An Efficient Single-Fault Detection Technique for Micro-fluidic Based Biochips
20 Jun 2010-pp 10-14
TL;DR: A new technique is presented to traverse all the cells and cell boundary, for the purpose of detecting a single fault within the bio-chip, and results show that the proposed technique improves the fault detection time to a great extent.
Abstract: This paper presents a new fault detection technique for digital micro-fluidic based biochips. Due to recent advances in microfluidics, digital micro-fluidic biochips are revolutionizing laboratory procedures, e.g., biosensing, clinical diagnostics etc. Because of the underlying mixed-technology and mixed energy domains, biochips exhibit unique failure mechanisms and defects. Off-line and on-line test techniques are required to ensure system dependability. In this paper, a new technique is presented to traverse all the cells and cell boundary, for the purpose of detecting a single fault within the bio-chip. Experimental results show that the proposed technique improves the fault detection time to a great extent.
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TL;DR: A multitarget sample preparation algorithm that extensively exploits the ideas of waste recycling and intermediate droplet sharing to reduce both reactant usage and waste amount for digital microfluidic biochips is proposed.
Abstract: Sample preparation is one of essential processes in biochemical reactions. Raw reactants are diluted in this process to achieve given target concentrations. A bioassay may require several different target concentrations of a reactant. Both the dilution operation count and the reactant usage can be minimized if multiple target concentrations are considered simultaneously during sample preparation. Hence, in this paper, we propose a multitarget sample preparation algorithm that extensively exploits the ideas of waste recycling and intermediate droplet sharing to reduce both reactant usage and waste amount for digital microfluidic biochips. Experimental results show that our waste recycling algorithm can reduce the waste and operation count by 48% and 37%, respectively, as compared to an existing state-of-the-art multitarget sample preparation method if the number of target concentrations is ten. The reduction can be up to 97% and 73% when the number of target concentrations goes even higher.
46 citations
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TL;DR: The proposed technique for detecting a single fault and identifying the fault location within the biochip can also calculate the traversal time if the bio chip is fault free and represents significant improvement in fault detection and calculating traverse time of a fault free biochip over existing methods.
Abstract: Microfluidic biochip has facilitated a revolutionary improvement in biomedical operation or safety critical application like clinical diagnosis, parallel DNA sequencing, toxicity monitoring, immunoassay, air or water quality monitoring, food safety testing etc. But it has faced a major setback from malfunction in fluidic operation due to the defect in the electrodes. In this paper, we are proposing a novel and efficient technique for detecting a single fault and identifying the fault location within the biochip. Along with that it can also calculate the traversal time if the biochip is fault free. The traversal of the microarray is carried out by scanning the intermediate cells and the edges by special types of movement pattern RDRD (Right-Down-Right-Down) and DRDR (Down-Right-Down-Right) for left and right diagonal electrode traversal respectively and the boundary cells and edges are traversed in clockwise direction by moving the test droplets. If a fault is detected then the proposed technique also locates it by backtracking the droplet. The simulated result suggests that the proposed technique is efficient and represents significant improvement in fault detection and calculating traversal time of a fault free biochip over existing methods.
9 citations
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07 Nov 2011
TL;DR: The key idea is to manipulate multiple droplets in parallel to test the micro-array in a scan-like manner and show significant improvement in fault detection over existing methods.
Abstract: With the recent advancement of micro-fluidic technology, application of digital micro-fluidic biochips have been rapidly increased in bio-sensing, clinical diagnostics and other laboratory works. As the bio-chips occasionally work on safety critical operations, correctness and dependability are important requirement for these devices. Therefore, these devices must be tested after manufacturing and during bioassay operations. We are proposing a novel multi droplets detection technique for single-fault in digital micro-fluidic biochips in this paper. The key idea is to manipulate multiple droplets in parallel to test the micro-array in a scan-like manner. The traversal of micro-array is carried out by scanning the intermediate cells and edges by a special type of movement pattern RURD (Right-Up-Right-Down) and the boundary cells and edges by anti-clockwise movement of the test stimuli droplets. The experimental results suggest that the proposed technique is an efficient one and show significant improvement in fault detection over existing methods.
6 citations
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TL;DR: This work is presenting an image segmentation based testing methodology to detect the catastrophic faults and to locate the faulty cells and it is shown that faults can be located and tolerated by providing alternative paths in biochips.
