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Developments in Nanotechnology

13/02/2012


Dr Éilis McGrath and Dr David McGovern of Trinity College Dublin outline recent work on nanostructures and nanocoatings for an expanding range of applications.

In the world of nanoscience, as surface areas increase relative to volume, materials can take on intriguing new properties. Insulators can become conductive, soft materials can display incredible strength and coloured materials can become transparent. These remarkable changes provide exciting opportunities for traditional businesses to develop improved devices or processes and for new enterprises to develop revolutionary products. The possibilities in the field of nanoscience are immense and nanotechnology touches almost all areas of human endeavour, from advanced technologies and silicon chips to medical devices and new ways to treat and diagnose disease.

A nanoscale material is defined as, "A material with one or more dimensions of <100 nm.”1 In practice, nano has come to describe many different forms of materials and technologies such as nanowires, nanosheets, nanocrystals, nanobiology, nanoscience and nanomedicine, to name a few. To put it in perspective, one nanometre is 10-9 metres, that is one billionth of a metre. A human hair is approximately 50,000 nm in width and one nanoparticle is approximately one million times smaller than the full stops used in this article.

Figure 1 shows the range of colours available for nanoparticles of cadmium telluride (CdTe) of different diameters. These particles are small semiconducting crystals known as quantum dots, which can absorb a range of colours depending on their size. Nanoparticles are being used in a variety of applications including as excellent dyes for biological applications.

    

Figure 1: These images show CdTe quantum dots of between 2.5 and 5 nm in size as the colour changes from green to red (left to right).

Images supplied by Professor Yurii Gun`ko, Ms Valerie Gerard and Professor John Donegan2,3


Nanoresearch in Ireland
In Ireland, nanoscience underpins major sectors of the economy. In 2007, Ireland exported €13.2 billion in goods, of which it is estimated 10% were enabled by nanoscience and related technologies. Ireland is already home to fifteen of the world’s top twenty medical device manufacturers. Nanotechnology is fast becoming one of the most important areas in the advancement of technology in this industry.

The Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) at Trinity College Dublin, which operates in partnership with University College Cork, is recognised internationally as a leading institute for nanoscience research and collaborative industry engagement. CRANN is funded through Science Foundation Ireland (SFI) and has more than 250 researchers. It works at the frontiers of research in nanoscale chemical, physical and biological phenomena, with a particular focus on medical device and sensor technologies. CRANN researchers publish more than 150 peer review articles annually. A Thomson-Reuters report in late 2010 placed Ireland eighth globally for materials science research based on citations per publication for the decade 2000 to 2010. CRANN researchers were responsible for more than 70% of the outputs associated with this national ranking.

CRANN’s industry engagement has grown significantly during the past two years. Through the support of SFI, Enterprise Ireland, European Union and Higher Education Authority research funding, as well as industrial support from companies such as Hewlett-Packard and Intel, CRANN offers industry access to leading research facilities. Its new Advanced Microscopy Laboratory houses many of the world’s most advanced microscopy tools for examination of materials on the atomic scale. These tools include the only helium ion microscope (HeIM) in Ireland and one of only approximately one dozen in the world. The HeIM has recently been used to image uncoated mammalian cancer cells for the first time yielding a wealth of information about cell surfaces.2

Many exciting nano-enabled medical devices are being developed at CRANN. One area has been the development of micron-sized sensors for use with micro-organisms such as Methicillin-resistant Staphylococcus aureus (MRSA), which if detected later than 72 hours after infection can become resistant to treatment. Unlike traditional methods of detection, which may take hours or overnight incubation, the CRANN sensors can detect growth of just a few micro-organisms within minutes.

Other work includes the evaluation of the diagnostic and therapeutic potential of nanoparticles, development of bar-coded nanowires for multiplexed detection of bio-markers molecules for disease, and nanoscale coatings for medical devices and biological applications.

Surfaces
Understanding how materials work and react with the body at the nano level will revolutionise medical devices and CRANN is helping companies to get a closer look at the surfaces that matter. From stents to artificial joints, it is the surface layer of the medical device that interacts with the body and/or biofluids. In a matter of milli- or micro-seconds biomolecules will adhere to implanted surfaces and it is this vital initial interaction and interfacial layer that will determine an implanted device’s ultimate success. Nanoscience is at the forefront of this dynamic interfacial layer formation because nanostructures are generally smaller than cells, which range in size from 10,000 to 20,000 nm.3 Cells can interact specifically with nano-textured surfaces and in particular to ordered symmetries, because they have inherent features that can detect this nanotopography.4 Nanofeatures may help to influence which cells will adhere and thrive on a surface.

