Richard Moore

Transcript

1. Richard Moore Biomimesis
2. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 2 What’s next for medical devices? Richard Moore richard@biomimesis.co Med-Tech Innovation Expo 2013 Image: Plessey
3. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 Clinical drivers for innovation 3
4. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 4 Current healthcare challenges
5. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 5 Health trends in the developed world Societal trends • Growing elderly population: demands to stay active at an older age • Longer life spans: increased incidence of degenerative disease • Unhealthy modern lifestyles: leading to chronic diseases • Reduction of birth rates: reduced tax base Economic trends • Economic constraints and dncreasing drive for cost-effective treatments
6. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 6 Clinical needs driving innovation
7. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 Nanotechnology in medical devices 7
8. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 8 E-Medicine Telemedicine Bioinformatics Micro- and nano-electronics Regenerative medicine Nanotechnology Biophotonics Biological sciences Information technology Materials science An increasingly convergent approach in medical technology
9. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 9 Nanotechnology: an increasing impact on medicine Before the late 1980s, the term “nanotechnology” was virtually unknown in medicine. Medical technology has now evolved from being mainly pharmacologically- and engineering-based into a new era characterised by a high degree of convergence of different branches of science. Understanding at the nanoscale is underpinning almost all aspects of this evolution.
10. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 10 The basic building blocks of biology operate at the nanoscale A greater understanding of how living systems work at the nanoscale is leading to better understanding of disease mechanisms and better ways to prevent and treat disease Why is small important for healthcare?
11. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 11 Nanoscale materials and biological entities
12. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 12 Nanomedicine: possible trends and timelines
13. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 Some nanotechnology applications in devices 13
14. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 14 Dendrimers: drug delivery Nanowires: biosensors Nanocoatings: surgical implants, tools Quantum dots: imaging, sequencing Lab-on-a-chip devices: diagnostics Some examples of current nanoscale applications in medicine
15. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 15 Nanomedicine: Imaging - quantum dots Neuronal glycine receptors on dendrites of cultured spinal cord neurons Quantum dots Quantum dots as visible marker in mouse colon cancer study Quantum dots in blood flow velocity measurement
16. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 16 Nanomedicine: Imaging - imaging occult nodal metastases with superparamagnetic iron oxide nanoparticles Top: 3D of prostate, iliac vessels & metastases (red), normal (green) Bottom left: MION-CT: spatial distribution of metastases within pelvic LN (prostate) Bottom right: Solitary LN metastasis (red) adjacent to normal (green) LN in breast cancer
17. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 17 Implant topography Nanostructuring of implant surfaces to improve properties and performance Nanoscale “grooves” can increase cell adhesion and direct cell growth in a desired direction, whereas “pits” and “pillars” can decrease cell adhesion Pits are 125 nm wide by 75 nm deep.
18. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 18 Gesellschaft für Diamantprodukte (GFD) Ultra sharp diamond scalpel Cutting edge is only a few atoms wide (~3 nm) - approx. 1/1000 of a metal blade. Produced by “plasma polishing” Applications in eye and minimally invasive surgery Nanoscale coatings for improved performance of surgical tools
19. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 19 Nanocontoured and nanoengineered scaffolds for regenerative medicine Scaffold-guided tissue regeneration for skin and cartilage - commercially available. Bone, liver, nerve and blood vessels - in various stages of research and development Pittsburg Tissue Engineering Initiative Structuring surfaces of scaffolds at the nanoscale and coating them with different proteins and growth factors can improve cell adhesion, motility, growth and differentiation
20. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 20 Ellis-Behnke, Rutledge G. et al, (2006) Proc. Natl. Acad. Sci. USA 103, 5054-5059 Use of self-assembling peptide nanofibre scaffold to regenerate axons through a lesion site in hamster brain
21. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 21 Diamond-like coatings (DLCs) Prevent mechanical wear and biofouling in catheters and stents Hardwearing Reduce friction Sterilisable Do not react chemically with their environment University of Bonn Nanoscale coatings for prevention of biofouling
22. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 22 Novel MEMS/NEMS implantable devices 2mm artificial retina chip with 5000 microphotodiodes. Wireless and powered by incident light. Implanted into 30 patients with retinitis pigmentosa in a 2 hour microsurgical procedure. One of several studies on biointerface devices employing nanotechnology (artifical retina, artificial cochlear, neural interface devices). Nerves can interface with the chip components and the brain can learn to reinterpret signals. Optobionics Corp BrainGate Neural Interface System Cyberkinetics Inc
23. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 23 Lab-on-a-chip Commercial microfluidic lab-on-a-chip technology utilizes a network of channels and wells that are etched onto glass or polymer chips to build mini- labs. Pressure or electrokinetic forces move picolitre volumes in a finely controlled manner through the channels. Lab-on-a-chip approaches enable sample handling, mixing, dilution, electrophoresis and chromatographic separation, staining and detection on single integrated systems. The main advantages are ease-of-use, speed of analysis, low sample and reagent consumption and high reproducibility due to standardisation and automation. www.chem.agilent.com
24. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 24 On-chip attomolar-sensitivity protein detection Edgar D Goluch et al, Lab Chip (2006) 6, 1293-1299. Copyright © 2008 Yi Ge 16 Further functionalisation is possible at the nanoscale
25. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 25 Biosensors The (Nano)Biosensor Analytes (Bio)receptor Transducer Electronics
26. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 26 Some nano-functionalised biosensor surfaces Direct surface imprinting Microcontact surface imprinting Protein nanopatterning via nanografting
27. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 27 Some nano-functionalised biosensor surfaces Ferrocene units Multiwalled carbon nanotube HBP layer
28. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 28 Nanotechnology and biosensors One of the most important challenges in medicine is to detect the onset of disease or metabolic change at the earliest possible stage, allowing more effective treatment and better prognosis. QuantuMDx’s Q-POC device uses silicon-based nanowire biosensor arrays to provide point-of-care testing in minutes for a range of diseases, e.g. TB, HIV, using interchangeable cartridges for different tests. These devices can deliver very fast and accurate results, with implications for professional practice. Biosensor systems also lend themselves to networking solutions, e.g. for remote monitoring of the ill or elderly. Image: Harvard University Image: QuantuMDx
29. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 29 Nano drug delivery systems: some other nanoparticle types used for drug delivery gold nanoparticles nanosponges nanosomes nanodiamonds nanovesicles nanoshells nanocrystals liposomes
30. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 30 Core: for example metallic/semi-metallic, can react with external energy sources or contain a delivered agent Shell: Metallic or biodegradable Targeting biomolecules: for delivery to specific target sites, e.g. cancer cells Image contrast agent: for tracking movement and accumulation of particles within the body Payload: precise and tiny quantities of highly potent or difficult-to-deliver drugs PEG: to counter immune system attack Size: size of multifunctional nanoparticle can be tailored. Very high surface area. Longer term: multifunctional nanoparticles?
31. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 31 Longer-term: molecular machines to produce materials in vivo?
32. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 Addressing risks 32
33. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 The importance of risk management Risk is an inherent part of any form of technological advance. Elements that are always important with any novel technology are minimising risk and achieving an acceptable balance between risk and benefit The Perfexion™ gamma knife
34. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 34 Nanoscale hazard and risks As there is rather limited information available on the safety of some novel medical nanomaterials, identifying hazards and estimating the risks associated with them will be one of the major challenges in applying nanotechnology to medicine. Regulatory authorities are unlikely to have any more knowledge than researchers but will require data and evidence. It is important therefore to build up knowledge on safety aspects in parallel with scientific development so as not to risk regulatory delays in drug or device approvals.
35. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 35 Example: quantum dots - some possible risk issues • Known in-vivo toxicity • High-energy irradiation of QDs (e.g. with UV) may be close to covalent bond energy with potential to release metal ions • May remain inside cells for weeks or months • Little is known about how they metabolize inside the body or their routes of excretion • With stable polymer coating may be non-toxic (hence one means of risk reduction) • What might the environmental effects be upon excretion?
36. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 36 Some toxicological aspects of nanomaterials Key factors appear to be: – Dose: as with other toxicologically active materials, though the most applicable metric for dose may be surface area rather than mass – Composition: reactivity per unit surface area. – Kinetics and distribution in the body – Shape and form: recent studies on CNTs None of these are new but neither has any been sufficiently studied to allow accurate prediction of the toxicology of a novel nanomaterial. UK Government Report, DEFRA, December 2007
37. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 37 Some toxicological aspects of nanomaterials • Surface area is inversely related to size of the NP and the extent of any agglomeration • Surface reactivity, e.g. with cellular contents or extracellular fluids, is dependent on chemical composition as well as surface area • In the case of metal oxide nanoparticles, physical effects (particle size and surface area) tend to dominate rather than chemistry. For other NPs a combination of both may be important. • Agglomeration is a complex issue. Agglomeration in air may lead to deposition in the conducting airways rather than in the gas exchange zone. But once deposited the agglomerates may break down into individual nanoparticles that react with the cells. How tightly the nanoparticles bind in the agglomerates is thus a key factor UK Government Report, DEFRA, December 2007
38. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 38 Some toxicological aspects of nanomaterials • Nanoparticles may react with cell surface receptors or may pass into cells and react with intracellular receptors • Physical properties, specifically size, are important in governing the inter- and intracellular distribution. Generally nanoparticles with sizes: – above 200-300nm will not penetrate cells, although they can be taken up by cells such as macrophages – around 50-80nm will enter cells but not organelles such as the nucleus or mitochondria – below 20nm will enter organelles • Macrophage recognition and uptake more likely with larger particles and perhaps more likely if the particles are in an aggregated state UK Government Report, DEFRA, December 2007
39. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 ? ? ? ? dissolved? converted? trapped? grow? Lifecycles: what happens to nanomaterials in the body? Diagram courtesy of Dr Robert Dorey, Cranfield University
40. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 40 Nanoparticle characteristics that could give rise to novel hazards • catalytic properties • composition • concentration • crystalline phase • water solubility/hydrophilicity • fat solubility/oleophilicity • size • hydrodynamic size • particle size measurement/distribution • length • shape • surface area • surface charge • surface chemistry • zeta potential • purity (OECD Working Party on Manufactured Nanoparticles - Study Group 4)
41. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 Risk management will need appropriate adaptation This is an overview of the process flowchart from EN ISO 14971. The standard comprises a series of action stages and decision stages that must be fully documented. It currently contains no specific guidance on nanoscale risks but the underlying process is deemed to be appropriate by EC experts Improved measurement methods for nanomaterials and their interactions within the body will be crucial in addressing data gaps on nanoscale hazards and risks to complement this standard
42. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 Further challenges to commercialisation 42
43. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 43 Public concerns Many groups in society have legitimate concerns about how nanotechnology may develop or be used, or about safety issues. Badly handled risk communication about other technologies, e.g. GMOs, BSE, contaminated blood, has not helped Some of these possible nanotechnology developments lie far in the future or have been seriously overhyped by uninformed media reporting Text: ETC Group. Artist: Stig www.etcgroup.org
44. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 44 Predictive medicine: - we presume the information will be useful More information than expected? - for example from a blood test What is a well person? - if we can monitor at so many levels? Too much data to handle? - what does my genetic read-out mean? - who can make real sense of all the data? Ethical aspects
45. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 45 Temptation to reduce medicine to ‘engineering’ solutions? – Losing sight of the patient? Medicine is more than just health engineering to correct dysfunctions – Nano-engineers may not be good doctors – (Re-)defining medical “success”? Values in medicine – The whole person… beyond illness? – Healing expectations? Limits of cure? – The patient’s right not to know? Dr D Bruce Ethical aspects
46. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 46 Further challenges for nanomedicine Regulatory challenges: Does the product fit comfortably within existing regulatory regimes? Are there new aspects that fall outside of existing legislation? Healthcare technology assessment (HTA): Are existing HTA schemes capable of assessing the benefits, risks and long and short term costs? Reimbursement: Will the product be taken up and reimbursed by healthcare systems? Professional uptake: Will the product be accepted and used by professionals? Will there be a “disruptive” effect on clinical practice, e.g. “smart” products, e.g. handheld diagnostic devices that alter current testing protocols.
47. Med-Tech Innovation 2013 What’s next for medical devices 11 April 2013 47 Summary: to realise the promise of nanomedicine… • treatments will need to be better or more efficient than those offered by existing products • access to new treatments based on nano- and other enabling technologies needs to be facilitated • long-term benefits, e.g. better prognosis or reduced hospital stays, need to be clear and outweigh any additional costs • all risks, including any novel risks relating to nanoscale characteristics, need to be systematically assessed and reduced where necessary to an acceptable level • some ethical issues may need to be addressed