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

10 25 50
 
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 IBioIC Spin-Out Feasibility Project
Amount £18,888 (GBP)
Funding ID FF-2022-08 
Organisation IBioIC 
Sector Academic/University
Country United Kingdom
Start 08/2022 
End 03/2023
 
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 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
 
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