A novel biohybrid electronic device architecture for environmental and physiological sensing
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Biological Sciences
Abstract
The Bacterial Flagellar Motor is one of nature's rare rotary molecular machines. It enables bacterial swimming and is a key part of the bacterial chemotactic network that enables bacteria to direct their movement given the chemical environment. This network is one of the best-studied chemical signalling networks in biology, sensing down to nanomolar concentrations of specific chemicals on the time scale of seconds. The motor's rotational speed is linearly proportional to the bacterial electrochemical gradients, most notably of proton or sodium ions, while its direction is regulated by the chemotactic network. Recently, it has been discovered that the motor is also a mechanosensor. Given these properties, the motor has the potential to serve as a multimodal biosensor with unprecedented speed and sensitivity, and thus a tool for characterizing and studying the external environment, but also bacterial physiology itself. However, at the resolution needed, motor speed and rotational direction are currently detected optically, one motor at a time. A step-change in harnessing the unprecedented potential of this rotary molecular machine would be to detect each motor's rotation electrically and with high throughput. Here I propose to achieve this by specifically attaching individual bacteria to a precise location on the surface and testing two electrical means of detecting the motor's rotation: an integrated circuit and a graphene surface. The detection method will also be employed to fully characterize the three different sensing modalities offered by the flagellar motor: that of cells own physiology, of mechanical forces and of a given set of chemicals. The success of the project we will enable portable biosensor-on-a-chip configuration of the motor speed and rotational direction detection, which can be a game-changer in the biosensing field.
Publications
Lo W
(2024)
Bacterial Electrophysiology
in Annual Review of Biophysics
Terradot G
(2024)
Escherichia coli Maintains pH via the Membrane Potential
in PRX Life
Related Projects
| Project Reference | Relationship | Related To | Start | End | Award Value |
|---|---|---|---|---|---|
| EP/V03264X/1 | 01/12/2021 | 28/02/2025 | £1,514,120 | ||
| EP/V03264X/2 | Transfer | EP/V03264X/1 | 01/03/2025 | 30/11/2026 | £561,628 |
| Description | We have demonstrated that we can electrically detect the rotation of the bacterial flagellar motor. Doing so is the basis of a novel class of biosensors. We have also demonstrated that any thus far built whole-cell biosensor can be successfully 'wired' to the motor, so that biosensor output is a change in the direction of flagellar motor rotation, rather than the standard fluorescent protein. Such new sensor has a tunable sensitivity range, which we also demonstrated theoretically and experimentally. |
| Exploitation Route | We are anticipating spinning out a company in March 2025. |
| Sectors | Aerospace Defence and Marine Agriculture Food and Drink Chemicals Digital/Communication/Information Technologies (including Software) Electronics Environment Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| URL | https://www.labnews.co.uk/article/2094225/outsmarting-contaminants |
| Description | The findings are anticipated to be the basis of a spinout. The spinout is anticipated for May 2025 and the team is currently in the process of approaching the investors in order to secure the funding. It is also anticipated that this type of research might inform responsible innovation and regulatory practices of similar technology. |
| First Year Of Impact | 2024 |
| Sector | Aerospace, Defence and Marine,Agriculture, Food and Drink,Chemicals,Construction,Digital/Communication/Information Technologies (including Software),Electronics,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal Economic Policy & public services |
| Description | CONACYT PhD Scholarship |
| Amount | £49,830 (GBP) |
| Organisation | National Council on Science and Technology (CONACYT) |
| Sector | Public |
| Country | Mexico |
| Start | 01/2023 |
| End | 01/2025 |
| Description | High Growth Spin-out Programme - Opportunity Qualification |
| Amount | £74,635 (GBP) |
| Funding ID | PS7305112C |
| Organisation | Scottish Enterprise |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2022 |
| End | 11/2023 |
| Description | High Growth Spinout Programme - Company Creation |
| Amount | £199,042 (GBP) |
| Funding ID | PS7305112C |
| Organisation | Scottish Enterprise |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2024 |
| End | 02/2025 |
| Description | IBioIC Spin-Out Feasibility Project |
| Amount | £18,888 (GBP) |
| Funding ID | FF-2022-08 |
