Electro-Optically Modulated SPR: Densely Multiplexed High-Sensitivity Biosensor

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DESCRIPTION (provided by applicant): The overall objective of this Fast Track project is to develop products based on a technique that radically alters the way a mature biosensor technology - surface plasmon resonance (SPR) - is used. This new approach has the potential to dramatically improve SPR throughput for drug discovery, and could lead to the creation of practical hand-held SPR biosensors. Phase I will show that modifying the conventional SPR "stack" by adding an extra layer with an electronically controlled refractive index creates a structure in which plasmon resonance can be detected at a fixed angle, even as analyte binding changes the refractive index at the top of the stack. This solves a problem that has bedeviled SPR biosensors for more than 20 years: the fundamental incompatibility of angle-based measurement with SPR imaging of high spot-count (100's or 1,000's) biochips. Phase I will also demonstrate, by applying a time-varying voltage to the electro-optic (E-O) layer, and thereby modulating the resonance condition, synchronous detection of biomolecular binding using SPR. This also represents a significant advance, since it will enable the employment of a wide variety of sensitivity-enhancing techniques hitherto impossible, or extremely impractical, using other SPR detection approaches. Phase II will build on the Phase I demonstration of the fundamental advantages of index-modulated surface plasmon resonance (MSPR) detection. This phase will culminate in the creation and characterization of a complete system that produces real-time SPR sensograms from hundreds of biorecognition sites on a single chip simultaneously. This will be achieved by imaging the surface of the chip onto a CMOS detector array and rapidly scanning the index of the E-O layer. When the E-O layer's index gets to a value for which the "stack" together with a biospot reaches resonance, the image of that spot will disappear. By recording the bias voltage at which a particular spot's image disappears, its refractive index can be unambiguously determined. Thus, each time the MSPR array's E-O layer is swept, a complete image of the refractive index on the surface will be created. Because no "angular fan-out" is required to detect resonance, biorecognition spots can be packed very closely on the surface -virtually at the same density as for label-based systems. "Dithering" the E-O bias voltage during the sweep will have the effect of modulating the resonance condition directly at the binding site, allowing the use of "lock-in" detection, which can potentially increase refractiv index sensitivity by an order of magnitude or more over the already-impressive ?n < 10-7 achieved by the commercial Biacore device.