Towards Single-Cell Control of Hypoxia in Microfluidic Cancer Assays

Hypoxia has been repeatedly demonstrated to have an adverse prognostic impact in various types of tumors [1]. A growing body of evidence indicates its central role in both, malignant progression, as well as in resistance to cancer treatment. While diminishing the efficiency of some forms of therapy, hypoxia also provides an opportunity for a new class of drugs, so called bioreductive drugs, specifically engineered to require hypoxic conditions for activation [2]. The development and in-vitro evaluation of these compounds however requires precise control over the cellular micro-environment, something not easily accomplished with traditional well-based cell-culture assays performed in air (~21 % O2). However, the use of microfluidics, a new fast-growing area of research and development, promises to overcome the limitations of open culture systems by relocating cells and reactions into enclosed microchannels on Lab-on-a-Chip devices. Recently we have introduced a novel optical oxygen sensor capable of resolving biologically relevant oxygen levels in such devices via fluorescence microscopy [3]. When combined with microfluidic flow control, cells cultured inside a parallel-plate microchamber could be exposed to custom transverse oxygen gradients with intermediate levels ranging between hypoxic (0 mg/L O2) to hyperoxic (34 mg/L O2, saturation