spinal muscular atrophy [106], cancers [77] and thalassemia [105]. DBS, which is a fairly inexpensive sampling and storage method, is also a good choice for genetic material biobanks [125]. For instance, the Danish national biobank for neonatal screening includes over 2 million DBS which virtually corresponds to all Danish people born since 1982.

Conclusions

The use of DBS has many advantages in terms of sampling, transportation, storage and biosafety when compared to classical collection methods. One interesting aspect of DBS is the possibility of simplified “self/home blood sampling”. The patient will be able to independently and safely collect a blood sample. The DBS will then be sent to the laboratory by mail. As described in this review, many clinical analytes are already available on DBS, and more are to follow, thanks to innovative approaches. Indeed, development of microfluidics, multiplex immunological/genomic detection systems, mass spectrometry and automated DBS processing open new interesting clinical prospects. The detection and follow-up of metabolic, infectious and chronic diseases could therefore rely on the use of DBS. Both the patient and society could benefit from this technology. Already, several public and commercial laboratories in both Europe and USA are offering DBS kits for a broad range of analytes often grouped into panels for hormonal, metabolic or cardiovascular diseases. This evolution could dramatically change how clinical chemistry pre-analytics are handled in the future.

The authors thank Rachel Almeras, Bader Al Taweel, Domitille Héron and Thibault Fortane for their initial help in the writing of this review and Brigitte Lehmann for editing the manuscript.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

  • 1.

    Bang I. Ein verfahren zur mikrobestimmung von blutbestandteilen. Biochem Ztschr 1913;49:19–39.Google Scholar

  • 2.

    Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 1963;32:338–43.PubMedGoogle Scholar

  • 3.

    Mei JV, Alexander JR, Adam BW, Hannon WH. Use of filter paper for the collection and analysis of human whole blood specimens. J Nutr 2001;131:1631S–6S.Google Scholar

  • 4.

    Parker SP, Cubitt WD. The use of the dried blood spot sample in epidemiological studies. J Clin Pathol 1999;52:633–9.CrossrefPubMedGoogle Scholar

  • 5.

    Costa X, Jardi R, Rodriguez F, Miravitlles M, Cotrina M, Gonzalez C, et al. Simple method for alpha1-antitrypsin deficiency screening by use of dried blood spot specimens. Eur Respir J 2000;15:1111–5.CrossrefGoogle Scholar

  • 6.

    Xu H, Zhao Y, Liu Z, Zhu W, Zhou Y, Zhao Z. Bisulfite genomic sequencing of DNA from dried blood spot microvolume samples. Forensic Sci Int Genet 2012;6:306–9.PubMedCrossrefGoogle Scholar

  • 7.

    Tuaillon E, Mondain AM, Meroueh F, Ottomani L, Picot MC, Nagot N, et al. Dried blood spot for hepatitis C virus serology and molecular testing. Hepatology 2010;51:752–8.PubMedGoogle Scholar

  • 8.

    Uttayamakul S, Likanonsakul S, Sunthornkachit R, Kuntiranont K, Louisirirotchanakul S, Chaovavanich A, et al. Usage of dried blood spots for molecular diagnosis and monitoring HIV-1 infection. J Virol Methods 2005;128:128–34.PubMedCrossrefGoogle Scholar

  • 9.

    Little RR, Wiedmeyer HM, England JD, Knowler WC, Goldstein DE. Measurement of glycosylated whole-blood protein for assessing glucose control in diabetes: collection and storage of capillary blood on filter paper. Clin Chem 1985;31:213–6.PubMedGoogle Scholar

  • 10.

    Caggana M, Conroy JM, Pass KA. Rapid, efficient method for multiplex amplification from filter paper. Hum Mutat 1998;11:404–9.PubMedCrossrefGoogle Scholar

  • 11.

    Strenger V, Pfurtscheller K, Wendelin G, Aberle SW, Nacheva EP, Zohrer B, et al. Differentiating inherited human herpesvirus type 6 genome from primary human herpesvirus type 6 infection by means of dried blood spot from the newborn screening card. J Pediatr 2011;159:859–61.CrossrefGoogle Scholar

  • 12.

    Lewensohn-Fuchs I, Osterwall P, Forsgren M, Malm G. Detection of herpes simplex virus DNA in dried blood spots making a retrospective diagnosis possible. J Clin Virol 2003;26:39–48.Google Scholar

  • 13.

    De Crignis E, Re MC, Cimatti L, Zecchi L, Gibellini D. HIV-1 and HCV detection in dried blood spots by SYBR green multiplex real-time RT-PCR. J Virol Methods 2010;165:51–6.PubMedCrossrefGoogle Scholar

  • 14.

    Jardi R, Rodriguez-Frias F, Buti M, Schaper M, Valdes A, Martinez M, et al. Usefulness of dried blood samples for quantification and molecular characterization of HBV-DNA. Hepatology 2004;40:133–9.PubMedCrossrefGoogle Scholar

  • 15.

    Gohring K, Dietz K, Hartleif S, Jahn G, Hamprecht K. Influence of different extraction methods and PCR techniques on the sensitivity of HCMV-DNA detection in dried blood spot (DBS) filter cards. J Clin Virol 2010;48:278–81.CrossrefPubMedGoogle Scholar

  • 16.

    Scanga L, Chaing S, Powell C, Aylsworth AS, Harrell LJ, Henshaw NG, et al. Diagnosis of human congenital cytomegalovirus infection by amplification of viral DNA from dried blood spots on perinatal cards. J Mol Diagn 2006;8:240–5.PubMedCrossrefGoogle Scholar

  • 17.

