A low-cost fluid-level synthesis for droplet-based microfluidic biochips integrating design convergence, contamination avoidance, and washing (original) (raw)
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IET Computers & Digital Techniques, 2018
Production of correct bioassay outcome is the foremost objective in digital microfluidic biochips (or DMFBs). In highfrequency 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.
Droplet Routing in the Synthesis of Digital Microfluidic Biochips
Proceedings of the Design Automation & Test in Europe Conference, 2006
same level of system-level CAD support that is now commonplace in the IC industry. Recent advances in microfluidics are expected to lead to sensor systems for high-throughput biochemical analysis. CAD tools are needed to handle increased design complexity for such systems. Analogous to classical VLSI synthesis, a top-down design automation approach can shorten the design cycle and reduce human effort. We focus here on the droplet routing problem, which is a key issue in biochip physical design automation. We develop the first systematic droplet routing method that can be integrated with biochip synthesis. The proposed approach minimizes the number of cells used for droplet routing, while satisfying constraints imposed by throughput considerations and fluidic properties. A real-life biochemical application is used to evaluate the proposed method. Analogous to classical VLSI synthesis, a top-down system-level design automation approach can be used to relieve biochip users from the burden of manual optimization of assays and time-consuming hardware design. We can divide the synthesis procedure for a digital microfluidic biochip into two major phases, i.e., architectural-level synthesis and physical design. A behavioral model for a set of bioassays is first obtained from their laboratory protocols. Architectural-level synthesis is then used to generate a macroscopic structure of the biochip; this is analogous to a structural RTL model in electronic CAD [5]. Next, physical design creates the final layout of the biochip, consisting of the placement of microfluidic modules such as mixers and storage units, the routes that droplets take between different modules, and other geometrical details [6].
Module-Based Synthesis of Digital Microfluidic Biochips with Droplet-Aware Operation Execution
ACM Journal on Emerging Technologies in Computing Systems, 2013
Microfluidic biochips represent an alternative to conventional biochemical analyzers. A digital biochip manipulates liquids not as continuous flow, but as discrete droplets on a two-dimensional array of electrodes. Several electrodes are dynamically grouped to form a virtual device, on which operations are executed by moving the droplets. So far, researchers have ignored the locations of droplets inside devices, considering that all the electrodes forming the device are occupied throughout the operation execution. In this article, we consider a droplet-aware execution of microfluidic operations, which means that we know the exact position of droplets inside the modules at each time-step. We propose a Tabu Search-based metaheuristic for the synthesis of digital biochips with droplet-aware operation execution. Experimental results show that our approach can significantly reduce the application completion time, allowing us to use smaller area biochips and thus reduce costs.
Design and realization of flexible droplet-based lab-on-a-chip devices
e & i Elektrotechnik und Informationstechnik, 2020
This article provides an overview on the emerging field of droplet-based microfluidic networks. In such networks, droplets i.e., encapsulating biochemical samples can be adaptively transported via microchannels through different operations for particular experiments. This approach is particularly promising for the next generation of lab-on-a-chip devices, which should support more complex operations and more flexibility. We give an accessible introduction to droplet-based microfluidics and describe the principles, of microfluidic switches, which are the main components in microfluidic networks. Based on these principles we present the addressing schemes for microfluidic bus networks. Since the design of microfluidic networks is a rather complex task, which requires the consideration of a huge number of physical parameters, we introduce design automation methods and simulation tools. Finally, we present a method for the precise generation of individual droplets, which enables the pra...
ACM Journal on Emerging Technologies in Computing Systems, 2007
Microfluidics-based biochips, also referred to as lab-on-a-chip, are devices that integrate fluid-handling functions such as sample preparation, analysis, separation, and detection. This emerging technology combines electronics with biology to open new application areas such as point-of-care diagnosis, on-chip DNA analysis, and automated drug discovery. We propose a design automation method for pin-constrained biochips that manipulate nanoliter volumes of discrete droplets on a microfluidic array. In contrast to the direct-addressing scheme that has been studied thus far in the literature, we assign a small number of independent control pins to a large number of electrodes in the biochip, thereby reducing design complexity and product cost. The design procedure relies on a droplet-trace-based array partitioning scheme and an efficient pin assignment technique, referred to as the “Connect-5 algorithm.” The proposed method is evaluated using a set of multiplexed bioassays.
