MAGNETIC NANOPARTICLE ENGINEERING via MICROREACTION TECHNOLOGY

Lead Research Organisation: University College London
Department Name: Chemical Engineering

Abstract

Inorganic nanoparticles (NPs) have the potential to dramatically modify existing materials as well as engineer a broad range of transformative new products. They have unique magnetic, optical, electronic, catalytic properties not encountered in bulk materials and as such they present the opportunity to address some of the most pressing global challenges in healthcare, energy, transport, climate and security. Nanoparticles offer ideal solutions for detecting and treating many diseases. Used as targeted drug-delivery systems, they can improve the performance of medicines already on the market. They enable the development of new therapeutic strategies such as anti-cancer drug delivery, extending product life cycles and reducing healthcare costs. Magnetic nanoparticles (MNPs) have exciting potential biomedical applications. They have been considered for diagnostics, such as magnetic resonance imagining, magnetic particle imaging and magnetic immunoassay for sensing, as well as in therapeutics, such as hyperthermia cancer treatment (using targeted magnetic heating to kill cancer cells). Cancer is a leading cause of disease worldwide with an estimated 12.7 million new cancer cases occurring in 2008. If recent trends in major cancers continue, the burden of cancer will increase to 22.2 million new cases each year by 2030. Cancer is also a leading cause of death worldwide, with 7.6 million deaths (around 13% of all deaths) in 2008.

Magnetic iron oxide NPs currently available in the market have low saturation magnetisation, and therefore require high concentration as well as high external magnetic field to achieve effective heating. This proposal aims to fabricate higher magnetic moment NPs, with enhanced performance as compared to currently used magnetic nanoparticles (MNPs). The proposed transition elements MNPs are highly desirable, but it has been notoriously difficult to synthesise them with accurate control of size and size distribution. Moreover, they are prone to oxidation which has detrimental effects, as their magnetic properties (magnetic moment) are significantly reduced or entirely lost. Coating pure metal and alloy MNPs with inert materials such as silica and gold has been the obvious approach to protect the core MNPs from oxidation. This has proved challenging due to incomplete coating, and leads to long term chemical instability of NPs. Furthermore, most of MNP synthesis is currently done in batch, which suffers from poor reproducibility. In this project, we will use a novel approach for "bridge" coating of MNPs. We will further employ continuous flow technology which is an enabling tool for better control of the synthesis of MNPs. It allows accurate control of operating conditions, as well as spatial separation of the nucleation, growth and coating steps. We have a multidisciplinary team of engineers, chemists and physicists who will combine their strong expertise in flow microreactor technology, materials chemistry and physics to push the frontiers in materials design and discovery by engineering novel synthetic routes and by taking advantage of the enhanced functionalities offered by continuous flow processing. We will demonstrate the success of our synthetic approach in magnetic hyperthermia, one of the most sought after clinical applications in combating cancer, by testing the MNPs efficacy for killing cancer cells in vitro.

Planned Impact

Impact on economy. Nanotechnologies are important to the UK future because of their potential to improve many types of consumer products. The worldwide transition toward the use of nanotechnologies is a significant economic opportunity for the UK. Even the most conservative forecast predicts that the global market in nano-enabled products is expected to to grow to $81 billion in 2015. This work will contribute to keeping the UK at the forefront of nanotechnology by enhancing UK's strategic capability. The materials, healthcare and chemical industries will be the main beneficiaries of this work, by accessing novel technology and nanoparticles for improved therapeutic/diagnostic applications. Such magnetic nanoparticles will be more robust and efficient. The outcome of this research will give a significant competitive advantage to the materials industry, assisting it to remain at the forefront of innovation worldwide. Nanomedicine is still in its infancy, so cutting edge technology will play a key role in developments in this potentially lucrative area. The research proposed can lead to technology which is applicable to other materials manufacturing industries ranging from catalysts to energy storage materials, thus benefiting in the longer term other manufacturing sectors.

Impact on knowledge. This work will assist Research & Development laboratories involved in nanoparticle research, both in industry and academia, to optimize nanomaterial synthesis. The crystallisation processes associated with nanoparticle synthesis are still not well understood, so that no accurate theory can substitute empirical investigation. Microfluidic reactors offer unequalled experimentation conditions to explore nanomaterials synthesis processes, since small scales facilitate excellent control of flow patterns, transport phenomena and crystallisation processes.

Impact on society. Nanoparticles offer the opportunity to radically change how we diagnose and treat diseases through ground-breaking advances in targeted and time-controlled drug delivery, radiotherapy, cancer treatment and regenerative tissue engineering. They will enable more efficient and less harmful diagnostic and therapeutic techniques. Thus, the health of the wider public will benefit through the provision of new materials which can help diagnosis and treatment of critical illnesses. Should this technology become established and readily available, it will greatly benefit the society at large, improving life-quality and life-expectancy.

Impact on people. The project will result in highly trained researchers with professional skills in a wide range of areas, including nanotechnology, microfluidics technology and flow materials chemistry. It will develop their ability to work independently and in a team, expose them to interdisciplinary research and facilitate the acquisition of transferable skills that will enhance their learning process and broaden their horizons. These will make them valuable assets to academic departments or R&D departments of high-tech companies.
 
Description Magnetic nanoparticles have been synthesised in a millifluidic reaction exploring a parametric space that enables syntheses under higher pressure and high temperatures. These systems were used to explore the effect of the experimental parameters on the size, monodispersity and properties of resulting nanoparticles. Novel synthesis protocols are being developed taking advantage of the attractive features of microfluidic technologies; rapid heating and tight control over the reaction parameters. Coating of the synthesised magnetic particles is investigated in order to prevent further oxidation and to enable further functionalisation of the nanoparticles for biomedical applications.
Exploitation Route The nanoparticle synthesis reactors developed in this project provide a platform that can be used by academics and industrialists to explore a parametric space that is not possible with batch experiments. Additionally, the synthesis of magnetic nanoparticles can be achieved in a continuous mater to enable tighter control over the experimental conditions.
Sectors Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description COST - RADIOMAG2017 Poster presentation - Continuous millifluidic synthesis of core-shell Fe/FexOy NPs 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation: Katerina Loizou, Stephanos Mourdikoudis, Andreas Sergides, Nguyen T. K. Thanh and Asterios Gavriilidis - Continuous millifluidic synthesis of core-shell Fe/FexOy NPs
Year(s) Of Engagement Activity 2018
 
Description EUROMAT2017:"Continuous Millifluidic Synthesis of Monodisperse Fe/FexOy Nanoparticles" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral Presentation: K. Loizou, S. Mourdikoudis, A. Sergides, A. LaGrow, L. Mazzei, N. Thanh, A. Gavriilidis, "Continuous Millifluidic Synthesis of Monodisperse Fe/FexOy Nanoparticles", EUROMAT 2017, Thessaloniki, Greece, 17-22 September 2017.
Year(s) Of Engagement Activity 2017
 
Description UK Colloids 2017: "Fe-based nanoparticles synthesized by 'batch' chemical routes - Modified synthetic approaches, novel routes and perspectives" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral Presentation: S.Mouridkoudis K. Loizou A.Gavriilidis N.Thanh Fe-based nanoparticles synthesized by 'batch' chemical routes - Modified synthetic approaches, novel routes and perspectives
Year(s) Of Engagement Activity 2017