A system for performing an assay on a sample to determine qualitatively presence of a target analyte, or to semi-quantitatively or quantitatively determine concentration of a target analyte, the system comprising: a cartridge having (a) planar waveguide with a planar surface and a plurality of capture molecules bound thereto, (b) refractive volume for optically coupling a light beam to the planar waveguide, the refractive volume including a lens and being configured for refracting the light beam such that all of the light beam focuses at a non-zero, internal propagation angle at the planar surface, and (c) sample chamber for receiving and containing the sample such that the sample comes in contact with the plurality of capture molecules; and a reader instrument having (a) receiving mechanism for positioning the cartridge therein, (b) laser for delivering the light beam along a propagation direction parallel to the planar surface and offset from the planar waveguide when incident on the refractive volume, (c) diffuser for removing non-uniformity from the light beam, the diffuser being configured to rotate through the light beam and about an axis parallel to, but offset from, the propagation direction; (d) imaging system for capturing an image of a light signal from a portion of the planar surface on which the plurality of capture molecules is bound; and (e) analysis module for receiving and analyzing the light signal from the imaging system. a cartridge having (a) planar waveguide with a planar surface and a plurality of capture molecules bound thereto, (b) refractive volume for optically coupling a light beam to the planar waveguide, the refractive volume including a lens and being configured for refracting the light beam such that all of the light beam focuses at a non-zero, internal propagation angle at the planar surface, and (c) sample chamber for receiving and containing the sample such that the sample comes in contact with the plurality of capture molecules; and (a) planar waveguide with a planar surface and a plurality of capture molecules bound thereto, (b) refractive volume for optically coupling a light beam to the planar waveguide, the refractive volume including a lens and being configured for refracting the light beam such that all of the light beam focuses at a non-zero, internal propagation angle at the planar surface, and (c) sample chamber for receiving and containing the sample such that the sample comes in contact with the plurality of capture molecules; and a reader instrument having (a) receiving mechanism for positioning the cartridge therein, (b) laser for delivering the light beam along a propagation direction parallel to the planar surface and offset from the planar waveguide when incident on the refractive volume, (c) diffuser for removing non-uniformity from the light beam, the diffuser being configured to rotate through the light beam and about an axis parallel to, but offset from, the propagation direction; (d) imaging system for capturing an image of a light signal from a portion of the planar surface on which the plurality of capture molecules is bound; and (e) analysis module for receiving and analyzing the light signal from the imaging system. (a) receiving mechanism for positioning the cartridge therein, (b) laser for delivering the light beam along a propagation direction parallel to the planar surface and offset from the planar waveguide when incident on the refractive volume, (c) diffuser for removing non-uniformity from the light beam, the diffuser being configured to rotate through the light beam and about an axis parallel to, but offset from, the propagation direction; (d) imaging system for capturing an image of a light signal from a portion of the planar surface on which the plurality of capture molecules is bound; and (e) analysis module for receiving and analyzing the light signal from the imaging system.