Cascaded amplifying circuits enable ultrasensitive cellular sensors for toxic metals

Xinyi Wan, Francesca Volpetti, Ekaterina Petrova, Christopher French, Sebastian J. Maerkl, Baojun Wang

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Cell-based biosensors have great potential to detect various toxic and pathogenic contaminants in aqueous environments. However, frequently they cannot meet practical requirements due to insufficient sensing performance. To address this issue, we investigated a modular, cascaded signal amplifying methodology. We first tuned intracellular sensory receptor densities to increase sensitivity, and then engineered multi-layered transcriptional amplifiers to sequentially boost output expression level. We demonstrated these strategies by engineering ultrasensitive bacterial sensors for arsenic and mercury, and improved detection limit and output up to 5,000-fold and 750-fold respectively. Coupled by leakage regulation approaches, we developed an encapsulated microbial sensor cell array for low-cost, portable and precise field monitoring, where the analyte can be readily quantified via displaying an easy-to-interpret volume bar-like pattern. The ultrasensitive signal amplifying methodology along with the background regulation and the sensing platform will be widely applicable to many other cell-based sensors, paving the way for their real-world applications.
Original languageEnglish
Pages (from-to)540–548
Number of pages9
JournalNature Chemical Biology
Publication statusPublished - 25 Mar 2019

Keywords / Materials (for Non-textual outputs)

  • cell-based sensor
  • signal amplification
  • sensor cell array
  • synthetic biology
  • arsenic
  • toxic metals
  • mercury


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