786 Development of microfluidic devices for islet physiology and transplantation
Wednesday November 18, 2015 from 15:30 to 17:00
Plenary Room 1

Yong Wang MD, United States

Assistant Professor

Department of Surgery

Unviersity of Illinois at Chicago


Development of microfluidic devices for islet physiology and transplantation

Yong Wang1, Mohammad Nourmohammadzadeh1, Xing Yuan1, Joshua E. Mendoza-Elias1, Jose Oberholzer1.

1surgery, university of Illinois at Chicago, chicago, IL, United States

Introduction: Microfluidic has been emerging as a valuable tool for analytical applications. It allows consumption of minimal reagents and analytes, easy implementation of experimental modalities not possible for macroscale tools, easy integration of multiple analytical tools. However, its application for islet studies is very limited, as only a few laboratories have this technology. Here, we present a set of microfluidics developed at UIC and their applications.
Methods and Materials: Microfluidic was designed using AutoCAD and then translated onto photomask by lithography.  SU8 was used as for molding by spinning on silicon wafer and then exposing to UV with desired geometry by photo-polymerization. PDMS (Sylgard 184) and cross-linkers were added and then cured.  Flow dynamics were simulated using COMSOL Multiphysics.
Results and Discussion: (1) Microfluidic perifusion and imaging multiplexer (Fig.1A): Five-parallel perifusion device has three-layers consisting of inlet and outlet (top layer), perifusion chamber (middle layer), and microwells holding islet (bottom layer). The system provides uniform flow dynamics in perifusion chamber (Fig.2A) and can create various chemical concentrations (Fig.2B). The simultaneous multi assay can be performed including calcium signaling, mitochondrial potentials, and insulin secretion (Fig.2C). C-peptide, proinsulin, glucagon can also be also measured from perifusates (data not shown). The system can be used not only for islets, but also for single beta-cells and encapsulated islets (Fig.2D).
(2) Microfluidic perifusion system integrated with concentration generators (Fig.1B): This device can create various chemical gradients in four chambers useful for investigating long-term effects of chemicals (antidiabetics and immunosuppressants) on islets. We applied it for understanding rapamycin toxicity on human islets, showing that rapamycin impaired mitochondrial function related to NOX activated ROS production.
(3) Microfluidic perifusion integrated with oxygen control (Fig.1C): The integrated oxygen control was achieved by adding 100 nm thin PDMS beneath perifusion chamber, showing that oxygen can be delivered in much faster and more efficiently and takes only 30 s from % O2-21% O2, while oxygen glove takes 1 hr to reach targeted [O2]. This device is very useful for studying ischemia-reperfusion and ROS signaling.
(4) Microfluidic-based islet array and encapsulated islet array (Fig.1D and E): In order to achieve high resolution and throughput analysis, two microarrays for naked islets and encapsulated islets were developed based on inertial focusing and hydrodynamic trapping mechanism with 99% trapping efficiency which allows simultaneously imaging of 200 islets.
(5) Pumpless driven microfluidic: Microfluidics require specialized pumps and tubing. We developed a pumpless delivery system driven by surface tension, which significantly simplifies the microfluidic operation. Also, the system reduced liquid volume from mL to  10-20 μl.
(6) Microfluidic integrated smartphone application: We developed this device for human islet quantification since current counting method is manual, time-consuming, less accurate, and high operator variation.
Conclusion: We developed a set of microfluidics designed specially for islets. The microfluidics enhance diabetes research and treatment, which will have significant impact on research community.

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