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3. We propose the on-line droplet-routing method that has low computational
complexity, and the response time of the cyberphysical system becomes negli-
gible. Therefore, the degeneration of intermediate products for the bioassay can
be avoided.
The remainder of this chapter is organized as follows. Section 4.2 presents the
design of microfluidic biochips that uses multiple clock frequencies. Section 4.3
introduces the framework of operation-dependency-aware synthesis. Based on
results derived from the proposed synthesis algorithm, integrated on-line decision-
making for droplet transportation path is presented in Sect. 4.4 . Simulation results
for three widely used bioassays are presented in Sect. 4.5 . Section 4.6 concludes the
chapter.
4.2
Biochips with Multiple Clock Frequencies
When an actuation voltage is applied, electrodes tend to undergo oxidation (loss
of electrons), which is referred to as “electrolytic corrosion”. This leads to the
degradation extent of electrodes on biochips [ 14 , 15 ]. Experimental results published
in the literature demonstrate that the degradation of an electrode is directly related
to the number of times that it is switched on and off [ 16 ]. With the same sequence
of electrode actuation vectors, electrodes will degrade faster under higher clock
frequency. On the other hand, an increase in the clock frequency can reduce the
execution time of fluidic operations [ 5 ]. Hence, in order to ensure the reliability of
electrodes on the biochip, and complete the bioassay under timing constraints in the
meantime, it is important to choose an appropriate clock frequency.
Fluidic operations are divided into two categories: frequency-sensitive operations
and frequency-insensitive operations. The completion time of droplet transportation
and dispensing is determined by clock frequency, because the droplet will be moved
from one electrode to another adjacent electrode during each clock cycle; hence
the rate at which a droplet is transported or dispensed is proportional to the clock
frequency. Note that, if the transportation or dispensing path for a droplet consists
of P electrodes, then the number of clock cycles required to dispense or move
the droplet is also P . This number of clock cycles is only related to the length
of the transportation path, and independent of the clock frequency. If we increase
the electrode switching frequency for droplet transposition and dispensing, the time
needed for these operations can be shortened. Hence, we conclude that by increasing
the clock frequency, the transportation and dispensing time of droplets can be
accelerated without affecting the chip reliability.
The execution times of mixing and dilution operations cannot be significantly
reduced by increasing the clock frequency. For example, experimental results for
droplet mixing show that, at a frequency of 8 Hz, the time spent on the mixing
operation is 12 s; when the frequency is increased to 16 Hz, the mixing time
decreases to 11 s [ 5 ]. Hence the mixing time only decreases 8:3 % while the rate of
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