Method of detecting surface features of a microarray. The method includes providing a microarray to an optical scanner, wherein the microarray includes a surface having features. The method also includes carrying out a scanning process using the optical scanner, wherein the scanning process includes: (i) acquiring images of sequential regions on the surface, wherein a defocus spread is applied to the optical scanner during the acquiring, (ii) determining a focus score for the images, (iii) adjusting the optical scanner to a different defocus spread based on the focus score, and (iv) repeating (i) through (iii) at the different defocus spread, thereby acquiring images of further sequential regions on the surface. The method also includes analyzing the images to distinguish different target molecules at the features of the microarray. The images that are analyzed were acquired at the defocus spread and at the different defocus spread during the scanning process.