Digital microfluidic biochips

Abstract

The 2010 International Technology Roadmap for Semiconductors (ITRS) predicted that bio-medical chips will soon revolutionize the healthcare market. These bio-medical chips should be able to sense and actuate, store and manipulate data, and transmit information. To realize such bio-medical chips, the integration of embedded systems and microfluidics inevitably leads to a new research dimension for More than Moore and beyond. This tutorial will introduce attendees to the emerging technology of digital microfluidics, which is poised to play a key role in the transformation of healthcare and the interplay between biochemistry and embedded systems. Advances in droplet-based “digital” microfluidics have led to the emergence of biochip devices for automating laboratory procedures in biochemistry and molecular biology. These devices enable the precise control of nanoliter-volume droplets of biochemical samples and reagents. Therefore, integrated circuit (IC) technology can be used to transport and transport “chemical payload” in the form of micro/nanofluidic droplets. As a result, non-traditional biomedical applications and markets (e.g., high-throughout DNA sequencing, portable and point-of-care clinical diagnostics, protein crystallization for drug discovery), and fundamentally new uses are opening up for ICs and systems. However, continued growth (and larger revenues resulting from technology adoption by pharmaceutical and healthcare companies) depends on advances in chip integration and design-automation tools. In particular, design-automation tools are needed to ensure that biochips are as versatile as the macro-labs that they are intended to replace. This is therefore an opportune time for the semiconductor industry and circuit/system designers to make an impact in this emerging field. This tutorial offers attendees an opportunity to bridge the semiconductor ICs/systems industry with the biomedical and pharmaceutical industries. The audience will see how a “biochip compiler” can translate protocol descriptions provided by an end user (e.g., a chemist or a nurse at a doctor's clinic) to a set of optimized and executable fluidic instructions that will run on the underlying digital microfluidic platform. Testing techniques will be described to detect faults after manufacture and during field operation. Sensor integration and close coupling between the underlying hardware and the control software in a cyberphysical framework will also be described. A number of case studies based on representative assays and laboratory procedures will be interspersed in appropriate places throughout the tutorial. Commercial devices and advanced prototypes from the major company in this market segment (Advanced Liquid Logic, Inc.) will be described, and ongoing activity on newborn screening using digital microfluidic biochips at several large hospitals in Illinois will be highlighted. The topics covered in the tutorial include the following: 1) Technology and application drivers: Motivation and background, actuation methods, electrowetting and digital microfluidics, review of micro-fabrication processes, applications to biochemistry, medicine, and laboratory procedures. 2) System-level design automation: Synthesis techniques: scheduling of fluidic operations, resource binding (mapping of operations to on-chip resources), module placement. 3) Physical-level design automation: droplet routing, defect tolerance, chip-level design, and design of pin-constrained biochips. 4) Testing and design-for-testability: Defects, fault modeling, test planning, reconfiguration techniques, sensor integration and cyberphysical system design.