Joanne Macdonald*1,2


1. Genecology Research Centre, Inflammation and Healing Research Cluster, and School of Science and Engineering, University of the Sunshine Coast, QLD, Australia
2. Division of Experimental Therapeutics, Department of Medicine, Columbia University, NY, USA


Molecular computing is highly relevant for the design of light-weight biosensors that can process biomolecular information without requiring batteries or wires. Previously, molecular computers made from molecular logic gates were shown to play games interactively with a human opponent. This generic technology can be applied for the detection of nearly any nucleic acid sequence. To demonstrate, the gates were adapted to analyse disease nucleic acids such as Ebola and Marburg viruses, and display diagnoses in dot-matrix text without requiring any post-processing of results (Figure 1A). The underlying use of molecular logic gates is critical for diagnosis, as the gates can be pre-programmed to respond selectively to a panel of biomarkers using layers of the basic logic functions AND, NOT, and OR. The embedded display concept was subsequently adapted for multiplex analysis of biomarkers on a lateral-flow device, using the principles of binary and molecular encoding. The resultant device contains an embedded 7-segment display that can be pre-programmed to display the numbers 0-9 in response to the presence of biomarkers (Figure 1B). This 7-segment display lateral flow device is also generic and can be used for detection of many different biomarkers without requiring reconfiguration of the manufacturing protocol, because the encoding is performed using simple sample-side pre-processing.  Importantly, when integrated with isothermal amplification technologies, nucleic acids can be sensitively and rapidly detected in multiplex format. This technology thus provides a pathway to sensitive, rapid, lightweight and easy-to-interpret multiplex disease diagnosis without requiring external readers to interpret signals.

Figure 1. (A) A circuit board of molecular logic gates (left) enables solution-phase fluorogenic displays able to discriminate Ebola and Marburg virus nucleic acid sequences (right). (B). Binary and molecular encoding (right) enables displays showing the numbers 0-9 (left) for sensitive and specific nucleic acid detection