A microplate mounting system to mount a microplate relative to an optical reader to control an angle of incidence of an interrogation beam at the microplate comprising: a microplate with a bottom and a skirt; a skirt mount nest member configured to receive the microplate; a mechanical reference plane having at least one set of mount features, wherein at least one set of mount features comprises from 4 to 10 spheres, pins, vias, or a combination thereof and is located on or partially embedded in the reference plane; an optical reader received in the reference plane configured to interrogate the microplate through an aperture in the reference plane; a first positioning mechanism, cooperating with the skirt mount nest member, configured to lower the microplate until one or both of the bottom of the microplate and the skirt of the microplate engages at least three mount features of the at least one set of mount features or the first positioning mechanism configured to elevate the reference plane to engage at least three mount features of the at least one set of mount features and one or both of the bottom of the microplate and the skirt of the microplate such that a reversible and predetermined separation in the vertical direction is provided between a plane formed by the bottom of the microplate and the optical reader to control the angle of incidence of the interrogation beam at the microplate; and a second positioning mechanism configured to provide relative lateral alignment motion between the microplate and the reference plane such that the microplate is laterally movable with respect to the reference plane to positions for interrogation when the microplate is not engaging at least three mount features of the at least one set of mount features. a microplate with a bottom and a skirt; a skirt mount nest member configured to receive the microplate; a mechanical reference plane having at least one set of mount features, wherein at least one set of mount features comprises from 4 to 10 spheres, pins, vias, or a combination thereof and is located on or partially embedded in the reference plane; an optical reader received in the reference plane configured to interrogate the microplate through an aperture in the reference plane; a first positioning mechanism, cooperating with the skirt mount nest member, configured to lower the microplate until one or both of the bottom of the microplate and the skirt of the microplate engages at least three mount features of the at least one set of mount features or the first positioning mechanism configured to elevate the reference plane to engage at least three mount features of the at least one set of mount features and one or both of the bottom of the microplate and the skirt of the microplate such that a reversible and predetermined separation in the vertical direction is provided between a plane formed by the bottom of the microplate and the optical reader to control the angle of incidence of the interrogation beam at the microplate; and a second positioning mechanism configured to provide relative lateral alignment motion between the microplate and the reference plane such that the microplate is laterally movable with respect to the reference plane to positions for interrogation when the microplate is not engaging at least three mount features of the at least one set of mount features.