Magnetite synthesis in biomimietic nanovesicles: innovative synthetic routes to tailored bio-nanomagnets

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


Scientific and economic interest in nanotechnology has grown in recent years. Within this the quest to produce tiny and highly tailored magnetic particles, or nanomagnets is crucial. Nanomagnets have a range of practical uses. Historically they have been used for information storage such as tapes and hard drives. Recently this has expanded with the development of 3D information storage systems providing high density data storage. There is much interest in the medical applications of nanomagnets. Magnetic particles are being developed to provide targeted medicine within the body. For example, if drugs are tied to nanomagnets at the molecular level then they can be directed by a magnet to specific sites within the patient. This allows a drug to be delivered to a specific area, without harming the rest of the body. Similarly, nanomagnets can be used in hyperthermic therapies. This is where, after being directed to specific tumour sites, magnetic particles are heated to either destroy a tumour or activate a drug. Such particles also already have used as image enhancers for diagnostic medicine. However, as nanotechnology grows, so too does the need to develop precisely engineered nanomagnets. Different applications demand different shapes and sizes of particles and different magnetic properties. Producing nanomagnets with highly controlled; composition, size and shapes, in large enough amounts to be of use to these industries, has therefore become a key goal of researchers.Biomineralisation is the process that occurs in living organisms to produce minerals such as bones. Because genetics control biomineralisation processes the materials produced exhibit very precise, uniform and intricate formations down to the nanoscale. Magnetotactic bacteria biomineralise high quality uniform nanoparticles of the iron-oxide magnetite within biological shells (or vesicles) called magnetosomes, within the bacterial cell. Because magnetosomes exhibit considerable uniformity and precision they present a novel and attractive route to produce high quality nanoparticles.However, the biomineralisation method produces inefficient yields for commercial production and is also not very flexible, as the cell strictly controls morphology and composition, so the particles cannot be easily adapted (e.g. maximum cobalt doping 1.4%).In order to synthesise precision customised magnetic nanoparticles, we will explore a biomimetic approach where we take inspiration from nature to develop a nano-magnetite precipitation system within artificial magnetosome vesicles outside the cell. We will perform a simple ambient temperature chemical precipitation of magnetite within nano-vesicles to help control the particle size and incorporate biomineralisation proteins into the interior of the vesicles to further impose biologically precise morphology over the particles. The system will combine all the benefits of biomineralisation such as morphological precision and a biocompatible coating, with all the benefits of a chemical precipitation such as high yields and a more malleable system with respect to variation, so particles can be customised.Additionally this formation technique uses environmentally friendly conditions and the addition of a biocompatible lipid coating to the particles is also highly advantageous for healthcare applications.


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Description Inspired by magnetotactic bacteria, this research project developed for the first time a bio-mimetic, simple, multi-step electrically driven process for the synthesis of magnetite nanoparticles within nano-vesicles (fine shells encapsulating liquid). Lipid nano-vesicles, encapsulating sodium hydroxide (NaOH) were synthesized using a single-needle bi-port electrically driven device. Optimization of various parameters was done to achieve uniform sized nano-vesicles, which were to be used as reaction vessels for synthesizing magnetite within nano-vesicles. These nano-vesicles were then electroporated (perforated without breaking using an electric pin) with ferrous/ferric ions, mimicking the bacterial methodology of external iron transport into bio-vesicles (magnetosome), ultimately reacting inside the vesicle with NaOH to furnish magnetite nano-crystals. The whole approach of synthesizing magnetite in the laboratory, mimicked the magnetotactic bacteria where the process is controlled by specialized enzymes and genes.
Exploitation Route Magnetite has been used widely for recording data in compact disks. Nano-sized magnetite has been known to significantly increase the capacity of recording. The application of nano-magnetite in MRI is well known. There are several other important applications of single domain nano-magnetite and this kind of magnetite, quantity-wise is in demand. Thus, the methodology reported to generate nano-sized magnetite is hence very important for many consumers. Synthesis of magnetite within nano-vesicle mimicking bio-mimicking magnetotactic bacteria has been achieved under this research project. What has been lacking is the application of mass production amenable processing and forming/manufacturing.This project developed a novel methodology to prepare nano-vesicles of lipids using electrohydrodynamic (EHD) technology. Different types of EHD needles were used and they individually yielded nano-vesicles but in different size ranges. This methodology to prepare nano-vesicles is far easier this way as well as high yielding in comparison to conventional methods of preparing vesicles. This methodology can be used successfully to prepare uniform sized nano-vesicles. There are many biomedical routes of exploitation well advertised in the literature. This can be further extended to synthesize tailored sizes, single crystals, high quality magnetite which has several other engineering applications and the exploitation is rather limitless. The impetus developed by this grant has enabled younger researchers like Bain and Staniland et al. speahead their research - see:
Sectors Chemicals,Construction,Creative Economy,Digital/Communication/Information Technologies (including Software),Education,Electronics,Energy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Other

