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Human on Chip : Microsensor unit and control algorithm integration for brain on a chip drug testing applications and development

Periodic Reporting for period 1 - BrainChip (Human on Chip : Microsensor unit and control algorithm integration for brain on a chip drug testing applications and development)

Reporting period: 2017-09-15 to 2018-09-14

The treatment of conditions and diseases of the central nervous system (CNS) related to ageing as well as environmental, genetic and other incidental factors depends on gaining deeper understanding of the brain complexity. Therapeutic drugs development, evaluation and patient’s personalization require realistic test systems able to improve the predicted outcome provided by current animal testing and clinical trials. In vivo tests are labour-intensive and time-consuming processes associated to high costs, experimental variability and low-throughput. On the other hand, alternative current in vitro systems fail to reproduce the CNS complexity, due to their two-dimensional character, which restricts the reproduction of cellular clusters shapes and interactions, such as those of astrocytes with numerous neurons or those originating from the existence of the blood-brain barrier (BBB). When studying how neurological conditions impact connected regions of the brain, it is very important to implement different brain regions into more realistic in vitro models.

Cherry Biotech is working in the development of an automated system based in the use of microfluidics, extracellular matrices and perfused three-dimensional multi-cellular environments to achieve a better reproduction of in vivo models while improving inter-cellular connectivity, cells survival, interconnected cellular niches separation and neuronal differentiation in vitro. The system will be conceived since the beginning as an application affordable, usable and comprehensive, disposable cartridges -based device for automated and controlled drug-testing using patient specific cells in the long run. The overall device will exploit current Cherry Biotech developed temperature control technologies by adding new optical, fluidic and electrical components, as well as information processing and data retrieval capabilities, to achieve a self-standing, or alternatively microscope-adaptable, system applicable to theranostics, to drug development and to fundamental life sciences research.

The resulting system and collateral knowledge will be also applied to target other human organ models with the wider aim to achieve an integrated testing platform for personalised therapeutic molecules and for controlled cell differentiation. The full system is intended to allow accurate spatial control of cells placement and local extracellular matrices in a disposable microfluidic chip as well as automated monitoring of a range of previously defined parameters related to temporally defined infusion protocols. This development is expected to also build internal strong synergies towards the human-on- a-chip Cherry Biotech long-term purpose.
The project had the main objective of proposing, studying and evaluating a device for Brain-on-a-Chip functions control and monitoring. The work done during these 12 months period has focused into developing two integrated multi-sensing platforms (BrainChip Platform 1, an specific modification of CherryTEMP©, and CubiX© Platform (formerly named BrainChip Platform 2) associated to keep healthy cell cultures in controlled 3D microenvironments while concurrently assessing their functions under controlled stimulus such as these originated by therapeutic drugs or electrophysiology stimulation. Effort has been put in both, developing and prototyping the controlling platforms and creating 2 microfluidic disposables able to mimic and monitor parts of brain physiology when combined with the corresponding platform. The two expected products have been architected and developed after accurate study of the market and communication with potential customers, mainly academic researchers, Contract Research Organizations (CROs) and pharma companies, through emailing campaigns, data-gathering web pages, phone calls and direct meetings. A design-thinking linked to minimum viable product (MVP) approach has been followed during the process to understand the market needs and start producing some revenues from the developments.

The first and simpler prototype (BrainChip Platform 1) targets the electrophysiology research community and is already being sold as an optional feature for the CherryTEMP© product. The disposable associated to this product is based in a petri dish and facilitates electrophysiological recordings when needed. The device has been tested in relevant environments, used by early adopters, and finally commercialized.

The second prototype, the CubiX© platform (formerly presented as the BrainChip Platform 2), targets a much more complex, ambitious, and integrated device, powered by artificial intelligence and aimed to partially substitute animal testing during drug development in the near future, while reducing pharma industry costs. Its range of applications is not limited to mimicking brain environments and can be expanded by updating its hardware, changing the organ model, and introducing new disposables, in the future. A first minimum viable product (working prototype) for the the CubiX© platform has been integrated and software has been developed to allow its autonomous functioning. However, full test in a relevant environment of this platform has been hindered by the contingencies experimented and the delays occurred in the fabrication of its associated brain-blood barrier (BBB) mimicking disposable.

A communication plan has been followed also since the beginning by assisting to meetings of the Human Brain Project and developing presentations for the targeted potential customers. Dedicated contents (scientific notes, application notes, youtube videos) have been uploaded in the Cherry Biotech website. Written contents have been produced exploiting the Google search engine optimization (SEO). The online content has been promoted though social media (Twitter, Facebook, Researchgate, Linkedin). In order to more accurately target potential end-users/buyers a list was prepared, for both platforms, at the early beginning of the project, identifying potential actors that could be interested in these new technologies. Specific software tools to measure the impact (time spent/page, recurrent visits, total browsing time, ...) of the dissemination strategies (web, emailing campaigns) were applied and used to eventually change the value proposition of the new product. IP protection and freedom to operate surveillance studies have been carried out during the project.
Two products have resulted at the end of the project. One, already commercialized, targets the electrophisiology and life sciences research communities while the second one, which needs to be further evolved, has a broader audience due to its versatility. So far, besides the socioeconomic implications of creating wealth and job positions in the European Union area the project with its associated products may become in the future a plausible alternative to animal testing. This is an important objective to be achieved since, besides the ethical concerns, the cosmetic industry is switching testing methods after EU directive 2010/63/EU and the development of new marketable therapeutical compounds has been hindered the last decades due to the failure of these new therapies during the clinical experimentation phases as a result of the low predictability provided by animal models.
CubiX(c) Platform Prototype
Brain Mimicking Drug Testing Platform Scheme