title: Surface enhanced Raman spectroscopic direct determination of low molecular weight biothiols in umbilical cord whole blood.
abstract: Biothiols play an essential role in a number of biological processes in living organisms including detoxification and metabolism. Fetal to neonatal transition poses a pro-oxidant threat for newborn infants, especially those born prematurely. A reliable and rapid tool for the direct determination of thiols in small volume whole blood (WB) samples would be desirable for its application in clinical practice. This study shows the feasibility of Surface Enhanced Raman Spectroscopy (SERS) using a silver colloid prepared by reduction of silver nitrate using hydroxylamine, as the SERS substrate for the quantification of thiols in WB samples after a simple precipitation step for protein removal. Bands originating from biothiols (790, 714 and 642 cm(-1)) were enhanced by the employed SERS substrate and the specificity of the detected SERS signal was tested for molecules presenting -SH functional groups. A statistically significant correlation between the obtained SERS signals and the thiol concentration measured using a chromatographic reference method in umbilical cord WB samples could be demonstrated. Using WB GSH concentrations obtained from the chromatographic reference procedure, a Partial Least Squares (PLS) regression model covering GSH concentrations from 13 to 2200 μM was calculated obtaining a root mean square error of prediction (RMSEP) of 381 μM when applied to an external test set. The developed approach uses small blood sample volumes (50 μL), which is important for clinical applications, especially in the field of neonatology. This feasibility study shows that the present approach combines all the necessary characteristics for its potential application in clinical practice.
authors.affiliation: Neonatal Research Unit, Health Research Institute Hospital La Fe, Avda Fernando Abril Martorell 106, 46026 Valencia, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Kuligowski
authors.affiliation: Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/151, A-1060 Vienna, Austria. bernhard.lendl@tuwien.ac.at and Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut, Egypt.
authors.forename: Marwa R
authors.initials: MR
authors.lastname: El-Zahry
authors.affiliation: Neonatal Research Unit, Health Research Institute Hospital La Fe, Avda Fernando Abril Martorell 106, 46026 Valencia, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Sánchez-Illana
authors.affiliation: Safety & Sustainability, Leitat Technological Center, Avda Fernando Abril Martorell 106, 46026 Valencia, Spain and Analytical Unit, Health Research Institute Hospital La Fe, Avda Fernando Abril Martorell 106, 46026 Valencia, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Quintás
authors.affiliation: Neonatal Research Unit, Health Research Institute Hospital La Fe, Avda Fernando Abril Martorell 106, 46026 Valencia, Spain and Division of Neonatology, University & Polytechnic Hospital La Fe, Avda Fernando Abril Martorell 106, 46026 Valencia, Spain and National Coordinator Spanish Maternal and Child Health and Development Network SAMID, Instituto Carlos III (Spanish Ministry of Economy and Competitiveness), Spain.
authors.forename: Máximo
authors.initials: M
authors.lastname: Vento
authors.affiliation: Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/151, A-1060 Vienna, Austria. bernhard.lendl@tuwien.ac.at.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lendl
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D005240:Feasibility Studies; D005312:Fetal Blood / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007231:Infant, Newborn; D057230:Limit of Detection; D053768:Metal Nanoparticles / Q000737:chemistry; D008970:Molecular Weight; D012834:Silver / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D013438:Sulfhydryl Compounds / Q000097:blood* / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D013438:Sulfhydryl Compounds; D012834:Silver