This protocol describes how to measure the size and concentration of individual metallic nanoparticles using ICP-MS (inductively coupled plasma - mass spectrometry) in single particle (SP) mode. Accurately determining the size of individual nanoparticles on a per particle basis both quickly and accurately is an ever-increasing need within nanoparticle characterization. ICP-MS is capable of measuring a broad range of nanoparticle sizes with high resolution, thus allowing the measurement of multiple particle populations for the quality assessment of nanoformulations. Additionally, SP-ICP-MS can accurately determine particle concentrations without the need for concentration standards.
ICP-MS is an ultrasensitive technique which can determine the concentration of trace elements in solution down to the pg/g level. Delguard et al first demonstrated in 2006 that ICP-MS could accurately measure the mass of individual metallic nanoparticles in what has come to be known as SP-ICP-MS . By introducing a nanoparticle solution into the ICP, the individual nanoparticles are ionized into an ion cloud which then is carried as an intact unit to the detector. After a brief rapid expansion of the ion cloud, the duration of this cloud, defined as the time it first hits the detector to the time the last ion hits, is approximately 100-650 µs for 30-150 nm particles, respectively. This allows for two methods for measuring nanoparticles in SP mode, both of which will be outlined in the protocols below.
In method 1, a large integration time (10 ms) with respect to the duration of the ion cloud is used in combination with a sufficiently dilute solution to measure individual nanoparticles. Since the integration time is much larger than the particle cloud duration, this method measures the entire particle cloud as a single event. Due to this, it is extremely important that the nanoparticle solution is sufficiently dilute to prevent multiple particles from hitting the detector during the integration window. This method has the advantage of being usable for many modern ICP-MS instruments that do not have a dedicated single particle counting mode since most of these instruments are capable of integrations times as low as 10 ms. Additionally, the long integration times allow for a longer time period for the detector to recover after a nanoparticle event, leading to a lower occurrence of detector saturation and small particle events.
Method 2 uses a shorter integration time than the duration of the ion cloud which allows for the measurement of nanoparticle events by rastering multiple points across the detection event. The 50 µs integration time is generally available in instruments with a dedicated single particle mode and provides a few advantages over 10 ms integration measurements. The faster integration time allows for the collection of more information than the 10 ms integration which is limited to the total or summed intensity of the nanoparticle event. Three types of information are available due to the ability to raster across the peak. Like 10 ms integrations, the total or summed intensity is available, however, also available are the max height intensity of the peak and the duration of the ion cloud. Additionally, due to the faster integration time, samples about ten times higher in concentration than the 10 ms method can be accurately analyzed simplifying the sample preparation process.
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