Design of faulttolerant and dynamicallyreconfigurable. Routingbased synthesis of digital microfluidic biochips. Technology issues, implementation platforms, and designautomation challenges ieee transactions on computeraided design of integrated circuits and systems, february, 2006, vol. Functional testing of digital microfluidic biochips. Pdf microfluidic devices for biomedical applications. This book presents exact, that is minimal, solutions to individual steps in the design process for digital microfluidic biochips dmfbs, as well as a onepass approach that combines all these steps in a single process. Microfluidics or labonachip loc is an important technology suitable for numerous applications from drug delivery to tissue engineering. Pdf droplettracebased array partitioning and a pin. Digital microfluidic systems provide a more scalable. These composite microsystems, also known as labonachip or bio mems, offer several advantages over conventional laboratory procedures. Flow based microfluidic biochips morten foged schmidt, wajid hassan minhass, paul pop, jan madsen dtu compute technical university of denmark dk2800 kgs. As in digital circuit design, a module based method can be applied to the design of digital microfluidic biochips. The design and architecture of biochips changes all the time and designers need to know how their biochip designs will work before physically building them. We show that routing based synthesis can lead to deadlocks and livelocks in specific cases, and that dynamically detecting them and adjusting the probabilities associated with.
Design automation challenges for microfluidicsbased. The basic unit cell of a ewod based digital microfluidic biochip consists of two parallel glass plates, as shown in figure 1a. These devices are connected by microchannels to transport intermediate experiment results. Systemlevel design automation tools for digital microfluidic. Currently, most commerciallyavailable biochips are either based on microarrays. Publishers pdf, also known as version of record link back to dtu orbit citation apa. Droplet routing in the synthesis of digital microfluidic biochips. In contrast to conventional biochemical analyzers, they automate highly. Low yield is a deterrent to large scale and highvolume production, and it tends to increase production cost. This emerging technology combines electronics with biology to open new application areas including. Microfluidics based biochips, also referred to as labonachip loc, are devices that integrate fluidhandling functions such as sample preparation, analysis, separation, and detection.
As the use of digital microfluidicsbased biochips increases, their complexity is expected to become significant due to the need for multiple and concurrent assays on the. This method maps a digital microfluidic biochip to an. Flow based microfluidic biochips are one of the most promising platforms used in biochemical and pharmaceutical laboratories due to their high efficiency and low costs. Design of continuous flow based microfluidics using valves e. Synthesis of errorrecovery protocols for meda digital microfluidic biochips 94. In preparation for submission to ieee transactions on computeraided design of integrated circuits and systems tcad. The operation of digital microfluidics based biochips is based on the principle of electrowetting actuation. The bottom plate contains a patterned array of individually controllable electrodes, and the top plate is coated with a continuous ground electrode. In this paper we are interested in flow based biochips, in which the fluidic flow is manipulated using integrated microvalves. The development of microfluidic biochips is in a hasty development phase and the need for simulation and design tools is increasing.
The detection of dna hybridisation is obtained through a variety of different electrochemical techniques, including electroactive hybridisation indicators, enzymes, and. Multichannel and faulttolerant control multiplexing for. In international conference on compilers, architecture and synthesis for embedded. There are two technologies for the microfluidic biochips. Note that even though the systemlevel design automation methodology described herein is applied to ewod based biochips, it can easily be extended for dep based digital microfluidic biochips. A microfluidic hepatic coculture platform for cellbased. Introduction microfluidics based biochips for biochemical analysis. Typically biochip circuits are produced using photolithography which is a slow and costly process. Electrowetting refers to the modulation of the interfacial tension between a conductive fluid and a solid electrode by applying an electric field between them.
