Emerging Nanomedical Applications and Their Metrology Needs

Emerging Nanomedical Applications and Their Metrology Needs

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Description: Nanotechnology is a part of an increasingly convergent approach in medicine. 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.

The characteristics of nanomaterials can profoundly affect the way that they interact with cells or cell components and may indeed form part of the desired functionality.

 
Author: Richard Moore (Fellow) | Visits: 2718 | Page Views: 3310
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Contents:
Co-Nanomet European Workshop
Session 5: Nanobiotechnology

Emerging nanomedical applications and their metrology needs
Richard Moore Institute of Nanotechnology www.nanomednet.org

Co-Nanomet European Workshop Session 5: Nanobiotechnology

1

Nanotechnology: part of an increasingly convergent approach in medicine

Biological sciences

E-Medicine Telemedicine Bioinformatics Micro- and nano-electronics Regenerative medicine Nanotechnology Biophotonics
Information technology

Materials science

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Why is small important for healthcare?

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

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Nanoscale materials and biological entities

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Possible trends and timelines

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Nanomaterials in medicine

The characteristics of nanomaterials can profoundly affect the way that they interact with cells or cell components and may indeed form part of the desired functionality, e.g. by providing cells with a physical or chemical microenvironment in which they can successfully grow or differentiate, e.g. in scaffolds for regenerative medicine.

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Measurement needs in nanomedicine
� Nanomedicine has a very wide range of measurement needs These range from the relatively simple, e.g. measurement of size or surface topography to complex interactions between nanoscale surfaces and cells, receptors, membranes, organelles, proteins and other biomolecules These measurements are important for the characterization of materials, and for hazard identification, risk assessment and toxicological studies





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Nanomaterials in medicine



There are knowledge gaps with many manufactured nanomaterials and, in many cases, their novel properties and mechanisms of interaction with the body are poorly understood In cases such as the above (a novel mode of toxicity discovered for 30nm Co-Cr nanoparticles) metrology will play a vital role in contributing to this knowledge ( both positive and negative effects)



Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Some examples of current nanoscale applications in medicine

Dendrimers: drug delivery

Hyperbranched polymers: drug delivery

Lab-on-a-chip devices: diagnostics

Nanocoatings: surgical implants, tools

Antibody fragments: drug design

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Some current applications: different nanoparticles used for drug delivery

nanoshells gold nanoparticles nanosomes

nanovesicles nanocrystals

liposomes

Size, size distribution, shape, surface area, solubility, concentration, surface charge and other measurement needs

nanodiamonds

nanosponges

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Some current applications: nanoscale coatings for improved performance

Ultra sharp diamond scalpel Cutting edge is only a few atoms wide (~3 nm) - approx. 1/1000 of a metal blade. Produced by a plasma process Applications in eye and minimally invasive surgery
Measurement of nanoscale surface characteristics (composition, impurities, surface charge, surface energy, coating thickness, etc.), topography, chemical stability/degradability, etc. 11

Gesellschaft f�r Diamantprodukte (GFD)

Co-Nanomet European Workshop Session 5: Nanobiotechnology

Some current applications: nanostructuring of implant surfaces to improve properties and performance
Implant topography

Nanoscale "grooves" can increase cell adhesion and direct cell growth in a desired direction, whereas "pits" and "pillars" can decrease cell adhesion
Measurement of nanoscale surface characteristics (composition, impurities, surface charge, surface energy, coating thickness, etc.), topography, chemical stability/degradability, protein adsorption, cell viability and proliferation, cell expression, etc.

Pits are 125 nm wide by 75 nm deep.

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Some current applications: nanobiosensors
� Analytical devices incorporating a biological or biomimetic material (e.g. cell receptors, enzymes, antibodies, nucleic acids, etc.) associated with or integrated within a physicochemical transducer or microsystem Diverse range of biosensing surfaces and transducer systems
Surface characterizations and measurements. Physical, chemical, optical measurements associated with transducer component. Identification, detection and quantitative determination of concentrations of biological molecules such as drugs, toxins, metabolites, peptides, proteins, enzymes, lipids, DNA, etc.



Nanowire array (Harvard University)

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Some current applications: advanced imaging for improved treatment/prognosis

Photo: Surgery of breast cancer sentinel lymph nodes using quantum dot markers Apart from imaging aspects and localization and quantification of quantum dots, wide range of measurements associated with the toxicity, distribution and fate of the nanoparticles in the body

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Some current applications: microfluidic and lab-on-achip systems for early and rapid diagnosis
Lab-on-a-chip systems enable sample handling, mixing, dilution, electrophoresis and chromatographic separation, staining and detection on single integrated systems. Key advantages are ease-of-use, speed of analysis, low sample and reagent consumption and high reproducibility due to standardization and automation.
Wide range of physical and chemical measurements at micro- and nanoscale, surface characterisation and measurement, topography of functionalised surfaces, cellto-cell signalling, etc.

