Autonomous Light-Based Robotic Control of Cellular Dynamics for Cancer Applications

Lead Research Organisation: University of Bristol
Department Name: Electrical and Electronic Engineering

Abstract

"The main aim of the project is to design a light-based robotic device for the automatic and personalised treatment of skin cancer. This will require us to understand the biological reaction modes of cancer cells to light. We will investigate the interactions between normal and cancerous cells as they undergo swarm-controlled manipulations. Collective behaviours of large populations of cells are known to underpin many biological systems. By engineering micro-swarms to react to the environment, in this case, light, we can control individual cellular dynamics. Personalisation of the treatment is achieved by learning the cellular dynamics on the go and impacting appropriate cells through machine learning.
We will demonstrate a proof-of-concept treatment of cancer cells using the existing Dynamic Optical Micro Environment (DOME). The DOME contains a digital light projector that controls thousands of pixels with a cell-size resolution, a camera, and custom optics for image capture at the desired magnification and fluorescence, and computation for onboard machine learning algorithms to enable a closed-loop system for feedback. The existing DOME will be altered, to be able to house living cells by adding gas and temperature control as well as changing the light source to enable illumination in the UV range.
Several biological questions should be explored: we need to understand which stresses make cancer cells more susceptible to UV and how much photodamage can we use for lethal versus sublethal outcomes. We can optogenetically induce oncogenes (a gene that has the potential to cause cancer) and measure the response of the surrounding untreated cells. Additionally, induce p53 (a tumour suppressor gene and a facilitator of DNA repair) by UV in a subset of cells and investigate their effect on those cells and the surrounding unirradiated cells. General explorations around controlling individual cellular dynamics will be investigated to understand the closed-loop system, by continuously imaging and illuminating specific cells to ensure actions are fined tuned to the desired tissue-scale outcome. Initially, MCDK cells will be used, but then can move into human keratinocytes and possible tissue structures (including 3D organ-typic human skin).
We will take lessons learned to miniaturise the DOME into a wearable robotic device for future outpatient treatment (CANCER_DOME). As well as engage with patients to assess their acceptance of a device with the ability to control cellular dynamics and cell death and, even uses machine learning to optimise treatments to individual patients."

Planned Impact

Impact on Health and Care
The CDT primarily addresses the most pressing needs of nations such as the UK - namely the growth of expenditure on long term health conditions. These conditions (e.g. diabetes, depression, arthritis) cost the NHS over £70Bn a year (~70% of its budget). As our populations continue to age these illnesses threaten the nation's health and its finances.

Digital technologies transforming our world - from transport to relationships, from entertainment to finance - and there is consensus that digital solutions will have a huge role to play in health and care. Through the CDT's emphasis on multidisciplinarity, teamwork, design and responsible innovation, it will produce future leaders positioned to seize that opportunity.

Impact on the Economy
The UK has Europe's 2nd largest medical technology industry and a hugely strong track record in health, technology and societal research. It is very well-placed to develop digital health and care solutions that meet the needs of society through the creation of new businesses.

Achieving economic impact is more than a matter of technology. The CDT has therefore been designed to ensure that its graduates are team players with deep understanding of health and social care systems, good design and the social context within which a new technology is introduced.

Many multinationals have been keen to engage the CDT (e.g. Microsoft, AstraZeneca, Lilly, Biogen, Arm, Huawei ) and part of the Director's role will be to position the UK as a destination for inwards investment in Digital Health. CDT partners collectively employ nearly 1,000,000 people worldwide and are easily in a position to create thousands of jobs in the UK.

The connection to CDT research will strongly benefit UK enterprises such as System C and Babylon, along with smaller companies such as Ayuda Heuristics and Evolyst.

Impact on the Public
When new technologies are proposed to collect and analyse highly personal health data, and are potentially involved in life or death decisions, it is vital that the public are given a voice. The team's experience is that listening to the public makes research better, however involving a full spectrum of the community in research also has benefits to those communities; it can be empowering, it can support the personal development of individuals within communities who may have little awareness of higher education and it can catalyse community groups to come together around key health and care issues.

Policy Makers
From the team's conversations with the senior leadership of the NHS, local leaders of health and social care transformation (see letters from NHS and Bristol City Council) and national reports, it is very apparent that digital solutions are seen as vital to the delivery of health and care. The research of the CDT can inform policy makers about the likely impact of new technology on future services.

Partner organisation Care & Repair will disseminate research findings around independent living and have a track record of translating academic research into changes in practice and policy.

Carers UK represent the role of informal carers, such as family members, in health and social care. They have a strong voice in policy development in the UK and are well-placed to disseminate the CDTs research to policy makers.

STEM Education
It has been shown that outreach for school age children around STEM topics can improve engagement in STEM topics at school. However female entry into STEM at University level remains dramatically lower than males; the reverse being true for health and life sciences. The CDT outreach leverages this fact to focus STEM outreach activities on digital health and care, which can encourage young women into computer science and impact on the next generation of women in higher education.

For academic impact see "Academic Beneficiaries" section.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023704/1 01/04/2019 30/09/2027
2452328 Studentship EP/S023704/1 01/10/2020 20/09/2024 Neshika Wijewardhane