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a
b
Gold detection spot
Detection electrode
with gold spot
Control electrode
Laser source
Prism
CCD camera
Fig. 5.2 ( a ) Three-dimensional view with the bottom and top plates aligned for a biochip with
integrated detection electrodes; ( b ) view of the gold detection spot with DNA attached [ 11 , 13 ]
Despite offering numerous benefits, prior work on PCR implementations on a
DMFB suffers from the following four shortcomings:
1. In all prior work, the functional modules used in the three stages of the
PCR procedure are designed separately [ 3 , 7 ], and they cannot be efficiently
integrated on the same layout. This mismatch of the three steps often restricts
the effectiveness and feasibility of execution of the complete bioassay.
2. The inherent randomness and complexity of bioanalyses are not considered.
When a droplet is dispensed into the biochip, there is a probability that the droplet
may not contain sufficient amount of DNA for the PCR (referred to as an “empty
droplet”) [ 15 ]. The biochips designed in prior work are unable to monitor the
presence of empty droplets; hence they cannot terminate the wasteful execution
of the PCR.
3. The interferences (electrical, thermal, optical, fluidic) among the devices on the
biochip, which arise due to proximity effects, are not considered in the previous
work. For example, high temperature around the heater may lead to degeneration
of a biological sample in a reservoir [ 16 ]; therefore, the heater and the reservoir
cannot be placed too close to each other.
4. The previously designed PCR biochips are oblivious to the schedule of mixing
operations [ 6 ]. This may lead to excessive transportation of droplets during
mixing/dilution/detection operations in the PCR procedure, which may adversely
affect the performance and speed of the biochip.
To overcome the above shortcomings, we propose the first design method that can
optimize the PCR procedure on cyberphysical digital microfluidic biochips. The key
contributions of this paper are as follows:
1. To overcome the empty-droplet recognition problem, a statistical model for DNA
amplification is used to predict whether the droplet has sufficient amount of
DNA strands to carry out the PCR. The intensity of fluorescence detected by
the photodetectors (PDs) [ 17 - 19 ] or fluorescent microscope are fed back to the
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