title: High-throughput and automated diagnosis of antimicrobial resistance using a cost-effective cellphone-based micro-plate reader.
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.
authors.affiliation: Electrical Engineering Department, University of California, Los Angeles, California 90095, United States.|Bioengineering Department, University of California, Los Angeles, California 90095, United States.
authors.forename: Steve
authors.initials: S
authors.lastname: Feng
authors.affiliation: Electrical Engineering Department, University of California, Los Angeles, California 90095, United States.|Bioengineering Department, University of California, Los Angeles, California 90095, United States.
authors.forename: Derek
authors.initials: D
authors.lastname: Tseng
authors.affiliation: Bioengineering Department, University of California, Los Angeles, California 90095, United States.|California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095, United States.
authors.forename: Dino
authors.initials: D
authors.lastname: Di Carlo
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, United States.
authors.forename: Omai B
authors.initials: OB
authors.lastname: Garner
authors.affiliation: Electrical Engineering Department, University of California, Los Angeles, California 90095, United States.|Bioengineering Department, University of California, Los Angeles, California 90095, United States.|California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, California 90095 United States.
authors.forename: Aydogan
authors.initials: A
authors.lastname: Ozcan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001331:Automation; D040421:Cell Phone; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis* / Q000382:microbiology; D057166:High-Throughput Screening Assays; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000302:isolation & purification; D046228:Microarray Analysis / Q000191:economics / Q000295:instrumentation / Q000379:methods*; D008826:Microbial Sensitivity Tests / Q000191:economics / Q000295:instrumentation / Q000379:methods*; D009391:Nephelometry and Turbidimetry
chemical_list: D000900:Anti-Bacterial Agents