Synthetic Biology Enables Programmable Cell‐Based Biosensors

Abstract

Cell‐based biosensors offer cheap, portable and simple methods of detecting molecules of interest but have yet to be truly adopted commercially. Issues with their performance and specificity initially slowed the development of cell‐based biosensors. With the development of rational approaches to tune response curves, the performance of biosensors has rapidly improved and there are now many biosensors capable of sensing with the required performance. This has stimulated an increased interest in biosensors and their commercial potential. However the reliability, long term stability and biosecurity of these sensors are still barriers to commercial application and public acceptance. Research into overcoming these issues remains active. Here we present the state‐of‐the‐art tools offered by synthetic biology to allow construction of cell‐based biosensors with customisable performance to meet the real world requirements in terms of sensitivity and dynamic range and discuss the research progress to overcome the challenges in terms of the sensor stability and biosecurity fears.

Advances in Cell‐Free Biosensors: Principle, Mechanism, and Applications

“…[ 34 ] Second, optimizing transcription factor concentration can reduce the LOD of the sensor. [ 9 ] Third, selecting the appropriate promoter, RBS, and degradation tags can reduce the expression and improve the dynamic range of the cell‐free biosensors to improve the response of them. [ 50 ] Finally, Pandi et al.…”

“…Synthetic biology has great potential in the application of biosensors by designing genetic circuits and logic operations for biological components, resulting in a variety of genetic devices and biological modules. [ 7 – 9 ] It has promoted the construction of customized biological function system, which can finally realize sensors with customized programming sensitivity, specificity and dynamic range, and expand the scope of sensor detection target, [ 10,11 ] providing transformative tools for improving the performance of biosensors.…”

“…[ 12 ] Moreover, the sensitivity and specificity of biosensors can be improved by the introduction of corresponding genetic modules. [ 9,13 ] Heavy metals, pesticides, vitamins, and some macromolecules can be detected using cell biosensors. For example, Wang et al.…”

Computer-Aided Whole-Cell Design: Taking a Holistic Approach by Integrating Synthetic With Systems Biology

“…The application of WCMs to the design, prototyping and testing of whole-cell biosensors could suggest rational approaches to tune their sensitivity, stability, and dynamic range while facilitating the choice of the ideal chassis and, if needed, guide its re-engineering to optimize biosensor performance ( Hicks et al, 2020 ). If WCMs become available for different chassis and entire organisms, they could also support the design of optimized targeted delivery of genetically encoded biosensors.…”

Biological Materials: The Next Frontier for Cell-Free Synthetic Biology

“…Ultimately, the synthetic biology approach is geared toward the rational engineering or repurposing of biological parts, devices and systems into solutions that can help address societal challenges (Ausländer et al, 2017). Synthetic biologists envision a broad application space for the field and anticipate positive societal impacts in medical technologies (Pardee, 2018;Hicks et al, 2020) (e.g., biosensors and therapeutics), food security and sustainable energy (Russo et al, 2019;Roell and Zurbriggen, 2020) (e.g., biofuels and synthetic photosynthesis), bioremediation (Dvořák et al, 2017;Wan et al, 2019) (e.g., pollution monitoring and sequestration), education (Kelwick et al, 2015a;Huang et al, 2018;Dy et al, 2019) (e.g., iGEM competition) and biomanufacturing (Le Feuvre and Scrutton, 2018;Choi K.R. et al, 2019;Gilbert and Ellis, 2019;Roberts et al, 2019) (e.g., fine chemicals and materials production).…”