dc.description.abstract |
<p>Digital microfluidics is an emerging technology that provides fluid-handling capability
on a chip. Biochips based on digital microfluidics have therefore enabled the automation
of laboratory procedures in biochemistry. By reducing the rate of sample and reagent
consumption, digital microfluidic biochips allow continuous sampling and analysis
for real-time biochemical analysis, with application to clinical diagnostics, immunoassays,
and DNA sequencing. Recent advances in technology and applications serve as a powerful
driver for research on computer-aided design (CAD) tools for biochips.</p><p>This
thesis research is focused on a design automation framework that addresses chip synthesis,
droplet routing, control-pin mapping, testing and diagnosis, and error recovery. In
contrast to prior work on automated design techniques for digital microfluidics, the
emphasis here is on practical CAD optimization methods that can target different design
problems in a unified manner. Constraints arising from the underlying technology and
the application domain are directly incorporated in the optimization framework.</p><p>The
avoidance of cross-contamination during droplet routing is a key design challenge
for biochips. As a first step in this thesis research, a droplet-routing method based
on disjoint droplet routes has been developed to avoid cross-contamination during
the design of droplet flow paths. A wash-operation synchronization method has been
developed to synchronize wash-droplet routing steps with sample/reagent droplet-routing
steps by controlling the order of arrival of droplets at cross-contamination sites.</p><p>In
pin-constrained digital microfluidic biochips, concurrently-implemented fluidic operations
may involve pin-actuation conflicts if they are not carefully synchronized. A two-phase
optimization method has been proposed to identify and synchronize these fluidic operations.
The goal is to implement these fluidic operations without pin-actuation conflict,
and minimize the duration of implementing the outcome sequence after synchronization.</p><p>Due
to the interdependence between droplet routing and pin-count reduction, this thesis
presents two optimization methods to concurrently solve the droplet-routing and the
pin-mapping design problems. First, an integer linear programming (ILP)-based optimization
method has been developed to minimize the number of control pins. Next an efficient
heuristic approach has been developed to tackle the co-optimization problem.</p><p>Dependability
is an important system attribute for microfluidic biochips. Robust testing methods
are therefore needed to ensure correct results. This thesis presents a built-in self-test
(BIST) method for digital microfluidic biochips. This method utilizes digital microfluidic
logic gates to implement the BIST architecture. A cost-effective fault diagnosis method
has also been proposed to locate a single defective cell, multiple</p><p>rows/columns
with defective cells, as well as an unknown number of rows/columns-under-test with
defective cells. A BIST method for on-line testing of digital microfluidic biochips
has been proposed. An automatic test pattern generation (ATPG) method has been proposed
for non-regular digital microfluidic chips. A pin-count-aware online testing method
has been developed for pin-constrained designs to support the execution of both fault
testing and the target bioassay protocol.</p><p>To better monitor and manage the execution
of bioassays, control flow has been incorporated in the design and optimization framework.
A synthesis method has been developed to incorporate control paths and an error-recovery
mechanism during chip design. This method addresses the problem of recovering from
fluidic errors that occur</p><p>during on-chip bioassay execution.</p><p>In summary,
this thesis research has led to a set of unified design tools for digital microfluidics.
This work is expected to reduce human effort during biochip design and biochip usage,
and enable low-cost manufacture and more widespread adoption for laboratory procedures.</p>
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