    Yourno J, Conroy J. A novel polymerase chain reaction method for detection of human immunodeficiency virus in dried blood spots on filter paper. J Clin Microbiol 1992;30:2887–92.PubMedGoogle Scholar

  • 18.

    Barin F, Plantier JC, Brand D, Brunet S, Moreau A, Liandier B, et al. Human immunodeficiency virus serotyping on dried serum spots as a screening tool for the surveillance of the aids epidemic. J Med Virol 2006;78(Suppl 1):S13–8.CrossrefPubMedGoogle Scholar

  • 19.

    Brindle E, Fujita M, Shofer J, O′Connor KA. Serum, plasma, and dried blood spot high-sensitivity C-reactive protein enzyme immunoassay for population research. J Immunol Methods 2010;362:112–20.PubMedCrossrefGoogle Scholar

  • 20.

    Cowans NJ, Stamatopoulou A, Liitti P, Suonpaa M, Spencer K. The stability of free-beta human chorionic gonadotrophin and pregnancy-associated plasma protein-A in first trimester dried blood spots. Prenatal Diagn 2011;31:293–8.CrossrefGoogle Scholar

  • 21.

    Worthman CM, Stallings JF. Measurement of gonadotropins in dried blood spots. Clin Chem 1994;40:448–53.PubMedGoogle Scholar

  • 22.

    Hoffman DL. Purification and large-scale preparation of antithrombin III. Am J Med 1989;87:23S–6S.PubMedCrossrefGoogle Scholar

  • 23.

    Mitchell ML, Hermos RJ, Moses AC. Radioimmunoassay of somatomedin-C in filter paper discs containing dried blood. Clin Chem 1987;33:536–8.PubMedGoogle Scholar

  • 24.

    Wang XL, Dudman NP, Blades BL, Wilcken DE. Changes in the immunoreactivity of APO A-I during storage. Clin Chim Acta 1989;179:285–93.PubMedCrossrefGoogle Scholar

  • 25.

    Macri JN, Anderson RW, Krantz DA, Larsen JW, Buchanan PD. Prenatal maternal dried blood screening with alpha-fetoprotein and free beta-human chorionic gonadotropin for open neural tube defect and down syndrome. Am J Obstet Gynecol 1996;174:566–72.CrossrefPubMedGoogle Scholar

  • 26.

    Yamaguchi A, Fukushi M, Arai O, Mizushima Y, Sato Y, Shimizu Y, et al. A simple method for quantification of biotinidase activity in dried blood spot and its application to screening of biotinidase deficiency. Tohoku J Exp Med 1987;152:339–46.CrossrefPubMedGoogle Scholar

  • 27.

    Song EY, Vandunk C, Kuddo T, Nelson PG. Measurement of CGRP in dried blood spots using a modified sandwich enzyme immunoassay. J Neurosci Methods 2006;155:92–7.CrossrefPubMedGoogle Scholar

  • 28.

    deWilde A, Sadilkova K, Sadilek M, Vasta V, Hahn SH. Tryptic peptide analysis of ceruloplasmin in dried blood spots using liquid chromatography-tandem mass spectrometry: application to newborn screening. Clin Chem 2008;54:1961–8.CrossrefPubMedGoogle Scholar

  • 29.

    O′Broin SD, Gunter EW. Screening of folate status with use of dried blood spots on filter paper. Am J Clin Nutr 1999;70:359–67.Google Scholar

  • 30.

    Lakshmy R, Gupta R. Measurement of glycated hemoglobin A1c from dried blood by turbidimetric immunoassay. J Diabetes Sci Technol 2009;3:1203–6.Google Scholar

  • 31.

    Daniel YA, Turner C, Haynes RM, Hunt BJ, Dalton RN. Quantification of hemoglobin A2 by tandem mass spectrometry. Clin Chem 2007;53:1448–54.CrossrefPubMedGoogle Scholar

  • 32.

    Jacomelli G, Micheli V, Peruzzi L, Notarantonio L, Cerboni B, Sestini S, et al. Simple non-radiochemical HPLC-linked method for screening for purine metabolism disorders using dried blood spot. Clin Chim Acta 2002;324:135–9.CrossrefPubMedGoogle Scholar

  • 33.

    Wang D, Wood T, Sadilek M, Scott CR, Turecek F, Gelb MH. Tandem mass spectrometry for the direct assay of enzymes in dried blood spots: application to newborn screening for mucopolysaccharidosis II (Hunter disease). Clin Chem 2007;53:137–40.PubMedGoogle Scholar

  • 34.

    Diamandi A, Khosravi MJ, Mistry J, Martinez V, Guevara-Aguirre J. Filter paper blood spot assay of human insulin-like growth factor I (IGF-I) and IGF-binding protein-3 and preliminary application in the evaluation of growth hormone status. J Clin Endocrinol Metab 1998;83:2296–301.CrossrefPubMedGoogle Scholar

  • 35.

    Fisher RS, Chan DW, Bare M, Lesser RP. Capillary prolactin measurement for diagnosis of seizures. Ann Neurol 1991;29:187–90.PubMedCrossrefGoogle Scholar

  • 36.

    McDade TW, Shell-Duncan B. Whole blood collected on filter paper provides a minimally invasive method for assessing human transferrin receptor level. J Nutr 2002;132:3760–3.PubMedGoogle Scholar

  • 37.

    Zimmermann MB, Moretti D, Chaouki N, Torresani T. Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt. Am J Clin Nutr 2003;77:1453–8.PubMedGoogle Scholar

  • 38.

