A method comprising: positioning a first carrier assembly on a system stage (130, 320), the first carrier assembly including a support frame having an inner frame edge that defines a window of the support frame, the first carrier assembly including a removable first substrate that is positioned within the window and surrounded by the inner frame edge, the first substrate having a sample thereon that is positioned within an imaging zone of an optical system; detecting optical signals from the sample of the first substrate using the optical system in accordance with a first imaging protocol; replacing the first carrier assembly with a second carrier assembly on the system stage (130, 320), the second carrier assembly having a removable second substrate, the second substrate having a sample thereon that is positioned within the imaging zone of the optical system, characterized in that: the first and second substrates are different types of substrates; and the method comprises detecting optical signals from the sample of the second substrate using the optical system in accordance with a second imaging protocol that is different from the first imaging protocol, wherein each of the first and second carrier assemblies includes apertures that extend into the respective carrier assembly, the apertures receiving corresponding datums when the respective carrier assembly is positioned on the system stage (130, 320), wherein the second carrier assembly includes an adapter plate that holds the second substrate, the datums engaging the first substrate when the first carrier assembly is positioned on the system stage (130, 320), and engaging the adapter plate, but not engaging the second substrate, when the second carrier assembly is positioned on the system stage (130, 320). positioning a first carrier assembly on a system stage (130, 320), the first carrier assembly including a support frame having an inner frame edge that defines a window of the support frame, the first carrier assembly including a removable first substrate that is positioned within the window and surrounded by the inner frame edge, the first substrate having a sample thereon that is positioned within an imaging zone of an optical system; detecting optical signals from the sample of the first substrate using the optical system in accordance with a first imaging protocol; replacing the first carrier assembly with a second carrier assembly on the system stage (130, 320), the second carrier assembly having a removable second substrate, the second substrate having a sample thereon that is positioned within the imaging zone of the optical system, characterized in that: the first and second substrates are different types of substrates; and the method comprises detecting optical signals from the sample of the second substrate using the optical system in accordance with a second imaging protocol that is different from the first imaging protocol, wherein each of the first and second carrier assemblies includes apertures that extend into the respective carrier assembly, the apertures receiving corresponding datums when the respective carrier assembly is positioned on the system stage (130, 320), wherein the second carrier assembly includes an adapter plate that holds the second substrate, the datums engaging the first substrate when the first carrier assembly is positioned on the system stage (130, 320), and engaging the adapter plate, but not engaging the second substrate, when the second carrier assembly is positioned on the system stage (130, 320). the first and second substrates are different types of substrates; and the method comprises detecting optical signals from the sample of the second substrate using the optical system in accordance with a second imaging protocol that is different from the first imaging protocol, wherein each of the first and second carrier assemblies includes apertures that extend into the respective carrier assembly, the apertures receiving corresponding datums when the respective carrier assembly is positioned on the system stage (130, 320), wherein the second carrier assembly includes an adapter plate that holds the second substrate, the datums engaging the first substrate when the first carrier assembly is positioned on the system stage (130, 320), and engaging the adapter plate, but not engaging the second substrate, when the second carrier assembly is positioned on the system stage (130, 320).