Personalized Clinical Diagnostics and Beyond: Integrated Ring Resonator Arrays

Summary

Principal Investigator: Ryan Bailey
Abstract: ABSTRACT Paradigm shifts in biology are often catalyzed by innovations in measurement technologies. Genomics and proteomics have revolutionized biology but would not have been possible without developments in capillary sequencing, cDNA microarrays, and mass spectrometry, amongst other enabling technologies. Cancer biology has significantly benefited from the molecular-level detail provided by these tools, allowing elucidation of many perturbations underlying disease onset and progression. Unfortunately, many of the same measurement approaches are not applicable in the clinical setting and thus physicians do not have access to the same detailed biochemical information enjoyed by the academician. As a result, despite our increased knowledge of the molecular bases of cancer, the translation to clinical medicine has lagged significantly behind. This proposal describes a revolutionary biological analysis technology which has the potential to profoundly change the face of clinical medicine and beyond. High density arrays of extraordinarily sensitive integrated microring resonators will allow many gene and protein signatures to be simultaneously quantitated from a single patient sample. Distinguishing features of this technology include: sensitivity allowing PCR-less gene and single protein detection, label-free and real time operation, ultra-high scalability (>50,000 sensors/cm2), automated microfluidic operation, and commercially validated manufacturability via CMOS-compatible processing. To demonstrate the power of this technology, we will generate a molecular disease fingerprint allowing differentiation between three clinically indistinguishable yet biochemically distinct disease pathways underlying the deadly brain cancer glioblastoma multiforme. Importantly, each of these pathways is known to respond effectively to different therapeutic agents, thus personalized diagnosis equates to personalized treatment. We will also utilize this enabling technology to provide insight into profound questions surrounding post-transcriptional gene regulation and heterogeneity within the secreted responses of individual immune cells. This technology promises to broadly impact the landscape of the biomedical sciences, both meeting the clinical diagnostic challenges of today and pioneering the paradigm-shifting discoveries of tomorrow.
Funding Period: 2007-09-30 - 2012-08-31
more information: NIH RePORT

Top Publications

  1. pmc Label-free technologies for quantitative multiparameter biological analysis
    Abraham J Qavi
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 S Mathews Ave, Urbana, IL 61801, USA
    Anal Bioanal Chem 394:121-35. 2009
  2. pmc Interfacing lipid bilayer nanodiscs and silicon photonic sensor arrays for multiplexed protein-lipid and protein-membrane protein interaction screening
    Courtney D Kuhnline Sloan
    Department of Chemistry, University of Illinois Urbana Champaign, Urbana, Illinois 61801, United States
    Anal Chem 85:2970-6. 2013
  3. pmc Single domain antibodies for the detection of ricin using silicon photonic microring resonator arrays
    Winnie W Shia
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 S Matthews Ave, Urbana, Illinois 61801, USA
    Anal Chem 85:805-10. 2013
  4. pmc Chaperone probes and bead-based enhancement to improve the direct detection of mRNA using silicon photonic sensor arrays
    Jared T Kindt
    Department of Chemistry, University of Illinois at Urbana Champaign, 61801, USA
    Anal Chem 84:8067-74. 2012
  5. pmc Nonlinear analyte concentration gradients for one-step kinetic analysis employing optical microring resonators
    Michael T Marty
    Department of Chemistry, University of Illinois Urbana Champaign, Urbana, Illinois 61801, United States
    Anal Chem 84:5556-64. 2012
  6. pmc Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening
    Jared T Kindt
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 South Matthews Avenue, Urbana, IL 61801, United States
    Curr Opin Chem Biol 17:818-26. 2013
  7. pmc Grand challenge commentary: Informative diagnostics for personalized medicine
    Ryan C Bailey
    Department of Chemistry, Institute for Genomic Biology, and the Micro and Nanotechnology Laboratory, University of Illinois at Urbana Champaign, Urbana, Illinois, USA
    Nat Chem Biol 6:857-9. 2010
  8. pmc Efficient bioconjugation of protein capture agents to biosensor surfaces using aniline-catalyzed hydrazone ligation
    Ji Yeon Byeon
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Langmuir 26:15430-5. 2010
  9. pmc Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators
    Adam L Washburn
    Department of Chemistry, Institute for Genomic Biology, and Micro and Nanotechnology Laboratory, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Anal Chem 81:9499-506. 2009
  10. pmc Sizing up the future of microRNA analysis
    Abraham J Qavi
    Department of Chemistry, Institute for Genomic Biology, and Micro and Nanotechnology Laboratory, University of Illinois, Urbana Champaign, 600 S Mathews Avenue, Urbana, IL 61801, USA
    Anal Bioanal Chem 398:2535-49. 2010

