iPROBE: in-vivo Platform for the Real-time Observation of Brain Extracellular activity

Lead Research Organisation: Imperial College London
Department Name: Electrical and Electronic Engineering

Abstract

Understanding how the trillions of action potentials of the brain's billions of neurons produce our thoughts, perceptions, and actions is one of the greatest challenges of 21st century science. Similarly, understanding how this activity is disrupted by neurological and psychiatric diseases is one of the greatest challenges of 21st century medicine. Due to the massively parallel nature of the brain's computations, answering these questions experimentally relies on being able to monitor very large numbers of neurons simultaneously. Advances in electrode microfabrication and high-throughput data analysis have allowed scientists to record from hundreds of neurons in a small local area of brain. However, as both healthy and unhealthy neural operation arises from interaction of multiple, widely-distributed brain circuits, its understanding requires a technological step-change that allows monitoring of much larger numbers of neurons over many brain areas. The research of this proposal will for the first time make this possible. This will not only provide a previously unimaginable opportunity for understanding how the healthy brain functions, but also allow us and others to develop empirically-based treatments for diseases such as Parkinson's, epilepsy, schizophrenia, and Alzheimer's.

Large-scale neuronal recording relies on the use of microfabricated multielectrode arrays (MEAs). Arrays capable of recording from hundreds of local neurons are now commercially available. In principle, these arrays provide the ability to record from thousands of neurons across multiple brain structures, simply by using a large number of probes simultaneously. However, accessing the data produced by these electrodes cannot be achieved with current technologies, as it is simply impossible to pass a sufficient number of very low amplitude analogue signals, as in current passive connection systems. We will solve this problem by using an approach common in computing: a daisy-chain digital serial interface. By allowing simple, robust, and low-noise connection of several multi-electrode arrays, this will allow us to monitor thousands of neurons from multiple structures using a single interface. The system will exploit cheap, commercially available microelectrode arrays (eg. NeuroNexus), connected to a custom CMOS Integrated Circuit (IC) via high-density flexible ribbon cables. CMOS ICs are low cost, produce high yield and area efficient active electronics suitable for amplifying, filtering, analog-to-digital conversion and encoding of each electrode array's spiking neuron data. Each daisy chain (i.e. group of serially-connected probes) will terminate into a standard USB interface. The new USB-3.0 protocol (marketed using the SuperSpeed term) can allow for serial data speeds of 5Gbps. For data sampled at 25kS/sec at 12-bit resolution, this could provide a bandwidth capable of supporting over 10,000 electrodes: two orders of magnitude beyond current technology.

The recording systems we develop will produce vast quantities of data. A second, and essential, part of the platform is thus to develop the algorithms and software that are essential for the timely conversion of this information to concise conclusions about brain function. We will do this by leveraging our previous work, now the de facto worldwide standard for processing of multi-neuron recordings.

Our aim is to produce a system that is widely adopted by the UK and worldwide neuroscientific communities, thereby maximizing its impact on the understanding and treatment of a very wide range of disorders. To ensure that the system meets the need of both basic and clinical brain research, our team includes the world's leading expert on neuronal population recording, as well as the UK's leading manufacturer of neural recording systems. We thus have the expertise needed not only to develop the system, but also enable its rapid commercialization and distribution to scientists worldwide.
 
Description This research has developed new electronic circuits for neural recording applications such as tools used in experimental neuroscience. The current trend is for such systems to record from more and more channels (for example, from arrays of tiny electrodes implanted in the cortex), however given hard constraints dictated by biological limits (e.g. the maximum allowable power/heat dissipation per unit volume of neural tissue), in order for such systems to scale to higher channel counts- significant advances in hardware efficiency are necessary. We have therefore developed new transistor-level circuit techniques, and integrated circuit system designs that place a key focus on resource efficiency (power, area/space, and also communication bandwidth). We have combined our new designs with outcomes of our previous research (low power on-node spike sorting), to do computation locally, within the implant thus to massively reduce the communication bandwidth- transmitting high level information rather than raw data.

Specific project outcomes include:

- A number of new circuit techniques for achieving low power, low noise, and low silicon area utilization in neural microsystems.

