Manufacturing Green Nanoparticles for Efficient Cell Manufacture

Lead Research Organisation: University of Strathclyde
Department Name: Chemical and Process Engineering

Abstract

Material-cell interface, which strongly depends on surface and materials properties, can augment cell growth and is extremely useful in enabling exquisite control of cellular manufacturing. We will address challenges related to the total efficiency of the cell production process starting with nature-inspired manufacture of bespoke green nanomaterials (GN), characterizing these nanoparticles, and evaluating how these materials affect the subsequent cell manufacture. As part of this call, we seek limited proof-of-concept funding 2 years.

In order to manufacture green nanomaterials for efficient cell manufacture, there are following challenges:
- Can we scale up green nanomaterial manufacture so as to be competitive?
- How can we control flow to control manufacturing?
- Can we showcase the application of green silicas for cell manufacture?
- What nanoscale properties make green silicas superior?
We will address these challenges from a unique perspective by collaborating across non-traditional disciplines involving nanomaterials chemistry, fluid dynamics, cell manufacturing and nanotechnology, and combining expertise from two EPSRC Centres for Innovative Manufacturing and two EPSRC Manufacturing Fellows.

We have shown that GN, which provide an environmentally friendly approach, are scalable and have promising biomedical applications, while establishing the importance of mixing in nanomaterials scale-up operations. We have also identified strategies to efficient and automated cell manufacturing and developed nano-probes to extensively investigate surfaces and interfaces at the nanoscale. In this project, we aim to build on this success and go significantly beyond to address a number of key challenges to deliver large scale manufacturing of green nanomaterials suitable for cellular manufacture.

Planned Impact

There are at least three potential socio-economic impacts from this project:
1. a greener manufacturing of nanomaterials;

2. cheaper and controllable cell manufacture; and

3. development of novel nano-probe measurement tools.

1. The chemical industry, which is one of the leading sectors in terms of delivering high levels of social return on research investment, is potentially one of the beneficiaries of this project. The proposed research will have a major long-term socio-economic impact. The UK's upstream chemicals industry and downstream using sectors contributed a combined total of £258 billion in value-added (equivalent to 21% of UK GDP).

Owing to their unique environmentally friendly manufacturing, GN have the potential to help save energy costs and reduce the use/ production of toxic and hazardous chemicals when compared to existing silica manufacturing. The current industrial capacity for precipitated silica production is 2.4 million tonnes per annum, equating to $3.6 billion industry covering a wide range of applications in catalysis, separations, food and drug technology, biomedical materials and paints. Our calculations show that replacing existing silica manufacturing by the proposed green process will reduce the carbon footprint by 90+% (reduction in ~9 tonnes CO2 per tonne silica produced), thus strongly highlighting the sustainability and long-term impact of the process on chemical and process industry.

2. The area of regenerative medicine is one of the government's priority technology areas due to its potential to grow the UK economy and its promise of reducing the unsustainable economic burden of our aging population through the development of therapies that are curative and reduce long term (costly) morbidity. There are currently multiple products undergoing clinical trials and there is significant investment globally in cell therapies for regenerative medicine, with a particular push to develop the tools and technologies (e.g. i manufacturing) that will support these products when produced at scale. However, existing technologies are limited in both scalability and control. Outcomes of our research, notably the development of cheaper and greener nanomaterials for controlled cell manufacture, will directly have a significant impact on regenerative medicine industry. Our calculations show that our products will allow reducing cell manufacturing costs by at least an order of magnitude as well as enhancing quality.

3. The third potential impact of this research will be the development of novel nano-probe tools for cell-materials nanoscale characterisation which can lead to new products. By seeking to quantify surface charges at nanoscales in the proposal, we will potentially open up an entire new method to characterise nanoparticle toxicity. Metrology is crucial for all manufacturing, but it is even more crucial when toxicity is involved, and an understanding of how manufacturing methods affect this is novel, scientifically interesting and extraordinarily important for future nanoparticle manufacture. We will take nanoscale charge quantification techniques developed in the lab to commercial applications and products. Their impact and importance is highlighted by the direct involvement of a nano-probe company (Oxford Instruments) and its willingness to help commercialise the outcomes.
 