    Mwaba P, Cassol S, Pilon R, Chintu C, Janes M, Nunn A, et al. Use of dried whole blood spots to measure CD4+ lymphocyte counts in HIV-1-infected patients. Lancet 2003;362:1459–60.CrossrefGoogle Scholar

  • 39.

    Helfand RF, Keyserling HL, Williams I, Murray A, Mei J, Moscatiello C, et al. Comparative detection of measles and rubella IGM and IGG derived from filter paper blood and serum samples. J Med Virol 2001;65:751–7.PubMedCrossrefGoogle Scholar

  • 40.

    Sorensen T, Spenter J, Jaliashvili I, Christiansen M, Norgaard-Pedersen B, Petersen E. Automated time-resolved immunofluorometric assay for toxoplasma gondii-specific IGM and IGA antibodies: study of more than 130,000 filter-paper blood-spot samples from newborns. Clin Chem 2002;48:1981–6.Google Scholar

  • 41.

    Dowlati B, Dunhardt PA, Smith MM, Shaheb S, Stuart CA. Quantification of insulin in dried blood spots. J Lab Clin Med 1998;131:370–4.PubMedCrossrefGoogle Scholar

  • 42.

    Chamoles NA, Niizawa G, Blanco M, Gaggioli D, Casentini C. Glycogen storage disease type II: enzymatic screening in dried blood spots on filter paper. Clin Chim Acta 2004;347:97–102.CrossrefPubMedGoogle Scholar

  • 43.

    Chamoles NA, Blanco MB, Gaggioli D, Casentini C. Hurler-like phenotype: enzymatic diagnosis in dried blood spots on filter paper. Clin Chem 2001;47:2098–102.PubMedGoogle Scholar

  • 44.

    Chamoles NA, Blanco M, Gaggioli D. Diagnosis of alpha-l-iduronidase deficiency in dried blood spots on filter paper: the possibility of newborn diagnosis. Clin Chem 2001;47:780–1.PubMedGoogle Scholar

  • 45.

    ten Brink HJ, van den Heuvel CM, Christensen E, Largilliere C, Jakobs C. Diagnosis of peroxisomal disorders by analysis of phytanic and pristanic acids in stored blood spots collected at neonatal screening. Clin Chem 1993;39:1904–6.Google Scholar

  • 46.

    Vladutiu GD, Glueck CJ, Schultz MT, McNeely S, Guthrie R. Beta-lipoprotein quantitation in cord blood spotted on filter paper: a screening test. Clin Chem 1980;26:1285–90.PubMedGoogle Scholar

  • 47.

    Laberge C, Grenier A, Valet JP, Morissette J. Fumarylacetoacetase measurement as a mass-screening procedure for hereditary tyrosinemia type I. Am J Hum Genet 1990;47:325–8.PubMedGoogle Scholar

  • 48.

    Skogstrand K, Ekelund CK, Thorsen P, Vogel I, Jacobsson B, Norgaard-Pedersen B, et al. Effects of blood sample handling procedures on measurable inflammatory markers in plasma, serum and dried blood spot samples. J Immunol Methods 2008;336:78–84.PubMedCrossrefGoogle Scholar

  • 49.

    Tanner S, McDade TW. Enzyme immunoassay for total immunoglobulin E in dried blood spots. Am J Human Biol 2007;19:440–2.CrossrefGoogle Scholar

  • 50.

    Fachiroh J, Prasetyanti PR, Paramita DK, Prasetyawati AT, Anggrahini DW, Haryana SM, et al. Dried-blood sampling for epstein-barr virus immunoglobulin g (IGG) and IGA serology in nasopharyngeal carcinoma screening. J Clin Microbiol 2008;46:1374–80.CrossrefPubMedGoogle Scholar

  • 51.

    Chamoles NA, Blanco MB, Iorcansky S, Gaggioli D, Specola N, Casentini C. Retrospective diagnosis of GM1 gangliosidosis by use of a newborn-screening card. Clin Chem 2001;47:2068–9.Google Scholar

  • 52.

    Xu YY, Pettersson K, Blomberg K, Hemmila I, Mikola H, Lovgren T. Simultaneous quadruple-label fluorometric immunoassay of thyroid-stimulating hormone, 17 alpha-hydroxyprogesterone, immunoreactive trypsin, and creatine kinase MM isoenzyme in dried blood spots. Clin Chem 1992;38:2038–43.Google Scholar

  • 53.

    Dussault JH, Morissette J, Letarte J, Guyda H, Laberge C. Thyroxine-binding globulin capacity and concentration evaluated from blood spots on filter-paper in a screening program for neonatal hypothyroidism. Clin Chem 1980;26:463–5.Google Scholar

  • 54.

    Kirby LT, Applegarth DA, Davidson AG, Wong LT, Hardwick DF. Use of a dried blood spot in immunoreactive-trypsin assay for detection of cystic fibrosis in infants. Clin Chem 1981;27:678–8.PubMedGoogle Scholar

  • 55.

    de Almeida LM, Azevedo RS, Guimaraes AA, Coutinho Eda S, Struchiner CJ, Massad E. Detection of antibodies against hepatitis a virus in eluates of blood spotted on filter-paper: a pilot study in Rio De Janeiro, Brazil. Trans R Soc Trop Med Hyg 1999;93:401–4.PubMedCrossrefGoogle Scholar

  • 56.