For instance, cyberphysical integration can be performed similarly for both dmfbs and. Brisk, journal2012 ieeeifip 20th international conference on vlsi and systemonchip vlsisoc, year2012, pages6 pp. Microfluidic very large scale integration mvlsi is the technology behind the creation of continuous flow based biochips. It has been predicted that, by providing miniaturization, automation and integration, microfluidic biochips will revolutionize laboratory procedures in molecular biology with applications to pointofcare diagnostics, dna analysis, and automated drug discovery 2,3. The primary difference is that microfluidics enables the miniaturization and combination of multiple steps of gel based electrophoresis separation, staining, destaining, imaging, and even basic data. Durham, nc 27708, usa abstract microfluidics based biochips are revolutionizing highthroughput sequencing, parallel immunoassays, clinical diagnostics, and drug discovery. Microfluidicsbased biochips duke microfluidics lab. Compared to nanolitervolume fluid droplets are manipulated on a 2d elec traditional benchtop procedures, biochips offer the advantages trode array. As in the case of integrated circuits ics, an increase in the density and area of microfluidics based biochips will lead to high defect densities, thereby reducing yield, especially for newer technologies. Performing organization names and addresses university of cincinnati p o box 210030, dept. Recent advances in fluidicoperation scheduling, module placement, droplet routing, pinconstrained chip design, and testing are presented. Performance improvements and congestion reduction for routing. As a result, system complexity and integration levels are increasing steadily.
Magnetic nanochain integrated microfluidic biochips nature. Biochips labchips microfluidics and nanomechanics lab. The digital biochips are manipulating liquids not as a continuous flow, but as discrete droplets on a twodimensional array of electrodes. Microfluidics based biochips, also known as labonachip or bio mems, are increasingly popular for dna analysis, clinical diagnostics, and the detection and manipulation of bio molecules, because. In this paper we are interested in flow based cell culture biochips. Routing algorithms for flowbased microfluidic very large. Tabu searchbased synthesis of dynamically reconfigurable. Architectural synthesis of flowbased microfluidic large. Although biochips are becoming more complex everyday, computeraided design cad tools for these chips are still in their infancy. The basic cell of a digital microfluidics based biochip is shown in figure 1a. A polymerbased microfluidic device for immunosensing.
May 01, 2018 microfluidic biochips hold great potential for liquid analysis in biomedical research and clinical diagnosis. Microfluidics based biochips, also known as labonachip or biomems, are becoming increasingly popular for dna analysis, clinical diagnostics, and the detectionmanipulation of biomolecules. Digital microfluidics based biochips controls discrete droplets through the entire process from dispensing to moving and mixing to detecting and discarding, but continuous flow systems use fixed channels to flow the fluid. Modeling and simulation framework for flowbased microfluidic. Design automation challenges for microfluidicsbased biochips. Pdf this chapter presents in detail how digital microfluidic biochips. Microfluidics based pathogen detectionmicrofluidic biochips for pathogen sensing have been applied to microarray technology. Yoon,ac haesik yang, ahyeonbong pyo,kwang hyo chung, asung jin kimand youn tae kim a biomems group, basic research laboratory, etri, daejeon 305600, korea b department of mechanical engineering, pusan national university, pusan 609735, korea. Pdf microfluidicsbased labonchip systems in dnabased. Bio chips labchips a microfluidic concentrator array for quantitative predaton assays of predatory microbes we present a microfabricated concentrator array device that makes it possible to quantify the predation rate of bdellovibrio bacteriovorus, a predatory microbe, toward its prey, escherichia coli str. These composite microsystems are also referred to as labonachip or bio mems interchangeably in the literature 1, 2, 3. Microfluidics based biochips for biochemical analysis are receiving much attention nowadays 1, 2, 3. Microfluidics based biochips for biochemical analysis are receiving much attention nowadays 1. Different actuation mechanisms for microfluidics based biochips, and associated design automation trends and challenges are also discussed.