Description The biomedical and nanotechnological potential of magnetosomes for multiple applications is huge, owing to the strict size and shape control of the magnetic nanoparticles and biocompatible lipid coating. However, magnetotactic bacteria are fastidious, slow-growing microbes and magnetosomes are restricted to the natural form, resulting in low-yields of inflexible nanomaterials. Therefore, a key challenge is to create artificial magnetosomes in vitro, offering a high-yield route to more adaptable functional magnetic nanoparticles and a model system for biomineralisation in magnetotactic bacteria . Here we realise this goal and are at present preparing a very high impact document for the public domain, a summary of which is given below: Magnetotactic bacteria produce magnetic nanoparticles (MNP) within lipid vesicles (magnetosomes) whose size and morphology is tightly controlled.1-3 Magnetosomes have huge biomedical and nanotechnological potential.4 However they are restricted to their natural form and the bacteria are fastidious and slow-growing, resulting in magnetosomes of inflexible nanomaterials in low-yields. Making artificial magnetosomes in vitro to overcome these issues is a key research goal, offering a high-yield route to more adaptable functional MNPs and representing a model system to investigate biomineralisation. Here we achieve this goal by formation of lipid nano-vesicles (liposomes) using high-throughput electrohydrodynamic atomisation (EHDA) followed by the use of electroporation to transport iron into the nano-liposome core resulting in magnetite crystallisation. A single-crystal of single-phase magnetite MNP of 58 nm (±8 nm) precipitated within each liposome, forming a near-monodisperse population. The particles were assessed by TEM, CryoTEM, fluorescence microscopy, DLS, Raman spectroscopy and magnetic susceptibility measurements. The results indicate the potential for a commercially viable route of producing high-yields of adaptable artificial magnetosomes. The work has now been published and featured on Advanced science News, see: The publication was chosen to feature as a cover page and achieved a very high altmetric score of 10. And this has given an impetus to co-PI Staniland to pursue further work in this area, see:
First Year Of Impact 2014
Sector Aerospace, Defence and Marine,Chemicals,Digital/Communication/Information Technologies (including Software),Education,Electronics,Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Security and Diplomacy
Impact Types Societal,Economic

Description Using electrohydrodynamics to make food-protein bubbles and vesicles 
Organisation University of Wageningen
Department Wageningen Food & Biobased Research
Country Netherlands 
Sector Academic/University 
PI Contribution Teaching them how to use electrohydrodynamics and related equipment to process porous food materials
Collaborator Contribution Supplying relevant meetings, visiting my lab and paying a researcher from their payroll to make the trial products
Impact Langmuir, 2014, 30 (23), pp 6694-6703
Start Year 2012
Description Key USA conferences such as TMS, MS&T and MRS -keynote/invited, annual invited participation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Sessions dedicated to novel manufacturing routes for biomedical engineering
Year(s) Of Engagement Activity 2015,2016,2017