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Recent advances in bio-sensing technologies have led to design of bio-sensor arrays for rapid identification and quantification of various biological agents such as drugs, gene expressions, proteins, cholesterol, fats, etc. Various dedicated sensing arrays are already available commercially to monitor some of these compounds in a sample. However, monitoring the simultaneous presence of multiple agents in a sample is still a challenging task. Multiple agents may often attach to the same probes on an array which makes it difficult to design a chip that can distinguish such agents (leading to low specificity). Thus, sophisticated algorithms for targets identification need to be implemented in biochip in order to maximize the number of distinguishable targets in the samples. The proposed algorithms are also required to introduce sophisticated signal processing and more intelligence on-chip. Dealing with these new processing and information technology demands constraints also require more innovative approaches towards hybrid integration technologies. To address such new demands, we discuss in this paper an innovative 3D-integrated bio-chips especially dedicated to label-free DNA detection.