Soft-polymer based microparticles are currently being applied in many biomedical applications, ranging from bioimaging and bioassays to drug delivery carriers. As one class of soft polymers, hydrogels are materials that can be used for delivering drug cargoes and can be fabricated in controlled sizes. Among the various hydrogel-forming polymers, poly(ethylene glycol) (PEG) based hydrogel systems are widely used due to their negligible toxicity and limited immunogenic recognition. Physical and chemical properties of particles (i.e., particle size, shape, surface charge, and hydrophobicity) are known to play an important role in cell-particle recognition and response. To understand the role of physicochemical properties of PEG-based hydrogel structures on cells, it is important to have geometrically precise and uniform hydrogel structures. To fabricate geometrically uniform structures, the authors have employed electron beam lithography and ultraviolet optical lithography using PEG or PEG diacrylate polymers. These hydrogel structures have been characterized by scanning electron microscopy, atomic force microscopy, optical microscopy, and attenuated total reflection Fourier transform infrared spectroscopy, confirming control of chemistry, size, and shape. (C) 2010 American Vacuum Society. [DOI: 10.1116/1.3517716]