Rapid detection of the aspergillosis biomarker triacetylfusarinine C using interference-enhanced Raman spectroscopy
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RESEARCH PAPER
Rapid detection of the aspergillosis biomarker triacetylfusarinine C using interference-enhanced Raman spectroscopy Susanne Pahlow 1,2,3 & Thomas Orasch 4,5 & Olga Žukovskaja 1,2,3 & Thomas Bocklitz 3 & Hubertus Haas 5 & Karina Weber 1,2,3 Received: 13 December 2019 / Revised: 20 February 2020 / Accepted: 2 March 2020 # The Author(s) 2020
Abstract Triacetylfusarinine C (TAFC) is a siderophore produced by certain fungal species and might serve as a highly useful biomarker for the fast diagnosis of invasive aspergillosis. Due to its renal elimination, the biomarker is found in urine samples of patients suffering from Aspergillus infections. Accordingly, non-invasive diagnosis from this easily obtainable body fluid is possible. Within our contribution, we demonstrate how Raman microspectroscopy enables a sensitive and specific detection of TAFC. We characterized the TAFC iron complex and its iron-free form using conventional and interference-enhanced Raman spectroscopy (IERS) and compared the spectra with the related compound ferrioxamine B, which is produced by bacterial species. Even though IERS only offers a moderate enhancement of the Raman signal, the employment of respective substrates allowed lowering the detection limit to reach the clinically relevant range. The achieved limit of detection using IERS was 0.5 ng of TAFC, which is already well within the clinically relevant range. By using an extraction protocol, we were able to detect 1.4 μg/mL TAFC via IERS from urine within less than 3 h including sample preparation and data analysis. We could further show that TAFC and ferrioxamine B can be clearly distinguished by means of their Raman spectra even in very low concentrations. Keywords Raman spectroscopy . Interference-enhancedRaman spectroscopy . Siderophores . Aspergillosis . Infectiousdiseases . Biomarkers
Introduction Invasive aspergillosis (IA) is one of the most common invasive fungal infections, mainly affecting immunocompromised patients and predominantly caused by the mold Aspergillus
fumigatus [1]. This severe infection is associated with 90day mortality rates of more than 60% depending on the patient cohort [2]. One reason for these high mortality rates is the challenging diagnosis of Aspergillus infections. There is no single “gold standard” for IA diagnosis and the detection of
Published in the topical collection featuring Female Role Models in Analytical Chemistry. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00216-020-02571-2) contains supplementary material, which is available to authorized users. * Susanne Pahlow [email protected]
3
Leibniz Institute of Photonic Technology - Member of the research alliance “Leibniz Health Technologies”, Albert-Einstein-Straße 9, 07745 Jena, Germany
1
Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany
4
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Rese
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