DNA-enabled integrated molecular systems for computation and sensing.

CONSPECTUS: Nucleic acids have become powerful building blocks for creating supramolecular nanostructures with a variety of new and interesting behaviors. The predictable and guided folding of DNA, inspired by nature, allows designs to manipulate molecular-scale processes unlike any other material system. Thus, DNA can be co-opted for engineered and purposeful ends. This Account details a small portion of what can be engineered using DNA within the context of computer architectures and systems. Over a decade of work at the intersection of DNA nanotechnology and computer system design has shown several key elements and properties of how to harness the massive parallelism created by DNA self-assembly. This work is presented, naturally, from the bottom-up beginning with early work on strand sequence design for deterministic, finite DNA nanostructure synthesis. The key features of DNA nanostructures are explored, including how the use of small DNA motifs assembled in a hierarchical manner enables full-addressability of the final nanostructure, an important property for building dense and complicated systems. A full computer system also requires devices that are compatible with DNA self-assembly and cooperate at a higher level as circuits patterned over many, many replicated units. Described here is some work in this area investigating nanowire and nanoparticle devices, as well as chromophore-based circuits called resonance energy transfer (RET) logic. The former is an example of a new way to bring traditional silicon transistor technology to the nanoscale, which is increasingly problematic with current fabrication methods. RET logic, on the other hand, introduces a framework for optical computing at the molecular level. This Account also highlights several architectural system studies that demonstrate that even with low-level devices that are inferior to their silicon counterparts and a substrate that harbors abundant defects, self-assembled systems can still outperform conventional systems. Further, the domain, that is, the physical environment, in which such self-assembled computers can operate transcends the usual limitations of silicon machines and opens up new and exciting horizons for their application. This Account also includes a look at simulation tools developed to streamline the design process at the strand, device, circuit, and architectural levels. These tools are essential for understanding how to best manipulate the devices into systems that explore the fundamentally new computing domains enabled by DNA nanotechnology.

A wearable smartphone-based platform for real-time cardiovascular disease detection via electrocardiogram processing.

Cardiovascular disease (CVD) is the single leading cause of global mortality and is projected to remain so. Cardiac arrhythmia is a very common type of CVD and may indicate an increased risk of stroke or sudden cardiac death. The ECG is the most widely adopted clinical tool to diagnose and assess the risk of arrhythmia. ECGs measure and display the electrical activity of the heart from the body surface. During patients' hospital visits, however, arrhythmias may not be detected on standard resting ECG machines, since the condition may not be present at that moment in time. While Holter-based portable monitoring solutions offer 24-48 h ECG recording, they lack the capability of providing any real-time feedback for the thousands of heart beats they record, which must be tediously analyzed offline. In this paper, we seek to unite the portability of Holter monitors and the real-time processing capability of state-of-the-art resting ECG machines to provide an assistive diagnosis solution using smartphones. Specifically, we developed two smartphone-based wearable CVD-detection platforms capable of performing real-time ECG acquisition and display, feature extraction, and beat classification. Furthermore, the same statistical summaries available on resting ECG machines are provided.