The present invention relates in one aspect to a method of detecting a contaminant in a measurement chamber (201) of a sample analyzer (200). The sample analyzer (200) comprises an optical sensor with a sensor layer (205) comprising a luminophor (201), wherein the sensor layer (205) has a sensor surface (206) forming an interface to the measurement chamber (201). The method comprises steps of: filling the measurement chamber with a fluid sample; applying a stimulus to the luminophor in the sensor layer; detecting luminescence emitted from the luminophor in the sensor layer in response to the stimulus as a function of time; obtaining a time sequence of measurement values for the detected luminescence; based on the time sequence, determining an actual value of a first parameter and an actual value of a second parameter, wherein one of the first and second parameters is sensitive to a change in refractive index across the interface between the sensor layer and the measurement chamber, and wherein the other one of the first and second parameters is not sensitive to said change in refractive index across the interface between the sensor layer and the measurement chamber; developing an expected value for the second parameter based on the actual value of the first parameter; comparing the expected value for the second parameter to the actual value of the second parameter; and determining the presence (or absence) of a contaminant based on the comparison. In a further aspect, a sample analyzer configured for detecting contaminants in the measurement chamber using embodiments of the above method is provided.