A novel technique based on photonic crystals (PC) will be developed and used to construct an extremely sensitive instrument for the study of biomolecular affinities and binding kinetics. We have previously demonstrated that a narrow midgap transmission peak can be formed and a local field enhancement can be achieved when a defect layer is sandwiched between two PCs. In this R21 application, we will explore for the first time the possibility to use only one PC in a total internal reflection geometry, so that the defect layer becomes accessible for binding of analyte molecules. When the defect layer is doped with absorbing materials, the spectrum of the reflected light from this PC structure will have a very narrow but prominent dip due to the enhanced absorption in the defect layer. The dip wavelength will depend very sensitively on the thickness and/or refractive index of the biomolecules bound to the defect layer. This will enable highly sensitive measurements of the binding of biomolecules and the kinetics of this process. We will focus on developing this novel methodology and constructing a highly sensitive PC based instrument. First, we will optimize our design of the PC structure based on comprehensive theoretical modeling and numerical simulations in order to achieve the maximum detection sensitivity. Then we will construct a working system using the optimized PC structure as a critical component. We will also explore several possible detection modes and develop related software for data analysis and interpretation. Finally, this instrument will be tested using several biological model systems in order to demonstrate its applicability. This new instrument will possess a number of advantages over the currently widely used surface plasmon resonance (SPR) based instrument and other waveguide based instruments. It will have the capability to study, in a quantitative manner and without requirement of labeling, many different dynamic molecular interactions in real time, allowing affinity measurements, concentration determinations of specific analytes, and kinetic analyses. We will compare directly the sensitivity of our technique to that of commercially available state-of- the-art SPR-based systems. CRITIQIUE
| Thomas, Thommey P; Chang, Yu-Chung; Ye, Jing Yong et al. (2012) Optical fiber-based in vivo quantification of growth factor receptors. Cancer 118:2148-56 |
| Thomas, Thommey P; Goonewardena, Sascha N; Majoros, Istvan J et al. (2011) Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. Arthritis Rheum 63:2671-80 |
| Chang, Yu-Chung; Ye, Jing Yong; Thomas, Thommey P et al. (2010) Fiber-optic multiphoton flow cytometry in whole blood and in vivo. J Biomed Opt 15:047004 |
| Guo, Yunbo; Ye, Jing Yong; Divin, Charles et al. (2010) Real-time biomolecular binding detection using a sensitive photonic crystal biosensor. Anal Chem 82:5211-8 |
| Thomas, Thommey P; Shukla, Rameshwer; Kotlyar, Alina et al. (2010) Dendrimer-based tumor cell targeting of fibroblast growth factor-1. Bioorg Med Chem Lett 20:700-3 |
| Guo, Yunbo; Ye, Jing Yong; Divin, Charles et al. (2009) Label-free biosensing using a photonic crystal structure in a total-internal-reflection geometry. Proc SPIE Int Soc Opt Eng 7188:71880B-71880B12 |
| Chang, Yu-Chung; Ye, Jing Yong; Thomas, Thommey P et al. (2009) Two-photon in vivo flow cytometry using a fiber probe. Proc SPIE Int Soc Opt Eng 7173:71730I1-71730I10 |
| Thomas, Thommey P; Majoros, Istvan; Kotlyar, Alina et al. (2009) Cationic poly(amidoamine) dendrimer induces lysosomal apoptotic pathway at therapeutically relevant concentrations. Biomacromolecules 10:3207-14 |
| Thomas, Thommey P; Ye, Jing Yong; Chang, Yu-Chung et al. (2008) Investigation of tumor cell targeting of a dendrimer nanoparticle using a double-clad optical fiber probe. J Biomed Opt 13:014024 |
| Guo, Yunbo; Divin, Charles; Myc, Andrzej et al. (2008) Sensitive molecular binding assay using a photonic crystal structure in total internal reflection. Opt Express 16:11741-9 |
Showing the most recent 10 out of 12 publications
