Increased antimicrobial resistance presents a major threat to public health, and it is a global health problem due to the rapid globalization and transmission of infectious diseases. However, fast and precise diagnosis tool is lacking, and inappropriate antibiotic prescription leads to the unforeseen production of drug-resistant bacteria. Here, we report a Rapid and Accurate Nanoelectrokinetic Diagnostic System (RANDx) for detecting drug-resistant bacteria, which cause a common infectious disease called Urinary Tract Infection (UTI), within 7 min. We develop nanoelectrokinetic paper-based analytic device (NEK-PAD) as a sample prep module of RANDx and obtain >100-fold post-wetting preconcentration by balancing between ion concentration polarization (ICP) and radial imbibition for a constant flow rate. Simultaneously with preconcentration, our cathodic nanochannel design enables NEK-PAD to extract drug-resistant enzymes without denaturation and accelerate enzyme-linked reactions under electrical spontaneous heating at approximately 37 °C. Finally, using a cell phone camera, we detect label-free drug-resistant bacteria as low as 104 cfu/mL, which is higher than clinically required threshold (>105 cfu/mL) by enhancing 1000 times of the limit of detection (LOD) of colorimetric nitrocefin assay. We believe that the RANDx will be an innovative precision medicine tool for UTI and other infectious diseases in limited remote settings.
Bibliographical noteFunding Information:
This work is supported by Basic Research Laboratory Project ( NRF-2021R1A4A2001553 ) and Mid-Career Researcher Program ( NRF-2020R1A2C300616212 ) by the Ministry of Science and ICT . Wonseok Kim is mainly supported by Sejong Science Fellowship ( NRF-2021R1C1C201260311 ) by the Ministry of Science and ICT . Also, authors acknowledged the ﬁnancial supports from BK21 FOUR program of the Education and Research Program for Future ICT Pioneers, Seoul National University . Luke P. Lee would like to acknowledge funding from the National Institutes of Health (NIH) ( R01 AI117064-01 ) and the Air Force Office of Scientific Research ( AFOSR FA2386-20-1-4060 ). Bacteria were thankfully provided by Prof. S. W. Seo at School of Chemical and Biological Engineering, Seoul National University.
© 2022 Elsevier B.V.
- Drug-resistant bacterial detection
- Ion concentration polarization
- Label-free colorimetric detection
- Microfluidic paper-based analytical device
- Urinary tract infection diagnosis