Development of an on-demand sensor and monitoring technology based on switchable nanobodies for cell therapy bioprocessing

Lead Research Organisation: University of Birmingham
Department Name: Chemical Engineering

Abstract

Cell therapies, which use human cells to restore, maintain, or improve the functioning of human tissues or organs, hold enormous potential for the treatment of a wide range of diseases and conditions, including a variety of cancers. While cell therapies have the potential to improve healthcare for millions of patients worldwide, manufacturing remains a major hurdle for clinical translation. Today's cell therapies manufacturing processes, which include the use of patient's own cells or donor cells to manufacture the therapeutic product, involve manual, labour-intensive and open processes that require highly-skilled personnel. This in turn leads to high process variability, risk of contamination and high manufacturing costs, all of which are major obstacles for cell therapies to realise their full potential and bring about widespread access to the global patient population. New technologies are urgently needed to develop reliable and robust manufacturing processes that ensure quality and consistency of cell therapy products at an economically viable cost.
This project will develop an on-demand sensor and monitoring technology that will enable, for the first time, real-time, non-disruptive measurement of key biochemicals in cell culture media. These unprecedented capabilities will be enabled by an innovative microfluidic sensing platform comprising smart, switchable electrode-tethered nanobodies. In contrast with conventional offline analysis, the acquisition of real-time process data will allow immediate response to process variations, thus providing a fine level of process control. This is essential for the consistent production of high-quality therapeutic cells in high yields, independently of the patient's or donor's cells. It will provide an exceptional opportunity to implement fully automated, robust cell therapy culture processes and bring down production costs, ultimately delivering cost-effective and impactful therapeutics to patients in need.

Publications

10 25 50
 
Description The field of cell therapy is rapidly progressing, bringing new hope to patients in a wide range of diseases. However, the manufacture of these therapies remains a major barrier to meeting increased market demand and patient access. New technologies are needed to implement integrated process analytics, enabling real-time monitoring of process parameters and critical quality attributes of cell therapies during biomanufacture. The incorporation of biosensors into bioreactor systems would allow for fast, non-destructive sensing to achieve in-process monitoring of cell products within closed systems. This project addressed that need and has developed an electrochemical nanobody-based biosensor capable of sensing cell-specific proteins that will better inform cell culture processes. Furthermore, this sensing device incorporates switchable surface technology, enabling ON/ OFF electrical control of antigen- nanobody binding to achieve real-time, on-demand sensing of analytes. Thus, providing the capability to achieve in-process monitoring of cell products within closed systems.
Exploitation Route Following demonstration of the technology, we will explore it for licencing.
Sectors Healthcare

 
Description Prostate Cancer UK: From Ideas to Innovation (Member of Scientific Organising Committee), London, UK.
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a guidance/advisory committee
Impact It will enable to accelerate the impact of research in Prostate Cancer, ensuring the results of the scientific community hard work have the best chance of benefiting the lives of those affected by prostate cancer.
URL https://prostatecanceruk.org/research/for-researchers/from-ideas-to-innovation
 
Description Collaboration with Imec, Belgium 
Organisation Interuniversity Micro-Electronics Centre
Country Belgium 
Sector Academic/University 
PI Contribution PhD student from Imec, Belgium is visiting Mendes group for 6 months to collaborate and explore the technology together.
Collaborator Contribution PhD student fully funded working in Mendes lab for 6 months.
Impact It started in February 2023 and the aim is to get a publication together and further exploitation of the technology.
Start Year 2023
 
Title STIMULI-RESPONSIVE SURFACES 
Description A stimuli-responsive surface (3) comprising a substrate (20) on which is located a switchable molecule (2) which has a functional moiety (22) associated therewith, wherein the switchable molecule (2) has a first equilibrium state (2A) in which access to the functional moiety (22) is inhibited and a second stimulated state (2B), in which access to the functional moiety (22) is permitted. 
IP Reference WO2018185503 
Protection Patent / Patent application
Year Protection Granted 2018
Licensed No
Impact The patent is still pending in Europe and US but we are creatign data that we aim at providing the proof of concept for it to be licenced.
 
Description Facebook Live Q&A 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Facebook Live Q&A with Prostate Cancer UK supporters during the Women and Girls in STEM day
It allowed to explain how nanotechnology can be used to develop better sensors. The audience was very grateful and appreciated all the efforts we scientist are doing to enhance healthcare delivery.
Year(s) Of Engagement Activity 2022
 
Description Science Museum exhibition on "Cancer Revolution: Science, innovation and hope " 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact 2021-2023 on Science Museum exhibition on "Cancer Revolution: Science, innovation and hope ", Oct 2021-March 2022 Manchester Science and Industry Museum; May 2022-Jan 2023 - London Science Museum.

It provides awareness on how technology has been developed to improve quality of life and save lives.
Year(s) Of Engagement Activity 2021,2022,2023
 
Description Visit: Peter Kyle, Shadow Secretary for DSIT, Richard Parker, Labour Candididate for West Midlands Mayor 
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 Policymakers/politicians
Results and Impact Peter Kyle, Shadow Secretary for DSIT, Richard Parker, Labour Candidate for West Midlands Mayor have visited the Healthcare Technologies Institute at University of Birmingham and I spoke about the technology we develop in the group and how it will impact in peoples lives. Fund from UK government and Cancer UK was highlighted.
Year(s) Of Engagement Activity 2024