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.

Publications

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Pallares RM (2019) Quantifying the binding between proteins and open chromatin-like DNA sequences with gold nanorods. in Chemical communications (Cambridge, England)

 
Description Magnetic nanoparticles were initially synthesised through batch chemistry routes. Such protocols were then transferred to millifluidic reactors exploring a parametric space that enables syntheses under a wide range of pressures and 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 were developed taking advantage of the attractive features of microfluidic technologies; rapid heating and tight control over the reaction parameters. This approach was able to produce core-shell nanoparticles with high productivity and high values of heating under magnetic field. Flow synthesis allowed to produce iron carbide nanostructures in lower temperatures than those typically employed in batch synthesis. A passivating, naturally formed oxide layer helped to maintain remarkable magnetic properties for prolonged time, due to the compositional stability of the particles. Competitive hyperthermia properties were achieved for the iron carbide nanostructures. Silica coating of the synthesised magnetic particles was investigated and achieved in batch in order to prevent further oxidation and to enable further functionalisation of the nanoparticles for biomedical applications. However, it proved challenging to transfer to flow. Coating with noble metals was not achieved, due to the large lattice mismatch between the core and shell metallic elements. Furthermore, iron oxide nanoparticles of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods, such as thermal decomposition or co-precipitation, this process yielded nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere.
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 manner to enable tighter control over the experimental conditions.
Sectors Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description 10th International Conference on Materials for Advanced Technologies (ICMAT 2019) Symposium Y: "Colloidal Nanoparticle-Based Probes and Sensors" (Jointly organized with MRS Japan), Singapore. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". ICMAT 2019. Singapore. Jun. 2019
Year(s) Of Engagement Activity 2019
 
Description 10th International Conference on Materials for Advanced Technologies (ICMAT 2019) Symposium J "Micro/nano-technology for Drug Delivery and Imaging", Singapore. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications".ICMAT 2019. Singapore. Jun. 2019
Year(s) Of Engagement Activity 2019
 
Description 5th International Workshop on Novel Magnetism and Multifunctional Materials, Hanoi, Vietnam. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications".Hanoi, Vietnam. Jan. 2019
Year(s) Of Engagement Activity 2019
 
Description ACS Applied Materials & Interfaces, to be held at the Spring ACS National Meeting (March 31 - April 4, 2019) in Orlando, Florida 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". March 31 - April 4, 2019. Orlando, Florida
Year(s) Of Engagement Activity 2019
 
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 EU COST TD142 - Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (Radiomag), Bilbao, Spain 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Bilbao, Spain, Apr. 2017
Year(s) Of Engagement Activity 2017
 
Description EU COST TD142 Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (Radiomag), Annual Action Progress Conference, Florence, Italy 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Florence, Italy. Oct. 2018
Year(s) Of Engagement Activity 2018
 
Description EU COST TD142 Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (Radiomag), Annual Action Progress Conference, Timisoara, Romania 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Timisoara, Romania. Mar. 2018
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 European Nanomedicine Meeting, London, UK 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". European Nanomedicine Meeting, London, UK. Invited by Prof Steve Rannard. April 2017
Year(s) Of Engagement Activity 2017
 
Description Fourth Hellenic Forum for Science and Technology and Innovation, Athens, Greece 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Fourth Hellenic Forum for Science and Technology and Innovation, Athens, Greece. Invited by Prof Gorge Loudos. Jul. 2016
Year(s) Of Engagement Activity 2016
 
Description Functional Nanomaterials in Industrial Applications: Academic-Industry Meet, Preston, UK. Keynote speaker. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Functional Nanomaterials in Industrial Applications: Academic-Industry Meet, Preston, UK. Keynote speaker, Invited by Dr Tapas Sen. Mar. 2016
Year(s) Of Engagement Activity 2016
 
Description ICMAT symposium AA of advanced ceramics and nanohybrids for energy, environment and health. Singapore. Invited by Prof Federico Rosei. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications", ICMAT, Singapore.July 2015
Year(s) Of Engagement Activity 2015
 
Description Keynote Lecture at the 6th Annual Postgraduate symposium on Nanoscience and Nanotechnology, School of Chemistry at the University of Birmingham, UK. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". 6th Annual Postgraduate symposium on Nanoscience and Nanotechnology, School of Chemistry at the University of Birmingham, UK. Invited by Dr Dwaipayan Chakrabarti. Dec. 2016
Year(s) Of Engagement Activity 2016
 
Description Keynote, 2019 Hanoi International Symposium on Advanced Materials and Devices (HISAMD2019) Hanoi, Vietnam 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications".HISAMD2019. Hanoi, Vietnam. Jan.2019
Year(s) Of Engagement Activity 2019
 
