Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

published_or_final_version / abstract / Surgery / Master / Master of Philosophy

Xiao, Zigang. / "October 2010." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 62-66). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgement --- p.vi / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Microfluidic Technology --- p.2 / Chapter 1.1.1 --- Continuous Flow Microfluidic System --- p.2 / Chapter 1.1.2 --- Digital Microfluidic System --- p.2 / Chapter 1.2 --- Pin-Constrained Biochips --- p.4 / Chapter 1.2.1 --- Droplet-Trace-Based Array Partitioning Method --- p.5 / Chapter 1.2.2 --- Broadcast-addressing Method --- p.5 / Chapter 1.2.3 --- Cross-Referencing Method --- p.6 / Chapter 1.2.3.1 --- Electrode Interference in Cross-Referencing Biochips --- p.7 / Chapter 1.3 --- Computer-Aided Design Techniques for Biochip --- p.8 / Chapter 1.4 --- Placement Problem in Biochips --- p.8 / Chapter 1.5 --- Droplet Routing Problem in Cross-Referencing Biochips --- p.11 / Chapter 1.6 --- Our Contributions --- p.14 / Chapter 1.7 --- Thesis Organization --- p.15 / Chapter 2 --- Literature Review --- p.16 / Chapter 2.1 --- Introduction --- p.16 / Chapter 2.2 --- Previous Works on Placement --- p.17 / Chapter 2.2.1 --- Basic Simulated Annealing --- p.17 / Chapter 2.2.2 --- Unified Synthesis Approach --- p.18 / Chapter 2.2.3 --- Droplet-Routing-Aware Unified Synthesis Approach --- p.19 / Chapter 2.2.4 --- Simulated Annealing Using T-tree Representation --- p.20 / Chapter 2.3 --- Previous Works on Routing --- p.21 / Chapter 2.3.1 --- Direct-Addressing Droplet Routing --- p.22 / Chapter 2.3.1.1 --- A* Search Method --- p.22 / Chapter 2.3.1.2 --- Open Shortest Path First Method --- p.23 / Chapter 2.3.1.3 --- A Two Phase Algorithm --- p.24 / Chapter 2.3.1.4 --- Network-Flow Based Method --- p.25 / Chapter 2.3.1.5 --- Bypassibility and Concession Method --- p.26 / Chapter 2.3.2 --- Cross-Referencing Droplet Routing --- p.28 / Chapter 2.3.2.1 --- Graph Coloring Method --- p.28 / Chapter 2.3.2.2 --- Clique Partitioning Method --- p.30 / Chapter 2.3.2.3 --- Progressive-ILP Method --- p.31 / Chapter 2.4 --- Conclusion --- p.32 / Chapter 3 --- CrossRouter for Cross-Referencing Biochip --- p.33 / Chapter 3.1 --- Introduction --- p.33 / Chapter 3.2 --- Problem Formulation --- p.34 / Chapter 3.3 --- Overview of Our Method --- p.35 / Chapter 3.4 --- Net Order Computation --- p.35 / Chapter 3.5 --- Propagation Stage --- p.36 / Chapter 3.5.1 --- Fluidic Constraint Check --- p.38 / Chapter 3.5.2 --- Electrode Constraint Check --- p.38 / Chapter 3.5.3 --- Handling 3-pin net --- p.44 / Chapter 3.5.4 --- Waste Reservoir --- p.45 / Chapter 3.6 --- Backtracking Stage --- p.45 / Chapter 3.7 --- Rip-up and Re-route Nets --- p.45 / Chapter 3.8 --- Experimental Results --- p.46 / Chapter 3.9 --- Conclusion --- p.47 / Chapter 4 --- Placement in Cross-Referencing Biochip --- p.49 / Chapter 4.1 --- Introduction --- p.49 / Chapter 4.2 --- Problem Formulation --- p.50 / Chapter 4.3 --- Overview of the method --- p.50 / Chapter 4.4 --- Dispenser and Reservoir Location Generation --- p.51 / Chapter 4.5 --- Solving Placement Problem Using ILP --- p.51 / Chapter 4.5.1 --- Constraints --- p.53 / Chapter 4.5.1.1 --- Validity of modules --- p.53 / Chapter 4.5.1.2 --- Non-overlapping and separation of Modules --- p.53 / Chapter 4.5.1.3 --- Droplet-Routing length constraint --- p.54 / Chapter 4.5.1.4 --- Optical detector resource constraint --- p.55 / Chapter 4.5.2 --- Objective --- p.55 / Chapter 4.5.3 --- Problem Partition --- p.56 / Chapter 4.6 --- Pin Assignment --- p.56 / Chapter 4.7 --- Experimental Results --- p.57 / Chapter 4.8 --- Conclusion --- p.59 / Chapter 5 --- Conclusion --- p.60 / Bibliography --- p.62

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 180-198).

No description available.

