High-throughput and automated diagnosis of antimicrobial resistance using a cost-effective cellphone-based micro-plate reader

Sci Rep. 2016 Dec 15:6:39203. doi: 10.1038/srep39203.

Abstract

Routine antimicrobial susceptibility testing (AST) can prevent deaths due to bacteria and reduce the spread of multi-drug-resistance, but cannot be regularly performed in resource-limited-settings due to technological challenges, high-costs, and lack of trained professionals. We demonstrate an automated and cost-effective cellphone-based 96-well microtiter-plate (MTP) reader, capable of performing AST without the need for trained diagnosticians. Our system includes a 3D-printed smartphone attachment that holds and illuminates the MTP using a light-emitting-diode array. An inexpensive optical fiber-array enables the capture of the transmitted light of each well through the smartphone camera. A custom-designed application sends the captured image to a server to automatically determine well-turbidity, with results returned to the smartphone in ~1 minute. We tested this mobile-reader using MTPs prepared with 17 antibiotics targeting Gram-negative bacteria on clinical isolates of Klebsiella pneumoniae, containing highly-resistant antimicrobial profiles. Using 78 patient isolate test-plates, we demonstrated that our mobile-reader meets the FDA-defined AST criteria, with a well-turbidity detection accuracy of 98.21%, minimum-inhibitory-concentration accuracy of 95.12%, and a drug-susceptibility interpretation accuracy of 99.23%, with no very major errors. This mobile-reader could eliminate the need for trained diagnosticians to perform AST, reduce the cost-barrier for routine testing, and assist in spatio-temporal tracking of bacterial resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Automation
  • Cell Phone
  • Drug Resistance, Bacterial
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / diagnosis*
  • Gram-Negative Bacterial Infections / microbiology
  • High-Throughput Screening Assays
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / isolation & purification
  • Microarray Analysis / economics
  • Microarray Analysis / instrumentation
  • Microarray Analysis / methods*
  • Microbial Sensitivity Tests / economics
  • Microbial Sensitivity Tests / instrumentation
  • Microbial Sensitivity Tests / methods*
  • Nephelometry and Turbidimetry

Substances

  • Anti-Bacterial Agents