Design Optimization at the Fluid-Level Synthesis for Safe and Low-Cost Droplet-Based Microfluidic Biochips
01 Jan 2018-pp 127-132
TL;DR: A fluid-level design for DMFBs is proposed that is capable of handling reliability and also free from cross contamination, and a graph model has been used to tackle them.
Abstract: Droplet-based Digital Microfluidic Biochips (or DMFBs) are now being the prime platform for a number of point of care diagnostics, clinical studies, and sample preparations. Several design optimization methods exist at the fluid-level that automate the tasks of a DMFB. However, in high frequency applications, its performance heavily deteriorates in the order of degrading electrodes producing incorrect outcomes. Vague results may also be generated if cross contamination during droplet routing is not avoided. We define a DMFB to be safe if it is capable of handling reliability and also free from cross contamination. Alongside, as the fluid-level of DMFBs comprises several tasks that altogether introduces design cycles and leads to higher cost, a low-cost platform is urgently required. This paper proposes a fluid-level design for DMFBs that considers the above facts together. A graph model has been used to tackle them. An exact algorithm is presented. The obtained results are validated with several benchmarks.
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TL;DR: A pin addressing method based on a support vector machine (SVM) with the reliability constraint algorithm, which can fully consider the electrode addressing method and the reliability of the chip together is proposed.
Abstract: Digital microfluidic biochips (DMFBs) are increasingly important and are used for point-of-care, drug discovery, clinical diagnosis, immunoassays, etc. Pin-constrained DMFBs are an important part of digital microfluidic biochips, and they have gained increasing attention from researchers. However, many previous works have focused on the problem of electrode addressing and aimed to minimize the number of control pins in pin-constrained DMFBs. Although the number of control pins can be effectively redistributed through broadcast addressing technology, the chip reliability will be reduced if the signals are shared arbitrarily. Arbitrary signal sharing can lead to a large number of actuations for many idle electrodes, and as a result, a trapping charge or decreasing contact angle problem could occur for some electrodes, reducing the reliability of the chip. To address this problem, the appropriate electrode matching object should be carefully selected, and the influence of these factors on chip reliability should be fully considered. For this purpose, we aimed to fully consider electrode addressing and the reliability of the chip in improving the reliability of DMFBs. This paper proposed a pin addressing method based on a support vector machine (SVM) with the reliability constraint algorithm, which can fully consider the electrode addressing method and the reliability of the chip together. The proposed method achieved an average maximum number of electrode actuations that was 53.8% and 18.2% smaller than those of the baseline algorithm and the graph-based algorithm, respectively. The simulation experiment results showed that the proposed method can efficiently solve reliability problems during the DMFB design process.
7 citations
TL;DR: A complete fluid-level synthesis considering all the essential goals together instead of dealing with them in isolation is proposed effectively handles the trade-off scenarios and provides flexibility to the designer to decide the threshold of the individual optimisation objective leading to the construction of a good-quality solution as a whole.
Abstract: Production of correct bioassay outcome is the foremost objective in digital microfluidic biochips (or DMFBs). In high-frequency DMFBs, continuous actuation of electrodes leads to malfunctioning or even breakdown of the system. The improper functioning of a biochip tends to produce erroneous results. On the other hand, while transporting droplets, the residues may get stuck to electrode walls and cause contamination to other droplets. To ensure proper assay outcome, washing becomes mandatory, whose incorporation may delay the bioassay completion time significantly. Furthermore, each wash droplet possesses a capacity constraint within which the residues can be washed off successfully. Evidently, the design objectives possess a large degree of trade-offs among themselves and must be attacked to prepare an efficient platform. Here, the authors propose a complete fluid-level synthesis considering all the essential goals together instead of dealing with them in isolation. The presented approach effectively handles the trade-off scenarios and provides flexibility to the designer to decide the threshold of the individual optimisation objective leading to the construction of a good-quality solution as a whole. The performance is evaluated over several benchmark bioassays.
6 citations
TL;DR: The routing problem is identified as a dynamic path-planning problem and mixed path design problem under certain constraints, and an improved Dijkstra and improved particle swarm optimization (ID-IPSO) algorithm is proposed, which can accommodate more faulty electrodes for the same fault repair rate.
Abstract: Digital microfluidic biochips (DMFBs) are attractive instruments for obtaining modern molecular biology and chemical measurements. Due to the increasingly complex measurements carried out on a DMFB, such chips are more prone to failure. To compensate for the shortcomings of the module-based DMFB, this paper proposes a routing-based fault repair method. The routing-based synthesis methodology ensures a much higher chip utilization factor by removing the virtual modules on the chip, as well as removing the extra electrodes needed as guard cells. In this paper, the routing problem is identified as a dynamic path-planning problem and mixed path design problem under certain constraints, and an improved Dijkstra and improved particle swarm optimization (ID-IPSO) algorithm is proposed. By introducing a cost function into the Dijkstra algorithm, the path-planning problem under dynamic obstacles is solved, and the problem of mixed path design is solved by redefining the position and velocity vectors of the particle swarm optimization. The ID-IPSO routing-based fault repair method is applied to a multibody fluid detection experiment. The proposed design method has a stronger optimization ability than the greedy algorithm. The algorithm is applied to , , and fault-free chips. The proposed ID-IPSO routing-based chip design method saves 13.9%, 14.3%, and 14.5% of the experiment completion time compared with the greedy algorithm. Compared with a modular fault repair method based on the genetic algorithm, the ID-IPSO routing-based fault repair method has greater advantages and can save 39.3% of the completion time on average in the completion of complex experiments. When the ratio of faulty electrodes is less than 12% and 23%, the modular and ID-IPSO routing-based fault repair methods, respectively, can guarantee a 100% failure repair rate. The utilization rate of the electrodes is 18% higher than that of the modular method, and the average electrode usage time is 17%. Therefore, the ID-IPSO routing-based fault repair method can accommodate more faulty electrodes for the same fault repair rate; the experiment completion time is shorter, the average number of electrodes is lower, and the security performance is better.
