Microfluidic Control of Hypoxia Aids Investigations of Islet Pathophysiology

Hypoxia is a prevalent factor regulating numerous biological processes; and of specific interest here, hypoxia is a complication in clinical procedures such as islet transplantation. Recently, temporal oscillations between hypoxia and normoxia, termed intermittent hypoxia (IH), have shown “preconditioning” benefits to pancreatic islets [1-3]. In islet physiology, effects of static and transient hypoxia have not been well-understood or studied, primarily due to a lack of appropriate tools to control islet microenvironments. Addressing this gap of knowledge, this review will discuss the following points: 1) Discussion of the physiological and pathophysiological states of islet oxygenation will illustrate a significant diffusion limitation imposed on isolated islets. 2) Brief survey of current islet hypoxia studies will uncover the need for a microscaled oxygen modulation technique. 3) Novel microfluidic methods will be introduced that can manipulate oxygen microenvironments. 4) A technique based on microfluidics will be shown to precondition islets via intermittent hypoxia. The view of hypoxia as a key parameter in islet and transplant physiology is expanding. Our message here is that microscaled tools and techniques have developed to a level capable of experimentally addressing this increasingly important view on hypoxia.