Guided mode resonant filter biosensor using a linear grating surface structure

#The invention relates to compositions and methods for detecting biomolecular interactions. The detection can occur without the use of labels and can be done in a high-throughput manner. The invention also relates to optical devices.

#With the completion of the sequencing of the human genome, one of the next grand challenges of molecular biology will be to understand how the many protein targets encoded by DNA interact with other proteins, small molecule pharmaceutical candidates, and a large host of enzymes and inhibitors. See e.g., Pandey & Mann, “Proteomics to study genes and genomes,” Nature, 405, p. 837-846, 2000; Leigh Anderson et al., “Proteomics: applications in basic and applied biology,” Current Opinion in Biotechnology, 11, p. 408-412, 2000; Patterson, “Proteomics: the industrialization of protein chemistry,” Current Opinion in Biotechnology, 11, p. 413-418, 2000; MacBeath & Schreiber, “Printing Proteins as Microarrays for High-Throughput Function Determination,” Science, 289, p. 1760-1763, 2000; De Wildt et al., “Antibody arrays for high-throughput screening of antibody-antigen interactions,” Nature Biotechnology, 18, p. 989-994, 2000. To this end, tools that have the ability to simultaneously quantify many different biomolecular interactions with high sensitivity will find application in pharmaceutical discovery, proteomics, and diagnostics. Further, for these tools to find widespread use, they must be simple to use, inexpensive to own and operate, and applicable to a wide range of analytes that can include, for example, polynucleotides, peptides, small proteins, antibodies, and even entire cells.

#Biosensors have been developed to detect a variety of biomolecular complexes including oligonucleotides, antibody-antigen interactions, hormone-receptor interactions, and enzyme-substrate interactions. In general, biosensors consist of two components: a highly specific recognition element and a transducer that converts the molecular recognition event into a quantifiable signal. Signal transduction has been accomplished by many methods, including fluorescence, interferometry (Jenison et al, “Interference-based detection of nucleic acid targets on optically coated silicon,” Nature Biotechnology, 19, p. 62-65; Lin et al, “A porous silicon-based optical interferometric biosensor,” Science, 278, p. 840-843, 1997), and gravimetry (A. Cunningham, Bioanalytical Sensors, John Wiley & Sons (1998)).

#The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee.

#FIG. 1A shows a schematic diagram of one embodiment of an optical grating structure used for a calorimetric resonant reflectance biosensor. nsubstrate represents substrate material. n1 represents the refractive index of a cover layer. n2 represents the refractive index of a one- or two-dimensional grating. nbio represents the refractive index of one or more specific binding substances. t1 represents the thickness of the cover layer. t2 represents the thickness of the grating. tbio represents the thickness of the layer of one or more specific binding substances. FIG. 1 shows a cross-sectional view of a biosensor.

#FIG. 2 shows a schematic drawing of a one-dimensional linear grating surface structure.

#In one embodiment of the invention, a subwavelength structured surface (SWS) is used to create a sharp optical resonant reflection at a particular wavelength that can be used to track with high sensitivity the interaction of biological materials, such as specific binding substances or binding partners or both. A colormetric resonant diffractive grating surface acts as a surface binding platform for specific binding substances.

#SWSs are an unconventional type of diffractive optic that can mimic the effect of thin-film coatings. (Peng & Morris, J. Opt. Soc. Am. A, Vol. 13, No. 5, p. 993, May 1996; Magnusson, & Wang, Appl. Phys. Lett., 61, No. 9, p. 1022, August, 1992; Peng & Morris, Optics Letters, Vol. 21, No. 8, p. 549, April, 1996). A SWS structure comprises a surface-relief grating, such as a one-dimensional, two-dimensional, or three dimensional grating in which the grating period is small compared to the wavelength of incident light.

#The reflected or transmitted color of this structure can be modulated by the addition of molecules such as specific binding substances, binding partners, or both, or inorganic molecules to the upper surface of the cover layer or the grating surface. The dielectric susceptibility of the added molecules results in a modification of the wavelength at which maximum reflectance or transmittance will occur.