Biomedical Engineering Reference
In-Depth Information
tion has led to the improvement of the sensor's sensitivity and response time.
These developments are promising for the direct analysis of physiological sam-
ples, e.g. undiluted whole blood. The feasibility of microreactor fabrication on
the surface of silicon coupled to thermal detection using immobilized enzymes
is also trend-setting. The efficiency in such systems was much better when the
amount of immobilized enzyme was compared to the gain in sensitivity. In addi-
tion, integration of thin-film thermistors/ thermopiles permitted simultaneous
determination of multiple analytes. At present, four separate analytes have been
discriminated, and additional efforts to extend the range to the detection of
several analytes is in progress. Furthermore, the suitability of the construction
for small volume measurements, i.e. < 1
l, has resulted in an increased linear
range, for example in glucose sensing with glucose oxidase.
Application of the miniaturized biosensors for metabolite estimation in
whole blood is another important concept for future development. The impro-
vement in sensitivity, linear range and response time was achieved by miniatur-
ization of the sensors and has been proven in the case of whole-blood glucose,
urea and lactate. A useful feature of miniaturization is that the smaller the flow
channel, the smaller are the dispersion and dilution effects, favouring whole
blood measurement with minimum error. In the case of clinical estimations,
the results of the measurement on miniaturized thermal biosensor are more
reliable.
The concept of “the home doctor” is a multi-disciplinary project integrating
expertise from several areas of scientific research. It would include the develop-
ments in miniaturized biosensors coupled to communication technology. Addi-
tional help would be essential from computer scientists and clinical chemists. In
this regard it would be imperative to enhance the sensitivity of thermal bio-
sensors in order to make them more reliable and reproducible. This factor is
mainly governed by improvement in integrated circuit technology and reduc-
tion of the heat capacity of reactors. In addition, for such devices, optimizing the
doping concentration or the manufacturing process would improve the signal-
to-noise ratio of the thermistors. Moreover, the output of thermopiles could be
enhanced by integration of several thermocouples, especially in the case of mul-
tiple metabolite determination which requires larger transducer arrays to
decrease the thermal interference. This could be achieved by introducing a
micro-heat sink constructed of silicon or aluminium into the device, thus
immensely decreasing the thermal carry-over. Integrating the amplifier with the
thermopile on chips would further improve the stability of the thermal signal.
Diaphragm structures fabricated on crystal chips would also further improve
the reactor heat capacity.
Metabolites other than glucose, urea and lactate, can be monitored using the
thermometric technique. In the case of metabolites that cannot be estimated
enzymatically, other techniques, such as electrochemical and optical methods,
would have to be integrated in tandem with thermal sensing. Following ther-
mometric sensing, the clinical interpretation of the results is equally important.
This could be accomplished using data-processing systems, according to which
the clinical status and the correlation between the metabolites and various
disease states could be evaluated.
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