<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> / Dissertation

The biochip industry is characterized by high entry barrier in technology. For those firms in this industry, owning law-protected patents to lower the entry of the potential competitors is a key strategy in competition and competitive advantage. The firm¡¦s patent analysis not only discloses the firm¡¦s knowledge-base in biochip industry, it also impact other firms¡¦ innovation activity and technology development strategy in this industry. Previous patent analysis literatures usually focus on the performance implications of firm¡¦s patent number or the patent citation on the focal firm. However, the possible performance implications of patent contents between the focal firm and other firms in the biochip industry are relatively under-examined. From the network theory and resource-based theory viewpoint, this study tries to examine the performance implications by developing two patent indexes in patent content analysis, i.e., the patent status and the patent similarity. The results indicate that when the firm¡¦s patent status difference with each other is smaller, or the firm¡¦s patent similarity with each other is larger, the performance difference between the dyad firms will be smaller. In other words, the patent status and the patent similarity are solid indexes to predict the firm¡¦s performance difference in highly competitive and highly innovative industry, such as the biochip industry in this sample. The results provide referable value in addressing the performance issues of patent content analysis from network theory viewpoint. Moreover, it also provides complementary values in discussing market commonality and resource similarity in competitive issues.

The unabated silicon technology scaling makes design and manufacturing increasingly harder in nanometer VLSI. Emerging technologies on the horizon require strong design automation to handle the large complexity of future systems. This dissertation studies eight related research topics in design and manufacturing closure in nanometer VLSI as well as design optimization for emerging technologies from physical synthesis perspective. In physical synthesis for design closure, we study three research topics, which are key challenges in nanometer VLSI designs: (a) We propose a highly efficient floorplanning algorithm to minimize substrate noise for mixed-signal system-on-a-chip designs. (b) We propose a clock tree synthesis algorithm to reduce clock skew under thermal variation. (c) We develop a global router, BoxRouter to enhance routability which is one of the classic but still critical challenges in modern VLSI. In physical synthesis for manufacturing closure, we propose the first systematic manufacturability aware routing framework to address three key manufacturing challenges: (a) We develop a predictive chemical-mechanical polishing model to guide global routing in order to reduce surface topography variation. (b) We formulate a random defect minimize problem in track routing, and develop a highly efficient algorithm. (b) We propose a lithography enhancement technique during detailed routing based on statistical and macro-level Post-OPC printability prediction. Regarding design optimization of emerging technologies, we focus on two topics, one in double patterning technology for future VLSI fabrication and the other in microfluidics for biochips: (a) We claim double patterning should be considered during physical synthesis, and propose an effective double patterning technology aware detailed routing algorithm. (b) We propose a droplet routing algorithm to improve routability in digital microfluidic biochip design. / text

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 134-148).

Le développement de méthodes alternatives à la culture in vivo pour l’évaluation de la toxicité des molécules chimiques s’est accéléré ces dernières années, l’objectif étant de limiter l’utilisation d’animaux. Préconisés par l’OCDE (Organisation de coopération et de développement économiques), ces modèles alternatifs visent à mimer les conditions physiologiques en employant des systèmes in vitro ou in silico. Parmi les différents systèmes développés, les biopuces microfluidiques ont prouvé leur contribution à l’amélioration des fonctions cellulaires, ce qui permet des études toxicologiques pertinentes. Les travaux de ce doctorat sont basés sur l’emploi de ces biopuces pour cultiver des hépatocytes (cellules du foie) et portent sur la mise au point d’une méthode d’analyse d’images issues de ces cultures sous microscope au cours du temps. L’acquisition d’images tout au long de l’expérience permet de suivre, après traitement, l’évolution et le comportement des cellules au contact de molécules chimiques et d’évaluer les réponses toxicologiques. Les premiers résultats de ces travaux ont permis l’amélioration du procédé de culture microfluidique adaptée au matériel d’acquisition d’images, la sélection de sondes fluorescentes, et le choix d’un algorithme de traitement des images sur CellProfiler. Cela nous a permis de quantifier et caractériser certaines fonctions biologiques au sein de la biopuce comme l’activité mitochondriale. Le potentiel de cet outil pour évaluer la toxicité de molécule a été testé grâce à l’emploi d’un toxique connu : la staurosporine. Les résultats obtenus ont révélé l’impact de la mise en culture en dynamique sur le comportement des hépatocytes, et la toxicité de la staurosporine visible en biopuce. / The development of alternative methods of in vivo cultures for the toxicological evaluation of chemical molecules has accelerated this last years, in order to limit the use of animals. Recommended by the OECD (Organisation for Economic Cooperation and Development), these alternative models are designed to mimic the physiological conditions using in vitro or in silico systems. Among the developed systems, microfluidic biochips have proven their contribution to the improvement of cellular functions, which allows relevant toxicological studies. This PhD thesis is based on the use of these biochips for hepatocytes culture and focus on the development of an analysis method for study these cultures under microscope over time using imaging. Image acquisition throughout the experiment enables to analyze, after image processing, the evolution and the behavior of cells in contact with chemical molecules and to evaluate toxicological responses. The first results of this work led to the optimization of the microfluidic cultures under the microscope used to get the image sequences, the selection of fluorescent probes and the development of an image processing system with CellProfiler. These works allowed the quantification and the characterization of some biological functions within the biochip such as the mitochondrial activity. Staurosporine, a well-known toxic, has been used to test the potential of this tool to evaluate the toxicity of molecules. The results showed the impact of dynamic culture on the hepatocytes behavior, and the staurosporine toxicity, in biochip cultures.