Daniel T. Grissom

Fast online synthesis of generally programmable digital microfluidic biochips

We introduce an online synthesis flow for digital microfluidic biochips, which will enable real-time response to errors and control flow. The objective of this flow is to facilitate fast assay synthesis while minimally compromising the quality of results. In particular, we show that a virtual topology, which constrains the allowable locations of assay operations such as mixing, dilution, sensing, etc., in lieu of traditional placement, can significantly speed up the synthesis process without significantly lengthening assay execution time.

Path scheduling on digital microfluidic biochips

Since the inception of digital microfluidics, the synthesis problems of scheduling, placement and routing have been performed offline (before runtime) due to their algorithmic complexity. However, with the increasing maturity of digital microfluidic research, online synthesis is becoming a realistic possibility that can bring new benefits in the areas of dynamic scheduling, control-flow, fault-tolerance and live-feedback. This paper contributes to the digital microfluidic synthesis process by introducing a fast, novel path-based scheduling algorithm that produces better schedules than list scheduler for assays with high fan-out; path scheduler computes schedules in milliseconds, making it suitable for both offline and online synthesis.

A digital microfluidic biochip synthesis framework

Synthesis of digital microfluidic biochips (DMFBs) is a crucial to the advancement and realization of miniaturized, automated, programmable biochemistry solutions; synthesis is performed in three steps: scheduling, placement and routing. In principle, algorithms for specific steps should be interchangeable with one another; however, different research groups typically develop algorithms for each step in isolation from one another. Thus, it is difficult to compare algorithms against one another, or to determine which algorithms for different steps share synergies. We introduce an open source DMFB synthesis framework to encourage collaboration between researchers working in the area. We introduce a common interface and describe the internal data structures that must be updated to ensure that the interfaces are adhered to. We also present and describe a number of high-quality 2D and 3D debugging tools that provide graphical output for each stage of synthesis.

A field-programmable pin-constrained digital microfluidic biochip

As digital microfluidic biochips (DMFBs) have matured over the last decade, efforts have been made to 1.) reduce the cost, and 2.) produce general-purpose chips. While work done to generalize DMFBs typically depends on the flexibility of individually controlled electrodes, such devices have high wiring complexity, which requires costly multi-layer printed circuit boards (PCBs). In contrast, pin-constrained DMFBs reduce the wiring complexity, but reduce the flexibility of droplet coordination. We present a field-programmable pin-constrained DMFB that leverages the cost-savings of pin-constrained designs, but is general-purpose, rather than assay-specific. We show that with just a few more pins than the state-of-the-art pin-constrained designs, we can execute arbitrary assays almost as fast as the most recent general-purpose DMFB designs.

Fast Online Synthesis of Digital Microfluidic Biochips

We introduce an online synthesis flow, focusing primarily on the virtual topology and operation binder, for digital microfluidic biochips, which will enable real-time response to errors and control flow. The objective of this flow is to facilitate fast assay synthesis while minimally compromising the quality of results. In particular, we show that a virtual topology, which constrains the allowable locations of assay operations such as mixing, dilution, sensing, etc., in lieu of traditional placement, can significantly speed up the synthesis process without significantly lengthening assay execution time. We present a base virtual topology and show how it can be leveraged to reduce algorithmic runtimes and guarantee rout ability. We later present several variations of the virtual topology and present experimental results demonstrating best-design practices. We present two binding solutions. The first is a left-edge binding algorithm, while the second is a more intelligent path-based binding algorithm that leverages spatial and temporal locality to produce superior results.

Force-Directed List Scheduling for Digital Microfluidic Biochips

We introduce a Force-directed List Scheduling (FDLS) algorithm for resource-constrained assay compilation targeting Digital Microfluidic Biochips (DMFBs). This algorithm has been used in the past for high-level synthesis of digital signal processing systems, and is now applied to DMFB synthesis. The results show improvements compared to List Scheduling (LS) and Path Scheduling (PS), the most efficient heuristics that have been proposed, to date, for DMFBs. FDLS was also competitive with longer-running iterative improvement DMFB scheduling algorithms based on genetic algorithms.

Rapid online fault recovery for cyber-physical digital microfluidic biochips

Microfluidic technologies offer benefits to the biological sciences by miniaturizing and automating chemical reactions. Software-controlled laboratories-on-a-chip (LoCs) execute biological protocols (assays) specified using high-level languages. Integrated sensors and video monitoring provide a closed feedback loop between the LoC and its control software, which provide timely information about the progress of an ongoing assay and the overall health of the LoC. This paper introduces a cyber-physical control algorithm that rectifies hard and soft faults that are detected dynamically while executing an assay on a digital microfluidic biochip (DMFB), one specific LoC technology. The approach is scalable (i.e., there is no fixed limit on the number of faults that may occur), and runs efficiently in practice, thereby limiting the performance overhead incurred when a hard or soft fault occurs during assay execution.

An open-source compiler and PCB synthesis tool for digital microfluidic biochips

This paper describes a publicly available, open source software framework designed to support research efforts on algorithms and control for digital microfluidic biochips (DMFBs), an emerging laboratory-on-a-chip (LoC) technology. The framework consists of two parts: a compiler, which converts an assay, specified using the BioCoder language, into a sequence of electrode activations that execute out the assay on the DMFB; and a printed circuit board (PCB) layout tool, which includes algorithms to reduce the number of control pins and PCB layers required to drive the chip from an external source. The framework also includes a suite of visualization tools for debugging, and a collection of front-end algorithms that generate mixing/dilution trees for sample preparation.

Interpreting Assays with Control Flow on Digital Microfluidic Biochips

BioCoder is a C++ library developed at Microsoft Research, India, for the unambiguous specification of biochemical assays. This article describes language extensions to BioCoder along with a compiler and runtime system that translate and execute assays specified using BioCoder on a software simulator. The simulator mimics the behavior of laboratories-on-a-chip (LoCs) based on a droplet actuation technology called electrowetting on dielectric (EWoD). To date, prior compilers targeting similar EWoD devices are limited to assays specified as directed acyclic graphs (DAGs) and cannot handle arbitrary control flow or feedback from the LoC. The framework presented herein addresses these challenges through dynamic interpretation, thereby enlarging the space of assays that can be compiled onto EWoD devices.

A Low-Cost Field-Programmable Pin-Constrained Digital Microfluidic Biochip

This paper introduces a field-programmable pin-constrained digital microfluidic biochip (FPPC-DMFB), which offers general-purpose assay execution at a lower cost than general-purpose direct addressing DMFBs and highly optimized application-specific pin-constrained DMFBs. One of the key cost drivers for DMFBs is the number of printed circuit board (PCB) layers, onto which the device is mounted. We demonstrate a scalable single-layer PCB wiring scheme for several FPPC-DMFB variations, for PCB technology with orthogonal routing capacity of at least three; for PCB technology with orthogonal capacity of two, more PCB layers are required, but the FPPC-DMFB retains its cost advantage. These results offer new insights on the relationship between PCB layer count, pin count, and cost. Additionally, to reduce the execution time of assays on the FPPC-DMFB, we present efficient algorithms for droplet routing, with and without contamination removal via wash droplets.