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Proceedings ArticleDOI

Broadcast electrode-addressing for pin-constrained multi-functional digital microfluidic biochips

08 Jun 2008-pp 173-178
TL;DR: A broadcast-addressing-based design technique for pin-constrained multi-functional biochips that provides high throughput for bioassays and it reduces the number of control pins by identifying and connecting control pins with "compatible" actuation sequences.
Abstract: Recent advances in digital microfluidics have enabled lab-on-a-chip devices for DNA sequencing, immunoassays, clinical chemistry, and protein crystallization. Basic operations such as droplet dispensing, mixing, dilution, localized heating, and incubation can be carried out using a two-dimensional array of electrodes and nanoliter volumes of liquid. The number of independent input pins used to control the electrodes in such microfluidic "biochips" is an important cost-driver, especially for disposable PCB devices that are being developed for clinical and point-of-care diagnostics. However, most prior work on biochip design-automation has assumed independent control of the electrodes using a large number of input pins. Another limitation of prior work is that the mapping of control pins to electrodes is only applicable for a specific bioassay. We present a broadcast-addressing-based design technique for pin-constrained multi-functional biochips. The proposed method provides high throughput for bioassays and it reduces the number of control pins by identifying and connecting control pins with "compatible" actuation sequences. The proposed method is evaluated using a multifunctional chip designed to execute a set of multiplexed bioassays, the polymerase chain reaction, and a protein dilution assay.

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Citations
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Journal ArticleDOI
TL;DR: Although IoT eHealth has vastly expanded the possibilities to fulfill a number of existing healthcare needs, many challenges must still be addressed in order to develop consistent, suitable, safe, flexible, and power-efficient systems that are suitable fit for medical needs.
Abstract: The interaction between technology and healthcare has a long history. However, recent years have witnessed the rapid growth and adoption of the Internet of Things (IoT) paradigm, the advent of miniature wearable biosensors, and research advances in big data techniques for effective manipulation of large, multiscale, multimodal, distributed, and heterogeneous data sets. These advances have generated new opportunities for personalized precision eHealth and mHealth services. IoT heralds a paradigm shift in the healthcare horizon by providing many advantages, including availability and accessibility, ability to personalize and tailor content, and cost-effective delivery. Although IoT eHealth has vastly expanded the possibilities to fulfill a number of existing healthcare needs, many challenges must still be addressed in order to develop consistent, suitable, safe, flexible, and power-efficient systems that are suitable fit for medical needs. To enable this transformation, it is necessary for a large number of significant technological advancements in the hardware and software communities to come together. This keynote paper addresses all these important aspects of novel IoT technologies for smart healthcare-wearable sensors, body area sensors, advanced pervasive healthcare systems, and big data analytics. It identifies new perspectives and highlights compelling research issues and challenges, such as scalability, interoperability, device-network-human interfaces, and security, with various case studies. In addition, with the help of examples, we show how knowledge from CAD areas, such as large scale analysis and optimization techniques can be applied to the important problems of eHealth.

91 citations

Journal ArticleDOI
TL;DR: The droplet-based “digital” microfluidic technology platform and emerging applications are described, and computer-aided design tools for simulation, synthesis and chip optimization are presented.
Abstract: Microfluidics-based biochips enable the precise control of nanoliter volumes of biochemical samples and reagents. They combine electronics with biology, and they integrate various bioassay operations, such as sample preparation, analysis, separation, and detection. Compared to conventional laboratory procedures, which are cumbersome and expensive, miniaturized biochips offer the advantages of higher sensitivity, lower cost due to smaller sample and reagent volumes, system integration, and less likelihood of human error. This paper first describes the droplet-based “digital” microfluidic technology platform and emerging applications. The physical principles underlying droplet actuation are next described. Finally, the paper presents computer-aided design tools for simulation, synthesis and chip optimization. These tools target modeling and simulation, scheduling, module placement, droplet routing, pin-constrained chip design, and testing.

84 citations


Cites background from "Broadcast electrode-addressing for ..."

  • ...In this sense, the routes in microfluidic biochips can be viewed as virtual routes, which make droplet routing different from the classical wire very large scale integration routing problem....

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  • ...Compared to the state of the art of CAD for microelectronics, the system-level modeling aid for microfluidics system design and integration is far less mature and presents a significant challenge and thus opportunity....

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  • ...However, to this day quantitative analyses and descriptions of the many systems are still lacking....