- A range of scalable integrated circuits (currently available in 32 and 64-channel versions) for neural recording with local processing and event-driven output.

- An complete end-to-end platform (headstage, interface bridge, device drivers, PC and server software) for high-throughput realtime neural activity monitoring/visualization.

- Securing the background intellectual property to this invention.

Through this project, a number of existing and new collaborations have been forged, researchers trained in multidisciplanary research, and invaluable new know-how has been developed.
Exploitation Route We have published key findings in high impact journals, and presented results at key conference venues (as we continue to do), all of which is made freely available to the scientific community through open access license. We are additionally exploring opportunities to commercialize and/or license the technology we have developed so it becomes available as a product and/or service thus to directly benefit the intended end-user, i.e. the experimental neuroscientists.
Sectors Digital/Communication/Information Technologies (including Software),Electronics,Manufacturing, including Industrial Biotechology

URL http://www.imperial.ac.uk/next-generation-neural-interfaces/resources/spike-sorting-platform/
 
Description A US-based company is now reviewing research outcomes for possibility of incorporating into products- in field of scientific tools for neuroscience.
First Year Of Impact 2017
Sector Electronics,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description "Disruptive Semiconductor Technology for Advanced Healthcare Systems" (Platform Grant)
Amount £692,737 (GBP)
Funding ID EP/N002474/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 08/2015 
End 08/2020
 
Description "ENGINI: Empowering Next Generation Implantable Neural Interfaces" (Early Career Fellowship)
Amount £1,016,559 (GBP)
Funding ID EP/M020975/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 08/2015 
End 07/2020
 
Description "SenseBack: Enabling Technologies for Sensory Feedback in Next-Generation Assistive Devices" (IDEAS Workshop)
Amount £1,444,283 (GBP)
Funding ID EP/M025977/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 04/2015 
End 04/2018
 
Description Application Specific ICs for Neural Interfacing - Commercialisation and Market Evaluation
Amount £60,786 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 01/2018 
End 06/2019
 
Description Impact Accelerator Award for "Spike Streaming Platform: Community Engagement & Early-Stage Commercialization"
Amount £44,219 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 03/2017
 
Title Methods for computationally-efficient spike sorting (for hardware implementation) 
Description Have developed a number of methods for neural spike processing including feature extraction and classification, adaptive spike detection, template building/training and spike denoising. Also proposed new hardware architectures for implementing online, realtime spike sorting. 
Type Of Material Data analysis technique 
Year Produced 2013 
Provided To Others? Yes  
Impact Other researchers around the world are using/applying our methods to their data. 
 
Description ENGINI (UCL, GeorgiaTech, MSU, Newcastle) 
Organisation Georgia Institute of Technology
Country United States 
Sector Academic/University 
PI Contribution Developing a holistic methodology for the design, manufacture and test of mm-scale neural implants.
Collaborator Contribution UCL - micropackaging Newcastle University - experimental neuroscience Michigan State University - neural signal processing Georgia Institute of Technology - wireless/biotelemetry
Impact N/A
Start Year 2015
 
Description ENGINI (UCL, GeorgiaTech, MSU, Newcastle) 
Organisation Michigan State University
Country United States 
Sector Academic/University 
PI Contribution Developing a holistic methodology for the design, manufacture and test of mm-scale neural implants.
Collaborator Contribution UCL - micropackaging Newcastle University - experimental neuroscience Michigan State University - neural signal processing Georgia Institute of Technology - wireless/biotelemetry
Impact N/A
Start Year 2015
 
Description ENGINI (UCL, GeorgiaTech, MSU, Newcastle) 
Organisation Newcastle University
Department Institute of Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Developing a holistic methodology for the design, manufacture and test of mm-scale neural implants.
Collaborator Contribution UCL - micropackaging Newcastle University - experimental neuroscience Michigan State University - neural signal processing Georgia Institute of Technology - wireless/biotelemetry
Impact N/A
Start Year 2015
 
