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.

Public Health Relevance

Intelligent Optical Systems and GE Global Research will create a new way of using light to simultaneously and efficiently screen samples for large numbers of proteins, DNA fragments, and other biochemicals. Using special polymers whose optical properties can be electronically controlled;our method catapults a mature biosensor technology ahead of other techniques, enabling it to detect biochemical activity from biochips with hundreds, or even thousands, of spots without using fluorescence, radiation, or other artificial enhancers. Products based on this new method will include high-throughput laboratory instruments for rapid drug discovery to handheld biosensors for point-of-care medical testing or biohazard detection.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1-IMST-S (12))
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Korte, Brenda
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Intelligent Optical Systems, Inc.
United States
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