    Gil A, Gonzalez A, Dal-Re R, Dominguez V, Astasio P, Aguilar L. Detection of antibodies against hepatitis a in blood spots dried on filter paper. Is this a reliable method for epidemiological studies? Epidemiol Infect 1997;118:189–91.PubMedCrossrefGoogle Scholar

  • 57.

    Villar LM, de Oliveira JC, Cruz HM, Yoshida CF, Lampe E, Lewis-Ximenez LL. Assessment of dried blood spot samples as a simple method for detection of hepatitis B virus markers. J Med Virol 2011;83:1522–9.PubMedCrossrefGoogle Scholar

  • 58.

    Tappin DM, Greer K, Cameron S, Kennedy R, Brown AJ, Girdwood RW. Maternal antibody to hepatitis B core antigen detected in dried neonatal blood spot samples. Epidemiol Infect 1998;121:387–90.CrossrefPubMedGoogle Scholar

  • 59.

    Judd A, Parry J, Hickman M, McDonald T, Jordan L, Lewis K, et al. Evaluation of a modified commercial assay in detecting antibody to hepatitis C virus in oral fluids and dried blood spots. J Med Virol 2003;71:49–55.CrossrefPubMedGoogle Scholar

  • 60.

    Parker SP, Khan HI, Cubitt WD. Detection of antibodies to hepatitis C virus in dried blood spot samples from mothers and their offspring in Lahore, Pakistan. J Clin Microbiol 1999;37:2061–3.PubMedGoogle Scholar

  • 61.

    Corran PH, Cook J, Lynch C, Leendertse H, Manjurano A, Griffin J, et al. Dried blood spots as a source of anti-malarial antibodies for epidemiological studies. Malar J 2008;7:195–207.CrossrefPubMedGoogle Scholar

  • 62.

    Thanasekaraan V, Wiseman MS, Rayner RJ, Hiller EJ, Shale DJ. Pseudomonas aeruginosa antibodies in blood spots from patients with cystic fibrosis. Arch Dis Child 1989;64:1599–603.PubMedCrossrefGoogle Scholar

  • 63.

    Hofman LF, Foley TP, Henry JJ, Naylor EW. The use of filter paper-dried blood spots for thyroid-antibody screening in adults. J Lab Clin Med 2004;144:307–12.PubMedCrossrefGoogle Scholar

  • 64.

    Hong HA, Ke NT, Nhon TN, Thinh ND, van der Gun JW, Hendriks JT, et al. Validation of the combined toxin-binding inhibition test for determination of neutralizing antibodies against tetanus and diphtheria toxins in a vaccine field study in Vietnam. Bull World Health Organ 1996;74:275–82.Google Scholar

  • 65.

    Takkouche B, Iglesias J, Alonso-Fernandez JR, Fernandez-Gonzalez C, Gestal-Otero JJ. Detection of brucella antibodies in eluted dried blood: a validation study. Immunol Letters 1995;45:107–8.CrossrefGoogle Scholar

  • 66.

    Peralta RH, Macedo HW, Vaz AJ, Machado LR, Peralta JM. Detection of anti-cysticercus antibodies by ELISA using whole blood collected on filter paper. Trans R Soc Trop Med Hyg 2001;95:35–6.PubMedCrossrefGoogle Scholar

  • 67.

    de la Fuente L, Toro C, Soriano V, Brugal MT, Vallejo F, Barrio G, et al. HTLV infection among young injection and non-injection heroin users in Spain: prevalence and correlates. J Clin Virol 2006;35:244–9.CrossrefGoogle Scholar

  • 68.

    Fenollar F, Raoult D. Diagnosis of Rickettsial diseases using samples dried on blotting paper. Clin Diagn Lab Immunol 1999;6:483–8.PubMedGoogle Scholar

  • 69.

    Stevens R, Pass K, Fuller S, Wiznia A, Noble L, Duva S, et al. Blood spot screening and confirmatory tests for syphilis antibody. J Clin Microbiol 1992;30:2353–8.PubMedGoogle Scholar

  • 70.

    Backhouse JL. Dried blood spot technique for detecting treponema infection. Trans R Soc Trop Med Hyg 1998;92:469–76.CrossrefPubMedGoogle Scholar

  • 71.

    Zicker F, Smith PG, Luquetti AO, Oliveira OS. Mass screening for trypanosoma cruzi infections using the immunofluorescence, ELISA and haemagglutination tests on serum samples and on blood eluates from filter-paper. Bull World Health Organ 1990;68:465–71.PubMedGoogle Scholar

  • 72.

    Mason PR, Fiori PL, Cappuccinelli P, Rappelli P, Gregson S. Seroepidemiology of trichomonas vaginalis in rural women in Zimbabwe and patterns of association with HIV infection. Epidemiol Infect 2005;133:315–23.PubMedCrossrefGoogle Scholar

  • 73.

    Fujimoto A, Okano Y, Miyagi T, Isshiki G, Oura T. Quantitative beutler test for newborn mass screening of galactosemia using a fluorometric microplate reader. Clin Chem 2000;46:806–10.PubMedGoogle Scholar

  • 74.

    Hardelid P, Williams D, Dezateux C, Cubitt WD, Peckham CS, Tookey PA, et al. Agreement of rubella IGG antibody measured in serum and dried blood spots using two commercial enzyme-linked immunosorbent assays. J Med Virol 2008;80:360–4.CrossrefPubMedGoogle Scholar

  • 75.

    Balmaseda A, Saborio S, Tellez Y, Mercado JC, Perez L, Hammond SN, et al. Evaluation of immunological markers in serum, filter-paper blood spots, and saliva for dengue diagnosis and epidemiological studies. J Clin Virol 2008;43:287–91.PubMedCrossrefGoogle Scholar

  • 76.

