Researchers are developing computational elements and systems based on nucleic acids for use in biodetection applications. The elements are based on oligonucleotides (short single-strands of DNA) and deoxyribozymes (oligonucleotides that enzymatically act on other oligonucleotides). These elements are organized into information-processing systems as gates, cascades, amplifiers, and larger application-specific circuits.
Biodetection applications of the elements and systems being developed include gene expression profiling (in basic molecular biology research), human genetic screening (in public health), pathogen detection (in containment of infectious diseases in the field), and civil defense (in rapid detection of bioterrorism). The direct display devices the researchers are developing provide a read-out that is easy to interpret without specialist training and allows immediate practical decisions to be made; for instance, in the field, health care providers can select individual patient treatment, and public health professionals can select options for containment of infectious disease outbreaks.
Researchers are solving four practical problems. To reduce the expense of laboratory implementation procedures, they are studying oligonucleotide interaction models and devising libraries for modular circuit construction. To make the information-processing components interface to the relevant biodetection applications, they are building robust and selective biosensor modules. To make the visual display of biodetection results easy to use, they are experimenting with different display designs, with encoding schemes based on colors and patterns, including alphanumerics. Finally, to make the deployment of devices practical, they are establishing clear and easy to follow procedures for integrating with specific biological applications.
As a prototype, researchers are developing a biodetector for the class of mosquito-borne flaviviruses. The prototype allows identification of at least 11 different flavivirus species, among them the Yellow Fever virus and the West Nile virus, using equipment that is readily deployable in the field.
Miniaturizing computational systems to the nano-scale using biological components is readily achievable using recent advances in molecular technologies. Yet as system size decreases, our ability to monitor the success of computational events requires increasingly sophisticated technologies to provide an interface between the nano-scale and the everyday, usually by translating molecular events into electronic-decipherable signals. In this project we developed a visual display platform that operates analogously to electronic displays but is driven by molecules rather than electricity and wires. Our system uses molecular logic gates to interpret coded input nucleic acid mixtures and produce a fluorescent output of results. Highlights of our work include the demonstration of a molecular 7-segment display circuit, and a molecular calculator able to add and multiply the numbers 1, 2 and 3. While these display circuits do not match electronic displays in terms of speed and dynamic states, their modularity and static read-out is relevant in a variety of applications, including diagnostics. To demonstrate diagnostic potential, we constructed prototype automaton able to detect signature 15-mer sequences found in three pathogens, correctly diagnosing sequence identities as West Nile, St Louis Encephalitis, and Yellow Fever viruses by displaying a W, S or Y in a 5x3 dot matrix fluorescent display. We also demonstrate two-colour graphics processing units able to distinguish Ebola and Marburg viral signature sequences, displaying a green E or a pink M as a read-out. Finally we demonstrated a fully-featured Lyssavirus automaton engineered to account for genetic variability of viral families. Our demonstrated circuits represent the first simple graphics processing units and outputs for an integrated molecular computing platform that is minimally reliant on electronics. While in the short-term our displays are necessarily photographed and converted to electronic digital forms for long-term storage, ultimately they provide a read-out potential for alternative molecular data storage devices that need not require electronics to operate. They also demonstrate the engineering potential now available to build molecular systems on the nano-scale that are analogous to, but devoid of, electronic components.
