Hybrid Enhanced Regenerative Medicine Systems

HERMES - a project creating biohybrid neurotechnology to cure brain disorders.

An alliance of scientists are working across 7 countries to engineer next generation neural probes and artificial intelligence powered organoid microelectronic implants to restore and reshape brain tissue damaged by epileptic seizures.

This ambitious project is working in the following interdisciplinary branches of research:

Neuromorphic Engineering.
Tissue Engineering.
Artificial Intelligence.
In Vitro Electrophisiology.
Biohybrid Organoid Technology.
E-Beam Deposition.
Electroencephalography Recording System.
Deep Learning Neural Networks.

Specially designed neural probes which connect to a electroencephalography recording system in Università di Modena e Reggio Emilia.

E-beam evaporator machine that deposits metals onto substrates up to 6” in size, with angled deposition and an ion gun for plasma processing. Located at the James Watt Nanofabrication Centre (JWNC) at the University of Glasgow. 

Exposing a hippocampal brain slice to the convulsant drug 4-aminopyridine to induce seizure-like electrical activity. The tissue is maintained alive via a perfusion system enabling the constant flow of warm artificial cerebrospinal fluid.

My journey into the involute world of enhanced regenerative medicine and biohybrid neuronics began with a message from Art Director Rebecca Horne inviting me create a photo-led story for The Transmitter, an essential resource for the neuroscience community.

Enquires led to the cutting edge HERMES project funded by the European Union's Horizon 2020 programme. With a total cost of € 8,429,857.50 and entering its penultimate research year, contact was made with biophysicist Gabriella Panuccio, the HERMES principle investigator and coordinator who is based at Istituto Italiano di Tecnologia’s (IIT) in Genova.

Microscopic inspection of neural probe circuitry.

PhD Student María Cerezo Sánchez (left) & Dr Eve McGlynn (right) are key to the design, fabrication and characterisation of flexible neural probes, and their integration with microelectronics at the University of Glasgow's James Watt Nano Fabrication Centre.

The areas of research HERMES scientists are working on is deeply complex and combines neurobiology, electronic engineering, computer science, and social sciences. To present a simple explanation of the project’s objective, I feel the need to highlight the following text from Horizon 2020 to accompany my photographs:

Brain disorders have a significant impact on society and healthcare systems. Regenerative medicine (RM) attempts to restore brain function by rebuilding brain tissue. The hardest challenge in brain repair is the control of the integration of grafted cells or tissue with the host brain. Brain-inspired neuroprostheses represent innovative controllable devices for brain function replacement, but they cannot rebuild brain matter.

The EU-funded HERMES project aims to create a new field of enhanced RM and provide a proof-of-concept that the integration of bioengineered and mammalian brain tissue can be established and controlled, healing brain damage. The innovative solution involves intelligent bio-hybrids, made via the integration of bioengineered brain tissue, neuromorphic microelectronics and artificial intelligence.

Electronic interface made by the Electronic Design Laboratory’s head engineer Marco Crepaldi (left) and a neuromorphic emulator made by CSIC group engineers Bernabé Linares Barranco & Teresa Serrano Gotarredona (right). Though ‘Heath Robinson’ in looks, these bespoke components act as conduits to very powerful neuromorphic computing and neural network simulations. 

A prepared rat brain is placed into a vibrating blade microtome, ready to be sliced very precisely and very thinly before being mounted for in vitro electrophisiology.

Istituto Italiano di Tecnologia’s hillside complex.

Although HERMES involves a network of 70 scientists spread across Spain, Finland, Scotland, Italy, Denmark, Belgium and the Netherlands, 3 laboratories presented the strongest opportunity to photograph the core foundations of research:

Istituto Italiano di Tecnologia (IIT) in Genova for tissue engineering, biohybrid organoid technology and in vitro electrophysiology.

Università di Modena e Reggio Emilia (UNIMORE) for in vivo electrophysiology, intracerebral injections and device implantation.

University of Glasgow's James Watt Nano Fabrication Centre (JWNC) for the design, fabrication and characterisation of flexible neural probes, and their integration with microelectronics.

Gabriella Panuccio, HERMES PI and Coordinator in her Istituto Italiano di Tecnologia laboratoy nestled in the hills north of Genova.

