Hypoxia switches the metabolism of tumor cells and induces drug resistance. Currently, no therapeutic exists that effectively and specifically targets hypoxic cells in tumors. Development of such therapeutics critically depends on the availability of in vitro models that accurately recapitulate hypoxia as found in the tumor microenvironment. Here, we report on the design and validation of an easy-to-fabricate tumor-on-a-chip microfluidic platform that robustly emulates the hypoxic tumor microenvironment. The tumor-on-a-chip model consists of a central chamber for 3D tumor cell culture and two side channels for medium perfusion. The microfluidic device is fabricated from polydimethylsiloxane (PDMS), and oxygen diffusion in the device is blocked by an embedded sheet of polymethyl methacrylate (PMMA). Hypoxia was confirmed using oxygen-sensitive probes and the effect on the 3D tumor cell culture investigated by a pH-sensitive dual-labeled fluorescent dextran and a fluorescently labeled glucose analogue. In contrast to control devices without PMMA, PMMA-containing devices gave rise to decreases in oxygen and pH levels as well as an increased consumption of glucose after two days of culture, indicating a rapid metabolic switch of the tumor cells under hypoxic conditions towards increased glycolysis. This platform will open new avenues for testing anti-cancer therapies targeting hypoxic areas.

We report on the fabrication and modification of a top-down nanofabrication platform for enormous parallel silicon nanowire-based devices. We explain the nanowire formation in detail, using an additive hybrid lithography step, optimising a reactive ion etching recipe for obtaining smooth and vertical nanowires under a hybrid mask, and embedding the nanowire in a dielectric membrane. The nanowires are used as a sacrificial template, removal of the nanowires forms arrays of well-defined nano-pores with a high surface density. This platform is expected to find applications in many different physical domains, including nanofluidics, (3D) nanoelectronics, as well as nanophotonics. We demonstrate the employment of the platform as field emitter arrays, as well as a state-of-the-art electro-osmotic pump.

A novel wafer-scale silicon fractal fabrication method is presented here for forming pyramids only in the lateral direction using the crystal orientation of silicon. Fractals are fabricated in silicon by masking only the corners (corner lithography) of a cavity in silicon with silicon nitride, where the shape is determined by the crystal {111} planes of the silicon. The octahedral cavity shaped by the {111} planes was previously only used for forming octahedral fractals in all directions, but by using a planar silicon dioxide hard-mask on a silicon (100) wafer, the silicon octahedral cavity is “cut in half”. This creates a pyramid with sharper edges and vertices at its base than those determined by just the {111} planes. This allows selective corner lithography patterning at the vertices of the base while leaving the apex unpatterned, leading to lateral growing of pyramidal fractals. This selective patterning is shown mathematically and then demonstrated by creating a fractal of four generations, with the initial pyramid being 8 µm and the two final generations being of submicron size.

Known templating procedures mostly create out-ofplane nanowires where individual connections at both ends are complicated. Here we introduce a templating procedure for wafer scale fabrication of in-plane nanowires. The template fabrication process employs two simple interference lithography masking patterns and relies on self-aligned crystallographic processing. In-plane nanowires with diameters down to 10 nm can be fabricated wafer scale through this 3D templating procedure. As a first demonstration arrays of suspended silicon nitride wires have been created.