Engineering challenges for instrumenting and controlling integrated organ-on-chip systems

John P. Wikswo, Frank E. Block, David E. Cliffel, Cody R. Goodwin, Christina C. Marasco, Dmitry A. Markov, David L. McLean, John A. McLean, Jennifer R. McKenzie, Ronald S. Reiserer, Philip C. Samson, David K. Schaffer, Kevin T. Seale, Stacy D. Sherrod

Research output: Contribution to journalReview article

91 Scopus citations

Abstract

The sophistication and success of recently reported microfabricated organs-on-chips and human organ constructs have made it possible to design scaled and interconnected organ systems that may significantly augment the current drug development pipeline and lead to advances in systems biology. Physiologically realistic live microHuman (μHu) and milliHuman (mHu) systems operating for weeks tomonths present exciting and important engineering challenges such as determining the appropriate size for each organ to ensure appropriate relative organ functional activity, achieving appropriate cell density, providing the requisite universal perfusion media, sensing the breadth of physiological responses, and maintaining stable control of the entire system, while maintaining fluid scaling that consists of ∼5 mL for the mHu and ∼5 μL for the μHu. We believe that successful mHu and μHu systems for drug development and systems biology will require low-volume microdevices that support chemical signaling, microfabricated pumps, valves and microformulators, automated optical microscopy, electrochemical sensors for rapid metabolic assessment, ion mobility-mass spectrometry for real-time molecular analysis, advanced bioinformatics, and machine learning algorithms for automated model inference and integrated electronic control. Toward this goal, we are building functional prototype components and are working toward top-down system integration.

Original languageEnglish (US)
Pages (from-to)682-690
Number of pages9
JournalIEEE Transactions on Biomedical Engineering
Volume60
Issue number3
DOIs
StatePublished - Oct 1 2013

Keywords

  • Artificial biological organs
  • Biological systems
  • Biotechnology
  • Systems biology

ASJC Scopus subject areas

  • Biomedical Engineering

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    Wikswo, J. P., Block, F. E., Cliffel, D. E., Goodwin, C. R., Marasco, C. C., Markov, D. A., McLean, D. L., McLean, J. A., McKenzie, J. R., Reiserer, R. S., Samson, P. C., Schaffer, D. K., Seale, K. T., & Sherrod, S. D. (2013). Engineering challenges for instrumenting and controlling integrated organ-on-chip systems. IEEE Transactions on Biomedical Engineering, 60(3), 682-690. https://doi.org/10.1109/TBME.2013.2244891