Design automation methods and tools for microfluidicsbased. Pdf optimization of dilution and mixing of biochemical. For example, digital microfluidic biochips are under investigation for applications in biomedical fields. Tabu search based synthesis of dynamically reconfigurable digital microfluidic biochips. For the colorimetric protein assay, we applied the 223228, nov. A polymerbased microfluidic device for immunosensing biochips. Biochips offer miniaturized multiplexed point of care test mpoct capabilities. Often refereed to as labonachip or bio mems, these devices automate highly repetitive laboratory tasks by replacing cumbersome equipment.
Design automation for microfluidicsbased biochips faculty duke. Synthesis of errorrecovery protocols for microelectrode. Yield enhancement of digital microfluidicsbased biochips. Interest in droplet based microfluidics systems has been growing substantially in past decades. The main objective of this thesis is to develop topdown synthesis techniques for. In a digital microfluidic biochip, a group of adjacent cells in the microfluidic array can be configured to work as storage, functional operations, as well as for transporting fluid droplets dynamically.
A promising category of locs is digital microfluidic dmf based biochips, in which optimization, fabrication technology, and so on. Discrete droplet digital microfluidics based biochips face problems similar to that in other vlsi cad systems, but with new constraints and interrelations. The ewod technique for digital microfluidic biochips forms the basis of the work reported in this paper. Priority scheduling in digital microfluidicsbased biochips.
The proposed topdown design automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, timeconsuming. Droplet routing in highlevel synthesis of configurable. In flow based microfluidic biochips, the liquid flows continuously through predefined microchannels, with the flow being controlled through valves and pumps 7. A testing method based on euler paths in graphs is proposed in 23. Pdf placement of digital microfluidic biochips using the t. Droplet based microfluidics is a subcategory of microfluidics in contrast with continuous microfluidics.
Microfluidics based biochips consist of microfluidic arrays on rigid substrates through which, move ment of fluids is tightly controlled to facilitate biological reactions. A microfluidic module library, analogous to a standardcustom. Progress in reconfigurable microfluidic systems for. In contrast to continuousflow systems that rely on permanently etched microchannels, micropumps, and microvalves, digital microfluidics offers a scalable system architecture and dynamic reconfigurability.
Microfluidics based biochips, also known as labonachip or biomems, are increasingly popular for dna analysis, clinical diagnostics, and the detection and manipulation of biomolecules, because. These devices enable the precise control of microliter of nanoliter volumes of biochemical samples and reagents. Department of electrical and computer engineering 25 digital microfluidics idea. Digital microfluidic biochips using monte carlo simulation. Pdf broadcast electrodeaddressing for pinconstrained. Designfortestability for digital microfluidic biochips. Architecturallevel synthesis of colorimetric protein assay 6 and the multiplexed invitro diag digital microfluidics based biochips. We focus on one such problem of resource constrained scheduling for digital microfluidic biochips.
Microfluidics based biochips are revolutionizing laboratory procedures involving molecular biology 1, 2, 3. Forcedirected list scheduling for digital microfluidic. In asia and south pacific design automation conference aspdac, 2018. Pdf multidisciplinary microfluidic and nanofluidic labon. Most cad research has been focussed on devicelevel physical modeling of components, 7. Automated design of microfluidicsbased biochips iccd.
Systemlevel modeling and synthesis techniques for flowbased. Permanently etched microchannels, micropumps and microvalves digital microfluidic biochips. By combining miniaturized valves and channels it is possible to create various components that can be used to manipulate fluids, thus creating a microfluidic laboratory on a chip. Biochips microfluidics conductive technologies inc. Pdf synthesis of digital microfluidic biochips with. It describes emerging computeraided design cad tools for the automated synthesis and optimization of biochips from bioassay protocols. However, the architecture of the droplet based chips differs signi. Magnetic nanochain integrated microfluidic biochips. Microfluidics based biochips are soon expected to revolutionize clinical diagnosis, deoxyribonucleic acid dna sequencing, and other laboratory procedures involving molecular biology. Performance improvements and congestion reduction for. Manipulation of liquids as discrete droplets duke university 2002 university of michigan 1998 control electronics shown are suitable forsuitable for handheld or benchtop applications printed circuit board. Sound valvecontrol for programmable microfluidic devices.
