Nanoparticle tracking analysis
Encyclopedia
Nanoparticle Tracking Analysis (NTA) is a method for visualizing and analyzing particles in liquids that relates the rate of Brownian motion
to particle size. The rate of movement is related only to the viscosity
and temperature of the liquid, it is not influenced by particle density
or refractive index
. NTA allows the determination of a size distribution profile of small particles (10-1000nm) in liquid suspension.
The technique is used in conjunction with an ultramicroscope
which allows small particles in liquid suspension to be visualized moving under Brownian motion. Computer software is then be used to track particles’ movements and subsequently estimate their hydro-dynamic radius, using the Stokes–Einstein equation.
The light scattered by the particles is captured using a CCD
or EMCCD camera and the motion of each particle is tracked from frame to frame. This rate of particle movement is related to a sphere equivalent hydrodynamic radius as calculated through the Stokes–Einstein equation. The technique calculates particle size on a particle-by particle basis overcoming inherent weaknesses in ensemble techniques . Since video clips form the basis of the analysis, accurate characterisation of real time events such as aggregation and dissolution is possible.
Samples require minimal preparation so the time required to process one sample is much reduced. Speculators suggest that eventually the analysis may be done in real-time with no preparation e.g. when detecting the presence of viruses or biological weapons in air.
NTA currently operates for particles from 10 to 2,000 nm, depending on particle type. Analysis of 10 nm particles is only possible for particles with a high refractive index, such as gold and silver. The upper size limit is restricted by the limited Brownian motion. Above 1 micrometre, the particle moves very slowly and accuracy starts to diminish. The viscosity of the solvent also influences the movement of particles and it too plays a part in determining the upper size limit for a specific system.
(DLS) and Nanoparticle Tracking Analysis (NTA) measure the Brownian motion of nanoparticles whose speed of motion, or diffusion coefficient, Dt, is related to particle size through the Stokes–Einstein equation.
where
In NTA this motion is analyzed by video - individual particle positional changes are tracked in two dimensions from which the particle diffusion is determined. Knowing Dt, the particle hydrodynamic diameter can be then determined.
In contrast, DLS does not visualize the particles individually but analyses, using a digital correlator, the time dependent scattering intensity fluctuations. These fluctuations are caused by interference effects arising from the relative Brownian movements of an ensemble of a large number of particles within a sample. Through analysis of the resultant exponential autocorrelation function, average particle size can be calculated as well as a polydispersity index. For multi-exponential autocorrelation functions arising from polydisperse samples, deconvolution can furnish limited information about the particle size distribution profile.
Brownian motion
Brownian motion or pedesis is the presumably random drifting of particles suspended in a fluid or the mathematical model used to describe such random movements, which is often called a particle theory.The mathematical model of Brownian motion has several real-world applications...
to particle size. The rate of movement is related only to the viscosity
Viscosity
Viscosity is a measure of the resistance of a fluid which is being deformed by either shear or tensile stress. In everyday terms , viscosity is "thickness" or "internal friction". Thus, water is "thin", having a lower viscosity, while honey is "thick", having a higher viscosity...
and temperature of the liquid, it is not influenced by particle density
Density
The mass density or density of a material is defined as its mass per unit volume. The symbol most often used for density is ρ . In some cases , density is also defined as its weight per unit volume; although, this quantity is more properly called specific weight...
or refractive index
Refractive index
In optics the refractive index or index of refraction of a substance or medium is a measure of the speed of light in that medium. It is expressed as a ratio of the speed of light in vacuum relative to that in the considered medium....
. NTA allows the determination of a size distribution profile of small particles (10-1000nm) in liquid suspension.
The technique is used in conjunction with an ultramicroscope
Ultramicroscope
An ultramicroscope is a system of illumination for viewing tiny particles. When the diameter of a particle is below or near the wavelength of light , the particle cannot be seen in a light microscope with the usual method of illumination. The ultramicroscope system is based on light scattering, not...
which allows small particles in liquid suspension to be visualized moving under Brownian motion. Computer software is then be used to track particles’ movements and subsequently estimate their hydro-dynamic radius, using the Stokes–Einstein equation.
