Smartphone-based pathogen diagnosis in urinary sepsis patientsResearch in context
Lucien Barnes,
Douglas M. Heithoff,
Scott P. Mahan,
Gary N. Fox,
Andrea Zambrano,
Jane Choe,
Lynn N. Fitzgibbons,
Jamey D. Marth,
Jeffrey C. Fried,
H. Tom Soh,
Michael J. Mahan
Affiliations
Lucien Barnes
Department of Molecular, Cellular, and Developmental Biology, Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA
Douglas M. Heithoff
Department of Molecular, Cellular, and Developmental Biology, Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA
Scott P. Mahan
Department of Molecular, Cellular, and Developmental Biology, Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA
Gary N. Fox
Department of Materials and Department of Mechanical Engineering, University of California, Santa Barbara, CA 93106, USA
Andrea Zambrano
Department of Medical Education and Division of Infectious Diseases, Santa Barbara Cottage Hospital, Santa Barbara, CA 93105, USA
Jane Choe
Department of Microbiology, Pacific Diagnostic Laboratories, Santa Barbara, CA 93111, USA
Lynn N. Fitzgibbons
Department of Medical Education and Division of Infectious Diseases, Santa Barbara Cottage Hospital, Santa Barbara, CA 93105, USA
Jamey D. Marth
Department of Molecular, Cellular, and Developmental Biology, Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA; Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA 92037, USA
Jeffrey C. Fried
Department of Pulmonary and Critical Care Medicine, Santa Barbara Cottage Hospital, Santa Barbara, CA 93105, USA
H. Tom Soh
Department of Electrical Engineering and Department of Radiology, Stanford University, Stanford, CA 94305, USA; Correspondence to H. Tom Soh, Dept. of Electrical Engineering and Department of Radiology, Stanford University, Stanford, CA 94306, USA.
Michael J. Mahan
Department of Molecular, Cellular, and Developmental Biology, Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA; Correspondence to Michael J. Mahan, Dept. of Molecular, Cellular, and Developmental Biology, Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA.
Background: There is an urgent need for rapid, sensitive, and affordable diagnostics for microbial infections at the point-of-care. Although a number of innovative systems have been reported that transform mobile phones into potential diagnostic tools, the translational challenge to clinical diagnostics remains a significant hurdle to overcome. Methods: A smartphone-based real-time loop-mediated isothermal amplification (smaRT-LAMP) system was developed for pathogen ID in urinary sepsis patients. The free, custom-built mobile phone app allows the phone to serve as a stand-alone device for quantitative diagnostics, allowing the determination of genome copy-number of bacterial pathogens in real time. Findings: A head-to-head comparative bacterial analysis of urine from sepsis patients revealed that the performance of smaRT-LAMP matched that of clinical diagnostics at the admitting hospital in a fraction of the time (~1 h vs. 18–28 h). Among patients with bacteremic complications of their urinary sepsis, pathogen ID from the urine matched that from the blood – potentially allowing pathogen diagnosis shortly after hospital admission. Additionally, smaRT-LAMP did not exhibit false positives in sepsis patients with clinically negative urine cultures. Interpretation: The smaRT-LAMP system is effective against diverse Gram-negative and -positive pathogens and biological specimens, costs less than $100 US to fabricate (in addition to the smartphone), and is configurable for the simultaneous detection of multiple pathogens. SmaRT-LAMP thus offers the potential to deliver rapid diagnosis and treatment of urinary tract infections and urinary sepsis with a simple test that can be performed at low cost at the point-of-care. Fund: National Institutes of Health, Chan-Zuckerberg Biohub, Bill and Melinda Gates Foundation. Keywords: Smartphone-based pathogen diagnosis, Urinary sepsis, Urinary tract infection, Urinary diagnostic test
