CANDO: Controlling Abnormal Network Dynamics using Optogenetics

Visit CANDO website

Completed Project (2014-2021)

Research Team: Dorian Haci, Sara Ghoreishizadeh, Yan Liu, Timothy Constandinou
Collaborators: Andrew Jackson, Anthony O'Neil, Patrick Degenaar, Roger Whittaker, Andrew Sims, Mark Cunningham, Marcus Kaiser, Stuart Baker (Newcastle), Nick Donaldson (UCL)
Funding: Wellcome Trust/EPSRC Innovative Engineering for Health NS/A000026/1

CANDO concept

CANDO is a world class multi-site cross-disciplinary project to develop a cortical implant for optogenetic neural control. The goal is to create a first-in-man trial of the device in patients with focal epilepsy. This 7-year, £10m Innovative Engineering for Health Award, funded by the Wellcome Trust and EPSRC involves a team of over 30 neuroscientists, engineers and clinicians based at Newcastle University, Imperial College London, University College London, and Newcastle upon Tyne Hospitals NHS Foundation.

Within the brain nerve cells connect together to generate rhythmic activity visible as brain waves on an EEG. In many neurological diseases this network is disrupted, producing abnormal patterns of activity. In epilepsy, abnormal activity can be localised to a small ‘focus’, but this can spread across the whole brain as a seizure. Epilepsy affects 600,000 people in the UK alone and uncontrolled seizures have a devastating effect on patients’ quality of life. Most cases respond to drugs, but if these are ineffective it may be necessary to surgically remove the ‘focus’. However, surgery is not suitable in all patients and can damage cognitive function.

CANDO probe conceptThis project, led by Dr Andrew Jackson and Professor Anthony O’Neill from Newcastle University, proposes an alternative based on a small implant that continuously records the abnormal activity and provides precisely timed stimulation to prevent it ever developing into a seizure. This requires that some cells within the focus are genetically altered using a safe virus to become sensitive to light. The implant will monitor their activity and provide pulses of light from tiny LEDs to prevent the build of abnormal activity.

Publications

Publications

2023

  • B. Zaaimi, M. Turnbull, A. Hazra, Y. Wang, C. Gandara, E. McDermott, E. Escobedo-Cousin, A. Idil, R. G. Bailey, S. Tardio, A. Patel, N. Ponon, J. Gausden, F. Hutchings, M. Kaiser, M. Cunningham, G. Clowry, F. E. N. LeBeau, T. G. Constandinou, S. N. Baker, N. Donaldson, P. Degenaar, A. O’Neill, A. J. Trevelyan, and A. Jackson, “Closed-loop optogenetic control of normal and pathological network dynamics,” Nature Biomedical Engineering, vol. 7, pp. 559–575, 2023. doi: https://doi.org/10.1038/s41551-022-00945-8

2021

  • K. M. Szostak, M. Keshavarz, and T. G. Constandinou, “Hermetic chip-scale packaging using Au:Sn eu- tectic bonding for implantable devices,” Journal of Micromechanics and Microengineering, vol. 31, no. 9, p. 095003, 2021. doi: https://doi.org/10.1088/1361-6439/ac12a1

  • D. Firfilionis, F. Hutchings, R. Tamadoni, D. Walsh, M. Turnbull, E. Escobedo-Cousin, R. G. Bailey, J. Gausden, A. Patel, D. Haci, Y. Liu, F. LeBeau, A. Trevelyan, T. G. Constandinou, A. O’neill, M. Kaiser, P. Degenaar, and A. Jackson, “A closed-loop optogenetic platform,” Frontiers in Neuroscience, pp. 1–27, 2021. doi: https://doi.org/10.3389/fnins.2021.718311

2020

  • Y. Liu, A. Urso, R. M. da Ponte, T. Costa, V. Valente, V. Giagka, W. A. Serdijn, T. G. Constandinou, and T. Denison, “Bidirectional bioelectronic interfaces: System design and circuit implications,” IEEE Solid-State Circuits Magazine, vol. 12, no. 2, pp. 30–46, 2020. doi: https://doi.org/10.1109/MSSC.2020.2987506
  • D. Haci, Y. Liu, S. Ghoreishizadeh, and T. G. Constandinou, “Key considerations for power management in active implantable medical devices,” in IEEE Latin American Symposium on Circuits and Systems (LASCAS), 2020. doi: https://doi.org/10.1109/LASCAS45839.2020.9069004
  • J. Luo, D. Firflionis, M. Turnbull, W. Xu, D. Walsh, E. Escobedo-Cousin, A. Soltan, R. Ramezani, Y. Liu, R. Bailey, A. S. Idil, A. O’Neill, N. Donaldson, T. G. Constandinou, A. Jackson, and P. A. Degenaar, “The neural engine: A reprogrammable low power platform for closed-loop optogenetics,” IEEE Transactions on Biomedical Engineering, vol. 67, no. 11, pp. 3004–3015, 2020. doi: https://doi.org/10.1109/TBME.2020.2973934