6 citations
Cites methods from "Design Optimization at the Fluid-Le..."
...The authors of [22] proposed a fluid-level design for DMFBs that considered cross-contamination and degrading electrodes together, and a graph model was used to address them....
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TL;DR: In this article, the authors proposed an improved whale optimization algorithm (IWOA), which can reduce the excessive use of an electrode and reuse electrodes in an average manner to optimize the longest lifetime of digital microfluidic biochips.
1 citations
TL;DR: In this paper , a routing-based synthesis method based on a digital microfluidic biochip (DMFB) platform is presented, which can ensure a much higher chip utilization factor by removing the virtual modules on the chip and the extra electrodes needed as guard cells.
Abstract: With the continuous application and development of the digital microfluidic technology in various fields, many researchers have studied the design of digital microfluidic chips. Module-based chip design methods greatly simplify the design process but waste resources, including through the inadequate use of electrodes within the module and guard cells. To address this problem, a routing-based synthesis method based on a digital microfluidic biochip (DMFB) platform is presented. Routing-based DMFBs ensure a much higher chip utilization factor by removing the virtual modules on the chip and the extra electrodes needed as guard cells. Many previous works focused only on the problems of synthesis completion times, bioassay completion times, and electrode utilization rates. However, the reliability of chips has not been fully studied, and this factor is extremely important because faulty chips affect the test results. Thus, the influence of chip reliability should be fully considered. This paper proposes a design method based on Bayesian decision-making (BBD) for routing-based DMFBs that can fully consider the reliability of chips during the DMFB design process. Simulated experimental results showed that the method can address the reliability problems of chips. The efficiency and convergence performance of the algorithm were very good. The proposed method can achieve an average assay completion time that is shorter than those of the moduleless synthesis (MLS) and modified-MLS (MMLS) methods. The electrode usage rate of the proposed method is better than that of the module-based and improved Dijkstra and improved particle swarm optimization (ID-IPSO) methods.
1 citations
References
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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.
172 citations
"Design Optimization at the Fluid-Le..." refers background or methods in this paper
...Most of the previous works in fluid-level design pass through unified synthesis schemes that generally solve the sub-tasks one at a time [9]....
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...All the works use a unified synthesis method to generate a final outcome [9]....
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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
"Design Optimization at the Fluid-Le..." refers background or methods in this paper
...Following [8], an edge disjoint path connecting the modules is found out....
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...2-pin net implies a module at each end), then a net priority can be incorporated based on the bounding rectangle connecting the end points of each net [8]....
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...A considerable amount of researches have been made to avoid cross contamination at the routing phase [8], [11]....
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...Each sub-problem is solved in order to get a contamination free routing by reduction from disjoint-path (either vertex or edge disjoint) problem [8]....
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...A modified Lee’s algorithm [8] can be effectively applied to find out the edge disjoint routes in routej....
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TL;DR: In this paper, the authors considered the case of the weight constrained shortest path problem (WCSPP) defined on a graph without cycles and presented a new exact algorithm, based on scaling and rounding of weights.
78 citations
TL;DR: This tutorial paper describes emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips from bioassay protocols and recent advances in fluidic-operation scheduling, module placement, droplet routing, pin-constrained chip design, and testing are presented.
Abstract: Microfluidics-based biochips are revolutionizing high-throughput sequencing, parallel immunoassays, blood chemistry for clinical diagnostics, and drug discovery. These devices enable the precise control of nanoliter volumes of biochemical samples and reagents. They combine electronics with biology, and they integrate various bioassay operations, such as sample preparation, analysis, separation, and detection. Compared to conventional laboratory procedures, which are cumbersome and expensive, miniaturized biochips offer the advantages of higher sensitivity, lower cost due to smaller sample and reagent volumes, system integration, and less likelihood of human error. This tutorial paper provides an overview of droplet-based ?digital? microfluidic biochips. It describes emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips from bioassay protocols. Recent advances in fluidic-operation scheduling, module placement, droplet routing, pin-constrained chip design, and testing are presented. These CAD techniques allow biochip users to concentrate on the development of nanoscale bioassays, leaving chip optimization and implementation details to design-automation tools.
76 citations
"Design Optimization at the Fluid-Le..." refers background in this paper
...binding, scheduling, placement, and routing tasks from the input bioassay graph together with the chip architecture and design specification [4], [5]....
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TL;DR: This paper presents the first design automation flow that considers the cross-contamination problems on pin-constrained biochips, and proposes early crossing minimization algorithms during placement and systematic wash droplet scheduling and routing that require only one extra control pin and zero assay completion time overhead for practical bioassays.
Abstract: Digital microfluidic biochips have emerged as a popular alternative for laboratory experiments. Pin-count reduction and cross-contamination avoidance are key design considerations for practical applications with different droplets being transported and manipulated on highly integrated biochips. This paper presents the first design automation flow that considers the cross-contamination problems on pin-constrained biochips. The factors that make the problems harder on pin-constrained biochips are explored. To cope with these cross contaminations, this paper proposes: 1) early crossing minimization algorithms during placement, and 2) systematic wash droplet scheduling and routing that require only one extra control pin and zero assay completion time overhead for practical bioassays. Experimental results show the effectiveness and scalability of our algorithms for practical bioassays.
61 citations
"Design Optimization at the Fluid-Le..." refers background in this paper
...A considerable amount of researches have been made to avoid cross contamination at the routing phase [8], [11]....
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