    Sorensen KM, Agergaard P, Olesen C, Andersen PS, Larsen LA, Ostergaard JR, et al. Detecting 22q11.2 deletions by use of multiplex ligation-dependent probe amplification on DNA from neonatal dried blood spot samples. J Mol Diagn 2010;12:147–51.CrossrefGoogle Scholar

  • 77.

    Klotz J, Bryant P, Wilcox HB, Dillon M, Wolf B, Fagliano J. Population-based retrieval of newborn dried blood spots for researching paediatric cancer susceptibility genes. Paediatr Perinat Epidemiol 2006;20:449–52.PubMedCrossrefGoogle Scholar

  • 78.

    Waterboer T, Dondog B, Michael KM, Michel A, Schmitt M, Vaccarella S, et al. Dried blood spot samples for seroepidemiology of infections with human papillomaviruses, helicobacter pylori, hepatitis C virus, and JC virus. Cancer Epidemiol Biomarkers Prev 2012;21:287–93.CrossrefPubMedGoogle Scholar

  • 79.

    Quraishi R, Lakshmy R, Prabhakaran D, Mukhopadhyay AK, Jailkhani B. Use of filter paper stored dried blood for measurement of triglycerides. Lipids Health Disease 2006;5:20.CrossrefGoogle Scholar

  • 80.

    Zytkovicz TH, Fitzgerald EF, Marsden D, Larson CA, Shih VE, Johnson DM, et al. Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England newborn screening program. Clin Chem 2001;47:1945–55.PubMedGoogle Scholar

  • 81.

    Accinni R, Campolo J, Parolini M, De Maria R, Caruso R, Maiorana A, et al. Newborn screening of homocystinuria: quantitative analysis of total homocyst(e)ine on dried blood spot by liquid chromatography with fluorimetric detection. J Chromatogr B Analyt Technol Biomed Life Sci 2003;785:219–26.CrossrefGoogle Scholar

  • 82.

    Burrin JM, Price CP. Performance of three enzymic methods for filter paper glucose determination. Ann Clin Biochem 1984;21( Pt 5):411–6.PubMedGoogle Scholar

  • 83.

    Lacey JM, Minutti CZ, Magera MJ, Tauscher AL, Casetta B, McCann M, et al. Improved specificity of newborn screening for congenital adrenal hyperplasia by second-tier steroid profiling using tandem mass spectrometry. Clin Chem 2004;50:621–5.PubMedCrossrefGoogle Scholar

  • 84.

    Erhardt JG, Craft NE, Heinrich F, Biesalski HK. Rapid and simple measurement of retinol in human dried whole blood spots. J Nutr 2002;132:318–21.PubMedGoogle Scholar

  • 85.

    Chace DH, Singleton S, Diperna J, Aiello M, Foley T. Rapid metabolic and newborn screening of thyroxine (t4) from dried blood spots by MS/MS. Clin Chim Acta 2009;403:178–83.CrossrefGoogle Scholar

  • 86.

    Pacchiarotti A, Bartalena L, Falcone M, Buratti L, Grasso L, Martino E, et al. Free thyroxine and free triiodothyronine measurement in dried blood spots on filter paper by column adsorption chromatography followed by radioimmunoassay. Horm Metab Res 1988;20:293–7.PubMedCrossrefGoogle Scholar

  • 87.

    Schulze A, Schmidt C, Kohlmuller D, Hoffmann GF, Mayatepek E. Accurate measurement of free carnitine in dried blood spots by isotope-dilution electrospray tandem mass spectrometry without butylation. Clin Chim Acta 2003;335:137–45.PubMedCrossrefGoogle Scholar

  • 88.

    Kuhara T, Ohse M, Inoue Y, Yorifuji T, Sakura N, Mitsubuchi H, et al. Gas chromatographic-mass spectrometric newborn screening for propionic acidaemia by targeting methylcitrate in dried filter-paper urine samples. J Inherit Metab Dis 2002;25:98–106.PubMedCrossrefGoogle Scholar

  • 89.

    Kimura M, Yoon HR, Wasant P, Takahashi Y, Yamaguchi S. A sensitive and simplified method to analyze free fatty acids in children with mitochondrial beta oxidation disorders using gas chromatography/mass spectrometry and dried blood spots. Clin Chim Acta 2002;316:117–21.CrossrefPubMedGoogle Scholar

  • 90.

    Allard P, Grenier A, Korson MS, Zytkovicz TH. Newborn screening for hepatorenal tyrosinemia by tandem mass spectrometry: analysis of succinylacetone extracted from dried blood spots. Clin Biochem 2004;37:1010–5.PubMedCrossrefGoogle Scholar

  • 91.

    Carducci C, Santagata S, Leuzzi V, Artiola C, Giovanniello T, Battini R, et al. Quantitative determination of guanidinoacetate and creatine in dried blood spot by flow injection analysis-electrospray tandem mass spectrometry. Clin Chim Acta 2006;364:180–7.PubMedCrossrefGoogle Scholar

  • 92.

    D′Avolio A, Simiele M, Siccardi M, Baietto L, Sciandra M, Bonora S, et al. HPLC-MS method for the quantification of nine anti-HIV drugs from dry plasma spot on glass filter and their long-term stability in different conditions. J Pharm Biomed Anal 2010;52:774–80.Google Scholar

  • 93.

