"Barcode" cell sensor microfluidic system: Rapid and sample-to-answer antimicrobial susceptibility testing applicable in resource-limited conditions

Abstract

Many rapid antimicrobial susceptibility testing (AST) methods have been proposed to contain clinical antimicrobial resistance (AMR) and preserve the effectiveness of remaining antimicrobials. However, far fewer methods have been proposed to test AMR in resource-limited conditions, such as for frequent safety screenings of water/food/public facilities, urgent surveys of massive samples during a pandemic, or AMR tests in low-income countries. Rapid AST methods realized thus far have a variety of drawbacks when used for such surveys, e.g., high cost and the requirement of expensive instruments such as microscopy. A more reasonable strategy would be to screen samples via onsite testing first, and then send any sample suspected to contain AMR bacteria for advanced testing. Accordingly, a cost-efficient AST is demanded, which can rapidly process a large number of samples without using expensive equipment. To this end, current work demonstrates a novel "barcode" cell sensor based on an adaptive linear filter array as a fully automatic and microscope-free method for counting very small volumes of cells (~1.00 × 10⁴ cells without pre-incubation), wherein suspended cells concentrate into microbars with length proportional to the number of cells. We combined this sensor with an on-chip culture approach we had demonstrated for rapid and automated drug exposure and realized a low-cost and resource-independent platform for portable AST, from which results can be obtained simply through a cell phone. This method has a much shorter turnaround time (2-3 h) than that of standard methods (16-24 h). Thanks to its microscopy-free analysis, affordability, portability, high throughput, and user-friendliness, our "barcode" AST system has the potential to fulfill the various demands of AST when advanced facilities are not available, making it a promising new tool in the fight against AMR.

Keywords: "Barcode" Cell Sensor; Cell phone app; Chip; Cost-efficient; Microfluidic; Onsite detection; Portable analysis; Rapid antimicrobial susceptibility testing; Resource-limited condition.