Details
| Original language | English |
|---|---|
| Pages (from-to) | 4950-4961 |
| Number of pages | 12 |
| Journal | LAB on a chip |
| Volume | 22 |
| Issue number | 24 |
| Publication status | Published - 22 Nov 2022 |
Abstract
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.
ASJC Scopus subject areas
- Chemical Engineering(all)
- Bioengineering
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Chemistry(all)
- Engineering(all)
- Biomedical Engineering
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In: LAB on a chip, Vol. 22, No. 24, 22.11.2022, p. 4950-4961.
Research output: Contribution to journal › Article › Research › peer review
}
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 -