A focal point of CRANN’s current research is the production of nanostructured surfaces for enhancing the capabilities of medical devices. For decades, it had been noted that adding texture to implants increased their biocompatibility.5 Devices with a certain degree of nanoscale roughness function better in vitro than those with smooth or microrough surfaces.6,7 In addition, nanostructured materials show superior mechanical, electrical, magnetic, optical and biomechanical properties compared with micron-sized materials.8

Focus on porous polymers
Many biological systems display self-organising patterns, including the physiological development of living organisms as they grow.9 Biomimetics is the study and development of synthetic systems that imitate biological structures and processes. Work on porous polymers developed by CRANN is aimed at exploiting self-organisation biological principles with the ambition of influencing much broader technological applications (Figure 2).



Figure 2: Scanning electron microscopy image of ordered porous polymer surface
Images supplied by Dr Ronan Daly

Modern techniques have allowed us to use complex scientific methods to examine and produce features of ever decreasing dimensions, however, direct material machining approaches face increasingly significant challenges. The requirement for complex, patterned and controlled three-dimensional structures enforces strict design criteria that result in ever increasing energy and monetary costs. Nanomaterials differ in their production from conventional materials because they are preferably manufactured by a "bottom-up” additive process, as opposed to a "top-down” subtractive approach, as seen with traditional manufacturing techniques.10 This has led scientists to look to nature for ways to solve the problem of complex top-down approaches by seeking to mimic self-organising mechanisms observed throughout the natural world.

New coatings for medical devices are continuously being developed. These have lead, for example, to improvements in implant technology through the design and development of drug eluting stents; however, problems have arisen. Coatings that allow drugs to be embedded can have adverse drug interactions, incomplete stent apposition and increased in-stent thrombosis rates.11 A solution could come in the form of nanopatterned coatings that would lie beneath the drug eluting external layer. A porous polymer superhydrophobic coating could help to repel biomolecules and cells, thus leaving the stent clear and free from clotting.

Applications
Porous polymers have the potential to deliver new biocompatible nanodevices or nanotemplates for medical applications. Creating 2D and 3D ordered porous polymer films is of great interest in the biomedical field,12 where they enable a variety of applications, including:

  • drug infused films to treat wounds, or as surface coatings on heart stents or catheters
  • transdermal drug delivery
  • hydrophobic surfaces capable of repelling liquids
  • tissue scaffolds to promote cell growth
  • coatings that have the ability to elicit positive cell behaviours, depending on the use of the coated medical device (Figure 3). 




Figure 3: Microspheres on structured film. The polymer substrate is made using the self-organisation technique described herein. The SiO2 spheres are positioned extremely close, but not touching, which is essential for observations of photonic coupling between the spheres. This work was part of a collaboration between the groups of Professor John Boland and Professor John Donegan. 


Image supplied by Dr Ronan Daly


A study published in 2011 has used nanopores to test and measure how proteins move into a cell nucleus.13 This type of work can be used to look at how our innate natural systems select proteins to interact with, and could be used as a test platform for drug delivery studies. Currently, many ordered porous polymer surface production methods require costly, complex, multistage processing. For example, a multistage production method may utilise microspheres as a pore template followed by solvent washing to reveal the pores. This technique is limited in its control in terms of the total porosity and pore geometry, due to the use of a solid template. Other techniques use thermally induced phase separation, where after freeze drying, a highly porous but disordered product remains.

Manufacturing porous polymers
The self-organisation technique employed to produce porous polymer surfaces is based on the Breath Figure Method first reported in 1994.14 The name relates to the breath figures (patterns that form when a vapour is condensed onto a cold surface) of condensing water droplets that appear on the surface of polymer solutions, which lead to the structures observed above.

The introduction of water vapour over a polymer/solvent solution leads to water droplet condensation at the polymer solution surface (due to evaporative cooling at the surface), then trapping of the water droplets by the polymer, and ultimately the imprinting of their shape on the surface. This results in ordered hexagonally packed porous microstructure of micron-scale pores supported by walls of nano-scale thin films at their narrowest points. This discovery led to considerable interest in porous microstructures produced via this method. The spherical microstructure was believed to be an intrinsic feature of this system and only limited reports of any changes in this regard were found without any post-processing techniques.