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Proceedings ArticleDOI
07 Nov 2010
TL;DR: In this paper, the authors provide an overview of microfluidic biochips and describe emerging computer-aided design tools for the automated synthesis and optimization of bio-chips, from physical modeling to fluidic-level synthesis and then to chip-level design.
Abstract: Advances in droplet-based digital microfluidics have led to the emergence of biochips for automating laboratory procedures in biochemistry and molecular biology. These devices enable the precise control of microliter of nanoliter volumes of biochemical samples and reagents. They combine electronics with biology, and integrate various bioassay operations, such as sample preparation, analysis, separation, and detection. Compared to conventional laboratory procedures, which are cumbersome and expensive, miniaturized digital microfluidic biochips (DMFBs) offer the advantages of higher sensitivity, lower cost, system integration, and less likelihood of human error. This tutorial paper provides an overview of DMFBs and describes emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips, from physical modeling to fluidic-level synthesis and then to chip-level design. By efficiently utilizing the electronic design automation (EDA) technique on emerging CAD tools, users can concentrate on the development of nanoscale bioas-says, leaving chip optimization and implementation details to design-automation tools.

76 citations


Cites background from "Broadcast electrode-addressing for ..."

  • ...Nevertheless, current chip-level automations are only focus on electrode-addressing manners for control-pin minimization [41], [42], [43], [44], [45], while leaving the interconnect routing as other design consideration....

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  • ...Unfortunately, the chip-level design, including the controlpin assignment and wire routing, has been reported as a significant bottleneck in the fabrication of DMFBs [2], [40], [41], [42]....

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  • ...One of the major approaches, broadcast addressing, reduces the number of control pins by assigning a single control pin to multiple electrodes with mutually compatible control signals [42]....

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  • ...However, for large arrays, the high pin-count demand complicates the electrical connections, thus rendering this kind of chip unreliable and prohibitively expensive to manufacture [41], [42]....

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Journal ArticleDOI
TL;DR: This tutorial paper describes emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips from bioassay protocols and recent advances in fluidic-operation scheduling, module placement, droplet routing, pin-constrained chip design, and testing are presented.
Abstract: Microfluidics-based biochips are revolutionizing high-throughput sequencing, parallel immunoassays, blood chemistry for clinical diagnostics, and drug discovery. These devices enable the precise control of nanoliter volumes of biochemical samples and reagents. They combine electronics with biology, and they integrate various bioassay operations, such as sample preparation, analysis, separation, and detection. Compared to conventional laboratory procedures, which are cumbersome and expensive, miniaturized biochips offer the advantages of higher sensitivity, lower cost due to smaller sample and reagent volumes, system integration, and less likelihood of human error. This tutorial paper provides an overview of droplet-based ?digital? microfluidic biochips. It describes emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips from bioassay protocols. Recent advances in fluidic-operation scheduling, module placement, droplet routing, pin-constrained chip design, and testing are presented. These CAD techniques allow biochip users to concentrate on the development of nanoscale bioassays, leaving chip optimization and implementation details to design-automation tools.

76 citations


Cites background or methods from "Broadcast electrode-addressing for ..."

  • ...Thereby, a broadcast-addressing based design technique for pin-constrained and multi-functional biochips has been developed in [61]....

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  • ...Recent years have seen growing interest in the automated design and synthesis of microfluidic biochips [39], [44], [47]–[51], [53]–[56], [59]–[61], [63]–[67], [69]....

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Proceedings ArticleDOI
09 Oct 2011
TL;DR: An overview of DMFBs is provided and emerging CAD tools for the automated synthesis and optimization ofDMFB designs are described, from fluidic-level synthesis and chip-level design to testing.
Abstract: Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the basic functions for biochemical analysis. The “digital” microfluidic biochips (DM-FBs) are manipulating liquids not as a continuous flow, but as discrete droplets on a two-dimensional array of electrodes. Basic mi-crofluidic operations, such as mixing and dilution, are performed on the array, by routing the corresponding droplets on a series of electrodes. The challenges facing biochips are similar to those faced by microelectronics some decades ago. To meet the challenges of increasing design complexity, computer-aided-design (CAD) tools are being developed for DMFBs. This paper provides an overview of DMFBs and describes emerging CAD tools for the automated synthesis and optimization of DMFB designs, from fluidic-level synthesis and chip-level design to testing. Design automations are expected to alleviate the burden of manual optimization of bioassays, time-consuming chip designs, and costly testing and maintenance procedures. With the assistance of CAD tools, users can concentrate on the development and abstraction of nanoscale bioassays while leaving chip optimization and implementation details to CAD tools.