Istituto Italiano di Tecnologia

Gabriella Panuccio heads a team Dr Gemma Palazzolo, Giacomo Pruzzo and John Wesley Ephraim.

Between them they utilise in vitro electrophysiology and tissue engineering units. Equipped with a double microelectrode array set-up for advanced closed-loop in vitro electrophysiology and a field potential set-up for extracellular recording.

They also involved with 3D neuronal cultures, brain tissue bioengineering (brain organoids), calcium imaging, microscopy, molecular biology and in vivo fMRI.

The next image slideshow shows cultivated brain organoids and spheroids (see the tiny, regular dots in the centre of each dish are around 40μm each in size) to functionally replicate the hippocampus, where seizures often originate in mesial temporal lobe epilepsy.

Blue, red and green fluorescent tags mark the mature neurons in a slice of hippocampus from a rat in Università di Modena e Reggio Emilia.

Giulia Curia PhD, HERMES PI and Associate Professor of Physiology for Department of Biomedical, Metabolic and Neural Sciences in her offices in Università di Modena e Reggio Emilia.

Università di Modena e Reggio Emilia (UNIMORE)

Giulia Curia heads a team including Michele Zoli, Rita Bardoni, Giulia Puja, Giuseppina Leo, Elisa Ren, Beatrice Casadei Garofani, Stefania Bartoletti, Federica Raimondi and Arianna Capodiferro.

Between them they provides expertise in in vivo electrophysiology (video-EEG recording) and behavioral and cognitive assessment.

They support in vitro studies with biocompatibility assessment of implantable microelectronics and in vitro electrophysiology, and perform immunofluorescence, citotoxicity test and patch clamp recordings.

Members of the Università di Modena e Reggio Emilia research team.

Fixed brains extracted from epileptic rats are immersed in a post-fixative solution waiting to be frozen at -80ºC, sliced and then used for histological analysis at Unimore.

A Kopf stereotaxic instrument enabling precise 3D navigation along the skull mediolateral, anteroposterior, and dorsoventral axes.

Università di Modena e Reggio Emilia campus.

Neurosurgery room in Università di Modena e Reggio Emilia.

Hadi Heidari PhD, HERMES PI and Professor of Nanoelectronics at the Microelectronics Lab (meLAB) University of Glasgow.

University of Glasgow's James Watt Nano Fabrication Centre (JWNC)

Hadi Heidari heads a team including Dr Eve McGlynn and María Cerezo Sánchez.

Between them they provide expertise in biocompatible flexible microelectronics, including theoretical analysis, modeling and simulation, design, and fabrication. The testing and manufacture of the neural probes takes place in the James Watt Nanofabrication Centre (JWNC), housed in the same building as their laboratory.

JWNC is one of Europe’s largest clean rooms, measuring 1400 m2. Specific application areas include environmental and biological sensing; imaging and ranging; internet, communication and data storage; space and quantum technologies, alongside the latest metrology instruments.

You can read about my time in the clean room at the end of this gallery.

A buckling test of a flexible, polymer-based neural probe - which are more compatible with brain tissue than rigid, silicon-based probes. Once a silk fibroin coating is applied at a later stage, the buckling force increases from 0.31 to 75.99 mN (a force of at least 10 mN is required to implant into the brain without buckling).

Pliant neural probes being inspected under a microscope inside the University of Glasgow’s Nano Fabrication facility.

María Cerezo Sánchez pushes a neural probe into a agarose gel block that mimics the brain’s mechanical properties. Using the models, the researchers in Glasgow test whether flexible probes with different dissolvable coatings will buckle or break during surgical insertion.

I want to extend my gratitude to all 3 laboratories and the teams for setting aside time to allow me to document your research. The passion, care and attention to detail I witnessed was remarkable.

A special thank you to Rebecca Horne for entrusting me to load up my car and head into a world of cutting edge scientific intrigue. Further, in-depth reading:

JWNC’s clean room emits its own kind of sensory disorientation.The yellowy cast is not for stylish effect but a deliberate covering of light sources to filter out specific wavelengths from the electromagnetic spectrum that would interfere with certain experiments.

The resulting combination of the ultra low contrast of the yellowy tint with the constant ‘chirping’ of cryogenic cooling pumps, warm protective overalls and lack of facial recognition of others in the facility proved to be one of life’s more unusual, yet rewarding experiences