title: Screening the low molecular weight fraction of human serum using ATR-IR spectroscopy.
abstract: Vibrational spectroscopic techniques can detect small variations in molecular content, linked with disease, showing promise for screening and early diagnosis. Biological fluids, particularly blood serum, are potentially valuable for diagnosis purposes. The so-called Low Molecular Weight Fraction (LMWF) contains the associated peptidome and metabolome and has been identified as potentially the most relevant molecular population for disease-associated biomarker research. Although vibrational spectroscopy can deliver a specific chemical fingerprint of the samples, the High Molecular Weight Fraction (HMWF), composed of the most abundant serum proteins, strongly dominates the response and ultimately makes the detection of minor spectral variations a challenging task. Spectroscopic detection of potential serum biomarkers present at relatively low concentrations can be improved using pre-analytical depletion of the HMWF. In the present study, human serum fractionation by centrifugal filtration was used prior to analysis by Attenuated Total Reflection infrared spectroscopy. Using a model sample based on glycine spiked serum, it is demonstrated that the screening of the LMWF can be applied to quantify blinded concentrations up to 50 times lower. Moreover, the approach is easily transferable to different bodily fluids which would support the development of more efficient and suitable clinical protocols exploring vibrational spectroscopy based ex-vivo diagnostic tools. Revealing serum LMWF for spectral serological diagnostic applications.
authors: Université François-Rabelais de Tours, Faculty of Pharmacy, 31 avenue Monge, 37200, Tours, France. franck.bonnier@univ-tours.fr.
authors: Franck
authors: F
authors: Bonnier
authors: Université François Rabelais de Tours, UMR CNRS 7292 Génétique, Immunothérapie, Chimie et Cancer, Faculté de Médecine, 10 Bd Tonnellé, 37032, Tours, Cedex.
authors: Guillaume
authors: G
authors: Brachet
authors: Université François-Rabelais de Tours, Faculty of Pharmacy, 31 avenue Monge, 37200, Tours, France.
authors: Romain
authors: R
authors: Duong
authors: FOCAS Research Institute, Dublin Institute of Technology (DIT), Camden Row, Dublin 8, Ireland.
authors: Tobiloba
authors: T
authors: Sojinrin
authors: Université François-Rabelais de Tours, F-37032, Tours, France.
authors: Renaud
authors: R
authors: Respaud
authors: Université de Tours, 37200, Tours, France.|Institut National de la Recherche Agronomique, 37380, Nouzilly, France.
authors: Nicolas
authors: N
authors: Aubrey
authors: WestCHEM, Technology and Innovation Centre, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.
authors: Matthew J
authors: MJ
authors: Baker
authors: FOCAS Research Institute, Dublin Institute of Technology (DIT), Camden Row, Dublin 8, Ireland.
authors: Hugh J
authors: HJ
authors: Byrne
authors: Université François-Rabelais de Tours, Faculty of Pharmacy, 31 avenue Monge, 37200, Tours, France.
authors: Igor
authors: I
authors: Chourpa
mesh_terms: D015415:Biomarkers / Q000097:blood; D006801:Humans; D008970:Molecular Weight; D044967:Serum / Q000737:chemistry*; D013055:Spectrophotometry, Infrared
chemical_list: D015415:Biomarkers
keywords: Attenuated Total Reflection (ATR); IR spectroscopy; Low Molecular Weight Fraction (LMWF); Principal Component Analysis; centrifugal filtration; human serum