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Journal ArticleDOI

High-level synthesis of digital microfluidic biochips

TL;DR: This work proposes a system design methodology that attempts to apply classical high-level synthesis techniques to the design of digital microfluidic biochips and develops an optimal scheduling strategy based on integer linear programming and two heuristic techniques that scale well for large problem instances.
Abstract: Microfluidic 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 microfluidic components. We propose a system design methodology that attempts to apply classical high-level synthesis techniques to the design of digital microfluidic biochips. We focus here on the problem of scheduling bioassay functions under resource constraints. We first develop an optimal scheduling strategy based on integer linear programming. However, because 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 first used to illustrate and evaluate the proposed method. Next, the synthesis approach is applied to a protein assay, which serves as a more complex bioassay application. The proposed synthesis approach is expected to reduce human effort and design cycle time, and it will facilitate the integration of microfluidic components with microelectronic components in next-generation SOCs.

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Citations
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Journal ArticleDOI
TL;DR: In this paper, a review of the functionalities of spinwave devices, concepts for spin-wave based computing and magnonic crystals is presented. But the focus of this review is on the control over the interplay between localization and delocalization of the spinwave modes using femtosecond lasers.
Abstract: Novel material properties can be realized by designing waves' dispersion relations in artificial crystals. The crystal's structural length scales may range from nano- (light) up to centimeters (sound waves). Because of their emergent properties these materials are called metamaterials. Different to photonics, where the dielectric constant dominantly determines the index of refraction, in a ferromagnet the spin-wave index of refraction can be dramatically changed already by the magnetization direction. This allows a different flexibility in realizing dynamic wave guides or spin-wave switches. The present review will give an introduction into the novel functionalities of spin-wave devices, concepts for spin-wave based computing and magnonic crystals. The parameters of the magnetic metamaterials are adjusted to the spin-wave k-vector such that the magnonic band structure is designed. However, already the elementary building block of an antidot lattice, the singular hole, owns a strongly varying internal potential determined by its magnetic dipole field and a localization of spin-wave modes. Photo-magnonics reveal a way to investigate the control over the interplay between localization and delocalization of the spin-wave modes using femtosecond lasers, which is a major focus of this review. We will discuss the crucial parameters to realize free Bloch states and how, by contrast, a controlled localization might allow to gradually turn on and manipulate spin-wave interactions in spin-wave based devices in the future.

607 citations

Journal ArticleDOI
TL;DR: In this paper, a review of spin-wave properties and properties is presented, where the crucial parameters to realize free Bloch states and how, by contrast, a controlled localization might allow us to gradually turn on and manipulate spinwave interactions in spinwave based devices in the future.

604 citations

Journal ArticleDOI
TL;DR: A physical-aware system reconfiguration technique that uses sensor data at intermediate checkpoints to dynamically reconfigure the biochip and a cyberphysical resynthesis technique is used to recompute electrode-actuation sequences, thereby deriving new schedules, module placement, and droplet routing pathways, with minimum impact on the time-to-response.
Abstract: Droplet-based digital microfluidics technology has now come of age, and software-controlled biochips for healthcare applications are starting to emerge. However, today's digital microfluidic biochips suffer from the drawback that there is no feedback to the control software from the underlying hardware platform. Due to the lack of precision inherent in biochemical experiments, errors are likely during droplet manipulation; error recovery based on the repetition of experiments leads to wastage of expensive reagents and hard-to-prepare samples. By exploiting recent advances in the integration of optical detectors (sensors) into a digital microfluidics biochip, we present a physical-aware system reconfiguration technique that uses sensor data at intermediate checkpoints to dynamically reconfigure the biochip. A cyberphysical resynthesis technique is used to recompute electrode-actuation sequences, thereby deriving new schedules, module placement, and droplet routing pathways, with minimum impact on the time-to-response.

126 citations

Journal ArticleDOI
TL;DR: A droplet-routing method that avoids cross-contamination in the optimization of droplet flow paths and targets disjoint droplet routes and minimizes the number of cells used for droplet routing is proposed.
Abstract: Recent advances in digital microfluidics have enabled droplet-based biochip devices for DNA sequencing, immunoassays, clinical chemistry, and protein crystallization. Since cross-contamination between droplets of different biomolecules can lead to erroneous outcomes for bioassays, the avoidance of cross-contamination during droplet routing is a key design challenge for biochips. We propose a droplet-routing method that avoids cross-contamination in the optimization of droplet flow paths. The proposed approach targets disjoint droplet routes and synchronizes wash-droplet routing with functional droplet routing, in order to reduce the duration of droplet routing while avoiding the cross-contamination between different droplet routes. In order to avoid cross-contamination between successive routing steps, an optimization technique is used to minimize the number of wash operations that must be used between successive routing steps. Two real-life biochemical applications are used to evaluate the proposed droplet-routing methods.

100 citations


Cites background or methods from "High-level synthesis of digital mic..."

  • ..., 10% of a time-slot used in scheduling, in order that the droplet-routing time can be ignored for scheduling assay operations [12]....

    [...]

  • ...droplet-routing methods have been developed recently for the design of microfluidic biochips [3], [5], [9], [10], [12]–[16]....

    [...]

  • ...Given a schedule of bioassay operations (derived from architectural-level synthesis [12]) and the locations of these modules on the biochip floorplan (derived from module placement [13]), routing determines the paths for droplet transportation using the available cells in the microfluidic array....

    [...]

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

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

PatentDOI
24 Sep 2003-Science
TL;DR: The fluidic multiplexor as discussed by the authors is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs.
Abstract: High-density microfluidic chips contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large scale integration (LSI). A component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. These integrated microfluidic networks can be used to construct a variety of highly complex microfluidic devices, for example the microfluidic analog of a comparator array, and a microfluidic memory storage device resembling electronic random access memories.

2,292 citations