Applied Design

The Sensynova Biosensor Development Platform provides an elegant solution to various problems with current biosensor development and deployment, with these issues being the reasons behind the underuse of synthetic biology biosensors

Summary

• We have designed a modular, multicellular biosensor development platform
• We have looked at the problem of lack of synthetic biology biosensors used in everyday life
• We have evaluated the problems with whole cell biosensors e.g. such as lack of reusability, and addressed these problems with our design e.g. the ability to switch in-switch out different parts without further engineering
• The integration of this platform into current development and possible disruption
• The benefits of the lifecycle of this product for our lives and the environment

How the design of Sensynova solved a real-world problem

Synthetic biology biosensors have many advantages over their alternatives (e.g. mass spectrometery machines) such as the low level of equipment required for sensing, as well as their portability in the field. However, their potential is not being fully exploited for many reasons investigated in our human practices.

At the beginning of the design process of a product to aid biosensor development, we researched how biosensors are currently developed. We found that parts were rarely reused between designs, since biosensor components are typically tightly coupled in a single cell type. It was also found that a great deal of effort was required to optimise biosensors and tune their characteristics. We wanted to develop a more convenient, modular approach to facilitate reuse and ease the optimisation process.

Therefore, we propose an alternative, multicellular system for biosensor development with off-the-shelf, modular components. Novel biosensors can be developed simply by mixing three different cell types; a detector, processor and reporter. The biosensor response characteristics can be tuned simply by mixing different ratios of the three cell types.

This design paradigm is a product of iGEM projects of previous years and is steeped in the findings of 121 other iGEM sensors. We conducted a systematic review of all biosensors previously made in iGEM to identify design patterns. We showed how other tightly coupled designs could be converted to our modular framework. We also designed and implemented a range detectors, processors and reporters for others to use.

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Sensynova vs alternatives

Sensynova has no comparable platform as it is a truly innovative design paradigm. The alternative to this method of biosensor design is the genetic engineering of whole cell biosensors. As biosensor components are typically tightly coupled in a single cell type, it would require extensive engineering to optimise biosensors and tune their characteristics. To optimise a Sensynova biosensor, a simple reculturing of modules is needed to test and find the best variation of parts. Once this is found, the variant chose could be express in a whole cell biosensor or in a cell-free system. We have designed and created an optimised cell free system to facilitate this process.

Integration

To confirm that our design could successfully be applied to all biosensor systems, we looked back at our systematic review of all biosensors previously made in iGEM to identify design patterns. We also designed and implemented a range detectors, processors and reporters for others to use. This produced a biosensor development ‘kit’ where we designed and characterised many different modules for biosensor developers to use so they can look through our library of parts and test many variants of their biosensor without further genetic engineering. This allows our platform to be integrated into the biosensor development system.

To demonstrate how other biosensors can be designed to fit our system, we took the arsenic biosensor, created by Edinburgh 2006, and the psicose biosensor, created by Evry-Paris 2017, and designed their detector modules to fit our system.

We did this to show that working biosensors could be integrated into our system, as the only engineering step is the design a new detector each time. We also designed an adapter module to show how we can integrate other substrates into our system. Our chosen substrate was Glyphosate, a herbicide, which has no known binding sequence; we identified the C-P Lyase pathway in E. coli that breaks down Glyphosate to Sarcosine to Formaldehyde, which has a known biosensor.

Figure 3: Biochemical pathway of the degradation of glyphosate to glycine and formaldehyde.

One disruption would be any sensor that detected quorum sensing molecules as our system uses these molecules as biological ‘wires’ and so we couldn’t adapt this system be used to sense them.

Impact of our design solution for the wider world

We hope our approach will lead to the more rapid, cost-effective and efficient development of a new kind of multicellular biosensor that will ultimately impact on human health, the environment and industrial processes to name but few. The lifecycle of the product would further benefit biosensors as it would identify new problems, maybe not addressed by this current version that could be solved in the future. Our lives would undoubtedly benefit from biosensors involved in diagnostics such as and the environment through biosensors such as the arsenic biosensor, which can detect arsenic contamination in water, helping save wildlife as well as human life. The use of this system and the commitment to solving the problems it identified can lead to a new era of biosensors which can be used to aid all.