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Proceedings Paper

Towards non-invasive 3D hepatotoxicity assays with optical coherence phase microscopy
Author(s): Leonard J. Nelson; Andreas Koulovasilopoulos; Philipp Treskes; Peter C. Hayes; John N. Plevris; Pierre O. Bagnaninchi
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Paper Abstract

Three-dimensional tissue-engineered models are increasingly recognised as more physiologically-relevant than standard 2D cell culture for pre-clinical drug toxicity testing. However, many types of conventional toxicity assays are incompatible with dense 3D tissues. This study investigated the use of optical coherence phase microscopy (OCPM) as a novel approach to assess cell death in 3D tissue culture. For 3D micro-spheroid formation Human hepatic C3A cells were encapsulated in hyaluronic acid gels and cultured in 100μl MEME/10%FBS in 96-well plates. After spheroid formation the 3D liver constructs were exposed to acetaminophen on culture day 8. Acetaminophen hepatotoxicity in 3D cultures was evaluated using standard biochemical assays. An inverted OCPM in common path configuration was developed with a Callisto OCT engine (Thorlabs), centred at 930nm and a custom scanning head. Intensity data were used to perform in-depth microstructural imaging. In addition, phase fluctuations were measured by collecting several successive B scans at the same location, and statistics on the first time derivative of the phase, i.e. time fluctuations, were analysed over the acquisition time interval to retrieve overall cell viability. OCPM intensity (cell cluster size) and phase fluctuation statistics were directly compared with biochemical assays. In this study, we investigated optical coherence phase tomography to assess cell death in a 3d liver model after exposure to a prototypical hepatotoxin, acetaminophen. We showed that OCPM has the potential to assess noninvasively and label-free drug toxicity in 3D tissue models.

Paper Details

Date Published: 5 March 2015
PDF: 6 pages
Proc. SPIE 9322, Dynamics and Fluctuations in Biomedical Photonics XII, 93220H (5 March 2015); doi: 10.1117/12.2077997
Show Author Affiliations
Leonard J. Nelson, The Univ. of Edinburgh (United Kingdom)
Andreas Koulovasilopoulos, The Univ. of Edinburgh (United Kingdom)
Philipp Treskes, The Univ. of Edinburgh (United Kingdom)
Peter C. Hayes, The Univ. of Edinburgh (United Kingdom)
John N. Plevris, The Univ. of Edinburgh (United Kingdom)
Pierre O. Bagnaninchi, The Univ. of Edinburgh (United Kingdom)

Published in SPIE Proceedings Vol. 9322:
Dynamics and Fluctuations in Biomedical Photonics XII
Valery V. Tuchin; Kirill V. Larin; Martin J. Leahy; Ruikang K. Wang, Editor(s)

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