Label-free high-throughput optical technique for detecting biomolecular interactions
First Claim
Patent Images
1. A biosensor comprising:
- (a) a two-dimensional grating comprised of a material having a high refractive index;
(b) a substrate layer that supports the two-dimensional grating; and
(c) one or more specific binding substances immobilized on the surface of the two-dimensional grating opposite of the substrate layer;
wherein, when the biosensor is illuminated a resonant grating effect is produced on the reflected radiation spectrum, and wherein the depth and period of the two-dimensional grating are less than the wavelength of the resonant grating effect.
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Abstract
Methods and compositions are provided for detecting biomolecular interactions. The use of labels is not required and the methods can be performed in a high-throughput manner. The invention also provides optical devices useful as narrow band filters.
262 Citations
104 Claims
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1. A biosensor comprising:
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(a) a two-dimensional grating comprised of a material having a high refractive index;
(b) a substrate layer that supports the two-dimensional grating; and
(c) one or more specific binding substances immobilized on the surface of the two-dimensional grating opposite of the substrate layer;
wherein, when the biosensor is illuminated a resonant grating effect is produced on the reflected radiation spectrum, and wherein the depth and period of the two-dimensional grating are less than the wavelength of the resonant grating effect. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 50, 51, 52, 53, 54, 55, 56, 57, 58, 67, 68, 69, 70, 71, 72, 73, 74, 100, 101)
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23. A biosensor comprising:
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(a) a sheet material having a first and second surface, wherein the first surface defines relief volume diffraction structures;
(b) a reflective material coated onto the first surface of the sheet material; and
(c) one or more specific binding substances immobilized on the reflective material;
wherein the biosensor reflects light predominantly at a first single optical wavelength when illuminated with a broad band of optical wavelengths, and wherein the biosensor reflects light at a second single optical wavelength when the one or more specific binding substances are immobilized on the reflective surface, wherein the reflection at the second optical wavelength of light results from optical interference. - View Dependent Claims (24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 59, 60, 61, 62, 63, 64, 65, 66)
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- 37. A biosensor comprising a two-dimensional grating having a first and a second surface comprised of an optically transparent material that conducts electricity, wherein the first surface of the two-dimensional grating is coated with an electrical insulator, and wherein the second surface of the two-dimensional grating is deposited on a substrate, wherein when the biosensor is illuminated a resonant grating effect is produced on the reflected radiation spectrum, wherein the depth and the period of the two-dimensional grating are less than the wavelength of the resonant grating effect.
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75. A method for determining a location of a resonant peak for a binding partner in a resonant reflectance spectrum with a colormetric resonant biosensor, comprising:
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selecting a set of resonant reflectance data for a plurality of colormetric resonant biosensor distinct locations, wherein the set of resonant reflectance data is collected by illuminating a colormetric resonant diffractive grating surface with a light source and measuring reflected light at a pre-determined incidence, wherein the colormetric resonant diffractive grating surface is used as a surface binding platform for one or more specific binding substances, wherein binding partners can be detected without use of a molecular label, wherein the set of resonant reflectance data includes a plurality of sets of two measurements, where a first measurement includes a first reflectance spectra of one or more specific binding substances that are attached to the colormetric resonant diffractive grating surface and a second measurement includes a second reflectance spectra of the one or more specific binding substance after one or more binding partners are applied to colormetric resonant diffractive grating surface including the one or more specific binding substances, and wherein a difference in a peak wavelength between the first and second measurement is a measurement of an amount of binding partners that bound to the one or more specific binding substances;
determining a maximum value for a second measurement from the plurality of sets of two measurements from the set of resonant reflectance data for the plurality of binding partners, wherein the maximum value includes inherent noise included in the resonant reflectance data;
determining whether the maximum value is greater than a pre-determined threshold, and if so, defining a curve-fit region around the determined maximum value, performing a curve-fitting procedure to fit a curve around the curve-fit region, wherein the curve-fitting procedure removes a pre-determined amount of inherent noise included in the resonant reflectance data;
determining a location of a maximum resonant peak on the fitted curve; and
determining a value of the maximum resonant peak, wherein the value of the maximum resonant peak is used to identify an amount of biomolecular binding of the one or more specific binding substances to the one or more binding partners. - View Dependent Claims (76, 77, 78, 79, 80, 81, 82, 83, 84)
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- 85. A biosensor comprising a two-dimensional grating having a pattern of concentric rings, wherein the difference between an inside diameter and an outside diameter of each concentric ring is equal to about one-half of a grating period, wherein each successive ring has an inside diameter that is about one grating period greater than an inside diameter of a previous ring wherein when the structure is illuminated with an illuminating light beam, a reflected radiation spectrum is produced that is independent of an illumination polarization angle of the illuminating light beam, and wherein one or more specific binding substances are immobilized on the two-dimensional grating.
