Optoelectronic neural probes for in vivo manipulation of neural circuits

Optogenetics has become a powerful tool in neuroscience to study cortical circuit function. It relies on light sensitive proteins (opsins) that act as light switches, turning on or off specific populations of neurons in the brain. A major barrier in the application of optogenetics is the lack of high-density probe devices for precision light delivery across mm-to-cm volumes at depth through the mammalian brain.

We have been developing a multi-site optoelectronic device to solve this problem and deliver spatio-temporal patterns of light across a significant area of the cortex and at 2 independent depths (cortical surface and up to 1mm deep) [1]. However, this device has limitations in that it can only deliver light at one wavelength (l=450nm) and cannot monitor the induced neural activity. These two aspects are a severe limitation as novel optogenetic constructs have emerged that are sensitive to the red part of the visible spectrum and closed-loop neural modulation activity (which requires a method of monitoring neural activity) has become increasingly important as we learn more about brain-wide activity.

This PhD project aims to address this challenge by developing a multi-wavelength optrode array, integrated with a multi-electrodes that will allow a 5x5mm area of the mammalian cortex to be optogenetically manipulated across 181-sites, at 2 wavelengths and with 100 microelectrodes to map the induced activity. The device will enable large-scale, focal, multi-level and multi-colour optogenetic studies allowing the study of neural circuit function. No existing device offers this capability and, as many neurological and psychiatric disorders have been linked to abnormalities in cortical circuits, this technology can improve our understanding of the circuit-level basis of brain disorders.

The developed optical device will consist of a 10×10 array of transparent penetrating optical light guides with a 400mm pitch on top of a novel optical interposer layer used to eliminate optical cross-talk and stray light. This device is bonded to an active substrate containing a matrix-addressed mLED array formed by the transfer-printing of membrane mLEDs emitting at l = 450nm and 630nm. The light from each mLED is coupled through a single optical ‘via’ in the interposer into the optrode light guide. The penetrating optrodes bypass tissue absorption/attenuation limitations in order to reach otherwise optically-inaccessible structures. A second, array of mLEDs can be interleaved and matrix addressed for independent surface stimulation. The transparent conductor, ITO will be used to route electrical connections down the optical needles and connect to tracks that couple into a multi-channel amplifier device for monitoring the electrical activity from the cortical structures (action potential activity and low-frequency potentials).

 [1] McAlinden et al Neurophotonics, Vol. 6, Issue 3, 035010 (August 2019). https://doi.org/10.1117/1.NPh.6.3.035010 

Institute of Photonics: The Institute of Photonics (IoP), part of the Department of Physics, is a centre of excellence in applications-oriented research at the University of Strathclyde. The Institute’s key objective is to bridge the gap between academic research and industrial applications and development in the area of photonics. The IoP is located in the £100M Technology and Innovation Centre on Strathclyde’s Glasgow city centre campus, at the heart of Glasgow’s Innovation District, where it is co-located with the UK’s first Fraunhofer Research Centre. Researchers at the IoP are active in a broad range of photonics fields under the areas of Photonic Devices, Advanced Lasers and Neurophotonics, please see:

http://www.strath.ac.uk/science/physics/instituteofphotonics/ourresearch/.

Strathclyde Physics is a member of SUPA, the Scottish Universities Physics Alliance.

The University of Strathclyde has, in recent years, been the recipient of the following awards: The Queen’s Anniversary Prizes for Higher and Further Education 1996, 2019, 2021 & 2023; Times Higher Education University of the Year 2012 & 2019; Daily Mail University of the Year 2024 Runner-Up; Daily Mail Scottish University of the Year 2024; Triple E European Entrepreneurial University of the Year 2023.

Student eligibility:

To enter our PhD programme applicants require an upper-second or first class BSc Honours degree, or a Masters qualification of equal or higher standard, in Physics, Engineering or a related discipline. Full funding, covering fees and stipend, is available for applicants who are UK Nationals (meeting residency requirements) or have settled status (meeting residency requirements), pre-settled status or otherwise have indefinite leave to remain or enter.

How to apply:

Applicants should send an up-to-date CV to iop@strath.ac.uk