Description of Instrumentation and Procedures - Advances in Biochemical Engineering Biotechnology - page 16

temperature change relative to the other junction (cold junction) maintained
upstream at a constant temperature. The advantage of employing thermopiles
for the determination of multiple analytes derives from its high rejection ratio
of the common-mode thermal noise, and elimination of an additional element
for the reference temperature, as is the case in thermistor based sensors.
The integrated system, including transducer and enzyme reactor, provides
improved reliability and stability in multianalyte determinations, as compared
with discrete thermal sensor systems. In addition, application of micromachin-
ing and IC technologies is of benefit for the manufacture of uniform, cheap
thermal transducers with flexible shape, size, and resistance, as well as delicate
microstructure on the chips. The good thermal insulation of the transducers
from the flow stream eliminates interference from the reactants on the trans-
ducers, and the intrinsic stability of the transducers obviates the need for
frequent recalibration of the sensors.
2.5
Hybrid Biosensors
As the name indicates, hybrid biosensors are an integration of two or more mea-
surement principles for efficient detection of a specific analyte. In general, each
type of biosensor has its merits and shortcomings. Electrochemical biosensors
demonstrate good selectivity and can be regenerated electrochemically by using
electron transfer mediators and/or cofactors. However, while analyzing sample
mixtures, electrochemical measurements often suffer from interference by
molecules other than the electroactive species being measured. The interference
also depends on the applied potential. Although optical techniques have high
sensitivity and selectivity, they may be affected by interfering chromophores
and fluorophores, present or formed during the reactions. In the case of enzy-
me-based thermal biosensors, nonspecific heat has to be avoided or balanced by
differential measurement. On the other hand, since the thermal transducers are
insulated from reactants and buffer, the direct interference with the thermal
transducer by chemical compounds in the solution can be eliminated. This
enables the determination of complex samples, such as blood using thermal bio-
sensors.
A pioneering hybrid biosensor (Fig. 8a) was designed and demonstrated in
our group [21]. This sensor scheme utilizes electrochemical regeneration of the
electron mediator in combination with thermal detection, in order to extend
the linear range for glucose and catechol measurements (Fig. 8b). Such electro-
chemical methods had been applied previously in fiber-optic biosensors where
the indicator reagent was regenerated electrochemically. In principle, these
approaches could be applied for the development of hybrid biosensors based
on any oxidase or dehydrogenase. In addition, light-assisted regeneration of
NADH may also be of interest in the creation of an optically assisted hybrid bio-
sensor.