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

Synthesis of biochemical applications on digital microfluidic biochips with operation variability

Abstract—Microfluidic-based biochips are replacing the con-ventional biochemical analyzers, and are able to integrate on-chip all the necessary functions for biochemical analysis using microfluidics. The digital microfluidic biochips are based on the manipulation of liquids not as a continuous flow, but as discrete droplets. Researchers have presented approaches for the synthesis of digital microfluidic biochips, which, starting from a biochemical application and a given biochip architecture, determine the allocation, resource binding, scheduling and place-ment of the operations in the application. Existing approaches consider that on-chip operations, such as splitting a droplet of liquid, are perfect. However, these operations have variability margins, which can impact the correctness of the biochemical application. We consider that a split operation, which goes beyond specified variability bounds, is faulty. The fault is detected using on-chip volume sensors. We have proposed an abstract model for a biochemical application, consisting of a sequencing graph, which can capture all the fault scenarios in the application. Starting from this model, we have proposed a synthesis approach that, for a given chip area and number of sensors, can derive a fault-tolerant implementation. Two fault-tolerant scheduling techniques have been proposed and compared. We show that, by taking into account fault-occurrence information, we can derive better quality implementations, which leads to shorter application completion times, even in the case of faults. The proposed synthesis approach under operation variability has been evaluated using several benchmarks. I

Testing microelectronic biofluidic systems

According to the 2005 International Technology Roadmap for Semiconductors, the integration of emerging nondigital CMOS technologies will require radically different test methods, posing a major challenge for designers and test engineers. One such technology is microelectronic fluidic (MEF) arrays, which have rapidly gained importance in many biological, pharmaceutical, and industrial applications. The advantages of these systems, such as operation speed, use of very small amounts of liquid, on-board droplet detection, signal conditioning, and vast digital signal processing, make them very promising. However, testable design of these devices in a mass-production environment is still in its infancy, hampering their low-cost introduction to the market. This article describes analog and digital MEF design and testing method

Placement and routing for cross-referencing digital microfluidic biochips.

Xiao, Zigang."October 2010."Thesis (M.Phil.)--Chinese University of Hong Kong, 2011.Includes bibliographical references (leaves 62-66).Abstracts in English and Chinese.Abstract --- p.iAcknowledgement --- p.viChapter 1 --- Introduction --- p.1Chapter 1.1 --- Microfluidic Technology --- p.2Chapter 1.1.1 --- Continuous Flow Microfluidic System --- p.2Chapter 1.1.2 --- Digital Microfluidic System --- p.2Chapter 1.2 --- Pin-Constrained Biochips --- p.4Chapter 1.2.1 --- Droplet-Trace-Based Array Partitioning Method --- p.5Chapter 1.2.2 --- Broadcast-addressing Method --- p.5Chapter 1.2.3 --- Cross-Referencing Method --- p.6Chapter 1.2.3.1 --- Electrode Interference in Cross-Referencing Biochips --- p.7Chapter 1.3 --- Computer-Aided Design Techniques for Biochip --- p.8Chapter 1.4 --- Placement Problem in Biochips --- p.8Chapter 1.5 --- Droplet Routing Problem in Cross-Referencing Biochips --- p.11Chapter 1.6 --- Our Contributions --- p.14Chapter 1.7 --- Thesis Organization --- p.15Chapter 2 --- Literature Review --- p.16Chapter 2.1 --- Introduction --- p.16Chapter 2.2 --- Previous Works on Placement --- p.17Chapter 2.2.1 --- Basic Simulated Annealing --- p.17Chapter 2.2.2 --- Unified Synthesis Approach --- p.18Chapter 2.2.3 --- Droplet-Routing-Aware Unified Synthesis Approach --- p.19Chapter 2.2.4 --- Simulated Annealing Using T-tree Representation --- p.20Chapter 2.3 --- Previous Works on Routing --- p.21Chapter 2.3.1 --- Direct-Addressing Droplet Routing --- p.22Chapter 2.3.1.1 --- A* Search Method --- p.22Chapter 2.3.1.2 --- Open Shortest Path First Method --- p.23Chapter 2.3.1.3 --- A Two Phase Algorithm --- p.24Chapter 2.3.1.4 --- Network-Flow Based Method --- p.25Chapter 2.3.1.5 --- Bypassibility and Concession Method --- p.26Chapter 2.3.2 --- Cross-Referencing Droplet Routing --- p.28Chapter 2.3.2.1 --- Graph Coloring Method --- p.28Chapter 2.3.2.2 --- Clique Partitioning Method --- p.30Chapter 2.3.2.3 --- Progressive-ILP Method --- p.31Chapter 2.4 --- Conclusion --- p.32Chapter 3 --- CrossRouter for Cross-Referencing Biochip --- p.33Chapter 3.1 --- Introduction --- p.33Chapter 3.2 --- Problem Formulation --- p.34Chapter 3.3 --- Overview of Our Method --- p.35Chapter 3.4 --- Net Order Computation --- p.35Chapter 3.5 --- Propagation Stage --- p.36Chapter 3.5.1 --- Fluidic Constraint Check --- p.38Chapter 3.5.2 --- Electrode Constraint Check --- p.38Chapter 3.5.3 --- Handling 3-pin net --- p.44Chapter 3.5.4 --- Waste Reservoir --- p.45Chapter 3.6 --- Backtracking Stage --- p.45Chapter 3.7 --- Rip-up and Re-route Nets --- p.45Chapter 3.8 --- Experimental Results --- p.46Chapter 3.9 --- Conclusion --- p.47Chapter 4 --- Placement in Cross-Referencing Biochip --- p.49Chapter 4.1 --- Introduction --- p.49Chapter 4.2 --- Problem Formulation --- p.50Chapter 4.3 --- Overview of the method --- p.50Chapter 4.4 --- Dispenser and Reservoir Location Generation --- p.51Chapter 4.5 --- Solving Placement Problem Using ILP --- p.51Chapter 4.5.1 --- Constraints --- p.53Chapter 4.5.1.1 --- Validity of modules --- p.53Chapter 4.5.1.2 --- Non-overlapping and separation of Modules --- p.53Chapter 4.5.1.3 --- Droplet-Routing length constraint --- p.54Chapter 4.5.1.4 --- Optical detector resource constraint --- p.55Chapter 4.5.2 --- Objective --- p.55Chapter 4.5.3 --- Problem Partition --- p.56Chapter 4.6 --- Pin Assignment --- p.56Chapter 4.7 --- Experimental Results --- p.57Chapter 4.8 --- Conclusion --- p.59Chapter 5 --- Conclusion --- p.60Bibliography --- p.6

Scheduling and Fluid Routing for Flow-Based Microfluidic Laboratories-on-a-Chip

Microfluidic laboratories-on-a-chip (LoCs) are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis on-chip. There are several types of LoCs, each having its advantages and limitations. In this paper we are interested in flow-based LoCs, in which a continuous flow of liquid is manipulated using integrated microvalves. By combining several microvalves, more complex units, such as micropumps, switches, mixers, and multiplexers, can be built. We consider that the architecture of the LoC is given, and we are interested in synthesizing an implementation, consisting of the binding of operations in the application to the functional units of the architecture, the scheduling of operations and the routing and scheduling of the fluid flows, such that the application completion time is minimized. To solve this problem, we propose a list scheduling-based application mapping (LSAM) framework and evaluate it by using real-life as well as synthetic benchmarks. When biochemical applications contain fluids that may adsorb on the substrate on which they are transported, the solution is to use rinsing operations for contamination avoidance. Hence, we also propose a rinsing heuristic, which has been integrated in the LSAM framework