Biomedical Engineering Reference
In-Depth Information
Fig. 7. Schematic illustration of the thermal micro-biosensor fabricated onto a silicon chip
thermal detection. In this technique, a single microchannel column is serially
partitioned into several discrete detection regions. Each of the regions, corre-
sponding to the detection of one analyte, contains the corresponding enzyme
and a pair of film thermistors. Each thermistor placed after the enzyme matrix,
functions as the measurement transducer, whereas the other, placed before the
enzyme, serves as the reference. As a substrate mixture flows through this reac-
tion channel, multiple thermal signals generated from individual enzyme reac-
tions are detected nearly simultaneously. One advantage of this design is that all
determinations are performed under essentially identical conditions, such as
flow rate, sample volume, pressure, and working temperature. Additionally, the
effect of by-products of one enzyme reaction on the performance of other enzy-
mes in the series has been found to be minimal.
The feasibility of this approach was demonstrated in dual analytes such as
urea/penicillin and urea/glucose. In these investigations each detection region
was charged with a different enzyme-agarose bead conjugate (13
m in dia-
meter). The rest of the channel was charged with a similar bead but without the
immobilized enzyme. Complete filling of the channel is necessary to keep down
the residence time of the samples within the reactor, as they pass through it.
Consequently, determination of multiple analytes could be achieved nearly
simultaneously. The error in measurement in such system was primarily caused
by thermal carryover.This thermal effect,however,could be minimized by intro-
ducing a mini heat-sink between the reaction regions,using silicon or aluminum
strips connected with the chip. According to this principle, it would be possible
to determine even more analytes by this method, if additional thermal trans-
ducers are fabricated. In reactions where different reaction conditions of pH,
ionic strength and cofactors are required for the various groups of enzymes/
analytes, multi-channels can be supplied. In the case of whole blood and crude
samples, large bead size is preferred, in order to prevent clogging and to reduce
the back pressure in the flow channel. In addition, direct immobilization of
enzymes on a chip surface with extended coupling area would be a better choice
if adequate enlargement of surface area could be achieved. It is also possible to
employ an integrated thermopile as an alternative to the integrated thermistors
in this system. In this case, each thermopile relates to one enzyme. Its one junc-
tion (hot junction) is placed downstream of the enzyme matrix to determine the
m
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