Description We have invented a novel process for making nanomaterials using an eco-friendly process. This invention has led to a patent application on a biologically inspired 'green' process for the industrial-scale production of silica, with the following potential commercial and environmental benefits: Commercial: •Costs Production costs -removing the need for calcination, and reactor heating. A recycling step and use of tap water further reduce costs Capital costs -existing installations can be easily adapted •Revenues Higher quality and reproducibility Greater flexibility in product range which can be manufactured Environmental: •A process which operates at neutral pH, room T and P, uses tap water as a solvent •Processing times much shorter (5 min reaction time, down from hours and days) •Uses a mild, post-synthetic method of purifying bioinspired silica, avoiding energy-intensive calcination and allows for re-use of the organic material •Incorporates a novel recycling step, which removes much of the burden on the process of treating the process water: it reduces water consumption in the process by up to 90% and 25 fold reduction in amine use.

The results from experimentally studying the effect of mixing on the bioinspired silica process and the products helped us to gain fundamental insight on how mixing affected the bioinspired silica reaction process and final silica product. Moreover, these results suggest that mixing parameters could be used to control some of the final product characteristics and must be taken into account when this process is transferred from the laboratory to the industrial scale.
Exploitation Route We are working to commercialise the IP generated by licencing the patent and/or spinning-out a company.
Sectors Chemicals,Manufacturing, including Industrial Biotechology,Other

 
Description The outcomes of this project underpinned a patent application. This has now gone through GB, PCT and regional filings. Over the past 2 years, we have worked with various companies to develop the IP further and derisk it by addressing specific questions raised by industry. We also worked on process development and assessment of performance in a given application (collaborating with a company). These efforts are converting into potential licencing agreements. Further, these are also supporting a start-up company formation, to be registered soon. In terms of challenges in driving this IP, there have been plenty. These stem from a lack of support culture in the UK (and the host) in driving new IP and taking risks. Ultimately, the risks have always been passed down to the inventors, who are left with selecting to either spend a lot of time and resources for an uncertain outcome or lose the IP. The time taken and the uncertainty in securing resources for the next stage of IP development has meant that there is no continuity in terms of skills/personnel available in the group.
First Year Of Impact 2018
Sector Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Description EPSRC Fellowship in Design and green manufacturing of functional nanomaterials
Amount £1,011,132 (GBP)
Funding ID EP/R025983/1 
Organisation University of Sheffield 
Sector Academic/University
Country United Kingdom
Start 11/2018 
End 10/2023
 
Description Industrial R&D
Amount £60,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 10/2017 
End 02/2018
 
Description Scottish enterprise
Amount £60,000 (GBP)
Organisation Scottish Enterprise 
Sector Public
Country United Kingdom
Start 01/2018 
End 08/2020
 
Description Standard Research
Amount £1,550,000 (GBP)
Funding ID EP/P006892/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 12/2016 
End 11/2020
 
Description Collaboration with Daniele Marchisio 
Organisation Polytechnic University of Turin
Country Italy 
Sector Academic/University 
PI Contribution The data obtained during this EPSRC project was shared with the collaborator in order to formalise next projects.
Collaborator Contribution Access to expertise on understanding mixing mechanisms in multiphase fluids and developing scale-up rule.
Impact Submission of an EPSRC fellowship and development of a publication.
Start Year 2017
 
Description Collboration - Helen Grant, Andrew Urqhart and Dimitris Lampru 
Organisation Technical University of Denmark
Country Denmark 
Sector Academic/University 
PI Contribution As a result of this project, we established a collaboration with the aforementioned institute as apart of the supervisory team.
Collaborator Contribution Supervision, access to lab, equipment and expertise.
Impact A PhD student graduation and 2 publications.
Start Year 2012
 