Abstract: Digital microfluidic biochip has been developed as a promising alternative to the traditional approach of benchtop biochemical laboratory tests. Dependability is an important attribute for microfluidic biochips that are used for safety-critical applications, such as point-of-care health assessment, air-quality monitoring, and food-safety testing. Therefore, the robust offline and online test techniques are required after manufacturing and during bioassay operations. In this work, we are presenting an image segmentation based testing methodology to detect the catastrophic faults and to locate the faulty cells. The design-for diagnosability scheme is proposed, and it is shown that faults can be located and tolerated by providing alternative paths in biochips. Moreover this testing method also facilitates the testing of a biochip with other bioassay operations running concurrently.
4 citations
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TL;DR: An efficient fault detection mechanism is formulated to identify multiple numbers of defective/faulty electrodes on an m × n biochip array, where m and n can be of any positive number.
Abstract: The involvement of Digital Microfluidic Biochips (DMFBs) in the field of disease detection, automated drug discovery, on-chip DNA (Deoxyribonucleic acid) analysis has become well-accepted d...
3 citations
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References
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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.
1,071 citations
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TL;DR: In this paper, an alternative approach to microfluidics based upon the micromanipulation of discrete droplets of aqueous electrolyte by electrowetting is reported.
Abstract: The serviceability of microfluidics-based instrumentation including ‘lab-on-a-chip’ systems critically depends on control of fluid motion. We are reporting here an alternative approach to microfluidics based upon the micromanipulation of discrete droplets of aqueous electrolyte by electrowetting. Using a simple open structure, consisting of two sets of opposing planar electrodes fabricated on glass substrates, positional and formational control of microdroplets ranging in size from several nanoliters to several microliters has been demonstrated at voltages between 15–100 V. Since there are no permanent channels or structures between the plates, the system is highly flexible and reconfigurable. Droplet transport is rapid and efficient with average velocities exceeding 10 cm s−1 having been observed. The dependence of the velocity on voltage is roughly independent of the droplet size within certain limits, thus the smallest droplets studied (∼3
nl) could be transported over 1000 times their length per second. Formation, mixing, and splitting of microdroplets was also demonstrated using the same microactuator structures. Thus, electrowetting provides a means to achieve high levels of functional integration and flexibility for microfluidic systems.
1,038 citations
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TL;DR: A microfluidic lab-on-chip (LoC) for measuring the concentration of human body metabolites, using submicroliter droplets as reaction chambers, is presented in this article.
Abstract: A microfluidic lab-on-chip (LoC) for measuring the concentration of human body metabolites, using submicroliter droplets as reaction chambers, is presented in this paper. The device is based on the manipulation of droplets using the principle of electrowetting and is integrated with an optical absorbance measurement system for detection. We have demonstrated the detection of glucose using a colorimetric enzyme-kinetic assay in less than 40 seconds. The sensor response is linear in the range of 25mg/dl to 300mg/dl, with less than 5% deviation from linearity at the upper limit. In addition to glucose, we have also demonstrated the feasibility of lactate, glutamate, and pyruvate assays using our system.
167 citations
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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.
152 citations
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TL;DR: The first network-flow-based routing algorithm that can concurrently route a set of noninterfering nets for the droplet routing problem on biochips is presented and is presented as the first polynomial-time algorithm for simultaneous routing and scheduling using the global-routing paths with a negotiation- based routing scheme.
Abstract: Due to recent advances in microfluidics, digital microfluidic biochips are expected to revolutionize laboratory procedures. One critical problem for biochip synthesis is the droplet routing problem. Unlike traditional very large scale integration routing problems, in addition to routing path selection, the biochip routing problem needs to address the issue of scheduling droplets under practical constraints imposed by the fluidic property and timing restriction of synthesis results. In this paper, we present the first network-flow-based routing algorithm that can concurrently route a set of noninterfering nets for the droplet routing problem on biochips. We adopt a two-stage technique of global routing followed by detailed routing. In global routing, we first identify a set of noninterfering nets and then adopt the network-flow approach to generate optimal global-routing paths for nets. In detailed routing, we present the first polynomial-time algorithm for simultaneous routing and scheduling using the global-routing paths with a negotiation-based routing scheme. Our algorithm targets at both the minimization of cells used for routing for better fault tolerance and minimization of droplet transportation time for better reliability and faster bioassay execution. Experimental results show the robustness and efficiency of our algorithm.
96 citations
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