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Proceedings ArticleDOI

Architectural-level synthesis of digital microfluidics-based biochips

07 Nov 2004-pp 223-228
TL;DR: A system design methodology is proposed that attempts to apply classical architectural-level synthesis techniques to the design of digital microfluidics-based biochips and develops an optimal scheduling strategy based on integer linear programming and two heuristic techniques that scale well for large problem instances.
Abstract: Microfluidics-based biochips offer a promising platform for massively parallel DNA analysis, automated drug discovery, and real-time biomolecular recognition. Current techniques for full-custom design of droplet-based "digital" biochips do not scale well for concurrent assays and for next-generation system-on-chip (SOC) designs that are expected to include fluidic components. We propose a system design methodology that attempts to apply classical architectural-level synthesis techniques to the design of digital microfluidics-based biochips. We first develop an optimal scheduling strategy based on integer linear programming. Since the scheduling problem is NP-complete, we also develop two heuristic techniques that scale well for large problem instances. A clinical diagnostic procedure, namely multiplexed in-vitro diagnostics on human physiological fluids, is used to evaluate the proposed method.
Citations
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Journal ArticleDOI
TL;DR: The proposed top-down design-automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, time-consuming hardware design, and costly testing and maintenance procedures, and it will facilitate the integration of fluidic components with a microelectronic component in next-generation systems-on-chips (SOCs).
Abstract: Microfluidics-based biochips are soon expected to revolutionize clinical diagnosis, deoxyribonucleic acid (DNA) sequencing, and other laboratory procedures involving molecular biology. In contrast to continuous-flow systems that rely on permanently etched microchannels, micropumps, and microvalves, digital microfluidics offers a scalable system architecture and dynamic reconfigurability; groups of unit cells in a microfluidics array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. This paper presents an overview of an integrated system-level design methodology that attempts to address key issues in the synthesis, testing and reconfiguration of digital microfluidics-based biochips. Different actuation mechanisms for microfluidics-based biochips, and associated design-automation trends and challenges are also discussed. The proposed top-down design-automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, time-consuming hardware design, and costly testing and maintenance procedures, and it will facilitate the integration of fluidic components with a microelectronic component in next-generation systems-on-chips (SOCs).

253 citations

Proceedings ArticleDOI
06 Mar 2006
TL;DR: This work develops the first systematic droplet routing method that can be integrated with biochip synthesis, which minimizes the number of cells used fordroplet routing, while satisfying constraints imposed by throughput considerations and fluidic properties.
Abstract: Recent advances in microfluidics are expected to lead to sensor systems for high-throughput biochemical analysis. CAD tools are needed to handle increased design complexity for such systems. Analogous to classical VLSI synthesis, a top-down design automation approach can shorten the design cycle and reduce human effort. We focus here on the droplet routing problem, which is a key issue in biochip physical design automation. We develop the first systematic droplet routing method that can be integrated with biochip synthesis. The proposed approach minimizes the number of cells used for droplet routing, while satisfying constraints imposed by throughput considerations and fluidic properties. A real-life biochemical application is used to evaluate the proposed method.

228 citations


Cites methods from "Architectural-level synthesis of di..."

  • ...It is assumed in [5] that since droplet movement on a microfluidic array is very fast compared to assay operations (e....

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  • ...ICCAD, pp. 229-236, 2004....

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  • ...Thus, there is a pressing need for biochip-specific computer-aideddesign (CAD) tools for automated design and prototyping....

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  • ...Architectural-level synthesis is then used to generate a macroscopic structure of the biochip; this is analogous to a structural RTL model in electronic CAD [5]....

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  • ...We can map the microfluidic assay operations to available microfluidic modules, and then use architecturallevel synthesis techniques to determine a schedule of sets of bioassays subject to precedence constraints imposed by the corresponding assay protocols [5]....

