Choosing a particle analysis system can be a complex process. Here are 10 key questions to ask before making a decision.
Introduction to particle characterization techniques
There are numerous options available when searching for a particle analysis system. First, there are multiple technologies to choose from, including Laser Diffraction (LD), Dynamic Light Scattering (DLS), several types of Electron Microscopy, separation technologies such as HPLC or GPC, Small Angle X-Ray Scattering (SAXS), etc. Then, within DLS-based instruments, there are a number of specific options related to which measurements are available (size, zeta potential, molecular mass, transmittance, for example), as well as options concerning required sample volumes, cuvette types, and different angles of analysis. To help ensure that you make the right choice, here are 10 key questions to ask when considering which new technologies and instrumentation to use to analyze your particle systems.
1) How big are my particles?
This is a key question that can help narrow down the types of technologies that would be useful. In terms of technologies for analyzing large vs. small particles, the chart below provides the general ranges for several commonly used technologies. For larger particles ranging from low micron to low millimeter sizes, laser diffraction (LD) is often a good option. It works with either dry powders or in suspension, is fast, reasonably reproducible, and is well established for measuring the size of particles in the micron range.
For particles in the nanometer to low micron range, DLS is often the technology of choice. It’s fast, easy to use, and highly reproducible for measuring particles in a wide range of formulations and solvents. Additionally, many DLS-based instruments can also be used to assess the zeta potential and/or molecular mass of particles.
Other technologies such as TEM or SEM can also be used to size particles by taking a picture of them. While these are accurate and useful technologies, especially for particles that are non-spherical, they can be costly and time-consuming to run.
It can be helpful to have a general idea of the particle sizes you are studying as a first step in narrowing down the particle analysis technologies that will be useful in your work.
2) What do I need to know about my particles?
There are a number of different particle parameters that can be measured, including particle size, shape, charge, concentration, density, molecular mass, turbidity, count, porosity, and stability. Often, several of these parameters are combined in a single instrument. For example, a number of instruments provide a combination of nanoparticle size, zeta potential and molecular mass. However, other instruments may be required for particle counting, assessing particle shape, or to separate out particle mixtures. Make sure you know what particle parameters are most important to you before moving forward.
3) How are my particles formulated?
Some techniques, such as laser diffraction, are flexible and can analyze particles in dry powder form, in liquid suspension, or even in aerosol. Others, such as DLS, require the samples to be suspended in either an aqueous or organic solvent. If in suspension, the concentration of your particles is important because if it is as high as 40 %w/v to 50 %w/v some techniques such as DLS may struggle to provide good data whereas acoustic techniques may be more useful. However, for low concentration samples, the sensitivity of the instrument and technology will be a key parameter. Make sure that the formulation, concentration, and sensitivity specifications of the technology match up with your samples.
4) How much sample do I have?
Another question related to formulation is, how much sample do I have? In many cases, the sample is measured in liters and the sample volume is not an issue for most types of instrumentation. However, some samples, such as recombinant proteins or antibodies, are extremely expensive to produce and are therefore only made in quite small amounts and volumes. So, it’s important to know the sample volume you will have and make sure that the technique you want to use can cope with that. Many instruments for particle analysis such as DLS instruments require only a few microliters of solvent and often have special low-volume cuvettes available to measure this low-volume sample.
5) How stable are my samples?
This is a key question to ask, especially for zeta potential analysis of protein samples. Zeta potential works by applying a voltage to a sample of interest, measuring its rate of motion, and then correlating that to its zeta potential or effective charge in solution. This voltage, if applied too powerfully or for too long, can easily damage or degrade protein or nucleic acid samples. New developments in zeta potential technologies, such as the cmPALS technology from Anton Paar, help eliminate this issue by enabling much faster measurements and measurement at lower potentials. Additionally, new cuvette designs with an Omega-shaped sample loop also help limit protein loss when compared to the more traditional U-shaped cuvettes.
Stability is also important in terms of particle or protein aggregation. If your particles are aggregating over time, they may settle out of suspension and throw off the analysis or they may simply yield different results at different times and under different conditions. Knowing the stability of your particle formulation can help guide the technology you choose and also how to best interpret the results.
6) How easy are the instrument and software to use?
The quality and ease-of-use of the software running on a device will significantly impact your overall experience with an instrument. Make sure that the instrument you choose has software that is up to date and that it functions on the latest operating systems and will be supported in the future. Even more importantly, test-drive the software yourself. Make sure it feels intuitive, is easy to use, and that new users in your lab won’t have to spend weeks or months learning how to run the instrument.
Ask about data accessibility: will you have access to the raw data or will you be limited to the vendor’s proprietary reporting templates? Check to make sure that your data can be exported directly to Excel or to an ASCI or PDF format so you’re not limited to one specific template. Also, it’s good to check whether the report functions can be easily customized or whether you’ll be limited to whatever format the vendor prefers.
Finally, if you are working in a GMP- or FDA-regulated environment, make sure to ask whether the software is compliant with 21 CFR Part 11 and whether the vendor has the necessary compliance paperwork and IQ/OQ protocols ready to go.
7) How reproducible and accurate are the results?
As is the case with software, not all instruments and technologies are created equal either. Be sure to test multiple samples multiple times to make sure the data quality and reproducibility are sufficient for a publication or patent. Also, keep in mind that different technologies may give slightly different results, even with the same sample. For example, TEM results are based on a number analysis of a dry particle and thus tend to be smaller than DLS results, which are often based on intensity analysis of a hydrated particle.
8) How much does the instrument, service, and compliance paperwork cost?
The cost of instrumentation for particle analysis will vary quite a lot depending on the specific technology, level of automation and throughput, accessories, and consumables that are included or need to be added. Additional costs may come from service contracts or from pharmaceutical compliance offerings that ensure that your instrument will pass its annual inspection. Be sure to ask about the complete pricing for everything you need and work out how much it will cost to run for a whole year.
9) How will the vendor support me after I buy?
Ask about the vendor’s installation and training process to be sure that you and your team will be fully trained in using the instrument. Also, make sure that any pharmaceutical requirements such as a formal IQ/OQ/PQ will be completed upon installation. Check to make sure that the vendor has extended warranty and service options available as well as an experienced and responsive service team. Ask what happens if the instrument breaks down and how quickly you can expect a response, a loaner system, and a completed repair process.
10) What new developments can I expect in the next year or two?
It’s good to know whether a company is continuing to invest in R&D and technology development and whether they are planning to launch new features, accessories, and hardware. The sales representative may not be able to share specific information with you but should be able to describe the company’s vision for the instrument or the product line, and outline what developments are likely to come in the next year or two.
Some specific areas to ask about include analysis at lower volumes, higher throughput and automation, new software development, and new technologies. Developments in these areas indicate that a company is serious about continuing to grow their product line and provide up-to-date solutions.
Overall, these are 10 of the most critical questions to ask when searching for a particle analysis system. Litesizer™ 500 particle analyzer from Anton Paar, for example, may be among the search options. This device enables multiple parameters to be assessed, including size, zeta potential, molecular mass, and light transmittance. Also, it enables a size range from sub-nanometer particles all the way up to 100 micron particles for zeta potential analysis. It also includes an easy-to-use software interface and a modular design to ensure fast and efficient data collection and analysis.