A Synthetic Biology Approach to Developing Optical NanoAnalytics

Project Information

NanoBiOptics

Grant agreement ID: 853005

DOI

10.3030/853005

Project closed

EC signature date 8 November 2019

Start date 1 October 2020

End date 30 September 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 499 495,00

EU contribution

€ 1 499 495,00

Coordinated by

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Switzerland

Periodic Reporting for period 2 - NanoBiOptics (A Synthetic Biology Approach to Developing Optical NanoAnalytics)

Reporting period: 2022-04-01 to 2023-09-30

Summary of the context and overall objectives of the project

Single-walled carbon nanotubes (SWCNTs) emit stable light that is ideal for optical sensing applications. This light can optically penetrate biological tissue and most opaque materials, allowing them to be imaged inside the human body. Since this light responds to changes on the SWCNT’s environment, we can monitor different interactions on the SWCNT surface by characterizing the light that the SWCNT emits. However, these interactions are non-specific, and the primary challenge is to engineer the surface of the SWCNTs so that the emitted light responds only to the specific molecule(s) that one wants to detect.

The ability to control interactions on the surface of SWCNTs is critical for engineering sensors that are selective. This control allows one to create sensors that respond to specific analytes and markers for various diseases. These sensors are therefore important for enabling new, non-invasive diagnostics for detecting diseases and toxins.

The overall objective of this project is to control the surface interactions through bioengineering. The project focuses on leveraging the exceptional selectivity and tunability of biomolecules to engineer the light response of these sensors.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The project has made several key advancements in the bioengineering of SWCNT sensors. Our lab has established a new protocol that is inspired by the 2018 Nobel Prize approach to control the emitted light response of SWCNTs through DNA-engineering. We have engineered DNA-wrapped SWCNTs that respond selectively to specific food toxins. Through machine learning, we were able to develop a model for predicting new DNA sequences for improving the performance of these sensors.

We also engineered sensors based on artificial DNA, xeno nucleic acids (XNAs). DNA-wrapped SWCNTs can respond non-selectively to changes in pH and salt. The XNA sensors developed in this project restrict these non-selective responses. This advancement allowed us to develop a sensor that selectively responds to a cancer-associated biomolecule without an interfering response from changes in pH. We successfully used these sensors to detect this biomolecule in cancer cells.

In addition to DNA, we have developed sensors based on protein-wrapped SWCNTs. We developed a method for linking proteins to SWCNTs. We were able to monitor activity of the linked protein by monitoring the light emitted by the SWCNT. We have applied these advancements to create an optical glucose sensor that can be used to monitor blood sugar levels of diabetics.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project has made significant advancements on all fronts that go well beyond the state-of-the-art. Prior to this work, researchers were limited to low-performance DNA-wrapped sensors that they would find from a randomly checking a few different DNA sequences. This approach provided no means of creating sensors that respond to specific analytes of interest and no way of effectively improving the properties of existing sensors. The approach developed in this project allows researchers to control the light response of these sensors. Notably, it provides a way of creating and improving sensors in a more predictable and rational manner.

In addition, our advancements in XNA-wrapped SWCNTs allow us to further demonstrate sensors that are stable against undesired secondary effects. This resilience makes these XNA-based sensors more selective and robust compared to the state-of-the-art DNA-based sensor. This advancement allowed us to create the first optical SWCNT-based sensor for a specific cancer-related biomolecule.

The advancements in protein-based SWCNT sensors also go beyond the state-of-the-art. This project demonstrates for the first time the application of newly discovered chemical approaches to detect protein activity. We were able to monitor the proteins response to specific molecules of interest by monitoring the light emitted by the SWCNT. In this way, we were able to use the light to not only directly measure the protein’s response, but also indirectly detect the molecules to which they respond. The optical response of this sensor was further found to exceed that of the analogous sensor based on the previous state-of-the-art chemical approach.

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