Sensitivities would greatly exceed those of reflection-type SPR biosensors.
Biosensors of a proposed type would exploit scattering of light by surface plasmon resonance (SPR). Related prior biosensors exploit absorption of light by SPR. Relative to the prior SPR biosensors, the proposed SPR biosensors would offer greater sensitivity â€” in some cases, enough sensitivity to detect bioparticles having dimensions as small as nanometers.
A surface plasmon wave can be described as a light-induced collective oscillation in electron density at the interface between a metal and a dielectric. At SPR, most incident photons are either absorbed or scattered at the metal/dielectric interface and, consequently, reflected light is greatly attenuated. The resonance wavelength and angle of incidence depend upon the permittivities of the metal and dielectric.
An SPR sensor of the type most widely used heretofore includes a gold film coated with a ligand — a substance that binds analyte molecules. The gold film is thin enough to support evanescent-wave coupling through its thickness. The change in the effective index of refraction at the surface, and thus the change in the SPR response, increases with the number of bound analyte molecules. The device is illuminated at a fixed wavelength, and the intensity of light reflected from the gold surface opposite the ligand-coated surface is measured as a function of the angle of incidence. From these measurements, the angle of minimum reflection intensity is determined.
These measurements and the determination of the angle of minimum reflection intensity are performed before and after (and can be performed during) exposure of the sensor to a sample containing the analyte molecules. Any shift in the angle between such successive determinations is indicative of a change in the concentration of analyte molecules in the sample. This type of sensor is characterized by low sensitivity for the following reasons:
- A small number of analyte molecules gives rise to a small shift in the angle of minimum reflection intensity.
- Because one is measuring a reflection dip rather than a reflection peak, the measurement can be strongly affected by noise. The difficulty of determining the small angular shift is analogous to the difficulty of measuring the shift of a dark spot on a bright background.
A biosensor according to the proposal would afford a much greater signal-tonoise ratio by exploiting SPR in a different way that would involve, literally, a bright spot on a dark background. A proposed sensor (see figure) would include a coupling prism, an index-of-refraction matching liquid, a glass slide, and a metal film thin enough to support evanescent wave coupling. The metal surface to be exposed to the specimen would be coated with ligand in a regular array of patches. The array of patches would be observed by a miniature microscope that would include a lens and a complementary oxide/semiconductor (CMOS) image detector. The microscope would be designed so that each ligand patch would occupy many CMOS pixels and the resolution of the microscope would be close to the optical limit (about one wavelength of the incident light).
The sensor would be illuminated with collimated light at a wavelength and angle of incidence chosen so that SPR would occur whenever and wherever analyte molecules became bound to the ligand. In the absence of such binding, there would be little scattered light. In the presence of such binding at any spot on the ligand, the strong SPR scattering from that spot would cause the spot to be imaged brightly in the microscope. Even a bioparticle smaller than a wavelength of light could induce sufficient SPR scattering to be detectable.
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Refer to NPO-40683, volume and number of this NASA Tech Briefs issue, and the page number.
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