title: Highly efficient SERS-based detection of cerebrospinal fluid neopterin as a diagnostic marker of bacterial infection.
abstract: A highly efficient recognition unit based on surface-enhanced Raman spectroscopy (SERS) was developed as a promising, fast, and sensitive tool for detection of meningococcal meningitis, which is an extremely serious and often fatal disease of the nervous system (an inflammation of the lining around the brain and spinal cord). The results of this study confirmed that there were specific differences in SERS spectra between cerebrospinal fluid (CSF) samples infected by Neisseria meningitidis and the normal CSF, suggesting a potential role for neopterin in meningococcal meningitis detection and screening applications. To estimate the best performance of neopterin as a marker of bacterial infection, principal component analysis (PCA) was performed in a selected region (640-720 cm(-1)) where the most prominent SERS peak at 695 cm(-1) arising from neopterin was observed. The calculated specificity of 95 % and sensitivity of 98 % clearly indicate the effective diagnostic efficiency for differentiation between infected and control samples. Additionally, the limit of detection (LOD) of neopterin in CSF clinical samples was estimated. The level of neopterin was significantly higher in CSF samples infected by N. meningitidis (48 nmol/L), compared to the normal (control) group (4.3 nmol/L). Additionally, this work presents a new type of SERS-active nanostructure, based on polymer mats, that allows simultaneous filtration, immobilization, and enhancement of the Raman signal, enabling detection of spectra from single bacterial cells of N. meningitidis present in CSF samples. This provides a new possibility for fast and easy detection of bacteria in CSF and other clinical body fluids on a time scale of seconds. This method of detection produces consistent results faster and cheaper than traditional laboratory techniques, demonstrates the powerful potential of SERS for detection of disease, and shows the viability of future development in healthcare applications.
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland. akamin@ichf.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kamińska
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
authors.forename: Evelin
authors.initials: E
authors.lastname: Witkowska
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Kowalska
authors.affiliation: National Medicines Institute, Chełmska 30/34, 00-725, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Skoczyńska
authors.affiliation: National Medicines Institute, Chełmska 30/34, 00-725, Warsaw, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Gawryszewska
authors.affiliation: Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Guziewicz
authors.affiliation: Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668, Warsaw, Poland.
authors.forename: Dymitr
authors.initials: D
authors.lastname: Snigurenko
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.|Faculty of Mathematics and Natural Sciences, College of Science, Cardinal Stefan Wyszyński University, Dewajtis 5, 01-815, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Waluk
mesh_terms: D002555:Cerebrospinal Fluid / Q000737:chemistry*; D006801:Humans; D057230:Limit of Detection; D008585:Meningitis, Meningococcal / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000382:microbiology; D009345:Neisseria meningitidis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D019798:Neopterin / Q000134:cerebrospinal fluid*; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D019798:Neopterin
keywords: Bacterial infections; Cerebrospinal fluid; Neisseria meningitidis; Neopterin; Surface-enhanced Raman spectroscopy (SERS)