Detail Information

Publications25

  1. pmc Label-free technologies for quantitative multiparameter biological analysis
    Abraham J Qavi
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 S Mathews Ave, Urbana, IL 61801, USA
    Anal Bioanal Chem 394:121-35. 2009
    ..We describe the fundamental principles of these different methods and discuss advantages and disadvantages that might potentially help one in selecting the appropriate technology for a given bioanalytical application...
  2. pmc Interfacing lipid bilayer nanodiscs and silicon photonic sensor arrays for multiplexed protein-lipid and protein-membrane protein interaction screening
    Courtney D Kuhnline Sloan
    Department of Chemistry, University of Illinois Urbana Champaign, Urbana, Illinois 61801, United States
    Anal Chem 85:2970-6. 2013
    ..Using model systems, we demonstrate the applicability of this platform for the parallel screening of protein interactions with nanodisc-embedded lipids, glycolipids, and membrane proteins...
  3. pmc Single domain antibodies for the detection of ricin using silicon photonic microring resonator arrays
    Winnie W Shia
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 S Matthews Ave, Urbana, Illinois 61801, USA
    Anal Chem 85:805-10. 2013
    ..Given the rapidity, scalability, and multiplexing capability of this silicon-based technology, this work represents a step toward using microring resonator arrays for the sensitive and specific detection of biowarfare agents...
  4. pmc Chaperone probes and bead-based enhancement to improve the direct detection of mRNA using silicon photonic sensor arrays
    Jared T Kindt
    Department of Chemistry, University of Illinois at Urbana Champaign, 61801, USA
    Anal Chem 84:8067-74. 2012
    ....
  5. pmc Nonlinear analyte concentration gradients for one-step kinetic analysis employing optical microring resonators
    Michael T Marty
    Department of Chemistry, University of Illinois Urbana Champaign, Urbana, Illinois 61801, United States
    Anal Chem 84:5556-64. 2012
    ..The nonlinear analyte gradient method is demonstrated with a silicon photonic microring resonator platform to measure prostate specific antigen-antibody binding kinetics...
  6. pmc Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening
    Jared T Kindt
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 South Matthews Avenue, Urbana, IL 61801, United States
    Curr Opin Chem Biol 17:818-26. 2013
    ..Herein we highlight some of the most exciting recent uses of this technology for biosensing applications, with an eye towards future developments in the field...
  7. pmc Grand challenge commentary: Informative diagnostics for personalized medicine
    Ryan C Bailey
    Department of Chemistry, Institute for Genomic Biology, and the Micro and Nanotechnology Laboratory, University of Illinois at Urbana Champaign, Urbana, Illinois, USA
    Nat Chem Biol 6:857-9. 2010
    ..However, a grand challenge looms as informative diagnostic strategies must be developed to realize the full impact of these promising pharmaceutical agents...
  8. pmc Efficient bioconjugation of protein capture agents to biosensor surfaces using aniline-catalyzed hydrazone ligation
    Ji Yeon Byeon
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Langmuir 26:15430-5. 2010
    ....
  9. pmc Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators
    Adam L Washburn
    Department of Chemistry, Institute for Genomic Biology, and Micro and Nanotechnology Laboratory, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Anal Chem 81:9499-506. 2009
    ....
  10. pmc Sizing up the future of microRNA analysis
    Abraham J Qavi
    Department of Chemistry, Institute for Genomic Biology, and Micro and Nanotechnology Laboratory, University of Illinois, Urbana Champaign, 600 S Mathews Avenue, Urbana, IL 61801, USA
    Anal Bioanal Chem 398:2535-49. 2010
    ..In this critical review we describe recent improvements to classical methods of detection as well as innovative new technologies that are poised to help shape the future landscape of miRNA analysis...
  11. pmc Silicon photonic microring resonators for quantitative cytokine detection and T-cell secretion analysis
    Matthew S Luchansky
