Antifungal Susceptibility Testing of Aspergillus Niger on Silicon Microwells by Intensity-Based Reflectometric Interference Spectroscopy

Abstract

There is a demonstrated and paramount need for rapid, reliable infectious disease diagnostics, particularly those for invasive fungal infections. Current clinical determinations for an appropriate antifungal therapy can take up to 3 days using current antifungal susceptibility testing methods, a time-to-readout that can prove detrimental for immunocompromised patients and promote the spread of antifungal resistant pathogens. Herein, we demonstrate the application of intensity-based reflectometric interference spectroscopic measurements (termed iPRISM) on microstructured silicon sensors for use as a rapid, phenotypic antifungal susceptibility test. This diagnostic platform optically tracks morphological changes of fungi corresponding to conidia growth and hyphal colonization at a solid-liquid interface in real time. Using Aspergillus niger as a model fungal pathogen, we can determine the minimal inhibitory concentration of clinically relevant antifungals within 12 h. This assay allows for expedited detection of fungal growth and provides a label-free alternative to broth microdilution and agar diffusion methods, with the potential to be used for point-of-care diagnostics.