Description ENGINI (UCL, GeorgiaTech, MSU, Newcastle) 
Organisation University College London
Department Department of Medical Physics and Biomedical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Developing a holistic methodology for the design, manufacture and test of mm-scale neural implants.
Collaborator Contribution UCL - micropackaging Newcastle University - experimental neuroscience Michigan State University - neural signal processing Georgia Institute of Technology - wireless/biotelemetry
Impact N/A
Start Year 2015
 
Description NGNI (Newcastle/Leicester) 
Organisation Newcastle University
Department Institute of Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Integrated circuit design, hardware implementation, software development, system integration/overall system concept
Collaborator Contribution Newcastle - Experimental Neuroscience/Hardware test/Overall system concept Leicester - Algorithms for Spike Sorting/WaveClus/Software development/Overall system concept
Impact N/A
Start Year 2010
 
Description NGNI (Newcastle/Leicester) 
Organisation University of Leicester
Department Centre for Systems Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Integrated circuit design, hardware implementation, software development, system integration/overall system concept
Collaborator Contribution Newcastle - Experimental Neuroscience/Hardware test/Overall system concept Leicester - Algorithms for Spike Sorting/WaveClus/Software development/Overall system concept
Impact N/A
Start Year 2010
 
Description NGNI Oxford 
Organisation University of Oxford
Department Institute of Biomedical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Making technology available to the community.
Collaborator Contribution co-funding manufacture of further devices.
Impact Too early.
Start Year 2018
 
Description SenseBack (Newcastle/Leeds/Keele/Essex/Southampton) 
Organisation Keele University
Department Institute for Science and Technology in Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Integrated Circuit Design
Collaborator Contribution Newcastle - Experimental Neuroscience Leeds - Microfabrication/Electrodes Southampton - Artificial Skin/Tactile sensing Keele - Biomechanics Modelling Essex - Neuroscience/Experimental Validation
Impact N/A
Start Year 2015
 
Description SenseBack (Newcastle/Leeds/Keele/Essex/Southampton) 
Organisation Newcastle University
Department School of Electrical and Electronic Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Integrated Circuit Design
Collaborator Contribution Newcastle - Experimental Neuroscience Leeds - Microfabrication/Electrodes Southampton - Artificial Skin/Tactile sensing Keele - Biomechanics Modelling Essex - Neuroscience/Experimental Validation
Impact N/A
Start Year 2015
 
Description SenseBack (Newcastle/Leeds/Keele/Essex/Southampton) 
Organisation University of Essex
Department School of Computer Science and Electronic Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Integrated Circuit Design
Collaborator Contribution Newcastle - Experimental Neuroscience Leeds - Microfabrication/Electrodes Southampton - Artificial Skin/Tactile sensing Keele - Biomechanics Modelling Essex - Neuroscience/Experimental Validation
Impact N/A
Start Year 2015
 
Description SenseBack (Newcastle/Leeds/Keele/Essex/Southampton) 
Organisation University of Leeds
Department Faculty of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Integrated Circuit Design
Collaborator Contribution Newcastle - Experimental Neuroscience Leeds - Microfabrication/Electrodes Southampton - Artificial Skin/Tactile sensing Keele - Biomechanics Modelling Essex - Neuroscience/Experimental Validation
Impact N/A
Start Year 2015
 
Description SenseBack (Newcastle/Leeds/Keele/Essex/Southampton) 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution Integrated Circuit Design
Collaborator Contribution Newcastle - Experimental Neuroscience Leeds - Microfabrication/Electrodes Southampton - Artificial Skin/Tactile sensing Keele - Biomechanics Modelling Essex - Neuroscience/Experimental Validation
Impact N/A
Start Year 2015
 
Description iProbe (MSU - Spike Sorting) 
Organisation Michigan State University
Country United States 
Sector Academic/University 
PI Contribution Sharing methods we have developed- co-supervising students.
Collaborator Contribution Applying their expertise to further develop new methods.
Impact Research publication - "Computationally efficient feature denoising filter and selection of optimal features for noise insensitive spike sorting", IEEE EMBC 2014.
Start Year 2013
 