Using this novel technique, a porous film or coating with micron scale pores containing nanofeatures, whose depth, shape and function can all be controlled in a simple, robust, single step process, can be used to create porous polymer films for the medical device industry (Figure 3). The formation mechanism allows for a range of different pore geometries, thus adding significantly to the scope of potential applications. Furthermore, loading of active agents is typically achieved by solution dosing following porous film production, whereas this novel technique has the potential to load the active agents in a single step during film formation.

Advantages
These porous films have many advantages over current state-of-the-art products:
  • Single step synthesis allows for a complete production process integrated to one machine
  • Operation is simple and control over pore morphology is achieved using easily adjustable reaction conditions
  • Simple production techniques potentially allow for integration of many different materials into the polymer membrane and therefore provide a diverse range of functionality for this product
  • The technique used to create porous polymer surfaces is also capable of scale-up to produce high throughput thus making it suitable for industrial levels of production
  • This method of production is simple, cost-effective and has low material requirements.
Burgeoning potential
The remarkable self-ordering observed in these polymer samples mimics the ordering within
systemsin nature in a simple and elegant manner.
The vast array of nanoscale order in the natural world and how it is used to such great effect is in itself a wonder. This technique coupled with the enabling surface monitoring technologies at CRANN will hopefully lead to a range of technologies inspired by the nano-natural world, which is all around us.

Acknowledgements
We would like to thank the following contributors:
Dr Chris Keely, Professor John Boland, Professor John Donegan, Professor Yurii Gun`ko, Ms Valerie Gerard, Dr Paul Miney, Dr Ronan Daly and Ms Mary Colclough.

Additional Information
For more information regarding these porous polymers see the Trinity College Alumni video on
Med-Tech TV

To find out more about how companies can work with CRANN, contact Brendan Ring,
CRANN Commercialisation Manager, Trinity College Dublin,
tel. +353 (0)1 896 3088, e-mail: brendan.ring@tcd.ie.

References
1. ISO/TC229 Documentary standards for nanotechnology,
TR ISO, 2008.
2. D. Bazou et al., "Imaging of Human Colon Cancer Cells Using He-Ion Scanning Microscopy,” J. of Microscopy, 42, 3,  290–294 (2011).
3. S.E. McNeil, "Nanotechnology for the Biologist,” J. Leukoc. Biol., 78, 3 585–594 (2005).
4. A.S.G Curtis et al., "Cells React to Nanoscale Order and Symmetry in Their Surroundings,” IEEE Transactions on Nanobioscience, 3, 1, 61–65 (2004).
5. R.G. Flemming et al., "P. F. Effects of Synthetic Micro-and Nano-Structured Surfaces on Cell Behavior,” Biomaterials, 20,
6, 126 –135 (1999).
6. T.J. Webster et al., "Nanoceramic Surface Roughness Enhances Osteoblast and Osteoclast Functions for Improved Orthopaedic/Dental Efficacy,” Scripta Materilia, 44, 8–9, 1639–1642 (2001).
7. N. Gadegaard et al., Nano Patterned Surfaces for Biomaterials Applications,” Advances in Science and Technology, 53, 107–115 (2006).
8. S.J. Kalita et al., "Nanocrystalline Calcium Phosphate Ceramics in Biomedical Engineering,” Materials Science & Engineering, C 27, 3 441–449 (2007).
9. E. Karsenti, "Self-Organisation in Cell Biology: A Brief History,” Nature Reviews Molecular Cell Biology, 9, 255-262, (2008).
10. D. Vollath, Nanomaterials, Wiley-VCH (2008).
11. B.L. van der Hoeven et al., "Drug-Eluting Stents: Results, Promises and Problems, Intl J. of Cardiology, 99, 1 (2005).
12. S. Zhang et al., "Fabrication of Ordered Porous Polymer Film via a One-Step Strategy and Its Formation Mechanism,” Macromolecules, 42, 10, 3591–3597 (2009).
13. Mimicking Nature at the Nanoscale: Selective Transport Across a Biomimetic Nanopore – Physorg.com, www.physorg.com/news/2011-06-mimicking-nature-nanoscale-biomimetic-nanopore.html
14. G. Widawski et al., "Self-Organised Honeycomb Morphology of Star-Polymer Polystyrene Films," Nature, 369, 387–389 (1994).

Dr Éilis E. McGrath is Technical Marketing Officer and
Dr David A. McGovern is Commercialisation Technical Specialist at;
CRANN Innovating Nanoscience, Trinity College Dublin, Dublin 2, Ireland,
tel. +353 (0)86 847 2564,
e-mail: eilis.mcGrath@tcd.ie
www.crann.tcd.ie




   

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