- 88. A biosensor comprising an array of holes or posts arranged such that the holes or posts are centered on corners and in the center of hexagons, wherein the hexagons are arranged in a closely packed array, wherein when the structure is illuminated with an illuminating light beam, a reflected radiation spectrum is produced that is independent of an illumination polarization angle of the illuminating light beam, and wherein one or more specific binding substances are immobilized on the array of holes or posts.
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91. A biosensor comprising:
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(a) a first two-dimensional grating comprising a high refractive index material and having a top surface and a bottom surface;
(b) a second two-dimensional grating comprising a high refractive index material and having a top surface and a bottom surface, wherein the top surface of the second two-dimensional grating is attached to the bottom surface of the first two-dimensional grating; and
(c) one or more specific binding substances or one or more specific binding substances bound to their binding partners immobilized on the top surface of the first two-dimensional grating;
wherein, when the biosensor is illuminated two resonant grating effects are produced on the reflected radiation spectrum, and wherein the depth and period of both of the two-dimensional gratings are less than the wavelength of the resonant grating effects. - View Dependent Claims (92, 93, 94, 95)
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96. A biosensor comprising:
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(a) a first two-dimensional grating comprising a high refractive index material and having a top surface and a bottom surface;
(b) a substrate layer comprising a top surface and a bottom surface, wherein the top surface of the substrate supports the bottom surface of the first two-dimensional grating;
(c) a second two-dimensional grating comprising a high refractive index material and having a top surface and a bottom surface, wherein the bottom surface of the second two-dimensional grating is attached to the bottom surface of the substrate; and
(d) one or more specific binding substances or one or more specific binding substances bound to their binding partners immobilized on the top surface of the first two-dimensional grating;
wherein, when the biosensor is illuminated two resonant grating effects are produced on the reflected radiation spectrum, and wherein the depth and period of both of the two-dimensional gratings are less than the wavelength of the resonant grating effects. - View Dependent Claims (97, 98, 99)
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102. A method of detecting an interaction of a first molecule with a second test molecule comprising:
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(a) applying a mixture of the first and second molecules to a distinct location on a biosensor, wherein the biosensor comprises a two-dimensional grating comprising of a high refractive index material, and a substrate layer that supports the two-dimensional grating; and
wherein, when the biosensor is illuminated a resonant grating effect is produced on the reflected radiation spectrum, and wherein the depth and period of the two-dimensional grating are less than the wavelength of the resonant grating effect;
(b) applying a mixture of the first molecule with a third control molecule to a distinct location on the biosensor of (a) or a similar biosensor, wherein the third control molecule does not interact with the first molecule, and wherein the third control molecule is about the same size as the first molecule; and
(c) detecting a shift in the reflected wavelength of light from the distinct locations of step (a) and step (b);
wherein, if the shift in the reflected wavelength of light from the distinct location of step (a) is greater than the shift in the reflected wavelength in step (b), then the first molecule and the second test molecule interact. - View Dependent Claims (103, 104)
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Specification