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Biomedical Microdevices

, 19:101 | Cite as

A microfluidic in-line ELISA for measuring secreted protein under perfusion

  • Qiyue Luan
  • Stacey Cahoon
  • Agnes Wu
  • Shyam Sundhar Bale
  • Martin Yarmush
  • Abhinav BhushanEmail author
Article

Abstract

Recent progress in the development of microfluidic microphysiological systems such as ‘organs-on-chips’ and microfabricated cell culture is geared to simulate organ-level physiology. These tissue models leverage microengineering technologies that provide capabilities of presenting cultured cells with input signals in a more physiologically relevant context such as perfused flow. Proteins that are secreted from cells have important information about the health of the cells. Techniques to quantify cellular proteins include mass spectrometry to ELISA (enzyme-linked immunosorbent assay). Although our capability to perturb the cells in the microphysiological systems with varying inputs is well established, we lack the tools to monitor in-line the cellular responses. User intervention for sample collection and off-site is cumbersome, causes delays in obtaining results, and is especially expensive because of collection, storage, and offline processing of the samples, and in many case, technically impractical to carry out because of limitated sample volumes. To address these shortcomings, we report the development of an ELISA that is carried out in-line under perfusion within a microfluidic device. Using this assay, we measured the albumin secreted from perfused hepatocytes without and under stimulation by IL-6. Since the method is based on a sandwich ELISA, we envision broad application of this technology to not just organs-on-chips but also to characterizing the temporal release and measurement of soluble factors and response to drugs.

Keywords

Microfluidics ELISA In-line measurement Cellular response 

Notes

Acknowledgements

This work was supported by NIH grant (R00 DK095984). We thank Dr. Sonali Karnik and Alice Chen for helping facilitate the experiments. The authors have no professional or financial conflicts, or interest to disclose.

Supplementary material

10544_2017_244_MOESM5_ESM.jpg (19 kb)
Supplementary Figure 1 Image of microfluidic device. (JPEG 19 kb)
10544_2017_244_MOESM6_ESM.jpg (12 kb)
Supplementary Figure 2 Albumin secreted from hepatocytes in a tissue culture plate without and with IL-6 stimulation. (JPEG 12 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringIllinois Institute of TechnologyChicagoUSA
  2. 2.Center for Engineering in MedicineMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of Biomedical EngineeringRutgers UniversityPiscatawayUSA

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