Integrated Analytical System and Method
US-2015376694-A1 · Dec 31, 2015 · US
US9772284B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9772284-B2 |
| Application number | US-201113641897-A |
| Country | US |
| Kind code | B2 |
| Filing date | Apr 20, 2011 |
| Priority date | Apr 20, 2010 |
| Publication date | Sep 26, 2017 |
| Grant date | Sep 26, 2017 |
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A miniature optical biosensor and biosensor array where high sensitivity for detection of biomolecular interaction does not require a fluorescent label. Non-linear frequency-shifts of optical resonators (‘nanobeams’) provide a digital all-or-nothing response to equilibrium binding of a biomarker to surface-immobilized bio-recognition elements, a signal suitable to identify active components in genetic and proteomic circuits, as well as toxic substances. The threshold level for the digital response is adjustable to accommodate for varying receptor affinities. A bistable cavity sensing (BCS) method can be used to track the shift of the resonance induced by the analyte more precisely than the conventional cavity sensing method, where the resolution is limited by the cavity linewidth. BCS method can be used to quantitate the concentration of the analyte, and their binding kinetics, affinities and etc.
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What we claim is: 1. An optical device comprising: a laser source; input waveguides connected to said laser; a material structured on a micro-nanoscale to localize light in a modal volume where constructive interference produces optical resonance, wherein said material exhibits third-order nonlinearity and is modified with molecular recognition elements immobilized within some part of the optical field, said material being connected to said input waveguides; output waveguides connected to said material; and a photo-detector connected to said output waveguides; wherein said material is exposed on one or more sides to a liquid sample in a sample volume, and wherein a geometry of said material structured on the micro- or nanoscale is selected from a high quality factor (Q) photonic crystal defect cavity, a high quality factor (Q) photonic crystal nanobeam cavity, and a high quality factor (Q) photonic crystal. 2. An optical device according to claim 1 , where the geometry of the micro- or nanoscale structure is a geometry that produces an optical microcavity structure comprising at least one micro-cavity. 3. An optical device according to claim 1 , wherein said material comprises one of the following: silicon, silica, silicon nitrate, diamond, doped glass, high-index glass, quartz, polymer, polydimethylsiloxane, InP, and materials. 4. An optical device according to claim 1 , Wherein said non-linearity of said material originates from heating of said material b two-photon and/or free carrier absorption. 5. An optical device according to claim 1 , wherein said non-linearity of said material originates from at least one of the following: second order nonlinearity, optomechanically induced nonlinearity, and Kerr nonlinearity. 6. An optical device according to claim 1 , where a resonant frequency of said device is in the visible, in the near-infrared, in the mid-infrared or in the UV. 7. An optical device according to claim 2 , wherein a resonance frequency of each micro-cavity can be reconfigured mechanically, by heating, by carrier injection, or by nonlinear optical processes. 8. An optical device according to claim 2 , where each micro-cavity is individually excited, or simultaneously excited, where each micro-cavity is excited using optical fibers, tapered optical fibers, or through focused or non-focused optical beams. 9. An optical device according to claim 2 , wherein a signal from each micro-cavity is transferred to optical waveguides, arrays of optical fibers, imaging arrays, or detector arrays. 10. An optical device according to claim 1 wherein the sample volume comprises a microfluidic channel, an open reservoir, or a capillary. 11. A method for detection of biomolecular targets comprising the steps of: coupling of light to the device according to claim 1 at an optical frequency that is slightly blue-detuned from the resonance frequency; detecting transmitted power with the photodetector; exposing the molecular recognition elements to target molecules dissolved in the liquid sample; recording a discrete change of transmitted power in response to specific binding of target molecules to the recognition elements; recording a power versus time trace on a computer; and resetting the device by blue-detuning so that the new frequency is blue-detuned to the new resonance frequency of the device according to claim 1 . 12. An optical device according to claim 1 , wherein the geometry of the micro- or nanoscale structure is a geometry that produces an optical cavity structure comprising a plurality of nano- or micro-cavities; and wherein the plurality of nano- or micro-cavities are multiplexed in array or matrix format on a chip substrate. 13. An optical device according to claim 1 wherein molecular recognition elements comprise one of the following: DNA, single stranded DNA, proteins, antibodies, dendrimers, nanostructures, bacterial S proteins, lectins, glycoproteins, membranes, membrane components, lipid bilayers, and organelles. 14. A method of analyzing the concentration, binding kinetics and affinity of biomolecular targets comprising the steps of: coupling of light to the device according to claim 1 at various optical frequencies; detecting a transmitted power with said photodetector at each frequency; and analyzing a resonance obtained by the photodetector. 15. A method to accommodate for varying receptor affinity by blue detuning of the resonance frequency to a certain wavelength so that a certain number of molecules will trigger a discrete change in transmitted optical power. 16. The optical device according to claim 1 wherein the high quality factor (Q) is at least about 10 5 .
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