    Koal T, Burhenne H, Romling R, Svoboda M, Resch K, Kaever V. Quantification of antiretroviral drugs in dried blood spot samples by means of liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2005;19:2995–3001.Google Scholar

  • 94.

    Henderson LO, Powell MK, Hannon WH, Miller BB, Martin ML, Hanzlick RL, et al. Radioimmunoassay screening of dried blood spot materials for benzoylecgonine. J Anal Toxicol 1993;17:42–7.CrossrefPubMedGoogle Scholar

  • 95.

    Blessborn D, Romsing S, Bergqvist Y, Lindegardh N. Assay for screening for six antimalarial drugs and one metabolite using dried blood spot sampling, sequential extraction and ion-trap detection. Bioanalysis 2010;2:1839–47.PubMedCrossrefGoogle Scholar

  • 96.

    Lindkvist J, Malm M, Bergqvist Y. Straightforward and rapid determination of sulfadoxine and sulfamethoxazole in capillary blood on sampling paper with liquid chromatography and UV detection. Trans R Soc Trop Med Hyg 2009;103:371–6.PubMedCrossrefGoogle Scholar

  • 97.

    Burse VW, DeGuzman MR, Korver MP, Najam AR, Williams CC, Hannon WH, et al. Preliminary investigation of the use of dried-blood spots for the assessment of in utero exposure to environmental pollutants. Biochem Mol Med 1997;61:236–9.PubMedCrossrefGoogle Scholar

  • 98.

    Li PK, Lee JT, Conboy KA, Ellis EF. Fluorescence polarization immunoassay for theophylline modified for use with dried blood spots on filter paper. Clin Chem 1986;32:552–5.PubMedGoogle Scholar

  • 99.

    Conroy JM, Trivedi G, Sovd T, Caggana M. The allele frequency of mutations in four genes that confer enhanced susceptibility to venous thromboembolism in an unselected group of New York State newborns. Thromb Res 2000;99:317–24.CrossrefGoogle Scholar

  • 100.

    Bobillo Lobato J, Sanchez Peral BA, Duran Parejo P, Jimenez Jimenez LM. Detection of c. -32t>g (ivs1-13t>g) mutation of pompe disease by real-time PCR in dried blood spot specimen. Clin Chim Acta 2013;418C:107–8.Google Scholar

  • 101.

    Chien YH, Lee NC, Chiang SC, Desnick RJ, Hwu WL. Fabry disease: incidence of the common later-onset alpha-galactosidase a ivs4+919g–>a mutation in Taiwanese newborns–superiority of DNA-based to enzyme-based newborn screening for common mutations. Mol Med 2012;18:780–4.Google Scholar

  • 102.

    Abdallah MW, Larsen N, Grove J, Bonefeld-Jorgensen EC, Norgaard-Pedersen B, Hougaard DM, et al. Neonatal chemokine levels and risk of autism spectrum disorders: findings from a Danish historic birth cohort follow-up study. Cytokine 2012;61:370–6.PubMedGoogle Scholar

  • 103.

    McCandless SE, Chandrasekar R, Linard S, Kikano S, Rice L. Sequencing from dried blood spots in infants with “false positive” newborn screen for MCAD deficiency. Mol Genet Metab 2013;108:51–5.PubMedCrossrefGoogle Scholar

  • 104.

    Cordovado SK, Hendrix M, Greene CN, Mochal S, Earley MC, Farrell PM, et al. CFTR mutation analysis and haplotype associations in CF patients. Mol Genet Metab 2012;105: 249–54.PubMedCrossrefGoogle Scholar

  • 105.

    Karthipan SN, George E, Jameela S, Lim WF, Teh LK, Lee TY, et al. An assessment of three noncommercial DNA extraction methods from dried blood spots for beta-thalassaemia mutation identification. Int J Lab Hematol 2011;33:540–4.PubMedGoogle Scholar

  • 106.

    Harahap NI, Harahap IS, Kaszynski RH, Nurputra DK, Hartomo TB, Pham HT, et al. Spinal muscular atrophy patient detection and carrier screening using dried blood spots on filter paper. Genet Test Mol Biomarkers 2012;16:123–9.CrossrefPubMedGoogle Scholar

  • 107.

    Coffee B, Keith K, Albizua I, Malone T, Mowrey J, Sherman SL, et al. Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet 2009;85:503–14.CrossrefGoogle Scholar

  • 108.

    Resnick L, Veren K, Salahuddin SZ, Tondreau S, Markham PD. Stability and inactivation of HTLV-III/LAV under clinical and laboratory environments. J Am Med Assoc 1986;255:1887–91.CrossrefGoogle Scholar

  • 109.

    McDade TW, Williams S, Snodgrass JJ. What a drop can do: dried blood spots as a minimally invasive method for integrating biomarkers into population-based research. Demography 2007;44:899–925.PubMedCrossrefGoogle Scholar

  • 110.

    Burnett JE. Dried blood spot sampling: practical considerations and recommendation for use with preclinical studies. Bioanalysis 2011;3:1099–107.CrossrefPubMedGoogle Scholar

  • 111.

    Garcia Boy R, Henseler J, Mattern R, Skopp G. Determination of morphine and 6-acetylmorphine in blood with use of dried blood spots. Ther Drug Monit 2008;30:733–9.Google Scholar

  • 112.

    Hollegaard MV, Grauholm J, Borglum A, Nyegaard M, Norgaard-Pedersen B, Orntoft T, et al. Genome-wide scans using archived neonatal dried blood spot samples. BMC Genomics 2009;10:297–303.CrossrefPubMedGoogle Scholar

  • 113.

