Background. Analyte specificity and sensitivity for biosensing in general and multiplexed sensing of biomedically relevant compounds must be improved to provide clinical utility for these devices. In particular, improvement of sensor signal while limiting noise are two important performance enhancements sought with improved designs. This proposal is motivated by our observations that (1) immunobiosensing represents the most commonly exploited and developed bioanalytical device for non-invasive and invasive biomedical diagnosis; (2) detection limits for analytes scale with immunosensing array size; (3) submicron optical waveguides represent a technical frontier for this sensing modality; (4) advantages of reducing size scale in optical waveguides are feasible with a paradigm shift in this sensing device design. ? ? Hypothesis. To address these challenges, we propose our working hypothesis that increased bioananalyte sensitivity and device response for multianalyte sensing in complex milieu (e.g., physiological fluids, saliva, and serum) will be gained by integrating a new optical sensing mode with miniaturization of sensing components to the sub-micron scale. This hypothesis involves integrating issues of device scale (transport, arraying, optical reporting) with new optical waveguide device modalities appropriate for sensing constructs fabricated in this size scale ? ? Specific Aims. To test and validate our hypothesis, we propose the following five Specific Aims: ? Aim 1: Define by optical theory a mode for reagentless evanescent detection in this model; ? Aim 2: Use fluid transport theories to support rapid response and detection kinetics and waveguide sensing performance enhancements expected for this device operating in these small size (sub-micron) optical and fluid mechanical scales; ? Aim 3: Establish a functional prototype integrated optical waveguide sensing device based on a new submicron waveguide method and microarrayed immunoprobe regions specific for different analytes; ? Aim 4: Integrate NSOM far-field optics as a detection technology into a waveguide device for sub-micron evanescent sensing; ? Aim 5: Establish working bioanalytical definitions for sensitivity limits, detection, and kinetic response for four model analyte classes--small molecules, proteins, viruses, and DNA--using this device in complex fluid milieu relevant to physiological based sensing. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000726-02
Application #
6663155
Study Section
Special Emphasis Panel (ZRG1-SSS-F (02))
Program Officer
Korte, Brenda
Project Start
2002-09-25
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$604,773
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Stephens, Matthew D; Yuan, Guangwei; Lear, Kevin L et al. (2010) Optical and physical characterization of a local evanescent array coupled biosensor: Use of evanescent field perturbations for multianalyte sensing. Sens Actuators B Chem 145:769-774
Lynn, N Scott; Henry, Charles S; Dandy, David S (2009) Evaporation from microreservoirs. Lab Chip 9:1780-8
Murphy, Brian M; Dandy, David S; Henry, Charles S (2009) Analysis of oxidative stress biomarkers using a simultaneous competitive/non-competitive micromosaic immunoassay. Anal Chim Acta 640:1-6
Yan, Rongjin; Mestas, Santano P; Yuan, Guangwei et al. (2009) Label-free silicon photonic biosensor system with integrated detector array. Lab Chip 9:2163-8
Lynn, N Scott; Dandy, David S (2009) Passive microfluidic pumping using coupled capillary/evaporation effects. Lab Chip 9:3422-9
Murphy, Brian M; He, Xinya; Dandy, David et al. (2008) Competitive immunoassays for simultaneous detection of metabolites and proteins using micromosaic patterning. Anal Chem 80:444-50
Wu, Peng; Castner, David G; Grainger, David W (2008) Diagnostic devices as biomaterials: a review of nucleic acid and protein microarray surface performance issues. J Biomater Sci Polym Ed 19:725-53
He, Xinya; Dandy, David S; Henry, Charles S (2008) Microfluidic Protein Patterning on Silicon Nitride Using Solvent Extracted Poly(dimethylsiloxane) Channels. Sens Actuators B Chem 129:811-817
Lynn, N Scott; Dandy, David S (2007) Geometrical optimization of helical flow in grooved micromixers. Lab Chip 7:580-7
Dandy, David S; Wu, Peng; Grainger, David W (2007) Array feature size influences nucleic acid surface capture in DNA microarrays. Proc Natl Acad Sci U S A 104:8223-8

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