Profiling Particles

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 Profiling Particles

The performance of many products and processes depends on the size, shape and other features of the microscopic components

Imagine throwing a variety of marbles, nuts and bolts, children’s breakfast cereals and, oh, let’s say, ground-up asphalt into a big beaker. Then, mix this all together and shrink it down, making the pieces range in size from nanometers to millimeters. Now, here’s the challenge: Give this to a scientist who has no idea what you started with or what you did to it, and ask him or her to describe the sizes of the particles in this mixture. If you really want to get the data needed to put this mixture to work in a product or industrial process, you’ll probably want to know even more. We’ll discuss the features that make a difference in particle analysis and how new technologies quantify those characteristics.

Depending on the expected size of the particles, a variety of measurement techniques can be used, from dynamic light scattering (DLS) and electron microscopy to acoustic and centrifugal methods.

“In general,” says Yuanming Zhang, chief application scientist at Brookhaven Instruments Corporation (Holtsville, N.Y.), “particle sizing has a long history of applications in many industries.” In fact, the size of particles probably makes a difference in every industry.

Even more dynamic

According to Daniel Some, director of marketing and principal scientist at Wyatt Technology (Santa Barbara, Calif.), the two main trends in DLS are more accurate size distributions and high-throughput DLS analysis, primarily for formulating nanomedicines or other nanoparticles. For accurate size distributions, according to Some, “nothing comes close to the resolution and analytical rigor of” field-flow fractionation (FFF) with DLS. He says, “The reason is, asymmetric-flow FFF physically separates particles by hydrodynamic size prior to online DLS measurement.” He adds, “An example of such a setup is Wyatt’s Eclipse FFF system combined with a Wyatt DAWN HELEOS II detector equipped with an embedded WyattQELS DLS module.”

For high throughput, says Some, “Perhaps the most exciting trend in DLS particle-size analysis is the ability to measure hundreds, and even thousands, of samples per day in order to determine the optimal solvent conditions or processing protocol for uniform and stable nanoparticle suspensions.” He adds, “The best example of such an instrument is Wyatt’s DynaPro Plate Reader II, which carries out DLS measurements in situ in industry-standard microwell plates.” Instead of the traditional approach to DLS, which is carried out in individual cuvettes, he says, “high-throughput DLS is revolutionizing the field of nanoparticle sizing by making feasible the number of measurements required to map out a complete formulation or process space.”

As Some says, “The DynaPro provides orders-of-magnitude better productivity when many samples are to be tested.”

Go with the flow

At Brookfield Engineering Laboratories (Middleboro, Mass.), Robert McGregor, general manager of global marketing, says, “Our approach to powder measurement is from the viewpoint of flow behavior.” He adds, “We know that smaller particle sizes—100 microns and lower—will adversely affect flow in gravity discharge.”

Consequently, labs that deal with powders need some way to connect a material’s underlying properties with how well it will flow. As McGregor points out, these properties include particle size, morphology, electrostatic charge, moisture content and so on. “Particle-size analysis,” says McGregor, “is important for characterizing what happens to a powder during processing operations such as milling, granulation, fluidization, etcetera.” To make sure that a material meets its specifications, R&D and QC labs use a powder-flow tester and analyze particle size. “Evaluation of particle size is also necessary to confirm that the composition of the formulated product has remained consistent, especially if key active ingredients have distinctly smaller size compared to excipients,” McGregor explains.

For powder processors, combining powder flow and particle-size measurements completely characterizes raw materials and provides information that can be used in evaluating the final product. “There had been a time when particle-size analysis alone would be used to predict the flowability of the material,” McGregor says. “Now that is changing with the increased availability of easy-to-use flow testers.”

Super small

In the past decade, particle-size analysis more frequently dropped into the nano range. “At the nano scale, size actually makes a dramatic impact on product performance and even leads to new functionality or capabilities,” says Zhang. “So, you must monitor size very vigorously.”

