Although biosensors are by means suitable for continuous biomedical monitor
ing, due to fouling and blood clotting, in vivo performance is far from opt
imal. For this reason, ultrafiltration, microdialysis or open tubular flow
is frequently used as interface. To secure quantitative recoveries of the a
nalyte of interest, sampling at submicrolitre level will be necessary which
in turn necessitates the development of small and versatile biosensor devi
ces. Here, a miniaturised biosensor device, which directly can be connected
to various interfaces will be presented. The biosensor device consists of
a pulsefree pump and a biosensor with an internal volume of 10-20 nl. In th
is article, the production as well as the construction of the flow-through
cell of the biosensor will be discussed. The advantages and disadvantages o
f several production processes will be demonstrated and a detailed protocol
for the production of such a nanoliter flow-through cell will be presented
. With respect to the bio-selector, several permselective membranes have be
en tested on their performance characteristics. Results obtained with these
biosensors will be presented and discussed. Finally, a protocol based upon
in situ electropolymerisation for the immobilisation of the biological com
ponent was defined and several biosensors based upon this principle have be
en produced and tested for the monitoring of glucose respectively lactate.
To demonstrate, data obtained during a variety of in vivo studies at differ
ent clinical relevant applications will be presented. (C) 2001 Elsevier Sci
ence B.V. All rights reserved.