Description Mentor for Vietnam-UK Workshop on Microfluidics, Nanomaterials, and Point-of-Care in Healthcare for developing countries, Ho Chi Minh City, Vietnam. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Ho Chi Minh City, Vietnam. Jun. 2018
Year(s) Of Engagement Activity 2018
 
Description Micro /Nanotechnologies for Diagnostics and Therapeutics workshop organised by Royal Society Chemistry Biotechnology Group. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Apr. 2019
Year(s) Of Engagement Activity 2019
 
Description Nano-biotechnology on Interfaces Symposium at IUMRS-ICAM 2017, the 15th International Conference on Advanced Materials. Kyoto. Japan. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Kyoto. Japan, Sep. 2017
Year(s) Of Engagement Activity 2017
 
Description Oral presentation at "Nanoparticles for Cancer Diagnosis and Therapy" conference sponsored byBritish Society of Surgical Oncology and Royal Society of Medicine 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications".invited by Professor Riccardo Audisio. Nov. 2015
Year(s) Of Engagement Activity 2015
 
Description Oral presentation at CSIR, National Chemical Laboratory and IIT in India (2020) on "Metal manoparticle synthesis in millifluidic systems" 
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 by Prof Asterios Gavriilidis.
Gavriilidis, A. "Metal manoparticle synthesis in millifluidic systems", CSIR, National Chemical Laboratory, Pune and IIT, Mumbai, India, January 2020.
Year(s) Of Engagement Activity 2020
 
Description Oral presentation at St John's College, Cambridge (2019) on "Development of a nanoparticle synthesis millifluidic systems - A reaction engineering approach" 
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 by Prof Asterios Gavriilidis.
Gavriilidis, A. "Development of a nanoparticle synthesis millifluidic systems - A reaction engineering approach", Manufacturing of materials in flow, St John's College, Cambridge, UK, 22 - 24 September 2019.
Year(s) Of Engagement Activity 2019
 
Description Oral presentation at the NATO ASO series (2019) on "Iron oxide nanoparticles: Systematic improvement of particle properties and reduction of synthesis time" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An oral presentation by Dr Liudmyla Storozhuk.
Storozhuk, L., Besenhard, M.O., LaGrow, A.P., Gavriilidis, A. and Thanh, N.T.K. "Iron oxide nanoparticles: Systematic improvement of particle properties and reduction of synthesis time", NATO, ASI, Nanoscience and Nanotechnology in Security and Protection Against CBRN Threats, Sozopol, Bulgaria, 12-20 September 2019.
Year(s) Of Engagement Activity 2019
 
Description Plenary lecture in "Nanoparticle synthesis, structure, properties, safer-by-design" Section of 7th biannual International Meeting of The Institute of Metals in Biology of Grenoble (IMBG) "Metallic nanoparticles: health, environment, applications and safer-by-design", Grenoble, France. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Grenoble, France. Oct. 2017
Year(s) Of Engagement Activity 2017
 
Description Plenary talk at the 7th International Conference in Vietnam on the Development of Biomedical Engineering, Ho Chi Minh City, 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Ho Chi Minh City, Vietnam. Jun. 2018
Year(s) Of Engagement Activity 2018
 
Description Symposium N "Advanced Ceramics and Nanohybrids for Energy, Environment and Health symposium", ICMAT 2017, Singapore. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". ICMAT 2017, Singapore.
Year(s) Of Engagement Activity 2017
 
Description Symposium V "Nanomaterials": Design and hierarchical assemblies of nanomaterials (nanoparticles, carbon materials, molecules) towards energy, sensing, electronic, catalysis and detection applications, Strasbourg, France. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Strasbourg, France. May 2017
Year(s) Of Engagement Activity 2017
 
Description The 3rd Overseas Academicians Qingdao Tour & Qingdao International Academicians Conference, China 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". China. May 2019
Year(s) Of Engagement Activity 2019
 
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
 
Description UK Magnetics Society seminar on MRI and Magnetic Particles for MRI Diagnostics, University of Oxford, UK 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Oxford, UK. Feb. 2019
Year(s) Of Engagement Activity 2019
 
Description UK-India Education and Research Initiative (UKIERI) Workshop on Magnetic nanoparticles characterisation and applications, University of Centre Lancashire, UK. 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". University of Centre Lancashire, UK. Invited by Dr Tapas Sen. Aug. 2015
Year(s) Of Engagement Activity 2015
 
Description Worldwide Meeting of Young Academy and Nanomaterial for Health jointly organized with Global Young Academy and Vietnam Young Academy, Da nang, Vietnam 
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 by Prof. Nguyen T.K. Thanh "Plasmonic and magnetic nanoparticles for biomedical applications". Da nang, Vietnam. Jul. 2019
Year(s) Of Engagement Activity 2019