67 citations


Cites background or methods from "Broadcast electrode-addressing for ..."

  • ...The droplet-controlling information is stored in the form of electrode actuation sequences, where each bit in a sequence represents a signal status (“1” (actuated), “0” (de-actuated), or “X” (don’t-care)) of the electrode at a specific time step [42]....

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  • ...To tackle the computational cost, many heuristics have been proposed in the literature [39, 42, 43]....

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  • ...Researchers have utilized the compatibility graph to specify the broadcast addressing [42], where the vertex set represents the electrode set and an edge between two electrodes indicates their corresponding activation sequences are compatible....

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  • ...The work by [42] presents a greedy method of iterative clique recognitions with maximum cardinality on the compatibility graph....

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  • ...A promising solution, broadcast addressing, has been presented in [42]....

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References
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01 Jan 2005

19,250 citations

Book
30 Dec 1998
TL;DR: In this article, the authors present a model for drawing graphs and digraphs based on the topology of low dimensions Higher-Order Surfaces and a model of a graph.
Abstract: INTRODUCTION TO GRAPH MODELS Graphs and Digraphs Common Families of Graphs Graph Modeling Applications Walks and Distance Paths, Cycles, and Trees Vertex and Edge Attributes: More Applications STRUCTURE AND REPRESENTATION Graph Isomorphism Revised! Automorphisms and Symmetry Moved and revised! Subgraphs Some Graph Operations Tests for Non-Isomorphism Matrix Representation More Graph Operations TREES Reorganized and revised! Characterizations and Properties of Trees Rooted Trees, Ordered Trees, and Binary Trees Binary-Tree Traversals Binary-Search Trees Huffman Trees and Optimal Prefix Codes Priority Trees Counting Labeled Trees: Prufer Encoding Counting Binary Trees: Catalan Recursion SPANNING TREES Reorganized and revised! Tree-Growing Depth-First and Breadth-First Search Minimum Spanning Trees and Shortest Paths Applications of Depth-First Search Cycles, Edge Cuts, and Spanning Trees Graphs and Vector Spaces Matroids and the Greedy Algorithm CONNECTIVITY Revised! Vertex- and Edge-Connectivity Constructing Reliable Networks Max-Min Duality and Menger's Theorems Block Decompositions OPTIMAL GRAPH TRAVERSALS Eulerian Trails and Tours DeBruijn Sequences and Postman Problems Hamiltonian Paths and Cycles Gray Codes and Traveling Salesman Problems PLANARITY AND KURATOWSKI'S THEOREM Reorganized and revised! Planar Drawings and Some Basic Surfaces Subdivision and Homeomorphism Extending Planar Drawings Kuratowski's Theorem Algebraic Tests for Planarity Planarity Algorithm Crossing Numbers and Thickness DRAWING GRAPHS AND MAPS Reorganized and revised! The Topology of Low Dimensions Higher-Order Surfaces Mathematical Model for Drawing Graphs Regular Maps on a Sphere Imbeddings on Higher-Order Surfaces Geometric Drawings of Graphs New! GRAPH COLORINGS Vertex-Colorings Map-Colorings Edge-Colorings Factorization New! MEASUREMENT AND MAPPINGS New Chapter! Distance in Graphs New! Domination in Graphs New! Bandwidth New! Intersection Graphs New! Linear Graph Mappings Moved and revised! Modeling Network Emulation Moved and revised! ANALYTIC GRAPH THEORY New Chapter! Ramsey Graph Theory New! Extremal Graph Theory New! Random Graphs New! SPECIAL DIGRAPH MODELS Reorganized and revised! Directed Paths and Mutual Reachability Digraphs as Models for Relations Tournaments Project Scheduling and Critical Paths Finding the Strong Components of a Digraph NETWORK FLOWS AND APPLICATIONS Flows and Cuts in Networks Solving the Maximum-Flow Problem Flows and Connectivity Matchings, Transversals, and Vertex Covers GRAPHICAL ENUMERATION Reorganized and revised! Automorphisms of Simple Graphs Graph Colorings and Symmetry Burnside's Lemma Cycle-Index Polynomial of a Permutation Group More Counting, Including Simple Graphs Polya-Burnside Enumeration ALGEBRAIC SPECIFICATION OF GRAPHS Cyclic Voltages Cayley Graphs and Regular Voltages Permutation Voltages Symmetric Graphs and Parallel Architectures Interconnection-Network Performance NON-PLANAR LAYOUTS Reorganized and revised! Representing Imbeddings by Rotations Genus Distribution of a Graph Voltage-Graph Specification of Graph Layouts Non KVL Imbedded Voltage Graphs Heawood Map-Coloring Problem APPENDIX Logic Fundamentals Relations and Functions Some Basic Combinatorics Algebraic Structures Algorithmic Complexity Supplementary Reading BIBLIOGRAPHY General Reading References SOLUTIONS AND HINTS New! INDEXES Index of Applications Index of Algorithms Index of Notations General Index

