APR 30, 2019 8:00 AM PDT

Small platform enables big change - Nanotech-assisted discovery of novel biomarkers for disease diagnosis

Speaker
  • Associate Professor, Biodesign Institute, Arizona State University
    Biography
      Tony Hu is an Associate Professor at the Biodesign Institute at Arizona State University's Virginia G. Piper Center for Personalized Diagnostics and at the Ira A. Fulton Schools of Engineering's School of Biological and Health Systems Engineering.

      Hu's research focuses on developing and validating integrated nanotechnique-based strategies for marker discovery and molecular diagnostics in peripheral blood samples to provide a translatable solution for personalized medicine. His innovations aim to fill current gaps in early detection, real-time therapy monitoring and effective prognostics. He has assembled a diverse team with backgrounds in biochemistry, mass spectrometry, nanofabrication, and biomedical engineering to answer these needs.

      Hu received his Ph.D. in Biomedical Engineering from the University of Texas at Austin where he focused on developing nanomaterials as biosensors for disease diagnosis. He has published more than 50 journal articles and has received five U.S. patents (issued and pending) on these subjects since his first faculty appointment in 2011. Hu has also published four nanomedicine-related book chapters, and has given more than 40 seminars and invited presentations at major international scientific conferences. His research team has a history of grants from the NCI, NIAID, NICHD and DOD and awards from the Gates, Dunn, Kostas, and Cockrell family foundations. His team has in-depth knowledge of multiplex-detection method development for sample processing, mass spectrometry, biomarker identification and validation. This background ideally positions his team for a leadership role in these fields and for optimal clinical translation of their platforms for improved and comprehensive analysis of blood-based biomarkers that have broad potential clinical applications.

    Abstract

    DATE: April 30, 2019
    TIME: 8:00am PDT

    Most TB cases are diagnosed by slow and somewhat non-specific microbiological methods. PCR-based GeneXpert MTB/RIF, introduced to improve speed and specificity, has poor sensitivity at low bacterial loads, cannot distinguish live and nonviable bacilli, and has reduced performance in HIV and TB co-infected patients.Serum-based detection of Mtb virulence factors offers direct evidence of TB, but current methods lack adequate sensitivity and specificity. We have developed a blood-based assay for rapid, specific, and high-sensitivity TB diagnosis, which uses nanodisks to enrich Mtb-selective peptides from serum samples. Our approach incorporates several technical advances, including identification of strongly Mtb-selective antigen peptides, and development of antibody-conjugated nanodisks that markedly increase target peptide enrichment and laser desorption/ionization of nanodisk-bound peptides to enhance their detection. This approach disrupts protein complexes, releasing Mtb antigen likely missed by conventional immunoassays targeting intact Mtb proteins. Our method permits rapid multiplex quantification of serum markers specific for robust diagnosis of active TB cases and uses accepted clinical instrumentation to enhance its potential for clinical translation.

    Our NanoDisk-enabled TB detection assay addresses sensitivity and speed shortcomings associated with active TB diagnosis, and meets several criteria for a WHO-mandated noninvasive TB assay. Specifically, it (i) uses a small, noninvasive specimen; (ii) does not require bacterial isolation; (iii) has high sensitivity and specificity for active TB cases in extrapulmonary, culture-negative, and HIV-infected TB patients, where diagnosis often requires multiple tests, including invasive procedures. It also (iv) directly quantifies Mtb antigens for rapid monitoring of anti-TB therapy effects; (v) uses a streamlined process amenable to high-throughput operation in clinical and research settings; and (vi) can be performed using equipment already approved by the Food and Drug Administration for other diagnostic assays. However, further improvements in operator time, assay cost, and instrument portability are necessary to meet all WHO guidelines for an optimal noninvasive TB assay.

    To further expend the capability of the assay in serving the patients in resource-limited area, we have also developed the solid-state nanopore technology, which can recognize single detection events to quantify two Mtb-specific peptide biomarkers derived from blood samples, to develop a point-of-care diagnostic system. Based on our preliminary studies, we are confident that this diagnostic system will benefit the global tuberculosis control effort by improving the personalized management of TB.

     


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