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Monitoring hormone and small molecule secretion dynamics from islets-on-chip

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Abstract

Tissue functions such as hormone secretion involve the interplay of multiple chemical signals and metabolic processes over time. Measuring the different components involved is useful in unraveling the interactions, but often requires use of multiple analytical techniques. The challenge of measuring the necessary components with temporal resolution is greater when tissue samples are limited. Here, an accessible microfluidic platform compatible with multiple measurement techniques to monitor cell secretions has been developed. The platform is applied to islets of Langerhans, micro-organs involved in glucose homeostasis and diabetes. The device houses 1 to 8 islets and the perfusion fluid can be controlled to change conditions, e.g., glucose concentration, in seconds. Samples are collected in fractions and split for offline analysis. The device is paired with a scaled-down immunoassay, AlphaLISA, for hormone quantification and liquid chromatography-mass spectrometry for small molecule quantification to study secretion dynamics. The combined system allows the first simultaneous measurement of insulin, glucagon, biogenic amines, and amino acids from islet secretions. The combined measurements revealed correlation in secretion events and differences in timing of release between hormones and biogenic amines and amino acids. These efforts decreased the number of islets required compared to standard approaches, thus decreasing necessary animal use, reagent use, and cost, while increasing information content achievable from one sample. The microfluidic device is a suitable platform for in-depth characterization of secretion from small tissue samples.

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Acknowledgements

We acknowledge the University of Michigan (UM) Center for Chemical Genomics for use of their EnVision plate reader and the UM Center for Statistical Consultation and Research (CSCAR) for assistance with statistical analysis. We thank Peter-Philip Booth and Dr. Kelcie Zegalia for helpful conversation and Emory Payne for fluorescent device imaging.

Funding

This material is based upon work supported by the National Science Foundation Graduate Research Fellowship program under Grant No. DGE 1841052 (A.E.L.). This work was also supported by National Institute of Diabetes and Digestive and Kidney Diseases under Grant No. 5R01DK046960-28 (R.T.K.).

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  1. Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA

    Ashley E. Lenhart & Robert T. Kennedy

  2. Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA

    Robert T. Kennedy

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  1. Ashley E. Lenhart
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Correspondence to Robert T. Kennedy.

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Lenhart, A.E., Kennedy, R.T. Monitoring hormone and small molecule secretion dynamics from islets-on-chip. Anal Bioanal Chem 415, 533–544 (2023). https://doi.org/10.1007/s00216-022-04460-2

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