1,407 citations


"Broadcast electrode-addressing for ..." refers background in this paper

  • ...The general clique partitioning problem is known to be NP-hard [ 15 ]....

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  • ...Even though the general clique partitioning problem is known to be NP-hard [ 15 ], a number of heuristics are available in the literature to solve it in an efficient manner....

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  • ...A clique in a graph is defined as a complete subgraph, i.e., any two nodes in this subgraph are connected by an edge [ 15 ]....

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  • ...The problem of finding the minimum number of groups can be easily mapped to the clique-partitioning problem from graph theory [ 15 ]....

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Journal ArticleDOI
TL;DR: This work presents an alternative paradigm--a fully integrated and reconfigurable droplet-based "digital" microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids, and demonstrates reliable and repeatable high-speed transport of microdroplets.
Abstract: Clinical diagnostics is one of the most promising applications for microfluidic lab-on-a-chip systems, especially in a point-of-care setting. Conventional microfluidic devices are usually based on continuous-flow in microchannels, and offer little flexibility in terms of reconfigurability and scalability. Handling of real physiological samples has also been a major challenge in these devices. We present an alternative paradigm—a fully integrated and reconfigurable droplet-based “digital” microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. The microdroplets, which act as solution-phase reaction chambers, are manipulated using the electrowetting effect. Reliable and repeatable high-speed transport of microdroplets of human whole blood, serum, plasma, urine, saliva, sweat and tear, is demonstrated to establish the basic compatibility of these physiological fluids with the electrowetting platform. We further performed a colorimetric enzymatic glucose assay on serum, plasma, urine, and saliva, to show the feasibility of performing bioassays on real samples in our system. The concentrations obtained compare well with those obtained using a reference method, except for urine, where there is a significant difference due to interference by uric acid. A lab-on-a-chip architecture, integrating previously developed digital microfluidic components, is proposed for integrated and automated analysis of multiple analytes on a monolithic device. The lab-on-a-chip integrates sample injection, on-chip reservoirs, droplet formation structures, fluidic pathways, mixing areas and optical detection sites, on the same substrate. The pipelined operation of two glucose assays is shown on a prototype digital microfluidic lab-on-chip, as a proof-of-concept.

1,124 citations

Journal ArticleDOI
TL;DR: This paper studies the effects of varying droplet aspect ratios on linear-array droplet mixers, and proposes mixing strategies applicable for both high and low aspect ratio systems, and presents a split-and-merge mixer that takes advantage of the ability to perform droplet splitting at these ratios.
Abstract: The mixing of analytes and reagents for a biological or chemical lab-on-a-chip is an important, yet difficult, microfluidic operation. As volumes approach the sub-nanoliter regime, the mixing of liquids is hindered by laminar flow conditions. An electrowetting-based linear-array droplet mixer has previously been reported. However, fixed geometric parameters and the presence of flow reversibility have prevented even faster droplet mixing times. In this paper, we study the effects of varying droplet aspect ratios (height ∶ diameter) on linear-array droplet mixers, and propose mixing strategies applicable for both high and low aspect ratio systems. An optimal aspect ratio for four electrode linear-array mixing was found to be 0.4, with a mixing time of 4.6 seconds. Mixing times were further reduced at this ratio to less than three seconds using a two-dimensional array mixer, which eliminates the effects of flow reversibility. For lower aspect ratio (≤0.2) systems, we present a split-and-merge mixer that takes advantage of the ability to perform droplet splitting at these ratios, resulting in a mixing time of less than two seconds.

491 citations


"Broadcast electrode-addressing for ..." refers background in this paper

  • ...These lab-on-a-chip devices are now being advocated for a wide range of applications such as high-throughput DNA sequencing, immunoassays and clinical chemistry, environmental toxicity monitoring and the detection of airborne chemicals, detection of explosives such as TNT, and point-of-care…...

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