Page 181 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioTechnology

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Encyclopedia of Physical Science and Technology EN009J-69 July 19, 2001 22:50

Microanalytical Assays 681

taneously. For medical uses one can put the sensor in a
catheter to be inserted into a blood vessel, or an individual
could have a portable analyzer and periodically place a
drop of blood in contact with the sensor.
Usually the construction of a microsized analytical sys-
tem has components for the following functions: sam-
ple injection, preparation, separation, and detection. The
fabrication of these devices has been facilitated by the
application of techniques that were originally developed
for computing chip manufacture. While current tech-
niques for computer devices can make features at the
nanometer level, for microfabricated analytical devices
the usual feature dimensions are more likely at the micron
level.
The functions that are required for this devices are fluid
handling systems: for fluid movement, combining liq-
uid streams, splitting samples into multiple zones, reser-
voir zones for time delay and valves. There are several
techniques for moving fluids in these micron-sized chan-
FIGURE 1 Key functional elements of a biosensor. Usually there nels;theseincludecapillaryaction,centrifugalforce,grav-
is a membrane that separates the chemical and physical compo- ity, and pump mechanisms. Figure 2 illustrates a peristaltic
nents of the sensor from the external environment containing the pumpthathasbeenmicrofabricatedinapolymersubstrate.
analyte of interest. The analyte diffuses through the membrane The dimensions of the tubes are about 100 µ, and the rate
into the biochemical zone where it interacts with a biorecognition of pumping as a function of the frequency of air pressure
species to produce a change that is discernable by the detector
element. A signal processing system then interprets this change cycling is shown in the lower part of the figure.
(e.g., by comparing it to a calibration curve) to provide a readout One of the most effective techniques for fluid handling
of concentration. on microdevices utilizes electro-osmotic flow generation.
This type of flow depends on generating an electrical dou-
ble layer between the walls of the flow channel and the liq-
with the correct sensitivity that is needed for a particular uid in the channel. This mode of generating flow has one
application. advantage because it generates a plug flow pattern, rather
than a parabolic flow pattern that is typical of pressure-
driven laminar flow. A plug flow pattern has minimum dis-
I. MICROFABRICATION persion and thus limits the mixing between sample zones
that can occur with laminar flow situations.
Miniaturization of devices and mass production manufac- It was recently demonstrated that polynucleotide frag-
turing techniques are some of the key reasons for commer- ments can be separated in a microfluidic flow chamber
cial interest in biosensors at this time. Manufacturing tech- that includes a series of “molecular dams.” As illustrated
nologies developed for completely different applications, in Fig. 3, large fragments of DNA are hindered by nar-
such as micromachining for integrated circuits and fiber row passageways in the flow chamber. By appropriately
optics components for telecommunications, have allowed deploying these barrier sections, a separation device can
rather novel designs to be contemplated and developed for be constructed that can operate continuously.
biosensors. Another key feature of these technologies is Finally, electrophoresis is known as one of the most
the miniaturization of devices that one is able to achieve. powerful separation techniques for the separation of
This capability leads to the potential of very small, sensi- biological materials. Capillary electrophoresis provides
tive, and very stable devices that allow the development exceptionally high resolution of biomolecules. This tech-
of portable and perhaps disposable biosensors to permit nology has been microminiaturized as shown in Fig. 4.
bringing the analysis system very close to the source of The resolution of a series of proteins is excellent and,
the analyte rather the current mode of bringing samples of very importantly, the reproducibility of different lanes is
the analyte to centralized analysis laboratories. For exam- exceptional (Fig. 5).
ple, if the application is environmental, one could put the An example of a commercial microanalysis system that
sensor in remote locations to monitor many sites simul- utilized microfabrication and incorporated fluidic circuits