A New Fluid-Chip Co-Design for Digital Microfluidic Biochips Considering Cost Drivers and Design Convergence

A Design Optimization for Pin-Constrained Paper-based Digital Microfluidic Biochips Integrating Fluid-Control Co-Design Issues

Abstract: Paper-based digital microfluidic biochips (PDMFBs) are becoming highly effective among the microfluidic platforms due to its low-cost and in-place fabrication. The designed electrodes and wiring can be fabricated on a piece of paper by an inkjet printer and conductive ink containing carbon nanotube particles (CNTs). However, due to induced control interference, the wires cannot pass by an arbitrary electrode. Each wire that is to be routed possesses its conflict electrode group, which must be avoided for a feasible droplet movement. This paper presents a fluid-control co-design considering several important cost-driving issues like minimization of schedule length, control pin count, and wirelength, together with congestion-free and conflict-free wiring. Observably, design gaps exist among the sub-tasks of the fluid-level, control-level, and fluid-control as a whole, due to their separate considerations. It indeed introduces many design cycles lengthening the design process, and thus increases the overall cost. In this context, this work integrates the sub-tasks as a prior need to obtain a low cost and efficient platform. Several benchmarks have been studied to evaluate the performance.

A Predictive Model for Fluid-Control Codesign of Paper-Based Digital Biochips Following a Machine Learning Approach

Abstract: Paper-based digital microfluidic biochips (or P-DMFBs) are becoming highly impelling due to its low-cost and in-place fabrication of electrodes and control wiring on a single piece of paper having an inkjet printer and conductive ink. Despite enormous advantages, several complex design rules also subsist, such as avoidance of induced control interference, minimum separation among the control lines, and congestion-free wiring on a single layer, which is to be correlated leading toward overall feasibility of the design. Several cost raising issues, such as schedule length, control pin count, and wire length, must be considered for attaining a successful fluid-control codesign. Moreover, design gaps exist among the subtasks of the fluid level, control level, and fluid-control design as a whole, which undeniably impose expensive design cycles increasing overall cost. This article builds a machine learning-based model for the pin-constrained P-DMFBs to predict violation in control design beforehand and accordingly guides the fluid-control codesign to tackle important cost-driving issues while attaining congestion- and conflict-free wiring. This model effectively eliminates the design cycles producing a low-cost platform. The predictive model has been evaluated over a balanced data set. Several benchmarks for assessing the performance are studied.

An Integrated Co-Design of Flow-Based Biochips Considering Flow-Control Design Issues and Objectives

Abstract: With increasing effectiveness of flow-based microfluidic biochips in the field of biochemical experiments and point-of-care diagnosis, design automation demands enormous attention to integrate the ...

Electrowetting-based actuation of droplets for integrated microfluidics

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.

Digital microfluidics: is a true lab-on-a-chip possible?

Abstract: The suitability of electrowetting-on-dielectric (EWD) microfluidics for true lab-on-a-chip applications is discussed. The wide diversity in biomedical applications can be parsed into manageable components and assembled into architecture that requires the advantages of being programmable, reconfigurable, and reusable. This capability opens the possibility of handling all of the protocols that a given laboratory application or a class of applications would require. And, it provides a path toward realizing the true lab-on-a-chip. However, this capability can only be realized with a complete set of elemental fluidic components that support all of the required fluidic operations. Architectural choices are described along with the realization of various biomedical fluidic functions implemented in on-chip electrowetting operations. The current status of this EWD toolkit is discussed. However, the question remains: which applications can be performed on a digital microfluidic platform? And, are there other advantages offered by electrowetting technology, such as the programming of different fluidic functions on a common platform (reconfigurability)? To understand the opportunities and limitations of EWD microfluidics, this paper looks at the development of lab-on-chip applications in a hierarchical approach. Diverse applications in biotechnology, for example, will serve as the basis for the requirements for electrowetting devices. These applications drive a set of biomedical fluidic functions required to perform an application, such as cell lysing, molecular separation, or analysis. In turn, each fluidic function encompasses a set of elemental operations, such as transport, mixing, or dispensing. These elemental operations are performed on an elemental set of components, such as electrode arrays, separation columns, or reservoirs. Examples of the incorporation of these principles in complex biomedical applications are described.

The worst-case time complexity for generating all maximal cliques and computational experiments

Abstract: We present a depth-first search algorithm for generating all maximal cliques of an undirected graph, in which pruning methods are employed as in the Bron-Kerbosch algorithm. All the maximal cliques generated are output in a tree-like form. Subsequently, we prove that its worst-case time complexity is O(3n/3) for an n-vertex graph. This is optimal as a function of n, since there exist up to 3n/3 maximal cliques in an n-vertex graph. The algorithm is also demonstrated to run very fast in practice by computational experiments.

Approximating maximum independent sets by excluding subgraphs

Abstract: An approximation algorithm for the maximum independent set problem is given, improving the best performance guarantee known toO(n/(logn)2). We also obtain the same performance guarantee for graph coloring. The results can be combined into a surprisingly strongsimultaneous performance guarantee for the clique and coloring problems. The framework ofsubgraph-excluding algorithms is presented. We survey the known approximation algorithms for the independent set (clique), coloring, and vertex cover problems and show how almost all fit into that framework. We show that among subgraph-excluding algorithms, the ones presented achieve the optimal asymptotic performance guarantees.

Microfluidics-Based Biochips: Technology Issues, Implementation Platforms, and Design-Automation Challenges

Abstract: Microfluidics-based biochips are soon expected to revolutionize clinical diagnosis, deoxyribonucleic acid (DNA) sequencing, and other laboratory procedures involving molecular biology. In contrast to continuous-flow systems that rely on permanently etched microchannels, micropumps, and microvalves, digital microfluidics offers a scalable system architecture and dynamic reconfigurability; groups of unit cells in a microfluidics array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. This paper presents an overview of an integrated system-level design methodology that attempts to address key issues in the synthesis, testing and reconfiguration of digital microfluidics-based biochips. Different actuation mechanisms for microfluidics-based biochips, and associated design-automation trends and challenges are also discussed. The proposed top-down design-automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, time-consuming hardware design, and costly testing and maintenance procedures, and it will facilitate the integration of fluidic components with a microelectronic component in next-generation systems-on-chips (SOCs).