Yield Enhancement of Digital Microfluidics-Based Biochips Using Space Redundancy and Local Reconfiguration

As microfluidics-based biochips become more complex, manufacturing yield will have significant influence on production volume and product cost. We propose an interstitial redundancy approach to enhance the yield of biochips that are based on droplet-based microfluidics. In this design method, spare cells are placed in the interstitial sites within the microfluidic array, and they replace neighboring faulty cells via local reconfiguration. The proposed design method is evaluated using a set of concurrent real-life bioassays.Comment: Submitted on behalf of EDAA (http://www.edaa.com/

BioScript: programming safe chemistry on laboratories-on-a-chip

This paper introduces BioScript, a domain-specific language (DSL) for programmable biochemistry which executes on emerging microfluidic platforms. The goal of this research is to provide a simple, intuitive, and type-safe DSL that is accessible to life science practitioners. The novel feature of the language is its syntax, which aims to optimize human readability; the technical contributions of the paper include the BioScript type system and relevant portions of its compiler. The type system ensures that certain types of errors, specific to biochemistry, do not occur, including the interaction of chemicals that may be unsafe. The compiler includes novel optimizations that place biochemical operations to execute concurrently on a spatial 2D array platform on the granularity of a control flow graph, as opposed to individual basic blocks. Results are obtained using both a cycle-accurate microfluidic simulator and a software interface to a real-world platform

Directed Placement for mVLSI Devices

Continuous-flow microfluidic devices based on integrated channel networks are becoming increasingly prevalent in research in the biological sciences. At present, these devices are physically laid out by hand by domain experts who understand both the underlying technology and the biological functions that will execute on fabricated devices. The lack of a design science that is specific to microfluidic technology creates a substantial barrier to entry. To address this concern, this article introduces Directed Placement, a physical design algorithm that leverages the natural "directedness" in most modern microfluidic designs: fluid enters at designated inputs, flows through a linear or tree-based network of channels and fluidic components, and exits the device at dedicated outputs. Directed placement creates physical layouts that share many principle similarities to those created by domain experts. Directed placement allows components to be placed closer to their neighbors compared to existing layout algorithms based on planar graph embedding or simulated annealing, leading to an average reduction in laid-out fluid channel length of 91% while improving area utilization by 8% on average. Directed placement is compatible with both passive and active microfluidic devices and is compatible with a variety of mainstream manufacturing technologies

Testing Microfluidic Fully Programmable Valve Arrays (FPVAs)

Fully Programmable Valve Array (FPVA) has emerged as a new architecture for the next-generation flow-based microfluidic biochips. This 2D-array consists of regularly-arranged valves, which can be dynamically configured by users to realize microfluidic devices of different shapes and sizes as well as interconnections. Additionally, the regularity of the underlying structure renders FPVAs easier to integrate on a tiny chip. However, these arrays may suffer from various manufacturing defects such as blockage and leakage in control and flow channels. Unfortunately, no efficient method is yet known for testing such a general-purpose architecture. In this paper, we present a novel formulation using the concept of flow paths and cut-sets, and describe an ILP-based hierarchical strategy for generating compact test sets that can detect multiple faults in FPVAs. Simulation results demonstrate the efficacy of the proposed method in detecting manufacturing faults with only a small number of test vectors.Comment: Design, Automation and Test in Europe (DATE), March 201

A Software Toolchain for Physical System Description and Synthesis, and Applications to Microfluidic Design Automation

Microfluidic circuits are currently designed by hand, using a combination of the designer’s domain knowledge and educated intuition to determine unknown design parameters. As no microfluidic circuit design software exists to assist designers, circuits are typically tested by physically constructing them in silico and performing another design iteration should the prototype fail to operate correctly. Similar to how electronic design automation tools revolutionized the digital circuit design process, so too do microfluidic design packages have the potential to increase productivity for microfluidic circuit designers and allow more complex devices to be designed. Two of the primary software engineering problems to be solved in this space relate to design entry and design synthesis. First, the circuit designer requires a programming language to describe the behaviour and properties of the device they wish to build, and a compiler toolchain to convert this description into a model that can then be processed by other software tools. Second, once such a model is constructed, the remaining portions of the design toolchain must be constructed. It is necessary to implement software that can find unknown design parameters automatically to relieve the designer of much of the complexity that goes into creating such a circuit. Furthermore, automated testing and verification tools must be used to simulate the device and check for correctness and safety requirements before the engineer can have confidence in their design. In this thesis I outline work that has been done towards both of these goals. First, I describe a new programming language that has been developed for the purpose of describing and modelling physical systems, including but not limited to microfluidic circuits. This programming language, called “Manifold”, has been implemented following principles and features of modern functional programming languages, as well as drawing inspiration from VHDL and Verilog, the two industry-standard programming languages for EDA. The Manifold high-level language compiler carries out the process of translating a system description into a domain-agnostic intermediate representation. This representation is then passed to a domain-specific backend compiler which can perform further operations on the design, such as creating simulations, performing verification, and generating appropriate output products. Second, I perform a case study with respect to the creation of such a domain-specific backend for the domain of multi-phase microfluidic circuits. The process involved in taking a circuit description from design entry to device specification has a number of significant steps. I discuss in detail these steps with respect to the design of a multi-way droplet generator circuit. Such a circuit is difficult to design because of the behaviour of the key design parameter, the volume of generated droplets. The design goal is for each droplet generator on the device to produce droplets of a certain specified volume. However, the equation relating the properties of a droplet generator to the predicted droplet volume is complex and contains several nonlinearities, making it very difficult to solve by traditional methods. Recent advances in constraint solvers which can reason about nonlinear equations over real-valued terms make it possible to solve this equation efficiently for a given set of design constraints and goals, and produce many feasible specifications for droplet generators that meet the requirements. Another difficulty in designing these circuits is due to interactions between droplet generators. As the produced droplets have a significant hydrodynamic resistance, they affect the behaviour of the circuit by causing perturbations in the flow rates into the droplet generators. This has the potential to alter the volume of droplets that are being produced. Therefore, a means of regulating or controlling the flow rates must be found. I describe a potential solution in the form of a passive element analogous to a capacitor in an electrical circuit. Once an appropriate value for the capacitor is chosen, it remains to verify that it operates correctly under manufacturing variances in fabrication of the device. To perform this verification, a bounded model checker for real-valued differential equations is employed to demonstrate correctness or discover robustness issues. Furthermore, a simulation file for the MapleSim numerical simulation engine is generated in order to perform whole-design tests for further validation. The sequence in which these steps are performed closely follows the concept of “abstraction refinement” in formal methods, in which successively more detailed models are checked and a failure in one step can invoke a previous step with new information, allowing errors to be caught early and introducing the ability to iterate on the design. I describe such a refinement loop in place in the microfluidics backend that integrates these three steps in a coherent design flow, able to synthesize and verify many specifications for a microfluidic circuit, thereby automating a significant portion of the design process. The combination of the Manifold high-level language and microfluidics backend introduces a new design automation toolchain that demonstrates the effectiveness of constraint solvers in the tasks of design synthesis and verification. Further enhancements to the performance and capabilities of these solvers, as well as to the high-level language and backend, will in the future produce a general-purpose design package for microfluidic circuits that will allow for new, complex designs to be created and checked with confidence