NanoSight sizes up to nanotoxicology challenges

With the ever increasing industrial usage of nanoparticles that behave differently than larger particles made from the same materials, investigating their toxicity is becoming an increasingly important issue. Indeed, nanoparticle formulations are being used to deliver drugs because of their ability to travel through the body and accumulate in different areas to those that a differently formulated drug would. "The world has realised that if compounds have different properties as nanoparticles than as bulk materials, then you can't assume the toxicology of a nanoparticle is the same as in the bulk,"​ said Jeremy Warren, CEO of NanoSight. "There is therefore a huge amount of work required to retest just about everything that we know in its nano form." ​ However, in order to study the effects of a nanoparticle system, the particles need to be characterised accurately, with information about average particle size not being sufficient as the smallest particles may be the most toxic. With this in mind, Professor Kenneth Dawson of Ireland's University College Dublin has been investigating methods that enable more complete characterisation of nanoparticles, particularly to find complete particle distribution maps. "Whist we still use dynamic light scattering (DLS) to find average particle size, we really need the complete particle distribution map in the sub-micron area in our work,"​ said Prof. Dawson. "The NanoSight instrument identifies and tracks individual particles, enabling us to see how they are organized (into clusters or otherwise) for the first time. It is impressive to see just how limited DLS is in these respects, where it will often smear or mask true cluster distribution." ​ Better characterisation of particle sizes before testing for toxicological effects will enable researchers to investigate the interactions between nanoparticles and biological materials in a more comprehensive way. While DLS has enabled the characterisation of average nanoparticle size in solution and can detect the presence of binomial distributions of particle sizes, it has a tendency to bias towards larger particles as it is based on measuring the intensity of a scattering signal, which gets smaller as the particle gets smaller. ​"Instead of measuring the intensity of a signal, the NanoSight LM 'views' and individually tracks particles enabling particle speed determination,"​ said Warren. "This produces a much higher resolution particle size distribution chart than would be produced using DLS. In addition, they can go back and 'see' the particles moving around in real time." ​ NanoSight offers two instruments, the LM10 and LM20, with the LM10 featuring a microscope that lets users position a sample themselves, whereas the LM20 uses a sample holder that slots into place and removes the need to be an experience microscope user. The performance of the instruments is identical and they can determine sizes down to around 10-15nm, depending on the material. Size distribution measurements take around a minute for a monodispersed sample and 3 minutes for a polydispersed mixture. The software enables real-time dynamic nanoparticle visualisation from which quantitative particle size and size distribution can be calculated. In addition, the instruments can calculate the concentration of particles because the instruments count the number of particles in a given volume at any one time. Other applications for the instruments include studying virus particles, liposomes commonly used to protect drugs from being metabolised and the size of the drug particles themselves. The instrument has also been successfully used to measure the size of pigment particles such as those used in inkjet printers. According to Warren, NanoSight's technology is set to find widespread applicability in most nanoparticle dispersion assessment work.