Alignment markers are added to each layer of a multiple layer substrate for proper alignment. Optical alignment markers are applied on the surface of each substrate layer. Groups of alignment markers are arranged in localized areas on each substrate layer. Each localized group of alignment markers are referred to as alignment target areas. The alignment markers in a first alignment target area on the first substrate layer are to be aligned with corresponding alignment markers in a second alignment target area on the second substrate layer. In some embodiments, the first alignment target area includes an alignment marker configured for manual alignment and another alignment marker configured for machine alignment. The second alignment target area has a corresponding manual alignment marker and machine alignment marker.