IETE Journal of Research, 2020
Programmable Microfluidic Devices (PMDs) are revolutionizing the traditional biochemical experiments due to their flexibility of performing various functionalities on a platform without any amendment in the underlying hardware. To enhance the inherent tractability of a PMD, microchannels are frequently shared among the operations; however, this leads to cross-contamination problem due to the residues trapped on the channel. For producing safe outcomes, a flow-level synthesis minimizing contamination as well as an efficient washing strategy become immediate requisites. Moreover, each unit of wash fluid possesses a finite capacity for washing and therefore, cannot clean the entire contaminated area on a chip. Hence, capacity-aware washing scheme is the urgent requirement to fulfil the practical constraints of a flow-layer design. In this paper, a design synthesis minimizing the amount of contamination is proposed which is followed by a model for wash optimization targeting to reduce wash time and total loss of capacity, while removing all the contaminations. The efficacy of the proposed synthesis and the washing scheme has been assessed considering various baseline approaches and the existing works on the same.
Layout-Aware Solution Preparation for Biochemical Analysis on a Digital Microfluidic Biochip
2011
A biodroplet transportationchemical analysis is based on several laboratory protocols that require repeated mixing of samples with reagents. Sample preparation and analyte identification steps in such bioassays often involve mixing for solution preparation, i.e., various fluids are to be mixed in a certain volumetric ratio in their resulting mixture. We present an efficient approach for automated mixing of three or more fluids on a droplet based digital micro fluidic biochip and design a layout for implementing this algorithm. The proposed method reduces the droplet transportation time from boundary reservoirs to on chip mixers as well as cross-contamination among overlapping droplet routing paths. Simulation of several example solutions reveals encouraging results.
2006
Microfluidics-based biochips combine electronics with biology to open new application areas such as point-of-care medical diagnostics, on-chip DNA analysis, and automated drug discovery. Bioassays are mapped to microfluidic arrays using synthesis tools, and they are executed through the manipulation of sample and reagent droplets by electrical means. Most prior work on CAD for biochips has assumed independent control of electrodes using a large number of (electrical) input pins. Such solutions are not feasible for low-cost disposable biochips that are envisaged for many field applications. A more promising design strategy is to divide the microfluidic array into smaller partitions and use a small number of electrodes to control the electrodes in each partition. We propose a partitioning algorithm based on the concept of "droplet trace", which is extracted from the scheduling and droplet routing results produced by a synthesis tool. An efficient pin assignment method, referred to as the "Connect-5 algorithm", is combined with the array partitioning technique based on droplet traces. The array partitioning and pin assignment methods are evaluated using a set of multiplexed bioassays.
Multiphase bioreaction microsystem with automated on-chip droplet operation
Lab on a Chip, 2010
A droplet-based bioreaction microsystem has been developed with automated droplet generation and confinement. On-chip electronic sensing is employed to track the position of the droplets by sensing the oil/aqueous interface in real time. The sensing signal is also used to control the pneumatic supply for moving as well as automatically generating four different nanoliter-sized droplets. The actual size of droplets is very close to the designed droplet size with a standard deviation less than 3% of the droplet size. The automated droplet generation can be completed in less than 2 sec, which is 5 times faster than using manual operation that takes at least 10 sec. Droplets can also be automatically confined in the reaction region with feedback pneumatic control and digital or analog sensing. As an example bioreaction, PCR has been successfully performed in the automated generated droplets. Although the amplification yield was slightly reduced with the droplet confinement, especially while using the analog sensing method, adding additional reagents effectively alleviated this inhibition.