| Organisation | IBioIC |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2022 |
| End | 03/2023 |
| Description | ICURe Market Traction |
| Amount | £7,500 (GBP) |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2024 |
| End | 05/2024 |
| Description | Innovation to Commercialisation of University Research (ICURe) |
| Amount | £50,646 (GBP) |
| Funding ID | 38-11 / 520954119 |
| Organisation | SETsquared Partnership |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 11/2021 |
| End | 05/2022 |
| Description | University of Edinburgh Venture Builder Incubator Programme |
| Amount | £23,500 (GBP) |
| Organisation | University of Edinburgh |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2024 |
| End | 03/2025 |
| Title | µm-sized PDMS microfluidic device handling tool |
| Description | While PDMS microfluidic devices have microscale dimensions for the fluidic path, the devices themselves are usually cm-scale. So the device building processes like cutting, aligning and sticking of multiple layers of PDMS are suited for cm-scale devices and are usually done by hand or using simple tools. We developed a tool using micrometre stages and 3D printed blocks to cut out PDMS microfluidic layers as small as 100µm with µm precision under a stereoscope. This same device with a change in the arm can align microfluidic layers with microscale precision. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | This tool has allowed us to make a microfluidic device that could fit onto a 1mmx2mm integrated circuit with delicate wire bonds around it. Only a µm precisely cut microfluidic device with 100s of µm width could be made to fit onto the IC and allow control the volume and flow of liquid onto and away from the surface of interest on the IC. |
| Description | Collaboration with Chris Wood, University of Edinburgh |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We will be testing the strains with novel chemoreceptors as well as participating in their design. These strains can offer new sensing capabilities. |
| Collaborator Contribution | Chris' las has contributed knowhow in protein design to be able to develop strains with new sensing capabilities. |
| Impact | This collaboration is resulting in joint work and expected to lead to joint patents, publications and further grant applications. |
| Start Year | 2022 |
| Description | Collaboration with Michel Maharbiz at UC Berkeley |
| Organisation | University of California, Berkeley |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have tested the IC designed and produced by the collaborator and demonstrated that it can detect the rotation of bacterial flagellar motor on a single cell level. |
| Collaborator Contribution | The collaborator Michel Maharbiz, at the University of California Berkeley, and his lab have produced an integrated circuit with small electrodes for the detection of bacterial flagellar motor and fabricated by a commercial silicon foundry. The design drastically increases the frequencies across which perform spectroscopy (into the MHz range), significantly increasing the signal-to-noise ratios and the sensitivity with which we can detect the motor rotation. This first integrated circuit was taped out on the TSMC 0.18 UM CMOS High Voltage Mixed Signal based LDMOS FSG Al 1P6M 1.8/5/32V. It also contains several test circuits that allow for measurement of electrical impedance across electrodes at frequencies up to 1 MHz. The collaborator also contributed knowhow to testing the IC. |
| Impact | This partnership has resulted in a patent that is currently in submission. It is also expected to result in at least one joint publication. Lasty, it has resulted in establishment of another collaboration with a USA university. |
| Start Year | 2021 |
| Description | Collaboration with Soner Sonmezoglu, at Northeastern University, Boston |
| Organisation | Northeastern University - Boston |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Our team has demonstrated the capability of the IC developed in Michel Maharbiz lab to detect the rotation of bacterial flagellar motor on a single cell level. |
| Collaborator Contribution | Soner and his growing lab have contributed knowhow (especially during a visit to University of Edinburgh in 2022) to the testing of the IC circuit for bacterial flagellar motor detection. Soner was a postdoc in Michel Maharbiz lab and this is a collaboration with his newly established lab. |
| Impact | This collaboration has resulted in a patent that is currently filled. It will result in at least one publication and is expected to result in further joint NSF-EPSRC funding applications. |
| Start Year | 2021 |
| Title | Bioelectrical interface via bacterial flagellar motor |
