A device for base calling, comprising: a biosensor (102, 300, 400) and a receptacle configured to hold the biosensor, the biosensor having a sample surface including pixel areas (306', 1106', 1204') and configured to hold a plurality of clusters (306A, 1002, 1102A, 1202A) during a sequence of sampling events such that the clusters are distributed unevenly over the pixel areas, an array of sensors (306, 1106, 1204), where each sensor in the array is configured to sense information from one or more clusters disposed in corresponding pixel areas of the sample surface to generate a pixel signal in a sampling event, the array configured to generate the plurality of sequences of pixel signals, the array having a number N of active sensors, the sensors in the array disposed relative to the sample surface to generate respective pixel signals during the sequence of sampling events from the number N of corresponding pixel areas of the sample surface to produce the plurality of sequences of pixel signals, and a communication port which is configured to output the plurality of sequences of pixel signals; and a signal processor coupled to the receptacle, and configured to execute time sequence and spatial analysis of the plurality of sequences of pixel signals to detect patterns of illumination corresponding to a number N + M of individual clusters on the sample surface from the number N of active sensors, where M is a positive integer, and to classify the results of the sequence of sampling events for the number N + M of individual clusters, and is configured to use the plurality of sequences of pixel signals gathered from a group of the pixel areas on which at least two clusters are unevenly distributed to determine spatial characteristics of the at least two clusters, including location of the at least two clusters on the sample surface, wherein the plurality of sequences of pixel signals encodes differential crosstalk between the at least two clusters resulting from their uneven distribution over the group of pixel areas. a biosensor (102, 300, 400) and a receptacle configured to hold the biosensor, the biosensor having a sample surface including pixel areas (306', 1106', 1204') and configured to hold a plurality of clusters (306A, 1002, 1102A, 1202A) during a sequence of sampling events such that the clusters are distributed unevenly over the pixel areas, an array of sensors (306, 1106, 1204), where each sensor in the array is configured to sense information from one or more clusters disposed in corresponding pixel areas of the sample surface to generate a pixel signal in a sampling event, the array configured to generate the plurality of sequences of pixel signals, the array having a number N of active sensors, the sensors in the array disposed relative to the sample surface to generate respective pixel signals during the sequence of sampling events from the number N of corresponding pixel areas of the sample surface to produce the plurality of sequences of pixel signals, and a communication port which is configured to output the plurality of sequences of pixel signals; and a sample surface including pixel areas (306', 1106', 1204') and configured to hold a plurality of clusters (306A, 1002, 1102A, 1202A) during a sequence of sampling events such that the clusters are distributed unevenly over the pixel areas, an array of sensors (306, 1106, 1204), where each sensor in the array is configured to sense information from one or more clusters disposed in corresponding pixel areas of the sample surface to generate a pixel signal in a sampling event, the array configured to generate the plurality of sequences of pixel signals, the array having a number N of active sensors, the sensors in the array disposed relative to the sample surface to generate respective pixel signals during the sequence of sampling events from the number N of corresponding pixel areas of the sample surface to produce the plurality of sequences of pixel signals, and a communication port which is configured to output the plurality of sequences of pixel signals; and a signal processor coupled to the receptacle, and configured to execute time sequence and spatial analysis of the plurality of sequences of pixel signals to detect patterns of illumination corresponding to a number N + M of individual clusters on the sample surface from the number N of active sensors, where M is a positive integer, and to classify the results of the sequence of sampling events for the number N + M of individual clusters, and is configured to use the plurality of sequences of pixel signals gathered from a group of the pixel areas on which at least two clusters are unevenly distributed to determine spatial characteristics of the at least two clusters, including location of the at least two clusters on the sample surface, wherein the plurality of sequences of pixel signals encodes differential crosstalk between the at least two clusters resulting from their uneven distribution over the group of pixel areas.