Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743, Jena, Germany.
InfectoGnostics Research Campus Jena, Centre for Applied Research, Philosophenweg 7, 07743, Jena, Germany.
Anal Bioanal Chem. 2020 Sep;412(24):6351-6360. doi: 10.1007/s00216-020-02571-2. Epub 2020 Mar 14.
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.
三乙酰基麦角新碱 C（TAFC）是某些真菌物种产生的一种铁载体，可能是快速诊断侵袭性曲霉菌病的非常有用的生物标志物。由于其通过肾脏排泄，该生物标志物存在于患有曲霉菌感染的患者的尿液样本中。因此，从这种容易获得的体液进行非侵入性诊断是可能的。在我们的研究中，我们展示了拉曼光谱如何实现 TAFC 的灵敏和特异性检测。我们使用常规和干涉增强拉曼光谱（IERS）对 TAFC 铁复合物及其无铁形式进行了表征，并将其与相关化合物铁氧胺 B 的光谱进行了比较，铁氧胺 B 是由细菌物种产生的。尽管 IERS 仅提供了拉曼信号的适度增强，但使用相应的基底可以降低检测限，达到临床相关范围。使用 IERS 达到的检测限为 0.5ng TAFC，已经处于临床相关范围内。通过使用提取方案，我们能够在不到 3 小时的时间内，包括样品制备和数据分析，通过 IERS 从尿液中检测到 1.4μg/mL 的 TAFC。我们还进一步表明，即使在非常低的浓度下，TAFC 和铁氧胺 B 也可以通过它们的拉曼光谱清楚地区分。
