The invention relates to non-fouling hydrophobic reflective surfaces for a variety of applications which in one embodiment related to medical device applications comprises a method of performing a medical procedure using a surgical navigation system which includes the steps of placing one or more reflective spheres on a surgical instrument or apparatus, the reflective spheres comprising a hydrophobic coating on a sub-micron structured surface of the spheres, wherein the spheres substantially maintain their reflective properties after the spheres are contacted with a biological fluid； shining light on the reflective spheres； capturing reflected light from the spheres with a camera or other device； and registering and/or tracking a location and/or position of the spheres.
