System and method with fiducials having offset layouts

A method, comprising:

• disposing an oligonucleotide probe that is to hybridize to a biological sample at each of a plurality of reaction sites in a swath on a support, the biological sample comprising a nucleic acid sequence that responds in successive cycles of fluorescent imaging;
• and
• disposing six fiducial features in a hexagonal pattern on the support in the swath to define an image area, wherein each of the six fiducial features in the hexagonal pattern is a uniform distance from a center point of the image area, each of the six fiducial features comprising a fluorescent material in a single circle shape that separates an inner area where some of the plurality of reaction sites are located and an outer area where some other of the plurality of reaction sites are located, wherein the fluorescent material responds in the successive cycles of fluorescent imaging, wherein the six fiducial features are disposed in rows that are offset with respect to one another, wherein in the offset rows, fiducials of a first row do not align with fiducials of an adjacent second row, relative to a line perpendicular to the first row and the adjacent second row, and wherein the some of the plurality of reaction sites in the outer area are positioned within the hexagonal pattern.