Pdf routingbased synthesis of digital microfluidic biochips. When microfluidic chips are used for electrophoresis, the process is, overall, very similar to that of traditional gel based electrophoresis. Multiple fault diagnosis in digital microfluidic biochips. Abstract microfluidics based biochips are revolutionizing high throughput sequencing, parallel immunoassays, clinical diagnostics, and drug discovery. Yarmushc q1ahurel corporation, beverley hills, california, ca, usa b schering plough research institute, kenilworth, nj, usa q2c center for engineering and medicine, massachusetts general hospital, harvard medical school. Microfluidics based devices, capable of continuous sampling and realtime testing of airwater samples for biochemical toxins and other dangerous pathogens, can serve as an alwayson bio smoke. Microfluidics by repeated use of a small set of basic instructions on unit sized liquid. Microfluidics or labonachip loc involves the processing of small volume of fluids typically in the. As more bioassays are concurrently executed on digital microfluidic platforms 7, system complexity and the number of electrodes is expected to increase steadily. Bridging areas of electronic design automation with microfluidic biochip research, the authors present a systemlevel design automation framework that addresses key issues in the. However, the lack of integrated onchip liquid mixing, bioseparation and signal. We present an overview of an integrated systemlevel design methodology that attempts to address key issues in the synthesis, testing and reconfiguration of digital microfluidics based biochips.
Design, testing, and applications of digital microfluidics. A control flow was also proposed to connect local recoveries with global recovery. Microfluidics based biochips are rapidly emerging as a key enabling technology for biochemical analysis. Synthesis of errorrecovery protocols for microelectrodedot. It will take time to ramp up yield learning based on an understanding of defect types in such mixed. For digital microfluidic chips, techniques for defect classification, test planning, and test resource optimization were first presented 22. Microfluidics based biochips offer exciting possibilities for high throughput sequencing, parallel immunoassays, blood chemistry for clinical diagnostics. Lyngby, denmark abstract microfluidic biochips are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis onchip.
Security implications of cyberphysical flow based micro. Abstract microfluidic biochips are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis onchip. Since the problem is npcomplete, finding the optimal solution is a very time expensive task. A polymer based microfluidic device for immunosensing biochips jong soo ko,ab hyun c. Routing based synthesis for digital microfluidic biochips yields faster assay execution times compared to module based synthesis.
The mixedtechnology based microsystem has an emerging category known as microfluidics. Steps in the production and operation of a dna microarray. These composite microsystems, also known as labonachip or bio mems, offer a number of advantages over conventional laboratory procedures. Design automation and test techniques for microfluidic. The transportation of these results is controlled by microvalves which are. The proposed topdown design automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, timeconsuming hardware design, and costly testing and maintenance procedures. Pdf placement of digital microfluidic biochips using the. These chips reside on silicon or other solid substrates that permit numerous tests to be performed at the same time. Applications of digital microfluidic biochips droplet based microfluidic biochip drug discovery and biotechnology environmental and other applications medical diagnostics and therapeutics proteomics highthroughput screening genomics countering bioterrorism microoptics airwateragro food monitoring clinical chemistry nucleic acid tests. Therefore, we introduce a new, routing based, model of operation.
Digital microfluidic biochips focuses on the automated design and production of microfluidic based biochips for largescale bioassays and safetycritical applications. We show how topdown systemlevel design automation tools can relieve biochip users from the burden of manual optimization of assays, timeconsuming. Microfluidic biochips are an alternative to conventional biochemical laboratories, and are able to integrate onchip all the necessary functions for biochemical analysis. A vision for functional diversity and more than moore krishnendu chakrabarty department of electrical and computer engineering duke university.
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