Point-of-Care Serodiagnostic Test for Early-Stage Lyme Disease Using a Multiplexed Paper-Based Immunoassay and Machine Learning.

Journal: ACS nano
PMID: 31849225

Abstract

Caused by the tick-borne spirochete , Lyme disease (LD) is the most common vector-borne infectious disease in North America and Europe. Though timely diagnosis and treatment are effective in preventing disease progression, current tests are insensitive in early stage LD, with a sensitivity of <50%. Additionally, the serological testing currently recommended by the U.S. Center for Disease Control has high costs (>$400/test) and extended sample-to-answer timelines (>24 h). To address these challenges, we created a cost-effective and rapid point-of-care (POC) test for early-stage LD that assays for antibodies specific to seven antigens and a synthetic peptide in a paper-based multiplexed vertical flow assay (xVFA). We trained a deep-learning-based diagnostic algorithm to select an optimal subset of antigen/peptide targets and then blindly tested our xVFA using human samples ( = 42, = 54), achieving an area-under-the-curve (AUC), sensitivity, and specificity of 0.950, 90.5%, and 87.0%, respectively, outperforming previous LD POC tests. With batch-specific standardization and threshold tuning, the specificity of our blind-testing performance improved to 96.3%, with an AUC and sensitivity of 0.963 and 85.7%, respectively.

Authors

  • Hyou-Arm Joung
    Department of Electrical & Computer Engineering , University of California , Los Angeles , California 90025 , United States.
  • Zachary S Ballard
    Electrical Engineering Department, ‡Bioengineering Department, and §California NanoSystems Institute (CNSI), University of California , Los Angeles, California 90095, United States.
  • Jing Wu
    School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, Jiangsu, China.
  • Derek K Tseng
    Department of Electrical & Computer Engineering , University of California , Los Angeles , California 90025 , United States.
  • Hailemariam Teshome
    Department of Neuroscience , University of California , Los Angeles , California 90025 , United States.
  • Linghao Zhang
    Department of Mechanical Engineering , University of California , Los Angeles , California 90025 , United States.
  • Elizabeth J Horn
    Lyme Disease Biobank , Portland , Oregon 97221 , United States.
  • Paul M Arnaboldi
    Department of Microbiology/Immunology , New York Medical College , Valhalla , New York 10595 , United States.
  • Raymond J Dattwyler
    Department of Microbiology/Immunology , New York Medical College , Valhalla , New York 10595 , United States.
  • Omai B Garner
    Department of Pathology and Laboratory Medicine , University of California , Los Angeles , California 90025 , United States.
  • Dino Di Carlo
    2Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, PO Box 951600, Los Angeles, CA 90095 USA.
  • Aydogan Ozcan
    Electrical and Computer Engineering Department, University of California, Los Angeles, California 90095, USA.

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