Rapid and accurate nanoelectrokinetic diagnosis of drug-resistant bacteria

Abstract

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.

Keywords: Drug-resistant bacterial detection; Ion concentration polarization; Label-free colorimetric detection; Microfluidic paper-based analytical device; Nanoelectrokinetics; Urinary tract infection diagnosis.