A method of generating in-focus images of samples residing at various measurement locations, in particular sample wells, on a surface of a sample holder in a microscopy imaging system, the method comprising: (a) positioning (602, 604) a single camera sensor and an array of focusing optics associated with the camera sensor at a first focal distance from the sample holder using a camera controller; (b) acquiring a first image of measurement locations using the camera sensor and using the camera controller to direct a camera control module to actuate the camera sensor to obtain the first image therefrom, providing the first image to the camera controller using the camera control module, and receiving the first image by a pre-processing module which is associated with the camera controller; (c) developing a candidate output image associated with the camera sensor and the array of focusing optics in accordance with the first image; (d) positioning the camera sensor and the array of focusing optics at a second focal distance from the sample holder using the camera controller; (e) acquiring a second image of the measurement locations using the camera sensor and using the camera controller to direct the camera control module to actuate the camera sensor to obtain the second image therefrom, providing the second image to the camera controller using the camera control module, and receiving the second image by the pre-processing module which is associated with the camera controller; (f) updating a portion of the candidate output image with a portion of the second image in accordance with a selection criterion using the pre-processing module, wherein if the selection criterion is met, the portion of the candidate image is replaced with the corresponding portion of the second image; repeating steps (d) through (f) until the camera sensor has traversed a predetermined range of focus; and (g) transmitting the updated candidate output image; wherein only sections of each image that comprise measurement locations are provided from the camera sensor to the camera control module. (a) positioning (602, 604) a single camera sensor and an array of focusing optics associated with the camera sensor at a first focal distance from the sample holder using a camera controller; (b) acquiring a first image of measurement locations using the camera sensor and using the camera controller to direct a camera control module to actuate the camera sensor to obtain the first image therefrom, providing the first image to the camera controller using the camera control module, and receiving the first image by a pre-processing module which is associated with the camera controller; providing the first image to the camera controller using the camera control module, and receiving the first image by a pre-processing module which is associated with the camera controller; (c) developing a candidate output image associated with the camera sensor and the array of focusing optics in accordance with the first image; (d) positioning the camera sensor and the array of focusing optics at a second focal distance from the sample holder using the camera controller; (e) acquiring a second image of the measurement locations using the camera sensor and using the camera controller to direct the camera control module to actuate the camera sensor to obtain the second image therefrom, providing the second image to the camera controller using the camera control module, and receiving the second image by the pre-processing module which is associated with the camera controller; providing the second image to the camera controller using the camera control module, and receiving the second image by the pre-processing module which is associated with the camera controller; (f) updating a portion of the candidate output image with a portion of the second image in accordance with a selection criterion using the pre-processing module, wherein if the selection criterion is met, the portion of the candidate image is replaced with the corresponding portion of the second image; repeating steps (d) through (f) until the camera sensor has traversed a predetermined range of focus; and (g) transmitting the updated candidate output image; wherein only sections of each image that comprise measurement locations are provided from the camera sensor to the camera control module.