Tackling Global Health Challenges with Cell-Free Synthetic Biology: New Technologies for Rapid, on-Demand Water Quality Monitoring

Recent advances in cell-free synthetic biology have enabled the development of powerful new diagnostic technologies. These technologies leverage the ability of cell-free systems to support natural and engineered biosensing mechanisms to create detectable signals when target analytes are present. The ability to freeze-dry these systems for long-term storage and distribution prior to rehydrating with test samples has enabled the development of rapid, low-cost and programmable point-of-use diagnostics for a range of important targets of global health concern, with particular successes in nucleic acid diagnostics for pathogens and human health biomarkers. Here, we present our work on expanding the reach of cell-free, synthetic biology-enabled diagnostics by developing several platforms for the detection of toxic contaminants - including heavy metals, halides, drugs, pesticides, and personal care products - in aqueous samples. Our technologies combine several new innovations in biosensor programming, including protein and RNA-gated inducible regulators that sense a range of targets, RNA-level outputs for enhanced detection speed, downstream genetic circuit computation for signal processing, and coupling to metabolic bioconversion to expand the sensing repertoire. We have also partnered with global health and water experts to field-test these platforms by detecting both heavy metal contamination caused by wildfires in Paradise, CA as well as endemic fluoride contamination of freshwater in Costa Rica. Collectively, our work is enabling the transition of technologies from the lab into the real-world where they are needed most and will help achieve progress towards the United Nations Sustainable Development Goal 6 ensuring access to clean water across the globe. We hope that lessons learned will help the community to demonstrate the power of cell-free synthetic biology to solve major global challenges.