Recent microfluidic advancements in
oxygen gradients have greatly promoted controllable
oxygen-sensitive cellular investigations at microscale resolution. However, multi-gradient integration in a single
microfluidic device for tissue-mimicking cell investigation is not yet well established. In this study, we describe a method that can generate
oxygen and chemical concentration gradients in a single
microfluidic device via the formation of an
oxygen gradient in a chamber and a chemical concentration gradient between adjacent chambers. The
oxygen gradient dynamics were systematically investigated, and were quantitatively controlled using simple exchange between the aerial
oxygen and the
oxygen-free conditions in the gas-permeable
polydimethylsiloxane channel. Meanwhile, the chemical gradient dynamics was generated using a special channel-branched device. For potential medical applications of the established
oxygen and chemical concentration gradients, a
tumor cell therapy assessment was performed using two
antitumor drugs (
tirapazamine and
bleomycin) and two tumor cell lines (human
lung adenocarcinoma A549 cells and human cervical
carcinoma HeLa cells). The results of the proof-of-concept experiment indicate the dose-dependent antitumor effect of the drugs and
hypoxia-induced cytotoxicity of
tirapazamine. We demonstrate that the integration of
oxygen and chemical concentration gradients in a single device can be applied to investigating
oxygen- and chemical-sensitive cell events, which can also be valuable in the development of multi-gradient generating procedures and specific
drug screening.