The light scattered by the particles is captured using a CCD
Charge-coupled device
A charge-coupled device is a device for the movement of electrical charge, usually from within the device to an area where the charge can be manipulated, for example conversion into a digital value. This is achieved by "shifting" the signals between stages within the device one at a time...
or EMCCD camera and the motion of each particle is tracked from frame to frame. This rate of particle movement is related to a sphere equivalent hydrodynamic radius as calculated through the Stokes–Einstein equation. The technique calculates particle size on a particle-by particle basis overcoming inherent weaknesses in ensemble techniques . Since video clips form the basis of the analysis, accurate characterisation of real time events such as aggregation and dissolution is possible.
Samples require minimal preparation so the time required to process one sample is much reduced. Speculators suggest that eventually the analysis may be done in real-time with no preparation e.g. when detecting the presence of viruses or biological weapons in air.
NTA currently operates for particles from 10 to 2,000 nm, depending on particle type. Analysis of 10 nm particles is only possible for particles with a high refractive index, such as gold and silver. The upper size limit is restricted by the limited Brownian motion. Above 1 micrometre, the particle moves very slowly and accuracy starts to diminish. The viscosity of the solvent also influences the movement of particles and it too plays a part in determining the upper size limit for a specific system.
Applications
NTA has proved useful for companies working with:- Nanoparticle toxicology
- Drug deliveryDrug deliveryDrug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well...
- Exosomes
- Virology and vaccine production
- EcotoxicologyEcotoxicologyEcotoxicology is the study of the effects of toxic chemicals on biological organisms, especially at the population, community, ecosystem level. Ecotoxicology is a multidisciplinary field, which integrates toxicology and ecology....
- Protein aggregationProtein aggregationProtein aggregation is the aggregation of mis-folded proteins, and is thought to be responsible for many degenerative diseases, such as Alzheimer's. It has also been implicated in CAG repeat diseases....
- Orthopedic implants
- Inks and pigments
- Nanobubbles
Comparison to dynamic light scattering (DLS)
Both Dynamic Light ScatteringDynamic light scattering
thumb|right|350px|Hypothetical Dynamic light scattering of two samples: Larger particles on the top and smaller particle on the bottomDynamic light scattering is a technique in physics that can be used to determine the size distribution profile of small particles in suspension or polymers...
(DLS) and Nanoparticle Tracking Analysis (NTA) measure the Brownian motion of nanoparticles whose speed of motion, or diffusion coefficient, Dt, is related to particle size through the Stokes–Einstein equation.
where
- Dt is the diffusion constantFick's law of diffusionFick's laws of diffusion describe diffusion and can be used to solve for the diffusion coefficient, D. They were derived by Adolf Fick in the year 1855.- Fick's first law :...
, 
is Boltzmann's constant,- T is the absolute temperature,
- η is viscosity
- d is the radius of the spherical particle.
In NTA this motion is analyzed by video - individual particle positional changes are tracked in two dimensions from which the particle diffusion is determined. Knowing Dt, the particle hydrodynamic diameter can be then determined.
In contrast, DLS does not visualize the particles individually but analyses, using a digital correlator, the time dependent scattering intensity fluctuations. These fluctuations are caused by interference effects arising from the relative Brownian movements of an ensemble of a large number of particles within a sample. Through analysis of the resultant exponential autocorrelation function, average particle size can be calculated as well as a polydispersity index. For multi-exponential autocorrelation functions arising from polydisperse samples, deconvolution can furnish limited information about the particle size distribution profile.
External links
- http://www.nanosight.com/appnotes/M110B%20Application%20Review%20NTA%20April%202009.pdf explaining the core technology can be downloaded from here.
- The NanoSight homepage for an introduction to the company and applications.