A method of isolating cancer-derived circulating extracellular vesicles comprising: contacting a sample obtained from a subject with a surface of a substrate to bind circulating extracellular vesicles present in the sample to the surface of the substrate, thereby isolating the extracellular vesicles; and detecting the extracellular vesicles bound to the surface of the substrate using interferometric biosensing, wherein the sample is evaluated with a spectral reflectance imaging system for making interferometric measurements, and wherein the spectral reflectance imaging system comprises: the substrate having a first reflective surface and a partially transparent layer providing a second reflective surface, wherein the partially transparent layer is from 40 nm to 70 nm thick, and wherein light illuminating the substrate is spectrally reflected from these two layers of the substrate; a biolayer comprising a first set of one or more binding agents bound to the second reflective surface; an illumination source comprising at least one light source that provides light in a narrow frequency band and directs the frequency band of light at the substrate; and an imaging device directed at the second reflective surface of the substrate and adapted to produce imaging signals representative of light from the illumination source being reflected by the first reflective surface; the second reflective surface; and scattered light by the extracellular vesicles on the second surface. contacting a sample obtained from a subject with a surface of a substrate to bind circulating extracellular vesicles present in the sample to the surface of the substrate, thereby isolating the extracellular vesicles; and detecting the extracellular vesicles bound to the surface of the substrate using interferometric biosensing, wherein the sample is evaluated with a spectral reflectance imaging system for making interferometric measurements, and wherein the spectral reflectance imaging system comprises: the substrate having a first reflective surface and a partially transparent layer providing a second reflective surface, wherein the partially transparent layer is from 40 nm to 70 nm thick, and wherein light illuminating the substrate is spectrally reflected from these two layers of the substrate; a biolayer comprising a first set of one or more binding agents bound to the second reflective surface; an illumination source comprising at least one light source that provides light in a narrow frequency band and directs the frequency band of light at the substrate; and an imaging device directed at the second reflective surface of the substrate and adapted to produce imaging signals representative of light from the illumination source being reflected by the first reflective surface; the second reflective surface; and scattered light by the extracellular vesicles on the second surface. the substrate having a first reflective surface and a partially transparent layer providing a second reflective surface, wherein the partially transparent layer is from 40 nm to 70 nm thick, and wherein light illuminating the substrate is spectrally reflected from these two layers of the substrate; a biolayer comprising a first set of one or more binding agents bound to the second reflective surface; an illumination source comprising at least one light source that provides light in a narrow frequency band and directs the frequency band of light at the substrate; and an imaging device directed at the second reflective surface of the substrate and adapted to produce imaging signals representative of light from the illumination source being reflected by the first reflective surface; the second reflective surface; and scattered light by the extracellular vesicles on the second surface.