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Journal ArticleDOI
TL;DR: A polynomial-time algorithm for coordinating droplet movement under such hardware limitations is developed and described, and a layout-based system that can be rapidly reconfigured for new biochemical analyses is introduced.
Abstract: This paper describes a computational approach to designing a digital microfluidic system (DMFS) that can be rapidly reconfigured for new biochemical analyses. Such a “lab-on-a-chip” system for biochemical analysis, based on electrowetting or dielectrophoresis, must coordinate the motions of discrete droplets or biological cells using a planar array of electrodes. The authors have earlier introduced a layout-based system and demonstrated its flexibility through simulation, including the system's ability to perform multiple assays simultaneously. Since array-layout design and droplet-routing strategies are closely related in such a DMFS, their goal is to provide designers with algorithms that enable rapid simulation and control of these DMFS devices. In this paper, the effects of variations in the basic array-layout design, droplet-routing control algorithms, and droplet spacing on system performance are characterized. DMFS arrays with hardware limited row-column addressing are considered, and a polynomial-time algorithm for coordinating droplet movement under such hardware limitations is developed. To demonstrate the capabilities of our system, we describe example scenarios, including dilution control and minimalist layouts, in which our system can be successfully applied.

164 citations

Journal ArticleDOI
TL;DR: This paper presents BioStream, a portable language for describing biology protocols, and the Fluidic ISA, a stable interface for microfluidic chip designers, and develops abstraction layers that decouple software development from changes in the underlying device technology.
Abstract: Microfluidic devices are emerging as an attractive technology for automatically orchestrating the reactions needed in a biological computer. Thousands of microfluidic primitives have already been integrated on a single chip, and recent trends indicate that the hardware complexity is increasing at rates comparable to Moore's Law. As in the case of silicon, it will be critical to develop abstraction layers--such as programming languages and Instruction Set Architectures (ISAs)--that decouple software development from changes in the underlying device technology. Towards this end, this paper presents BioStream, a portable language for describing biology protocols, and the Fluidic ISA, a stable interface for microfluidic chip designers. A novel algorithm translates microfluidic mixing operations from the BioStream layer to the Fluidic ISA. To demonstrate the benefits of these abstraction layers, we build two microfluidic chips that can both execute BioStream code despite significant differences at the device level. We consider this to be an important step towards building scalable biological computers.

163 citations


Cites background or methods from "Architectural-level synthesis of di..."

  • ...represent protocols as acyclic sequence graphs and map them to droplet-based processors using automatic scheduling [25] and module placement [26]....

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  • ...Su et al. represent protocols as acyclic sequence graphs and map them to droplet-based processors using automatic scheduling (Su and Chakrabarty 2004) and module placement (Su and Chakrabarty 2005)....

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Proceedings ArticleDOI
13 Jun 2005
TL;DR: This work presents a synthesis methodology that unifies operation scheduling, resource binding, and module placement for such "digital" biochips and can also be used after fabrication to bypass defective cells in the microfluidic array.
Abstract: Microfluidic biochips promise to revolutionize biosensing and clinical diagnostics. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. This problem is also identified by the 2003 ITRS document as a major system-level design challenge beyond 2009. We focus here on the automated design of droplet-based microfluidic biochips. We present a synthesis methodology that unifies operation scheduling, resource binding, and module placement for such "digital" biochips. The proposed technique, which is based on parallel recombinative simulated annealing, can also be used after fabrication to bypass defective cells in the microfluidic array. A real-life protein assay is used to evaluate the synthesis methodology.