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Some examples where nanotechnology may be applied: novel medical devices
New generation cochlear implants No external wires/batteries, self-powered New generation retinal implants Improved sight for retinitis pigmentosa and macular degeneration sufferers

Wide range of measurements associated with surface properties, cell-surface interactions, biocompatibility tests, as well as a variety of measurements related to the function of the devices 16

Co-Nanomet European Workshop Session 5: Nanobiotechnology

Some examples where nanotechnology may be applied: regenerative medicine
Prosthesis 70's inert biomaterials 80's resorbable biomaterials 90's bioactive biomaterials

Tissue engineering

00's bioactive biomaterials +/- cells + growth factors

Regenerative medicine

20's intelligent biomaterials + bioactive molecules + cell homing

As the trend moves towards in-vivo regeneration of tissues and organs, increasingly complex measurement needs relating to characterisation of scaffold materials, biocompatibility, protein adsorption, cell viability, cell proliferation, cell expression, and tissue morphology. 17

Co-Nanomet European Workshop Session 5: Nanobiotechnology

Some examples where nanotechnology may be applied: Longer term: multifunctional nanoparticles
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.
Increasing complexity of measurement needs over simple nanoparticles, localization, quantification, interactions between binding molecules, etc. 18

Co-Nanomet European Workshop Session 5: Nanobiotechnology

Some examples where nanotechnology may be applied: Longer-term: molecular machines to produce materials in vivo?

Increasingly complex measurement needs - probably yet to be clearly defined for such self-assembling systems

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Longer-term trends: biomimetic nanotechnology
Measurement needs yet to be defined for biomimetic systems?

Biomimetic neural computing based on Y-branched carbon nanotubes Branching and switching of signals at each junction similar to what happens in a biological neural network. Neural tree can be trained to perform complex switching and computing functions Not restricted to electronic signals; possible to use acoustic, chemical or thermal signals.
NASA-Ames

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Nanoscale characteristics important for measurement from a functional and safety perspective
(from OECD Working Party on Manufactured Nanoparticles - Study Group 4)

� � � � � � � � � � � � � � � � �

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 dustiness
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Co-Nanomet European Workshop Session 5: Nanobiotechnology

Further challenges in the biological environment
� Most biomolecules exist in an aqueous environment, which is not particularly suitable for force or electron microscopy. New techniques are therefore needed for in vivo measurements For example, fluorescence resonance energy transfer (FRET) has been used to provide measurement of distances between fluorophores between 1nm and 10nm. The fluorophores can be attached to biological molecules and can be used to give indications of distances between actives sites or interacting molecules, such as proteins and ligands, proteins to other proteins, or DNA interactions Current advances on FRET such as plasmon coupling







Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Nanotechnology and medicinal regulation



Currently no specific guidance documents on nanomedicinal products Specific guidance on quality, toxicology, clinical development and monitoring aspects may be developed many of which will have major metrological implications and needs Those developing nanomedicinal products are encouraged to interact with the EMEA Innovation Task Force from the earliest stages of development





Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Nanotechnology and medical device regulation
The New & Emerging Technologies in Medical Devices Working Group of the EC concluded that, in general, the medical devices directives are an adequate framework to deal with devices manufactured utilizing nanotechnology. However, the risk management procedures commonly used, e.g. EN ISO 14971 require supplementary information concerning nanoscale hazard identification and risk estimation which has clear implications for metrology

Co-Nanomet European Workshop Session 5: Nanobiotechnology

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Some important questions in nanomaterials risk management

� � � � � � � �

How does the material enter the body? Where does it go and how does it change once it gets there? What aspects of the material end up causing harm? How much material is needed for serious harm to occur? How should the toxicity of the material be assessed? How will people end up being exposed to the material? How should exposure be measured? Can exposures be adequately controlled?

All of these questions have metrological implications

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Aims of the NanoMedNet network: � to provide nanomedical information (website, reports, conferences) � to provide education and training in nanomedicine (courses, workshops) � to raise the profile of nanomedicine and other novel medical technologies � to offer opportunities for clinicians, researchers and companies to interact and partner

www.nanomednet.org
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Co-Nanomet European Workshop Session 5: Nanobiotechnology

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