Advancing Cell-free Biocomputing

Researchers from the University of Minnesota have published a study in Nature Communications introducing a new biocomputing method, Transcriptional RNA Universal Multi-Purpose GatE PlaTform (Trumpet), which leverages biological enzymes as catalysts for DNA-based molecular computing. This innovative approach has the potential to address challenges in interfacing traditional computer hardware with living organs, a significant limitation in the development of medical devices.

Biocomputing has been typically conducted using live cells or non-living, enzyme-free molecules. While live cells offer self-sustenance and healing capabilities, they are difficult to repurpose for computation. Conversely, non-living molecules provide a simpler solution but suffer from weak output signals and difficulties in regulation.

The Trumpet platform, however, combines the simplicity of molecular biocomputing with enhanced signal amplification and programmability. The researchers demonstrated that the platform is capable of encoding all universal Boolean logic gates (NAND, NOT, NOR, AND, and OR), which are fundamental to programming languages. These logic gates can be stacked to create more complex circuits. Additionally, the team developed a web-based tool to facilitate the design of sequences for the Trumpet platform.

Co-author Kate Adamala, an assistant professor in the College of Biological Sciences, explains that Trumpet is a non-living molecular platform, avoiding many of the problems associated with live cell engineering. This provides the platform with greater stability and reliability, as well as overcoming leakage issues commonly found in live cell operations.

Although Trumpet is still in the experimental phase, it has immense potential for future applications, such as neural implants, nerve damage repair, prosthetic control, and even more advanced uses like augmented memory. Lead author Judee Sharon, a Ph.D. candidate, is currently exploring Trumpet for early cancer diagnosis applications. Another potential use lies in "theranostics," which combines diagnostics and therapeutics within the body, enabling biological circuits to detect and respond to medical conditions like low insulin levels in diabetes patients.

This development in biocomputing signifies a promising step forward in molecular computing, with the potential to revolutionize medicine, diagnostics, and computing applications in the future.

Topics: Tools & Methods