Development of a Microsphere-Based System to Facilitate Real-Time Insulin Monitoring

Lindy Kahanovitz; Erkin Seker; Robert S Marks; Martin L Yarmush; Tania Konry; Steven J Russell

doi:10.1177/1932296815625081

Development of a Microsphere-Based System to Facilitate Real-Time Insulin Monitoring

J Diabetes Sci Technol. 2016 May 3;10(3):689-96. doi: 10.1177/1932296815625081. Print 2016 May.

Authors

Lindy Kahanovitz¹, Erkin Seker², Robert S Marks³, Martin L Yarmush⁴, Tania Konry⁵, Steven J Russell⁶

Affiliations

¹ Department of Biotechnology Engineering, Ben Gurion University of the Negev, Beer Sheva, Israel Diabetes Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
² Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Shriners Burns Institute, Boston, MA, USA Department of Electrical and Computer Engineering, University of California, Davis, Davis, CA, USA.
³ Department of Biotechnology Engineering, Ben Gurion University of the Negev, Beer Sheva, Israel.
⁴ Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Shriners Burns Institute, Boston, MA, USA.
⁵ Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Shriners Burns Institute, Boston, MA, USA Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.
⁶ Diabetes Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA sjrussell@mgh.harvard.edu.

Abstract

Background: The speed of insulin absorption after subcutaneous delivery is highly variable. Incorrect assumptions about insulin pharmacokinetics compromise effective glycemic regulation. Our ultimate goal is to develop a system to monitor insulin levels in vivo continuously, allowing pharmacokinetic parameters to be calculated in real time. We hypothesize that a bead-based detection system can be run on a flow-through microfluidic platform to measure insulin in subcutaneous fluid sampled via microdialysis. As a first step in development, we focused on microsphere-based measurement of insulin.

Methods: Polystyrene microspheres coated with an anti-insulin monoclonal antibody were exposed to insulin-containing solutions, and after addition of a fluorescently labeled anti-insulin monoclonal antibody with a distinct epitope, bead-associated fluorescence was detected by fluorescence microscopy in 96-well plates or in a flow-through, microfluidic platform.

Results: The bead detection system in plates had a linear range in buffer for regular human insulin (RHI), insulin lispro, and insulin aspart of 15-1115 µIU/ml, 14-976 µIU/ml, and 25-836 µIU/ml, respectively. Measurement on plasma samples demonstrated proportionality between basal and peak insulin levels similar to the laboratory reference method. Preliminary results in a polydimethylsiloxane-based, flow-through, microfluidic platform showed a strong signal at peak insulin levels.

Conclusions: We have developed a microsphere-based system to rapidly measure levels of insulin and insulin analogs. We have further demonstrated proof of concept that this bead detection system can be implemented in a lab-on-a-chip format, which will be further developed and combined with microdialysis for real-time monitoring of insulin in vivo.

Keywords: insulin; insulin analogs; microfluidic; microsphere; pharmacokinetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Hypoglycemic Agents / blood*
Insulin / blood*
Lab-On-A-Chip Devices*
Microfluidic Analytical Techniques
Microspheres*

Substances

Hypoglycemic Agents
Insulin

Grants and funding

P41 EB002503/EB/NIBIB NIH HHS/United States