    O′Mara M, Hudson-Curtis B, Olson K, Yueh Y, Dunn J, Spooner N. The effect of hematocrit and punch location on assay bias during quantitative bioanalysis of dried blood spot samples. Bioanalysis 2011;3:2335–47.CrossrefGoogle Scholar

  • 114.

    Snijdewind IJ, van Kampen JJ, Fraaij PL, van der Ende ME, Osterhaus AD, Gruters RA. Current and future applications of dried blood spots in viral disease management. Antiviral Res 2012;93:309–21.CrossrefGoogle Scholar

  • 115.

    Lehmann S, Hoofnagle A, Hochstrasser D, Brede C, Glueckmann M, Cocho JA, et al. Quantitative clinical chemistry proteomics (QCCP) using mass spectrometry: general characteristics and application. Clin Chem Lab Med 2012:1–16.Google Scholar

  • 116.

    Johansson J, Becker C, Persson NG, Fex M, Torn C. C-peptide in dried blood spots. Scand J Clin Lab Invest 2010;70:404–9.PubMedCrossrefGoogle Scholar

  • 117.

    Chambers AG, Percy AJ, Yang J, Camenzind AG, Borchers CH. Multiplexed quantitation of endogenous proteins in dried blood spots by multiple reaction monitoring mass spectrometry. Mol Cell Proteomics 2012;12:781–91.PubMedGoogle Scholar

  • 118.

    Newman MS, Brandon TR, Groves MN, Gregory WL, Kapur S, Zava DT. A liquid chromatography/tandem mass spectrometry method for determination of 25-hydroxy vitamin D2 and 25-hydroxy vitamin D3 in dried blood spots: a potential adjunct to diabetes and cardiometabolic risk screening. J Diabetes Sci Technol 2009;3:156–62.Google Scholar

  • 119.

    Ruhaak LR, Miyamoto S, Kelly K, Lebrilla CB. N-glycan profiling of dried blood spots. Anal Chem 2012;84:396–402.PubMedCrossrefGoogle Scholar

  • 120.

    Henderson LO, Powell MK, Hannon WH, Bernert JT, Jr., Pass KA, Fernhoff P, et al. An evaluation of the use of dried blood spots from newborn screening for monitoring the prevalence of cocaine use among childbearing women. Biochem Mol Med 1997;61:143–51.CrossrefPubMedGoogle Scholar

  • 121.

    Stove CP, Ingels AS, De Kesel PM, Lambert WE. Dried blood spots in toxicology: from the cradle to the grave? Crit Rev Toxicol 2012;42:230–43.CrossrefPubMedGoogle Scholar

  • 122.

    Saussereau E, Lacroix C, Gaulier JM, Goulle JP. On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots. J Chromatogr B Analyt Technol Biomed Life Sci 2012;885–886:1–7.Google Scholar

  • 123.

    McCabe ER, Huang SZ, Seltzer WK, Law ML. DNA microextraction from dried blood spots on filter paper blotters: potential applications to newborn screening. Hum Genet 1987;75:213–6.CrossrefPubMedGoogle Scholar

  • 124.

    Makowski GS, Aslanzadeh J, Hopfer SM. In situ PCR amplification of guthrie card DNA to detect cystic fibrosis mutations. Clin Chem 1995;41:477–9.PubMedGoogle Scholar

  • 125.

    Sjoholm MI, Dillner J, Carlson J. Assessing quality and functionality of DNA from fresh and archival dried blood spots and recommendations for quality control guidelines. Clin Chem 2007;53:1401–7.CrossrefGoogle Scholar

About the article

Sylvain Lehmann

Prof. Sylvain Lehmann trained as an MD/PhD (1992, Strasbourg, France). He was the recipient of a Howard Hughes fellowship for physicians and spent 4 years in Washington University, St Louis, MO, USA, as a postdoctoral fellow and a research Assistant Professor. From 1997, he was a researcher of the French National Research Institut (INSERM) and in 2003 he obtained a position as Professor of Biochemistry at the Medical School of Montpellier (France). His research focuses on neurodegenerative disorders (Alzheimer, prion, etc.) and on clinical proteomics. He is a vice-president of the French National Society of Clinical Biology (SFBC) in charge of its Scientific Committee and he chairs the Working Group “Clinical Quantitative Mass Spectrometry Proteomics” of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

Constance Delaby

Constance Dalaby holds a PhD in Biology and graduated from University Paris 7 (France) in 2006. In 2005, she was recruited as a research assistant in Biochemistry by the Clinical Unit of Biochemistry at Pr Jean-Charles Deybach (Hôpital Louis Mourier, Colombes, France), as a member of the French Reference Center of Porphyrias. In 2008–2009, she collaborated with the Biochemistry Unit of the Hospital Clinic of Barcelona (Dr Jordi To-Figueras, Spain) and was recruited as an Assistant Professor in Biochemistry and Molecular Biology by the University Paris 7 (France) in 2009. Since 2011, she has been part of the Clinical Chemistry Laboratory (Proteomics Platform) of Pr Sylvain Lehmann (IRB, Hôpital Saint Eloi, CHRU Montpellier).

Jérôme Vialaret

Jérôme Vialaret was born in 1984 and studied Organic Chemistry at Montpellier II University (obtaining his Master’s degree in 2007). He specialized in proteomic while working for Pierre Fabre Laboratories, EPFL (Lausanne, Switzerland), INRA (Montpellier, France) and at Montpellier Hospital. Having amassed a wealth of experience in large scale proteomic (proteome and phosphoproteome) with dedicated quantitative methods (silac and label-free), he focused on the development of protein quantification using targeted mass spectrometry in a clinical environment. He is in charge of these method developments in the Clinical Proteomic Platform of the Laboratory of Biochemistry and Clinical Proteomic directed by Pr. Sylvain Lehmann in Montpellier.

