Biomedical Engineering Reference
In-Depth Information
Fig. 4 Different ''free''
spaces within the cartridge
for sensor integration. Sensor
integration will be performed
via a connecting layer (in
white: protective layer)
tests cyclic olefin copolymer (COC) seemed to be appropriate due to its ability to
be formed within injection-molding processes and especially due to its low
autofluorescence. For integration into the optical sensor system the polymer film
has a size of 10 9 40 mm and a height of 0.2 mm. This film acts simultaneously
as a wave-guiding element and as the substrate for the capture molecules. To act as
a waveguide the polymer film has two integrated prisms in which laser light from a
light source within the processing unit is coupled in and out. The effect of guiding
the light into the polymer film is that an evanescent field is created which illu-
minates just a volume 100 nm next to the surface. Hence, the fluorescence signal
arising from the dye-labeled detector antibodies has a much better signal-to-noise
ratio due to a smaller background signal. In this regard, the used total internal
reflectance fluorescence-principle (TIRF) is able to deliver a higher sensitivity
compared to normal fluorescence detection. As dye-labels in general many dif-
ferent fluorescence dyes can be used. In the specific case, the use is limited to one
dye with one defined excitation wavelength of 630 nm to simplify the need of a
laser and detector within the read-out unit.
In addition to the optical read-out also an electrochemical sensor can be chosen.
In this case the substrate made in a seven-step fabrication process is an electronic
chip with a size of 8 9 10 mm having 16 gold electrodes for the immobilization of
capture molecules, a gold counter electrode, and an iridium/iridium oxide refer-
ence electrode. The electrodes have a diameter of 350 lm and capture molecules
are immobilized that are specific to the desired analyte. The concentration of the
analytes can be determined via a secondary and detection antibody which is
conjugated with an enzyme. In many cases an alkaline phosphatase or a beta-
galactosidase is used as the enzyme which converts a substrate into an electro-
chemically active substance. This can then be determined locally by measuring the
current in a three-electrode set-up. While temperature stabilization during the
binding of analytes to the capture molecules in the case of the optical sensor is
performed with a heater on the cartridge itself, the electrochemical chip has an
additional heater.
Concerning the fabrication process of both sensors the electrochemical one
seems to be much more complicated. As stated above seven fabrication steps are