Scientists at Brookhaven Instruments use DLS to focus on macromolecules and particles that range in size from about a few nanometers to micrometers. According to Zhang, “Sizing in this range started out interesting chemical engineers and material scientists, but in the past decade it started to find its applications in the various fields of life science.” Particles in this range are important in the biotechnology and pharmaceutical industries.

These industries bring a couple of unique requirements. For one thing, noninvasive and label-free methods are highly desirable for the particles that are used in a medical diagnostic or treatment application. Zhang says, “Biotech and pharma place a great emphasis on detection sensitivity and measurement accuracy.” Trace amounts of particles with slightly altered size and charge can impact the safety and efficacy of products. To achieve ever-improved detection sensitivity and measurement accuracy, Zhang says that he and his colleagues use the best lasers, fiber optics and single-photon detectors available and implement innovative measurement techniques, such as using multiangle detection.

Mixing measurements and modalities

At U.K.-based Malvern, product group manager Paul Kippax sees many changes in particle-size analysis. He says there’s a general move toward applications in QC labs. “Like most analytical techniques, laser diffraction for particle-size analysis started in R&D, [where it was] used in early stage product formulation to understand how a product worked,” Kippax says. “Now, though, it’s also a routine QC tool for specifying product quality.” This creates a wider user base. So, Kippax says, “Many of our recent innovations for the Mastersizer 3000 system have focused on ease of use, productivity and ensuring data integrity, even for novice operators.”

Even where particle-size analysis is used in R&D, some scientists need more information. Rather than knowing about the average particle in a mixture, the sizes of different kinds of particles might matter just as much, or even more. “Component-specific data is crucial,” Kippax says, “if, for example, you are trying to determine the particle-size distribution of different active ingredients and excipients in a pharmaceutical—a routine task for generic developers.” A scientist might use that information to improve an existing product or develop a new one. As Kippax says, “Instruments that enable size, shape and component analysis, such as the Morphologi G3-ID, can be really valuable for applications such as these and are growing in use.”

Beyond gathering data about particles, some researchers might also like to see them. That can mean combining a method of particle-size analysis with an imaging technique. “Giving users access to image information could let people specify products based on size and shape, and can also be extremely helpful in diagnosing problems, with a process or even a measurement,” Kippax explains. “Seeing what is happening to particles is useful in laser diffraction particle sizing, for example, which is why we developed Hydro Sight.” This is an imaging accessory for the Mastersizer 3000 laser diffraction system that allows the user to see particles as they are being measured.

Scanning electron microscope image of volcanic ash reveals the potential complexity of particle analysis. (Image courtesy of U.S. Geological Survey/ photo by Pavel Izbekov.)

By getting more information about a sample, especially in manufacturing-related QC, companies could make a better product more efficiently. As Jason T. Noga, brand manager at Microtrac (Montgomeryville, Penn.), says, “If the QC team sees deviations in the morphology of the particles, a company could make proactive changes, rather than being reactive and wasting materials.” That’s part of the reason that Microtrac developed the 3D Dynamic Image Analyzer, which can characterize more than 30 morphological features of particles—all in three dimensions. This platform collects 100 images a second, and it measures particles that are 15 microns to 35 millimeters across. “You can look at the morphology and adjust the methodologies in nearly real time,” says Paul Cloake, president of Microtrac. “You can optimize the particle size and shape to get an increased yield of product.”

The user distribution

As more industries make more use of particle-size analysis, the range of users keeps expanding. Some users just want the results. “For those customers,” says Zhang, “we’ve increased the measurement automation. The user interface of instrument control and data analysis software becomes simpler and more intuitive.” He adds that intelligent features, like expert advice, help users avoid common technical pitfalls.

To accommodate more users, one platform could also cover more ground. Cloake says, “Our technology goes up to about 3000 microns and down to about 10 nanometers.” He adds, “You only need one instrument across that range.” For today’s R&D and manufacturing environments, the complex data needed from a variety of particle analysis applications requires vendors to make platforms that gather data on multiple characteristics of the particles and to let users actually see what is changing.

Mike May is a freelance writer and editor living in Ohio. He can be reached at [email protected].

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