163 citations

References
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Book
01 Jan 1979
TL;DR: The second edition of a quarterly column as discussed by the authors provides a continuing update to the list of problems (NP-complete and harder) presented by M. R. Garey and myself in our book "Computers and Intractability: A Guide to the Theory of NP-Completeness,” W. H. Freeman & Co., San Francisco, 1979.
Abstract: This is the second edition of a quarterly column the purpose of which is to provide a continuing update to the list of problems (NP-complete and harder) presented by M. R. Garey and myself in our book ‘‘Computers and Intractability: A Guide to the Theory of NP-Completeness,’’ W. H. Freeman & Co., San Francisco, 1979 (hereinafter referred to as ‘‘[G&J]’’; previous columns will be referred to by their dates). A background equivalent to that provided by [G&J] is assumed. Readers having results they would like mentioned (NP-hardness, PSPACE-hardness, polynomial-time-solvability, etc.), or open problems they would like publicized, should send them to David S. Johnson, Room 2C355, Bell Laboratories, Murray Hill, NJ 07974, including details, or at least sketches, of any new proofs (full papers are preferred). In the case of unpublished results, please state explicitly that you would like the results mentioned in the column. Comments and corrections are also welcome. For more details on the nature of the column and the form of desired submissions, see the December 1981 issue of this journal.

40,020 citations

Book
01 Jan 1994
TL;DR: This book covers techniques for synthesis and optimization of digital circuits at the architectural and logic levels, i.e., the generation of performance-and-or area-optimal circuits representations from models in hardware description languages.
Abstract: From the Publisher: Synthesis and Optimization of Digital Circuits offers a modern, up-to-date look at computer-aided design (CAD) of very large-scale integration (VLSI) circuits. In particular, this book covers techniques for synthesis and optimization of digital circuits at the architectural and logic levels, i.e., the generation of performance-and/or area-optimal circuits representations from models in hardware description languages. The book provides a thorough explanation of synthesis and optimization algorithms accompanied by a sound mathematical formulation and a unified notation. The text covers the following topics: modern hardware description languages (e.g., VHDL, Verilog); architectural-level synthesis of data flow and control units, including algorithms for scheduling and resource binding; combinational logic optimization algorithms for two-level and multiple-level circuits; sequential logic optimization methods; and library binding techniques, including those applicable to FPGAs.

2,311 citations

Journal ArticleDOI
TL;DR: In this article, a microactuator for rapid manipulation of discrete microdroplets is presented, which is accomplished by direct electrical control of the surface tension through two sets of opposing planar electrodes fabricated on glass.
Abstract: A microactuator for rapid manipulation of discrete microdroplets is presented. Microactuation is accomplished by direct electrical control of the surface tension through two sets of opposing planar electrodes fabricated on glass. A prototype device consisting of a linear array of seven electrodes at 1.5 mm pitch was fabricated and tested. Droplets (0.7–1.0 μl) of 100 mM KCl solution were successfully transferred between adjacent electrodes at voltages of 40–80 V. Repeatable transport of droplets at electrode switching rates of up to 20 Hz and average velocities of 30 mm/s have been demonstrated. This speed represents a nearly 100-fold increase over previously demonstrated electrical methods for the transport of droplets on solid surfaces.

1,471 citations

Journal ArticleDOI
TL;DR: A taxonomy that classifies 27 scheduling algorithms and their functionalities into different categories is proposed, with each algorithm explained through an easy-to-understand description followed by an illustrative example to demonstrate its operation.
Abstract: Static scheduling of a program represented by a directed task graph on a multiprocessor system to minimize the program completion time is a well-known problem in parallel processing. Since finding an optimal schedule is an NP-complete problem in general, researchers have resorted to devising efficient heuristics. A plethora of heuristics have been proposed based on a wide spectrum of techniques, including branch-and-bound, integer-programming, searching, graph-theory, randomization, genetic algorithms, and evolutionary methods. The objective of this survey is to describe various scheduling algorithms and their functionalities in a contrasting fashion as well as examine their relative merits in terms of performance and time-complexity. Since these algorithms are based on diverse assumptions, they differ in their functionalities, and hence are difficult to describe in a unified context. We propose a taxonomy that classifies these algorithms into different categories. We consider 27 scheduling algorithms, with each algorithm explained through an easy-to-understand description followed by an illustrative example to demonstrate its operation. We also outline some of the novel and promising optimization approaches and current research trends in the area. Finally, we give an overview of the software tools that provide scheduling/mapping functionalities.

1,373 citations