Title System for a brain-computer interface 
Description The invention provides a two-step approach to providing a BCI system. In a first step the invention provides a low-power implantable platform for amplifying and filtering the extracellular recording, performing analogue to digital conversion (ADC) and detecting action potentials in real-time, which is connected to a remote device capable of performing the processor-intensive tasks of feature extraction and spike classification, thus generating a plurality of predetermined templates for each neuron to be used in a second processing step. In the second step the low-power implantable platform amplifies and filters the extracellular recording, performs ADC and detects action potentials, which can be matched on-chip to the predetermined templates generated by the external receiver in the first step. This two-step approach exploits the advantages of both offline and online processing, providing an effective and safe method for performing multiple recordings of single-neuron activity, for research or monitoring applications or for control of a remote device. 
IP Reference GB1401613.3 
Protection Patent application published
Year Protection Granted
Licensed No
Impact N/A
 
Title NGNI Hardware Spike Sorting Platform 
Description Spike Sorting is the process of deinterleaving a recorded neural signal in order to determine the firing patterns of individual neurons from the aggregate spike stream. The NGNI platform is an end-to-end solution for on-node, real-time spike sorting. By using a compact, onboard (template based) spike sorting engine, together with offline training (WaveClus-based), a low power real-time solution is achievable. 
Type Of Technology Systems, Materials & Instrumental Engineering 
Year Produced 2017 
Impact N/A 
URL http://www.imperial.ac.uk/next-generation-neural-interfaces/resources/spike-sorting-platform/
 
Description "Neural Interfaces & Microsystems: from State-of-the-Art to the Next Generation", CNRS Workshop on Bioelectronics (Paris, France), 20 June 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited speaker at workshop in the CNRS headquarters in Paris, France on Bioelectronics. I gave a talk to an audience of approximately 100 professionals.
Year(s) Of Engagement Activity 2016
URL http://www.cnrs.fr/insis/recherche/evenements/workshop-electronique-vivant.htm
 
Description Friends of Imperial College "Behind the Scenes" tour at NGNI Labs 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Next Generation Neural Interfaces (NGNI) lab hosted a "Behind the Scenes" event for Friends of Imperial College on the evening of 25th January 2017. This event included a welcome and seminar on neural interfaces, lab tours and research demonstrations, and an interactive poster session with the entire group. For photos and further details see the "Behind the Scenes @ NGNI" Event page- see link below.
Year(s) Of Engagement Activity 2017
URL http://www.imperial.ac.uk/neural-interfaces/news-and-events/friendsofic/
 
Description Participation in eFutures event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talk increased awareness about my research in other communities (UK microelectronics community)

Regularly invited to participate in more such events.
Year(s) Of Engagement Activity 2013
URL http://efutures.ac.uk/
 
Description Science Museum "Creative Quarter" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Science Museum "Creative Quarter" (aimed at giving 13-19 year olds) on 13 Nov 2015. Researchers from the Centre for Bio-Inspired Technology (Lorena Freitas, Nicoletta Nicolaou, Dorian Haci, Adrien Rapeaux, Timo Lauteslager, Timothy Constandinou) hosted the section on "brain computer interfaces".
Year(s) Of Engagement Activity 2015
URL http://info.discoversouthken.com/creative-quarter/
 
Description Science Museum Festival "You have been Upgraded" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Science Museum Festival "You have been upgraded" on the topic of human enhancement in 25-29 March 2015. Researchers from the Centre for Bio-Inspired Technology (Ian Williams, Deren Barsakcioglu, Benjamin Evans, Nora Gaspar, Konstantin Nikolic, Timothy Constandinou) hosted the section on "implantable devices".
Year(s) Of Engagement Activity 2015
URL http://www.sciencemuseum.org.uk/visitmuseum/plan_your_visit/events/festivals/you-have-been-upgraded
 
Description Talk at Sutton Trust Summer School (6th form students with interest in EEE) entitled: \Microchips and Brain Implants", 4 August 2016. 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact 12 students enrolled on the "Sutton Trust" scheme attended a week long event at Imperial College EEE Department which involved various activities such as talks, lab sessions, tours, etc- which I gave a talk entitles "Microchips and Brain Implants".
Year(s) Of Engagement Activity 2016
URL http://www.suttontrust.com/programmes/summer-schools/