Since the genomic sequencing of more than 100 organisms first began, an almost overwhelming compendium of genetic and proteomic targets has been identified. Researchers are now beset with the task of characterizing these targets, as well as identifying and characterizing their extant natural variants. Combinatorial analytical techniques, such as microarray analysis, have emerged as the preferred tools for performing these characterizations and have enabled the recent commercialization of DNA [1][2][3][4] and proteomic [5] sensor arrays. A common attribute shared by all of these devices is the convention of distributing each sensor probe onto an exclusive array feature. This methodology imposes the requirement that the arrays possess a number of features equal to the number of probes, thus requiring array designers to investigate miniaturization to enable higher-density array construction. [6,7] However, decreasing the feature size correspondingly reduces the number of sensing molecules per feature, and the reduction of feature size and spacing is fundamentally limited by the array technology (namely, optimized feature spacing is at present on the order of hundreds of microns).A novel platform-independent probe-loading methodology has been developed that circumvents the need for the continual shrinkage of sensor features. This methodology increases the information density of the array not by miniaturizing the features in the array, but rather by changing the way probes are distributed within the array (see Figure 1). This technique, called feature multiplexing, achieves increases in density by incorporating multiple probes into each feature using a unique encoding system (see Figure 1). The use of this methodology allows a given number of features (n) to be used to deploy a much greater quantity of probes (up to 2 n Ă2) when sensing for a single analyte. This methodology can dramatically increase the capacity or information density of an array because there is this exponential relationship between the number of array Figure 1. Three-feature standard arrays (with one probe per feature) can only detect three targets, whereas multiplexed arrays can detect six target sequences.