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.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
3DP2OD002190-01S1
Application #
7937577
Study Section
Special Emphasis Panel (ZGM1-NDIA-G (03))
Program Officer
Basavappa, Ravi
Project Start
2007-09-30
Project End
2012-08-31
Budget Start
2007-09-30
Budget End
2012-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$99,500
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Washburn, Adam L; Shia, Winnie W; Lenkeit, Kimberly A et al. (2016) Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays. Analyst 141:5358-5365
Valera, Enrique; McClellan, Melinda S; Bailey, Ryan C (2015) Magnetically-actuated, bead-enhanced silicon photonic immunosensor. Anal Methods 7:8539-8544
Kindt, Jared T; Bailey, Ryan C (2013) Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening. Curr Opin Chem Biol 17:818-26
Shia, Winnie W; Bailey, Ryan C (2013) Single domain antibodies for the detection of ricin using silicon photonic microring resonator arrays. Anal Chem 85:805-10
Kindt, Jared T; Luchansky, Matthew S; Qavi, Abraham J et al. (2013) Subpicogram per milliliter detection of interleukins using silicon photonic microring resonators and an enzymatic signal enhancement strategy. Anal Chem 85:10653-7
Sloan, Courtney D Kuhnline; Marty, Michael T; Sligar, Stephen G et al. (2013) Interfacing lipid bilayer nanodiscs and silicon photonic sensor arrays for multiplexed protein-lipid and protein-membrane protein interaction screening. Anal Chem 85:2970-6
Marty, Michael T; Sloan, Courtney D Kuhnline; Bailey, Ryan C et al. (2012) Nonlinear analyte concentration gradients for one-step kinetic analysis employing optical microring resonators. Anal Chem 84:5556-64
Scheler, Ott; Kindt, Jared T; Qavi, Abraham J et al. (2012) Label-free, multiplexed detection of bacterial tmRNA using silicon photonic microring resonators. Biosens Bioelectron 36:56-61
Luchansky, Matthew S; Bailey, Ryan C (2012) High-Q optical sensors for chemical and biological analysis. Anal Chem 84:793-821
Kindt, Jared T; Bailey, Ryan C (2012) Chaperone probes and bead-based enhancement to improve the direct detection of mRNA using silicon photonic sensor arrays. Anal Chem 84:8067-74

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