Philipp Wiedemann and Jean S. Guez have contributed equally to this work.
In situ microscopic cytometry enables noninvasive viability assessment of animal cells by measuring entropy states†
Article first published online: 22 JUL 2011
Copyright © 2011 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 108, Issue 12, pages 2884–2893, December 2011
How to Cite
Wiedemann, P., Guez, J. S., Wiegemann, H. B., Egner, F., Quintana, J. C., Asanza-Maldonado, D., Filipaki, M., Wilkesman, J., Schwiebert, C., Cassar, J. P., Dhulster, P. and Suhr, H. (2011), In situ microscopic cytometry enables noninvasive viability assessment of animal cells by measuring entropy states. Biotechnol. Bioeng., 108: 2884–2893. doi: 10.1002/bit.23252
- Issue published online: 13 OCT 2011
- Article first published online: 22 JUL 2011
- Accepted manuscript online: 15 JUL 2011 01:40PM EST
- Manuscript Accepted: 29 JUN 2011
- Manuscript Revised: 4 JUN 2011
- Manuscript Received: 25 MAR 2011
Current state of the art to determine the viability of animal cell suspension cultures is based on sampling and subsequent counting using specific staining assays. We demonstrate for the first time a noninvasive in situ imaging cytometry capable of determining the statistics of a morphologic transition during cell death in suspension cultures. To this end, we measure morphometric inhomogeneity—defined as information entropy—in cell in situ micrographs. We found that the cells are partitioned into two discrete entropy states broadened by phenotypical variability. During the normal course of a culture or by inducing cell death, we observe the transition of cells between these states. As shown by comparison with ex situ diagnostics, the entropy transition happens before or while the cytoplasmatic membrane is loosing its ability to exclude charged dyes. Therefore, measurement of morphometric inhomogeneity constitutes a noninvasive assessment of viability in real time. Biotechnol. Bioeng. 2011;108: 2884–2893. © 2011 Wiley Periodicals, Inc.