Due to their low cost, amenability to high-throughput molding, and wide range of physical and chemical properties, polymers are becoming essential materials in the development of microdevices such as micro-optical, micromechanical, and microfluidic systems. A highly successful example is soft lithography, [1] based on micromolding of the elastomer poly(dimethylsiloxane) (PDMS) from a microfabricated master; due to their elasticity and inertness, the PDMS replicas can in turn be used repeatedly (either as molds, stamps, or microfluidic channels) for microstructuring a rich variety of materials.[1]However, any molding technique is limited by the fabrication of the first master mold, most often done by traditional photolithography. Photolithography typically results in a) features of uniform height and nearly vertical sidewallsÐa severe limitation in the fabrication of three-dimensional (3D) (i.e., multiple-height and/or smoothly varying height) microstructures; and b) features that cannot be easily alteredÐrequiring the photolithographic processing of a new mold for each design iteration. Three-dimensional features can be fabricated using techniques such as grayscale photolithography, [2] isotropic etching of glass or silicon, [3] photoresist reflow, [4] and serial stereolithography (e.g., using ion or laser beams [5] ), but the produced features are permanent. In most cases, only a small range of curvatures and depths (rounded-photoresist heights < 15 lm [4] ) is possible. Re-configurability is presently limited to thin films (e.g., using digital mirror projectors, [6] microfluidic delivery of proteins, [7] or etchants [8] ), serial patterning (e.g., using energetic beams [5] or ªinkjetº approaches [9] ), and/or sample-wide modifications (such as thermal treatments [10,11] or mechanical deformation [1,12±15] ). As an alternative to the mold fabrication strategies mentioned above, we have devised ªmicrotunableº molds (lTMs) whose microtopography can be tuned post-fabrication at certain pre-defined locations, as depicted in Figure 1. First, a photolithographically patterned master (Fig. 1A) is replicated in PDMS. The PDMS replica is bonded to a thin (ranging from 8±18 lm thick) membrane of PDMS (Figs. 1B, C) so as to form sealed cavities that can be individually or collectively pressurized. Shown in Figure 1C is a cross-section of a finished lTM (cut after being used) featuring six individually addressable 3 cm long, 250 lm wide rectangular membranes (thickness t = 17 lm) The 30 lm deep cavities can be inflated or deflated by applying a pressure difference between the two sides of the membrane (Figs. 1D±G), either by means of house vacuum (approx. ±75 kPa, solid arrows) or pressurized gas through a pressure regulator (hollow arrows); sliced crosssections of the corresponding polymer replicas (in PDMS) are shown on the right (optical pictures). Replication from lTMs with other polymers such as polyurethane is also possible (see Experimental). Pressure differentials can be re-configured in the time scale of a...