Microfluidic Array with Integrated Oxygenation Control for Real-Time Live-Cell Imaging: Effect of Hypoxia on Physiology of Microencapsulated Pancreatic Islets

Abstract

In this report, we present a novel microfluidic islet array based on a hydrodynamic trapping principle. The lab-on-a-chip studies with live-cell multiparametric imaging allow understanding of physiological and pathophysiological changes of microencapsulated islets under hypoxic conditions. Using this microfluidic array and imaging analysis techniques, we demonstrate that hypoxia impairs the function of microencapsulated islets at single islet level, showing a heterogeneous pattern reflected in intracellular calcium signaling, mitochondrial energetic, and redox activity. Our approach demonstrates an improvement over conventional hypoxia chambers that is able to rapidly equilibrate to true hypoxia levels through the integration of dynamic oxygenation. This work demonstrates the feasibility of array-based cellular analysis and opens up new modality to conduct informative analysis and cell-based screening for microencapsulated pancreatic islets.

Hypoxia‐enhanced adhesion of red blood cells in microscale flow

“…Most of the microfluidic devices in the literature have been fabricated via soft lithography by relying on PDMS, which is an optically transparent, gas‐permeable, and biocompatible material . Although soft‐lithography‐based systems have grown popular for their superior properties and a relatively rapid prototyping capability, fabrication of these microfluidic devices requires labor‐intensive processes and clean room facilities, which are limiting factors for high‐throughput clinical applications .…”

High-throughput screening approaches and combinatorial development of biomaterials using microfluidics

“…As a result, available options to comprehensively study the physiology and pathophysiology of structures like islets of Langerhans, are limited. A successful example was given by Nourmohammadzadeh et al [40], who, based on hydrodynamic trapping strategy coupled with islet microencapsulation in alginate microbeads demonstrated the hypoxia impairment of intracellular calcium signaling, and mitochondrial energetic and redox activity, with single islet resolution.…”

On-chip porous microgel generation for microfluidic enhanced VEGF detection

“…Microfluidic droplet generators have been used to create spheroidal cell encapsulations for tissue engineering (Tang and Takeuchi, 2007;Khademhosseini and Langer, 2007), and artificial organs (Wang et al, 1997;Nourmohammadzadeh et al, 2013) as well as high-throughput biological assays (Brouzes et al, 2009). Droplet-based chemical sensors can also provide fast time resolution as short as 50 milliseconds, providing protein detections such as monitoring insulin in real-time (Chen et al, 2008).…”