Transport or Store? Synthesizing Flow-based Microfluidic Biochips using Distributed Channel Storage

Flow-based microfluidic biochips have attracted much atten- tion in the EDA community due to their miniaturized size and execution efficiency. Previous research, however, still follows the traditional computing model with a dedicated storage unit, which actually becomes a bottleneck of the performance of bio- chips. In this paper, we propose the first architectural synthe- sis framework considering distributed storage constructed tem- porarily from transportation channels to cache fluid samples. Since distributed storage can be accessed more efficiently than a dedicated storage unit and channels can switch between the roles of transportation and storage easily, biochips with this dis- tributed computing architecture can achieve a higher execution efficiency even with fewer resources. Experimental results con- firm that the execution efficiency of a bioassay can be improved by up to 28% while the number of valves in the biochip can be reduced effectively.Comment: ACM/IEEE Design Automation Conference (DAC), June 201

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

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

Design and Optimization Methods for Pin-Limited and Cyberphysical Digital Microfluidic Biochips

<p>Microfluidic biochips have now come of age, with applications to biomolecular recognition for high-throughput DNA sequencing, immunoassays, and point-of-care clinical diagnostics. In particular, digital microfluidic biochips, which use electrowetting-on-dielectric to manipulate discrete droplets (or "packets of biochemical payload") of picoliter volumes under clock control, are especially promising. The potential applications of biochips include real-time analysis for biochemical reagents, clinical diagnostics, flash chemistry, and on-chip DNA sequencing. The ease of reconfigurability and software-based control in digital microfluidics has motivated research on various aspects of automated chip design and optimization.</p><p>This thesis research is focused on facilitating advances in on-chip bioassays, enhancing the automated use of digital microfluidic biochips, and developing an "intelligent" microfluidic system that has the capability of making on-line re-synthesis while a bioassay is being executed. This thesis includes the concept of a "cyberphysical microfluidic biochip" based on the digital microfluidics hardware platform and on-chip sensing technique. In such a biochip, the control software, on-chip sensing, and the microfluidic operations are tightly coupled. The status of the droplets is dynamically monitored by on-chip sensors. If an error is detected, the control software performs dynamic re-synthesis procedure and error recovery.</p><p>In order to minimize the size and cost of the system, a hardware-assisted error-recovery method, which relies on an error dictionary for rapid error recovery, is also presented. The error-recovery procedure is controlled by a finite-state-machine implemented on a field-programmable gate array (FPGA) instead of a software running on a separate computer. Each state of the FSM represents a possible error that may occur on the biochip; for each of these errors, the corresponding sequence of error-recovery signals is stored inside the memory of the FPGA before the bioassay is conducted. When an error occurs, the FSM transitions from one state to another, and the corresponding control signals are updated. Therefore, by using inexpensive FPGA, a portable cyberphysical system can be implemented.</p><p>In addition to errors in fluid-handling operations, bioassay outcomes can also be erroneous due the uncertainty in the completion time for fluidic operations. Due to the inherent randomness of biochemical reactions, the time required to complete each step of the bioassay is a random variable. To address this issue, a new "operation-interdependence-aware" synthesis algorithm is proposed in this thesis. The start and stop time of each operation are dynamically determined based on feedback from the on-chip sensors. Unlike previous synthesis algorithms that execute bioassays based on pre-determined start and end times of each operation, the proposed method facilitates "self-adaptive" bioassays on cyberphysical microfluidic biochips.</p><p>Another design problem addressed in this thesis is the development of a layout-design algorithm that can minimize the interference between devices on a biochip. A probabilistic model for the polymerase chain reaction (PCR) has been developed; based on the model, the control software can make on-line decisions regarding the number of thermal cycles that must be performed during PCR. Therefore, PCR can be controlled more precisely using cyberphysical integration.</p><p>To reduce the fabrication cost of biochips, yet maintain application flexibility, the concept of a "general-purpose pin-limited biochip" is proposed. Using a graph model for pin-assignment, we develop the theoretical basis and a heuristic algorithm to generate optimized pin-assignment configurations. The associated scheduling algorithm for on-chip biochemistry synthesis has also been developed. Based on the theoretical framework, a complete design flow for pin-limited cyberphysical microfluidic biochips is presented.</p><p>In summary, this thesis research has led to an algorithmic infrastructure and optimization tools for cyberphysical system design and technology demonstrations. The results of this thesis research are expected to enable the hardware/software co-design of a new class of digital microfluidic biochips with tight coupling between microfluidics, sensors, and control software.</p>Dissertatio

A Methodology to Design Pipelined Simulated Annealing Kernel Accelerators on Space-Borne Field-Programmable Gate Arrays

Increased levels of science objectives expected from spacecraft systems necessitate the ability to carry out fast on-board autonomous mission planning and scheduling. Heterogeneous radiation-hardened Field Programmable Gate Arrays (FPGAs) with embedded multiplier and memory modules are well suited to support the acceleration of scheduling algorithms. A methodology to design circuits specifically to accelerate Simulated Annealing Kernels (SAKs) in event scheduling algorithms is shown. The main contribution of this thesis is the low complexity scoring calculation used for the heuristic mapping algorithm used to balance resource allocation across a coarse-grained pipelined data-path. The methodology was exercised over various kernels with different cost functions and problem sizes. These test cases were benchedmarked for execution time, resource usage, power, and energy on a Xilinx Virtex 4 LX QR 200 FPGA and a BAE RAD 750 microprocessor

An Outlook on Design Technologies for Future Integrated Systems

The economic and social demand for ubiquitous and multifaceted electronic systems-in combination with the unprecedented opportunities provided by the integration of various manufacturing technologies-is paving the way to a new class of heterogeneous integrated systems, with increased performance and connectedness and providing us with gateways to the living world. This paper surveys design requirements and solutions for heterogeneous systems and addresses design technologies for realizing them