    Department of Chemistry, Institute for Genomic Biology, and Micro and Nanotechnology Laboratory, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Anal Chem 82:1975-81. 2010
    ....
  12. pmc Photonics-on-a-chip: recent advances in integrated waveguides as enabling detection elements for real-world, lab-on-a-chip biosensing applications
    Adam L Washburn
    Department of Chemistry, Institute for Genomic Biology and Micro and Nanotechnology Laboratory, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Analyst 136:227-36. 2011
    ..In addition, examples of multiplexed detection and sensing within complex matrices--important features for real-world applicability--are given special attention...
  13. pmc Label-free, multiplexed detection of bacterial tmRNA using silicon photonic microring resonators
    Ott Scheler
    Department of Biotechnology, Institute of Molecular and Cellular Biology, University of Tartu, Tartu, Estonia
    Biosens Bioelectron 36:56-61. 2012
    ..16×10(7) CFU of bacteria. The simplicity and scalability of this biosensing approach makes it a promising tool for the rapid identification of different bacteria via tmRNA profiling...
  14. pmc Label-free virus detection using silicon photonic microring resonators
    Melinda S McClellan
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 S Mathews Avenue, Urbana, IL 61801, USA
    Biosens Bioelectron 31:388-92. 2012
    ....
  15. pmc Rapid, multiparameter profiling of cellular secretion using silicon photonic microring resonator arrays
    Matthew S Luchansky
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    J Am Chem Soc 133:20500-6. 2011
    ..We also utilize this approach to probe the temporal secretion patterns of each T cell type using real-time binding analyses for direct cytokine quantitation down to ∼100 pM with just a 5 min-analysis...
  16. pmc Real-time monitoring of surface-initiated atom transfer radical polymerization using silicon photonic microring resonators: implications for combinatorial screening of polymer brush growth conditions
    F Ted Limpoco
    Department of Chemistry, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, United States
    J Am Chem Soc 133:14864-7. 2011
    ..This presents a powerful new platform for studying modified interfaces that may allow for the combinatorial optimization of surface-initiated polymerization conditions...
  17. pmc Anti-DNA:RNA antibodies and silicon photonic microring resonators: increased sensitivity for multiplexed microRNA detection
    Abraham J Qavi
    Department of Chemistry, University of Illinois at Urbana Champaign, Urbana Champaign, Illinois 61801, United States
    Anal Chem 83:5949-56. 2011
    ..The simplicity and sequence generality of this amplification method position it as a promising tool for high-throughput, multiplexed miRNA analysis as well as a range of other RNA based detection applications...
  18. pmc Sensitive on-chip detection of a protein biomarker in human serum and plasma over an extended dynamic range using silicon photonic microring resonators and sub-micron beads
    Matthew S Luchansky
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Lab Chip 11:2042-4. 2011
    ..This detection methodology is applied to CRP quantitation in human serum and plasma samples...
  19. pmc Multiplexed evaluation of capture agent binding kinetics using arrays of silicon photonic microring resonators
    Ji Yeon Byeon
    Department of Chemistry, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA
    Analyst 136:3430-3. 2011
    ....
  20. pmc Characterization of the evanescent field profile and bound mass sensitivity of a label-free silicon photonic microring resonator biosensing platform
    Matthew S Luchansky
    Department of Chemistry, Institute for Genomic Biology, and Micro and Nanotechnology Laboratory, University of Illinois at Urbana Champaign, 600 South Mathews Avenue, Urbana, IL 61801, United States
    Biosens Bioelectron 26:1283-91. 2010
    ..e. 0.8 zmol of IgG), demonstrating the remarkable sensitivity of this promising label-free biomolecular sensing platform...
  21. pmc DNA-encoding to improve performance and allow parallel evaluation of the binding characteristics of multiple antibodies in a surface-bound immunoassay format
    Adam L Washburn
    Department of Chemistry, University of Illinois at Urbana Champaign, 61801, United States
    Anal Chem 83:3572-80. 2011
    ....