TY - JOUR

T1 - A 3D-printed microfluidic gradient generator with integrated photonic silicon sensors for rapid antimicrobial susceptibility testing

AU - Heuer, Christopher

AU - Preuss, John Alexander

AU - Buttkewitz, Marc

AU - Scheper, Thomas

AU - Segal, Ester

AU - Bahnemann, Janina

N1 - Funding Information: This research was funded by the German Research Foundation (DFG) via the Emmy Noether program (project ID 346772917), by the VolkswagenStiftung via the program “Niedersächsisches Vorab: Research Cooperation Lower Saxony—Israel”, and by the DFG via the grant SCHE 279/32-2. We also wish to thank Dima Peselev and Orna Ternyak of the Technion's at the micro- and nano-fabrication and printing unit for the microfabrication of the photonic silicon chips. Part of the cartoons in Fig. 1 and 4 were obtained from https://BioRender.com under a publishing license. The open access publication of this article was supported by the DFG sponsored Open Access Fund of the University of Augsburg.

PY - 2022/11/22

Y1 - 2022/11/22

N2 - With antimicrobial resistance becoming a major threat to healthcare settings around the world, there is a paramount need for rapid point-of-care antimicrobial susceptibility testing (AST) diagnostics. Unfortunately, most currently available clinical AST tools are lengthy, laborious, or are simply inappropriate for point-of-care testing. Herein, we design a 3D-printed microfluidic gradient generator that automatically produces two-fold dilution series of clinically relevant antimicrobials. We first establish the compatibility of these generators for classical AST (i.e., broth microdilution) and then extend their application to include a complete on-chip label-free and phenotypic AST. This is accomplished by the integration of photonic silicon chips, which provide a preferential surface for microbial colonization and allow optical tracking of bacterial behavior and growth at a solid-liquid interface in real-time by phase shift reflectometric interference spectroscopic measurements (PRISM). Using Escherichia coli and ciprofloxacin as a model pathogen-drug combination, we successfully determine the minimum inhibitory concentration within less than 90 minutes. This gradient generator-based PRISM assay provides an integrated AST device that is viable for convenient point-of-care testing and offers a promising and most importantly, rapid alternative to current clinical practices, which extend to 8-24 h.

AB - With antimicrobial resistance becoming a major threat to healthcare settings around the world, there is a paramount need for rapid point-of-care antimicrobial susceptibility testing (AST) diagnostics. Unfortunately, most currently available clinical AST tools are lengthy, laborious, or are simply inappropriate for point-of-care testing. Herein, we design a 3D-printed microfluidic gradient generator that automatically produces two-fold dilution series of clinically relevant antimicrobials. We first establish the compatibility of these generators for classical AST (i.e., broth microdilution) and then extend their application to include a complete on-chip label-free and phenotypic AST. This is accomplished by the integration of photonic silicon chips, which provide a preferential surface for microbial colonization and allow optical tracking of bacterial behavior and growth at a solid-liquid interface in real-time by phase shift reflectometric interference spectroscopic measurements (PRISM). Using Escherichia coli and ciprofloxacin as a model pathogen-drug combination, we successfully determine the minimum inhibitory concentration within less than 90 minutes. This gradient generator-based PRISM assay provides an integrated AST device that is viable for convenient point-of-care testing and offers a promising and most importantly, rapid alternative to current clinical practices, which extend to 8-24 h.

UR - http://www.scopus.com/inward/record.url?scp=85142720394&partnerID=8YFLogxK

U2 - 10.1039/d2lc00640e

DO - 10.1039/d2lc00640e

M3 - Article

C2 - 36412200

AN - SCOPUS:85142720394

VL - 22

SP - 4950

EP - 4961

JO - LAB on a chip

JF - LAB on a chip

SN - 1473-0197

IS - 24

ER -