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Proceedings ArticleDOI

Digital microfluidic biochips: a vision for functional diversity and more than Moore

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.

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Citations
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Proceedings ArticleDOI
05 Nov 2012
TL;DR: REMIA is proposed, the first reactant minimization approach during sample preparation on digital microfluidic biochips (DMFBs) and can be extended to tackle the sample preparation problem with multiple target concentrations, and the extended version also successfully decreases the reactant usage further.
Abstract: Sample preparation is an indispensable process to biochemical reactions. Original reactants are usually diluted to the solutions with desirable concentrations. Since the reactants, like infant's blood, DNA evidence collected from a crime scene, or costly reagents, are extremely valuable, the usage of reactant must be minimized in the sample preparation process. In this paper, we propose the first reactant minimization approach, REMIA, during sample preparation on digital microfluidic biochips (DMFBs). Given a target concentration, REMIA constructs a skewed mixing tree to guide the sample preparation process for reactant minimization. Experimental results demonstrate that REMIA can save about 31%~52% of reactant usage on average compared with three existing sample preparation methods. Besides, REMIA can be extended to tackle the sample preparation problem with multiple target concentrations, and the extended version also successfully decreases the reactant usage further.

82 citations

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

Proceedings ArticleDOI
01 Jun 2014
TL;DR: This work presents a one-pass synthesis scheme which directly realizes the desired functionality onto the chip and, at the same time, guarantees minimality with respect to area and/or timing.
Abstract: With the advances of the microfluidic technology, the design of digital microfluidic biochips recently received significant attention. But thus far, the corresponding design tasks such as binding, scheduling, placement, and routing have usually been considered separately. Furthermore, often just heuristic results have been obtained. In this work, we present a one-pass synthesis scheme which directly realizes the desired functionality onto the chip and, at the same time, guarantees minimality with respect to area and/or timing. For this purpose, the deductive power of solvers for Boolean satisfiability is exploited. Experiments show how the approach leverages the design of the respective devices.

63 citations

Journal ArticleDOI
TL;DR: Experimental results demonstrate that the proposed technique can achieve reliability-oriented placement for DMFBs without excessive actuation in each electrode, while optimizing bioassay completion time.
Abstract: In recent studies, digital microfluidic biochips (DMFBs) have been a promising solution for lab-on-a-chip and bio-assay experiments because of their flexible application and low fabrication cost. However, the reliability problem is an imperative issue to guarantee the valid function of DMFBs. The reliability of DMFBs decreases when electrodes are excessively actuated, preventing droplets on DMFBs controlled successfully. Because the placement for bio-assays in DMFBs is a key step in generating corresponding actuating signals, the reliability of DMFBs must be considered during biochip placement to avoid excessive actuation. Although researchers have proposed several DMFB placement algorithms, they have failed to consider the reliability issue. In addition, previous algorithms were all based on the simulated-annealing (SA) method, which is time consuming and does not guarantee to obtain an optimal solution. This paper proposes the first reliability-oriented non-SA placement algorithm for DMFBs. This approach considers the reliability problem during placement, and uses the 3-D deferred decision making (3D-DDM) technique to enumerate only possible placement solutions. Large-scale DMFB placement can be synthesized efficiently by partitioning the operation sequential graph of bioassays. Experimental results demonstrate that the proposed technique can achieve reliability-oriented placement for DMFBs without excessive actuation in each electrode, while optimizing bioassay completion time.

56 citations

Proceedings ArticleDOI
07 Nov 2011
TL;DR: This paper proposes the first matching-based reliability-oriented broadcast-addressing algorithm for PDMFBs, and identifies the factors that affect reliability and incorporate into the design-technique attributes that enhance reliability.
Abstract: Designs for pin-constrained digital microfluidic biochips (PDMFBs) are receiving much attention because they simplify chip fabrication and packaging, and reduce product cost. To reduce the pin count, broadcast addressing, by minimally grouping electrode sets with non-conflict signal merging, has emerged as a promising solution. Nevertheless, naive signal merging has the potential to cause excessive electrode actuations, which has been reported to have direct and adverse effect on chip reliability. According to recent studies, reliability is an important attribute for PDMFBs particularly developed for medical applications as it directly affects the final medical decision making. However, no research findings have been reported on the reliability problem in pin-constrained designs. To make PDMFBs more feasible for practical applications, we propose in this paper the first matching-based reliability-oriented broadcast-addressing algorithm for PDMFBs. We identify the factors that affect reliability and incorporate into the design-technique attributes that enhance reliability. Experimental results demonstrate the effectiveness of the proposed algorithm.