| Description | The innovation is a biohybrid electronic device architecture that can be used for environmental and physiological sensing. The design is based on the rotation of bacterial flagellar motor (BFM). The motor is a unique rotary molecular machine whose evolutionary function is to enable the propulsion of the bacterium by rotating the flagellum. Because of its evolutionary function, the motor can serve as a multimodal sensor. Specifically, it can be used as a non-invasive single cell voltmeter (where it measures the electrochemical gradient of the cell itself), a mechanosensor for a viscous load or flow detection, and a chemosensor allowing detection of specific molecules. The sensor's response time and sensitivity can be up to seconds and down to nM concentrations, where the relevant output for a given sensing modality is either the motor's rotational speed or direction. Currently, available techniques to measure individual motor speed and direction, while high in spatiotemporal resolution, are low in throughput, complex to build and rely on optical detection. The innovation fully harnesses the BFM's sensing capability by measuring the rotation of the BFM electrically, in individual cells but with high throughput. |
| IP Reference | 2400532.4 |
| Protection | Patent / Patent application |
| Year Protection Granted | 2024 |
| Licensed | No |
| Impact | The technology is planned to be licensed to a new spinout company. The company is expected to spinout in the first half of 2025. |
| Title | DeLTASpin |
| Description | This software is an adaptation of the DeLTA image processing pipeline (O'Connor et al., 2022), originally built to segment and track cells growing on a surface. Our adaptation makes it suitable for tracking bacterial cells in high-frame rate recordings of cells rotating on a surface. |
| Type Of Technology | Software |
| Year Produced | 2024 |
| Impact | This software is used to quickly analyse the response of bacterial cells that act as the sensing unit, thus speeding up sensing strain design. |
| Description | Presentation to Regulatory Horizons Council workshop. |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | I gave a presentation to a Regulatory Horizons Council (RHC) working group workshop on the future of regulation of genetically modified and bioengineered microorganisms. This was held at the National Physical Laboratory and was to an audience of RHC members, civil servants (from Defra, DSIT, etc), and representatives from various interested national bodies (e.g. Environment Agency, Food Standards Authority, National Physical Laboratory). I presented our research as a case study for how developments in Engineering Biology require new thinking on regulation, then participated in the workshop discussion. |
| Year(s) Of Engagement Activity | 2024 |
| Description | Presented work at Cambridge Bioelectronics Symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | I presented a poster on my research activities. People showed a lot of interest in the project and also remarked on the difficulty of it. I had a discussion with one of the experts who worked on high conductivity interfaces for bioelectronic interfaces on the possible benefits in our technology, which made clear that it would not help in this device. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://bioelectronics.eng.cam.ac.uk/symposium-information |
| Description | Technology end-user engagement exercise |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | A concerted program over 4 months of arranging 1-to-1 and group meetings, plus attendance at conferences and workshops (online + in-person) to describe our technology, and to learn where our technology could be useful, and what the needs are of potential end-users of our technology. This resulted in us disseminating the potential for our technology to be used by various industries. It also expanded our knowledge of the various application spaces in which our technology could be deployed. It led directly to offers of collaboration, funding, and support, most of which we are still following up on. |
| Year(s) Of Engagement Activity | 2021,2022 |
| Description | Technology end-user engagement visit (aquaculture) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | A targeted program of visits to engage with the aquaculture sector in Norway. This was a series of 1-to-1 and small group meetings with key technology developers, innovation leads, industry professionals and academics in the aquaculture sector in Bergen. The purpose was to describe our technology, and to learn where and how our technology could be useful in the aquaculture sector, and what the needs are of potential end-users of our technology. This resulted in us disseminating the potential for our technology to be used in this industry, expanded our knowledge of how our technology could be used specifically in the industry, as well as leading to direct offers of future engagement. |
| Year(s) Of Engagement Activity | 2024 |