TY - JOUR

T1 - Antifungal Susceptibility Testing of Aspergillus Niger on Silicon Microwells by Intensity-Based Reflectometric Interference Spectroscopy

AU - Heuer, Christopher

AU - Leonard, Heidi

AU - Nitzan, Nadav

AU - Lavy-Alperovitch, Ariella

AU - Massad-Ivanir, Naama

AU - Scheper, Thomas

AU - Segal, Ester

N1 - Funding Information: This work was partially supported by the Israel Innovation Authority (Kamin program). C.H. acknowledges financial aid from the Leibniz Universitätsgesellschaft and the Technion. We thank Dima Peselev and Orna Ternyak (MNFPU, Technion) for the microfabrication of the photonic chips and Omer Sabach for his artwork depicting the microfluidic channels (A).

PY - 2020/10/9

Y1 - 2020/10/9

N2 - 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.

AB - 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.

KW - antifungal susceptibility testing

KW - Aspergillus Niger

KW - fungal resistance

KW - optical sensor

KW - sensor

UR - http://www.scopus.com/inward/record.url?scp=85092750049&partnerID=8YFLogxK

U2 - 10.1021/acsinfecdis.0c00234

DO - 10.1021/acsinfecdis.0c00234

M3 - Article

C2 - 32930571

AN - SCOPUS:85092750049

VL - 6

SP - 2560

EP - 2566

JO - ACS infectious diseases

JF - ACS infectious diseases

SN - 2373-8227

IS - 10

ER -