Optimization of On-Chip Polymerase Chain Reaction - Hardware/Software Co-Design and Optimization for Cyberphysical Integration in Digital Microfluidic Biochips - page 120

system on-line, in order to decide whether or not the thermal cycles are to be
continued. This helps us to design an efficient cyberphysical PCR biochip on a
DMFB platform.
2. We propose a layout design algorithm that considers the interferences among
the on-chip elements include reservoirs, sensors and thermal units. A heuristic
algorithm is applied to minimize the area and electrode count of the biochip
while satisfying the proximity constraints.
3. The placement of modules considers the time cost of droplet transportation and
defect tolerance for the PCR biochip. The overall mixing/dilution/detection time
for a given bioassay is optimized, and a droplet-routing method is developed to
bypass electrode defects.
4. The visibility of droplets in the sensing system for cyberphysical biochips is
considered. The mixing operations are scheduled to ensure that the sensing
system can perform real-time observations of the droplets from both top and
side views.

The remainder of this chapter is organized as follows. Section 5.2 describes the
statistical model for the amplification of DNA strands, and the on-line decision
making method during an actual experiment. Section 5.3 introduces the device
placement algorithm with the consideration of device interferences. Section 5.4
describes an application-specific reservoir allocation method. The consideration of
droplet visibility during operation scheduling is discussed in Sect. 5.5 . Simulation
results for three widely used bioassays are presented in Sect. 5.6 . Section 5.7
concludes the chapter.

5.2 Cyberphysical Biochip with On-line Decision Making

Figure 2.5 presents the laboratory setup for cyberphysical PCR biochip [ 9 ]. The
sensing system on biochip monitors the intensity of fluorescence in the droplet, and
provides input to the control software. In this way, the software is able to control the
execution of the PCR procedure based on the sensor feedback.
When a DNA-binding dye binds to a double-stranded DNA in PCR, it causes
fluorescence of the dye. An increase in the DNA product during PCR therefore
leads to an increase in fluorescence intensity [ 4 - 6 ]. The sensing system monitors the
intensity of fluorescence in the droplet, and provides input to the control software.
In this way, the software can control the execution of the PCR procedure based on
sensor feedback.