The need for stimuli-responsive components in microfluidic systems has led to the development of hydrogel-based patterned microstructures. The most commonly practiced means for fabricating micropatterned hydrogels is based on in situ photopolymerization using 365 nm UV light in a liquid medium. This approach has been found to be very successful for patterning hydrogel-based features with tens or hundreds of microns resolution, but its main drawback lies in having to contain the liquid prepolymer mixture within the device for irradiation. We instead propose an alternate approach that uses direct-write electron-beam radiation to cross-link a dry, spin-coated thin film of linear polymer. After exposure, the linear polymer is dissolved in water leaving behind the cross-linked regions. When immersed in water, the cross-linked regions assume the properties of hydrogel and undergo naturally thermoreversible swelling and shrinking. This direct-writing approach can be used to fabricate hydrogel-based nanostructures down to 100 nm linewidth and also is amenable to easy integration into nano and bio devices. We focus on patterning a well-known thermoreversible hydrogel, poly (N-isopropylacrylamide), and use it to discuss various aspects of process methodology, fabrication, characterization, and stimuli-response properties of nanosized hydrogels in detail. (c) 2005 American Vacuum Society.