Jacques Ducos

Dr. Jacques Ducos was trained as an MD (1983, Montpellier, France) and PhD (1993, Montpellier, France). He was a resident in the Montpellier Hospital (1979–1983). He specializes in Virology (HBV/ HCV/HIV) and his research is focusing on biological markers of viral infections. He is currently responsible for the functional unit of viral hepatitis at the Montpellier Hospital (Lapeyronie, France). He is the president of the Viral Hepatitis Network of the Languedoc Roussillon Camargue (RHEVIR).

Christophe Hirtz

Christophe Hirtz was born in 1972 and studied Biochemistry at Paul Sabatier University in Toulouse. Having got his Doctorate and an accreditation to supervise research in the proteomic field, he was recruited in 2008 as an Associate Professor at the University Montpellier I and is specialized in Biochemistry and Clinical Proteomic. His scientific interest includes the development of a new method of protein quantification using targeted mass spectrometry in a clinical environment. He is in charge of the Clinical Proteomic Platform of the Laboratory of Biochemistry and Clinical Proteomic directed by Pr. Sylvain Lehmann in Montpellier.


Corresponding author: Sylvain Lehmann, CHU Montpellier, IRB, 80 Avenue Augustin Fliche, Montpellier 34295, France, E-mail:


Received: 2013-03-26

Accepted: 2013-04-19

Published Online: 2013-06-01

Published in Print: 2013-10-01


Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2013-0228.

Export Citation

©2013 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Eva L. Kneepkens, Mieke F. Pouw, Gerrit Jan Wolbink, Tiny Schaap, Michael T. Nurmohamed, Annick de Vries, Theo Rispens, and Karien Bloem
British Journal of Clinical Pharmacology, 2017
[3]
Andrew G. Chambers, Andrew J. Percy, Juncong Yang, and Christoph H. Borchers
Molecular & Cellular Proteomics, 2015, Volume 14, Number 11, Page 3094
[4]
Kirsten A. Ganaja, Cory A. Chaplan, Jingyi Zhang, Nathaniel W. Martinez, and Andres W. Martinez
Analytical Chemistry, 2017, Volume 89, Number 10, Page 5333
[6]
S. Ghimenti, T. Lomonaco, D. Biagini, F.G. Bellagambi, M. Onor, M.G. Trivella, L. Ruocco, G. Pellegrini, F. Di Francesco, and R. Fuoco
Microchemical Journal, 2017
[7]
Cecilie Rosting, Astrid Gjelstad, and Trine Grønhaug Halvorsen
Analytical and Bioanalytical Chemistry, 2017, Volume 409, Number 13, Page 3383
[8]
Aleksandra Maleska, Christophe Hirtz, Elise Casteleyn, Orianne Villard, Jacques Ducos, Antoine Avignon, Ariane Sultan, and Sylvain Lehmann
Bioanalysis, 2017, Volume 9, Number 5, Page 427
[9]
AJ Lawson, L Bernstone, and SK Hall
Journal of Medical Screening, 2016, Volume 23, Number 1, Page 7
[10]
Josefa Mora Vallellano, Borja del Castillo Figueruelo, and Luis Manuel Jiménez Jiménez
Revista del Laboratorio Clínico, 2016, Volume 9, Number 4, Page 159
[11]
Judith Thijs, Wouter van Seggelen, Carla Bruijnzeel-Koomen, Marjolein de Bruin-Weller, and DirkJan Hijnen
Journal of Clinical Medicine, 2015, Volume 4, Number 3, Page 479
[12]
Christophe Hirtz and Sylvain Lehmann
Bioanalysis, 2015, Volume 7, Number 22, Page 2849
[13]
Tzu Chieh Chao, Omid Arjmandi-Tash, Diganta B. Das, and Victor M. Starov
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2016, Volume 505, Page 9
[14]
Tzu Chieh Chao, Omid Arjmandi-Tash, Diganta B. Das, and Victor M. Starov
Journal of Colloid and Interface Science, 2015, Volume 446, Page 218
[15]
Ramakrishnan Lakshmy, Mohamad Tarik, and Ransi Ann Abraham
Bioanalysis, 2014, Volume 6, Number 23, Page 3121
[16]
Niina Kleiber, Krista Tromp, Miriam G. Mooij, Suzanne van de Vathorst, Dick Tibboel, and Saskia N. de Wildt
Pediatric Drugs, 2015, Volume 17, Number 1, Page 43
[17]
Marie Konecna, Karel Novotny, Sona Krizkova, Iva Blazkova, Pavel Kopel, Jozef Kaiser, Petr Hodek, Rene Kizek, and Vojtech Adam
Spectrochimica Acta Part B: Atomic Spectroscopy, 2014, Volume 101, Page 220
[18]
Regina V Oliveira, Jack Henion, and Enaksha R Wickremsinhe
Bioanalysis, 2014, Volume 6, Number 15, Page 2027
[19]
Rosita Zakariaeeabkoo, Katrina J. Allen, Jennifer J. Koplin, Peter Vuillermin, and Ronda F. Greaves
Clinical Biochemistry, 2014, Volume 47, Number 9, Page 804

Comments (0)

Please log in or register to comment.
Log in