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Experiments and complimentary simulations are presented to demonstrate the size-dependent infiltration and detection of variable length nucleic acids in porous silicon with controllable pore diameters in the range of 15-60 nm. The pore diameter must be tuned according to target molecule size in order to most effectively balance sensitivity and size-exclusion. A quantitative relationship between pore size (15-60 nm), nucleic acid length (up to ~ 5.3 nm), and sensor response is presented with smaller molecules detected more sensitively in smaller pores as long as the pore diameter is sufficient to enable molecular infiltration and binding in the pores. The density of probe molecules on the pore walls and subsequent hybridization efficiency for target molecule binding are also reported and are shown to depend strongly on the method of infiltration as well as the target molecule size.