The working principle of molography is illustrated in Figure 1. Molography is based on diffraction of laser light at a special 2D nanopattern of molecular binding sites on the surface of a sensor chip, termed mologram.  A mologram is a coherent assembly of binding sites on a chip that form the blueprint of molecular hologram.  The hologram has the shape of a focusing diffractive lens and is illuminated by an evanescent wave. Evanescent waves occur when light is totally internally reflected at an interface of two dielectrics.  Biomolecules that bind to the mologram diffract laser light into a diffraction-limited focal spot in three dimensional space, the focal point of the mologram.  The intensity of the focused light correlates quadratically with the amount of bound molecules on the mologram and therefore also the number of biomolecular interactions that take place.    
In complex biological samples, the concentration of off-target molecules is usually significantly higher than the target molecules. Therefore, even in the absence of recognition elements the off-target molecules readily adsorb to the surface of the sensor.  However, this a random process and the off-target molecules do not bind to the ordered binding sites of the mologram.  Thus, scattering of off-target molecules is uniform in all spatial directions and therefore off-target molecules hardly contribute to the measured light intensity in the narrow solid angle of the focal spot.  In essence, focal molography forms a high-frequency spatial affinity lock-in that only measures the Fourier component of the refractive index distribution that corresponds to the binding modulation of the mologram.  Since the environmental noise (temperature gradients, buffer changes and nonspecific binding of off-target molecules) is inversely proportional to the spatial frequency and therefore situated mostly at "long" spatial periods most of the noise can be rejected. This property makes molography extremely robust and renders temperature stabilization or sensor equilibration obsolete.