Description Collboration - Helen Grant, Andrew Urqhart and Dimitris Lampru 
Organisation University of Strathclyde
Department Department of Biomedical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution As a result of this project, we established a collaboration with the aforementioned institute as apart of the supervisory team.
Collaborator Contribution Supervision, access to lab, equipment and expertise.
Impact A PhD student graduation and 2 publications.
Start Year 2012
 
Description Enabling green manufacturing (proposal) 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution We developed a large proposal for EPSRC tackling green manufacturing of nanomaterials, which is now funded. Some of the preliminary data for this proposal is obtained from this current grant.
Collaborator Contribution See above.
Impact N/A
Start Year 2014
 
Description Enabling green manufacturing (proposal) 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution We developed a large proposal for EPSRC tackling green manufacturing of nanomaterials, which is now funded. Some of the preliminary data for this proposal is obtained from this current grant.
Collaborator Contribution See above.
Impact N/A
Start Year 2014
 
Description Enabling green manufacturing (proposal) 
Organisation University of Strathclyde
Country United Kingdom 
Sector Academic/University 
PI Contribution We developed a large proposal for EPSRC tackling green manufacturing of nanomaterials, which is now funded. Some of the preliminary data for this proposal is obtained from this current grant.
Collaborator Contribution See above.
Impact N/A
Start Year 2014
 
Description IPDaC 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a commercial development work addressing TRL4 in order to make our technology more attractive for commercial update.
Collaborator Contribution IP development and commercialisation support.
Impact An internal confidential report.
Start Year 2017
 
Description Scottish enterprise project with a company 
Organisation Scottish Enterprise
Country United Kingdom 
Sector Public 
PI Contribution This is a commercial consultancy project to convert a certain waste to a valuable product. We are embarking on this project to perform the materials chemistry, scale-up and application testing work.
Collaborator Contribution Market and environmental legislation, connection with a supply chain and users. Access to waste samples.
Impact N/A
Start Year 2018
 
Title Silica Synthesis (Amine Removal) 
Description Room temperature purification of porous silica and a scalable method thereof. 
IP Reference WO2017037460 
Protection Patent application published
Year Protection Granted 2016
Licensed No
Impact None yet, in the process of spinning out a company.
 
Description 3rd Annual EPSRC Manufacturing the Future Conference 
Form Of Engagement Activity Scientific meeting (conference/symposium etc.)
Part Of Official Scheme? Yes
Type Of Presentation poster presentation
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact A national conference where my group presented a poster and I was the member of the panel discussion.

Introduction to new ECRs in manufacturing.
Connection with equipment suppliers.
Networking with various other academics.
Year(s) Of Engagement Activity 2014
URL http://www.ukmanufacturing.org/
 
Description British Science Week-Science Day at Kelham Island 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Activity Workshops 100 pupils secondary change British Science week stimulating, hands-on, discussions, thought process
Year(s) Of Engagement Activity 2017
 
Description European Materials Research Society's conference 
Form Of Engagement Activity Scientific meeting (conference/symposium etc.)
Part Of Official Scheme? No
Type Of Presentation paper presentation
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Discussions of our results with international experts.

-
Year(s) Of Engagement Activity 2014
 
Description Making Green Nanomaterials 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was the first scientific symposium that we organised focussing on the sustainability of producing nanomaterials. It engaged international audience, included panel discussions and it is leading to a special issue in the journal Current Opinions in Green and Sustainable Chemistry.
Year(s) Of Engagement Activity 2017
URL https://ep70.eventpilot.us/web/page.php?page=Session&project=ACS17GCEC&id=255334
 
Description ProcessAbility 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Key issues in processability were identified and fed back to policy makers, government and research community.

Shared outcome.
Year(s) Of Engagement Activity 2014
URL http://beyondthemolecule.org.uk/d6/node/8
 
Description RAMS conference 
Form Of Engagement Activity Scientific meeting (conference/symposium etc.)
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact New collaborations.
New contacts with RSC and academics.

Set-up of visits by 2 scientists to my group/department.
Year(s) Of Engagement Activity 2014
URL http://rams-materials.org/