50 citations

References
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Journal ArticleDOI
TL;DR: In this paper, the concept of a fractional volume of fluid (VOF) has been used to approximate free boundaries in finite-difference numerical simulations, which is shown to be more flexible and efficient than other methods for treating complicated free boundary configurations.

11,567 citations


"Digital microfluidic biochips: a vi..." refers methods in this paper

  • ...Examples of this approach include Marker-And-Cell [19], Volume-of-Fluid [20], and Level-Set [21]....

    [...]

Book
01 Jan 1960
TL;DR: In this paper, the authors discuss the nature and properties of liquid interfaces, including the formation of a new phase, nucleation and crystal growth, and the contact angle of surfaces of solids.
Abstract: Capillarity. The Nature and Thermodynamics of Liquid Interfaces. Surface Films on Liquid Substrates. Electrical Aspects of Surface Chemistry. Long--Range Forces. Surfaces of Solids. Surfaces of Solids: Microscopy and Spectroscopy. The Formation of a New Phase--Nucleation and Crystal Growth. The Solid--Liquid Interface--Contact Angle. The Solid--Liquid Interface--Adsorption from Solution. Frication, Lubrication, and Adhesion. Wetting, Flotation, and Detergency. Emulsions, Foams, and Aerosols. Macromolecular Surface Films, Charged Films, and Langmuir--Blodgett Layers. The Solid--Gas Interface--General Considerations. Adsorption of Gases and Vapors on Solids. Chemisorption and Catalysis. Index.

10,790 citations


"Digital microfluidic biochips: a vi..." refers methods in this paper

  • ...Below are a few practical examples: (1) utilizing the thermal Marangoni effect [ 11 ], either through an array of embedded microheaters [12] or laser heating [13] temperature gradients thus the net surface force can be established and modulated; (2) Non-uniform distribution of surface pressure can also result in a net surface force (e.g., T-channel [14]); (3) Magnetic field can be used for droplet manipulation [15]; and (4) The use of the ......

    [...]

Book
01 May 1997
TL;DR: Gaph Teory Fourth Edition is standard textbook of modern graph theory which covers the core material of the subject with concise yet reliably complete proofs, while offering glimpses of more advanced methods in each chapter by one or two deeper results.
Abstract: Gaph Teory Fourth Edition Th is standard textbook of modern graph theory, now in its fourth edition, combines the authority of a classic with the engaging freshness of style that is the hallmark of active mathematics. It covers the core material of the subject with concise yet reliably complete proofs, while offering glimpses of more advanced methods in each fi eld by one or two deeper results, again with proofs given in full detail.

6,255 citations

Book
01 Jan 1999
TL;DR: In this paper, the Hamilton-Jacobi equations and associated theory are used to formulate the interface propagation problem and then algorithms for the initial and boundary value formulations are proposed for semi-conductor manufacturing.
Abstract: Introduction 1 Formulations of interface propagation Part I Theory and Algorithms: 2 Theory of curve and surface evolution 3 Hamilton-Jacobi equations and associated theory 4 Numerical approximations: first attempt 5 Numerical schemes for hyperbolic conservation laws 6 Algorithms for the initial and boundary value formulations 7 Efficient schemes: adaptivity 8 Triangulated versions of level set and fast marching method: extensions and variations 9 Tests of basic methods Part II Applications: 10 Geometry 11 Grid generation 12 Image denoising 13 Computer vision: shape detection and recognition 14 Fluid mechanics and materials sciences: adding physics 15 Computational geometry and computer-aided-design 16 First arrivals, optimizations, and control 17 Applications to semi-conductor manufacturing 18 Comments, conclusions, future directions References Index

3,247 citations