2018

  • R. Ramezani, Y. Liu, F. Dehkhoda, A. Abd-el aal, D. Haci, H. Zhao, D. Firfilionis, A. Hazra, M. Cunning- ham, A. Jackson, T. G. Constandinou, and P. Degenaar, “On-probe neural interface ASIC for combined electrical recording and optogenetic stimulation,” IEEE Transactions in Biomedical Circuits and Systems, vol. 12, no. 3, pp. 576–588, 2018. doi: https://doi.org/10.1109/TBCAS.2018.2818818
  • D. Haci, Y. Liu, S. Ghoreishizadeh, and T. G. Constandinou, “Key considerations for power management in active implantable medical devices,” in IEEE Latin American Symposium on Circuits and Systems (LASCAS), 2020. doi: https://doi.org/10.1109/LASCAS45839.2020.9069004

  • F. Mazza, Y. Liu, N. Donaldson, and T. G. Constandinou, “Integrated devices for micro-package integrity monitoring in mm-scale neural implants,” in IEEE Biomedical Circuits and Systems (BioCAS) Conference, pp. 295–298, 2018. doi: https://doi.org/10.1109/BIOCAS.2018.8584761

2017

  • S. Ghoreishizadeh, D. Haci, Y. Liu, N. Donaldson, and T. G. Constandinou, “Four-wire interface ASIC for a multi-implant link,” IEEE Transactions in Circuits and Systems I: Regular Papers, vol. 64, no. 12, pp. 3056–3067, 2017. doi: https://doi.org/10.1109/TCSI.2017.2731659
  • A. Mifsud, D. Haci, S. Ghoreishizadeh, Y. Liu, and T. G. Constandinou, “Adaptive power regulation and data delivery for multi-module implants,” in IEEE Biomedical Circuits and Systems (BioCAS) Conference, pp. 584–587, 2017. doi: https://doi.org/10.1109/BIOCAS.2017.8325208
  • J. Luo, D. Firfilionis, R. Ramezani, F. Dehkhoda, A. Soltan, P. Degenaar, Y. Liu, and T. G. Constandi- nou, “Live demonstration: a closed-loop cortical brain implant for optogenetic curing epilepsy,” in IEEE Biomedical Circuits and Systems (BioCAS) Conference, p. 169, 2017. doi: https://doi.org/10.1109/BIOCAS.2017.8325099
  • C. Gao, S. Ghoreishizadeh, Y. Liu, and T. G. Constandinou, “On-chip ID generation for multi-node im- plantable devices using SA-PUF,” in IEEE International Symposium on Circuits and Systems (ISCAS), pp. 678–681, 2017. doi: https://doi.org/10.1109/ISCAS.2017.8050422
  • S. Ghoreishizadeh, D. Haci, Y. Liu, and T. G. Constandinou, “A 4-wire interface SoC for shared multi-implant power transfer and full-duplex communication,” in IEEE Latin American Symposium on Circuits and Systems (LASCAS), pp. 49–52, 2017. doi: https://doi.org/10.1109/LASCAS.2017.7948050
  • D. Haci, Y. Liu, and T. G. Constandinou, “32-channel ultra-low-noise arbitrary signal generation platform for biopotential emulation,” in IEEE International Symposium on Circuits and Systems (ISCAS), pp. 698– 701, 2017. doi: https://doi.org/10.1109/ISCAS.2017.8050427

2016

  • R. Ramezani, F. Dehkhoda, A. Soltan, P. Degenaar, Y. Liu, and T. G. Constandinou, “An optrode with built-in self-diagnostic and fracture sensor for cortical brain stimulation,” in IEEE Biomedical Circuits and Systems (BioCAS) Conference, pp. 392–395, 2016. doi: https://doi.org/10.1109/BioCAS.2016.7833814

2015

  • F. Dehkhoda, A. Soltan, R. Ramezani, H. Zhao, Y. Liu, T. G. Constandinou, and P. Degenaar, “Smart optrode for neural stimulation and sensing,” in Proc. IEEE Sensors Conference, 2015. doi: https://doi.org/10.1109/ICSENS.2015.7370687
  • H. Zhao, F. Dehkhoda, R. Ramezani, D. Sokolov, T. G. Constandinou, Y. Liu, and P. Degenaar, “A CMOS- based neural implantable optrode for optogenetic stimulation and electrical recording,” in IEEE Biomedical Circuits and Systems (BioCAS) Conference, pp. 286–289, 2015. doi: https://doi.org/10.1109/BioCAS.2015.7348357