CSEM Scientific and Technical Report 2008

A Microfluidic Chip for Cytotoxicological Screening Assays
S. Generelli, L. Barbe, O. T. Guenat
Initial results to use an ion-sensor-based platform for toxicology studies opens the way to a promising system to provide high throughput
toxicological screening assays.
Basic screening-level toxicity information is essential to
identify whether a chemical has the potential to damage
human health or the environment. The estimated 100’000
man-made pure chemicals and the enormous number of their
combinations exposed to mankind must be assessed for their
potentially adverse effects on health and the environment.
Today, the traditional way of testing these new compounds is
largely performed by animal testing. Nevertheless though,
deep concerns have risen among the scientific community
regarding the reliability of toxicological methodologies (due to
long tradition: Figure 1), in particular their poor capabilities to
predict human toxicology. In addition, other arguments against
animal testing for toxicology assays arose from commercial
and political sides regarding economic and ethical reasons. As
a clear sign of ethical concern, the European Parliament
passed a groundbreaking law in 2007 that prohibits the testing
of most cosmetic products on animals by 2009 and a request
to replace or reduce animal testing for other chemicals [1] .
The objective is to develop a microfluidic platform for cellbased
assays capable of determining the toxicity of chemicals
on targeted cells. The final aim of the project is to replace, or
at least to reduce, animal testing.
Figure 1: Switzerland has a very long tradition in toxicology:
Paracelsus, an alchemist, surgeon, theologist, philosopher, physician
and occultist, born in Einsiedeln in 1493, is considered the father of
toxicology.
Potassium is a key component in several cell events, in
particular in cell death and proliferation. Recently, it was
possible to detect and quantify (Figure 2) cell necrosis in real
time with potassium-selective microelectrodes integrated on a
microfluidic platform [ 2] . These preliminary results are very
promising, in particular since potassium effluxes appear early
in the cell death process [ 3] , and could thus be used as an
early marker of cell death.
In the previous non-optimal sensor geometry, the death of
only 200 cells could be detected. With an adequate redesign
of the platform, currently in production, the detection of a
single cell death is the goal.
Such assays could also be employed for even more
sophisticated cell-based assays, such as for the monitoring of
the regulation of tumor cell proliferation in cancer therapy for
individual patients [4] . This would represent significant progress
on the way to the envisaged “personalized medicine” of the
future.
Figure 2: Potentiometric recordings during a cell death assay. The K +
release from dying cells is clearly visible on the top curve, whereas
no change in potential is visible in the blank assay (grey area).
Comparing the potential rise during the necrosis assay and the
successive calibration, the number of necrotic cells can be estimated.
(figure adapted from [2] ).
[1] Regulation (EC) No 1907/2006 of the European Parliament and
of the Concil of 18 December 2006 concerning the Registration,
Evaluation, Authorization and Restriction of Chemicals (REACH);
Official Journal of the European Union 2007, 50, 3-282
[2] S. Generelli, et al., “Potentiometric platform for the quantification
of potassium efflux”, Lab Chip, 8 (2008), 1210-1215
[3] F. Hughes, et al., “Potassium is a critical regulator of apoptotic
enzymes in vitro and in vivo”, Adv. Enzyme Regulation, 39
(1999), 157-171
[4] A. Felipe, et al., “Potassium channels: new targets in cancer
therapy”, Cancer Detect. Prev., 30 (2006), 375-385
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