CSEM Scientific and Technical Report 2008

Absolute, Reference-free Biosensing Using Ion-selective Thin Films
S. Generelli, R. Rajkumar
A combination of novel types of ion-selective thin films and galvanometric readout makes it possible to realize miniaturized microsensors capable of
robust, absolute and calibration-free measurement of the concentration of clinically relevant ions in biological samples of volumes below a microliter
During the last decade, the classical field of ion-selective
electrode (ISE) research has experienced a small revolution.
The better understanding of the mechanisms occurring in the
ion selective membrane, as well as the research of new
materials, such as conductive polymers have led to new ideas
and approaches on how to exploit the unique properties of
such sensors [1] .
Besides the determination of pH, clinical analyses are still
nowadays the main field of application of ion-selective
electrodes. As the physiological ranges of relevant ions are
rather narrow, the precision and accuracy of a measurement
must be within a few percent only, which is rather demanding
in view of the small sample amounts and the complexity of
media such as whole blood [1] .
A well-known inadequate property of microfabricated ionselective
electrodes is the lack of temporal stability. The drift
of the electrodes makes it difficult to use such electrodes, and
the only way to use them in practice is to perform frequent
calibrations. These instabilities are due to the difficulty of
maintaining a well-controlled and stable electrode composition.
Very recently, the application of novel types of thin films
offering very specific chemical and electrochemical properties
suggested new ways of stabilizing the electrode response
over time. These new materials, which are for the moment not
used in routine ISE fabrication, open up the possibility for
absolute and highly robust measurement systems of ion
concentration, even in the presence of surface contamination
and biofilms [2] .
Another limiting factor for sensor miniaturization is the need to
use a regular, non-microfabricated reference electrode. In fact,
to this day, no satisfactory microfabricated reference electrode
has been described. This deficiency severely limits the
realization of a complete, miniaturized ion measurement
system, as is the case for the system of Figure 1.
Figure 1: Potentiometry does not depend on scaling laws. This
interesting feature realizes the measurement on extremely small
sample volumes, as this setup demonstrates, allowing
measurements on 11 µl samples.
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In collaboration with the renowned research group of
Prof. Eric Bakker at Curtin University of Technology in Perth,
Australia, CSEM is developing a new robust, absolute and
calibration-free microsensor, which is expected to overcome
all of the former limitations. These new microsensors will allow
the reliable measurement of the concentration of clinically
relevant ions in biological samples of volumes below a
microliter.
The exploitation of ion fluxes through the ion-selective thin film
is a key aspect of this research. All-solid-state multilayer films
are explored for this purpose, to obtain a sensor of the
geometry illustrated in Figure 2. If successful, this
methodology may become one of the most sensitive detection
techniques in terms of the total amount of measurable ions.
Further, the highly sensitive galvanometric detection is
coupled to analyte enrichment processes for a further
drastically improved detection limit that may surpass that of
any other routine electrochemical method [3] .
Figure 2: Schematic view of microfluidic cell now being used, and a
close-up of the electrode/sample interface, showing the thin-layer
structure of the all-solid-state sensor.
[1] E. Bakker, et al., “Modern potentiometry”, Angew. Chem. Int.
Ed., 46 (2007), 5660–5668
[2] E. Bakker, et al., “Nanoscale potentiometry”, TRAC, 27 (2008),
612-618
[3] http://nanochemistry.curtin.edu.au/people/staff/eric.cfm