Critical angle reflection imaging for quantification of molecular interactions
AssigneeArizona Board of Regents on behalf of Arizona State University
InventorsShaopeng WANG, Runli LIANG, Guangzhong MA
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Abstract
This disclosure describes systems and methods for critical angle reflection (CAR) imaging to quantify molecular binding kinetics on a glass surface in some embodiments. CAR is a label-free method that measures the reflectivity change near a critical angle in response to molecular binding induced refractive index changes on the sensor surface. The sensitivity and dynamic range of CAR is tunable by varying the incident angle of light, which allows for optimizing the measurement for ligands with different sizes in both biomolecular and cell-based studies.
Claims27
A method of quantifying molecular interactions, the method comprising:
- contacting a liquid comprising a ligand with a first surface of a substrate functionalized with a receptor, wherein the substrate is optically transparent and wherein a refractive index of the substrate exceeds a refractive index of the liquid;
- introducing an incident light into an optical prism toward a second surface of the substrate at an incident angle with respect to a plane perpendicular to the first surface of the substrate, wherein the second surface is opposite the first surface and the incident angle is less than a critical angle defined as sin−1(na/ng), wherein ng is the refractive index of the substrate and na is the refractive index of the liquid;
- and
- assessing a change in intensity of the light reflected at an interface between the liquid and the first surface of the substrate, wherein the change in intensity is responsive to binding of the ligand by the receptor.
A method of detecting a ligand in a liquid, the method comprising:
- contacting the liquid with a first surface of a substrate, wherein the first surface of the substrate comprises a receptor, wherein the substrate is optically transparent, and wherein a refractive index of the substrate exceeds a refractive index of the liquid;
- introducing an incident light into an optical prism toward a second surface of the substrate at an incident angle with respect to a plane perpendicular to the first surface of the substrate, wherein the second surface is opposite the first surface and the incident angle is less than a critical angle defined as sin−1(na/ng), wherein ng is the refractive index of the substrate and na is the refractive index of the liquid;
- and,
- measuring a resonance angle shift in the incident light reflected from an interface between the first surface of the substrate and the liquid, which resonance angle shift is indicative of the receptor binding the ligand, thereby detecting the ligand in the liquid.
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An optical imaging system comprising:
- an optically transparent substrate having a first surface and a second surface opposite the first surface;
- an optical prism configured to be coupled to the second surface of the optically transparent substrate;
- a light source configured to introduce collimated light into the optical prism at an incident angle with respect to a plane perpendicular to the second surface of the optically transparent substrate, wherein the incident angle is less than a critical angle defined as sin−1(na/ng), wherein ng is a refractive index of the substrate and na is a refractive index of the liquid;
- a detector configured to collect light reflected from an interface between the first surface of the optically transparent substrate and a liquid in contact with the first surface of the optically transparent substrate;
- and
- a processor configured to assess a change in intensity of the light reflected at the interface between the liquid and the first surface of the substrate, wherein the change in intensity is responsive to binding of a ligand in the liquid by a receptor on the second surface of the substrate.
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Dependencies are inferred from the claim text.