Particle Size Analyzers and Rheometers: Two Tools for R&D in Bio-Material Medical Devices

While conducting medical device research and development, you may hear these phrases:

• "Let's do a particle size analysis on this."
• "What is the G' value for this gel?"

At first, terms like D10·D50·D90 and G' and G'' might sound unfamiliar.
However, as you develop bio-material-based medical devices like hemostatic agents, bone grafts, medical device fillers, and hydrogels, you will realize that these numbers are not just exam results.
The particle size affects the handleability and manufacturing process of the product, while the viscoelasticity of the gel relates to injectability and shape retention.

In this article, we will summarize the basic principles and reading methods of the two devices frequently encountered in R&D: particle size analyzers and rheometers.

Particle Size Analyzer: "How big are these powder particles?"

In powder-based hemostatic agents or particle-type bone grafts, the size and distribution of particles are critical data for understanding product characteristics.
For powder-based hemostatic agents, particle size and distribution can affect handleability and spreadability; for bone grafts, it can impact filling characteristics and methods of use.

Even when using the same raw material, differing particle size distributions can change product characteristics and manufacturing processes.

Practical Tip

Thus, particle size analysis is more about confirming "Are the particle characteristics of our product being managed consistently?" rather than simply determining "What is the particle size of this raw material in μm?"

Principle of Laser Diffraction Method

The most common principle of particle size analyzers is the laser diffraction method.
When a laser is directed at particles, light is scattered; larger particles tend to scatter at a narrow angle, while smaller particles scatter at a wider angle.
The equipment analyzes this scattering pattern to calculate the particle size distribution.

Caution

The size measured by the laser diffraction method is not strictly the same concept as the diameter measured directly through a microscope.
Results may vary depending on particle shape and optical models.
The key issue is not simply stating "measured by laser diffraction method" but rather "Is this method appropriate for evaluating the particle characteristics of our product?"

Surprisingly Important: Sample Preparation

Problems frequently arise not from the equipment but rather from the sample preparation process in particle size analysis.
In wet analysis, samples are dispersed in a liquid; protein materials like gelatin or certain natural polymers may swell or dissolve when in contact with water.

If you carelessly disperse the material in water, you risk obtaining particles in a state that has been altered by water rather than the original powder.

Thus, when determining the testing method, consider the following:

• What dispersion medium will be used?
• Is the sample concentration appropriate?
• Is the dispersion time sufficient?
• Is stirring or ultrasonic treatment necessary?
• Is there a risk of swelling or dissolving the sample?
• Is there any agglomeration occurring during measurement?

Reading D10·D50·D90

Particle size analysis results yield three numbers:

• D10: 10% point of the particle size distribution
• D50: 50% point (commonly viewed as the representative diameter)
• D90: 90% point

While D50 is often regarded as the representative value, it alone does not sufficiently describe the distribution.
Two samples could have the same D50, but one might have uniformly sized particles while the other has a wide mixture of small and large particles.
Here, looking at D10 and D90 together reveals the difference between the two samples.

Rheometer: "How hard is this gel?"

When developing hydrogels or medical device fillers, you will encounter a rheometer.
Such products cannot simply be described visually as gel-like.
It's essential to know how easily they deform, how well they recover when force is removed, whether they have flow properties, and if they retain shape.

A rheometer is a device for evaluating this viscoelasticity.
For example, jelly can return to its original shape to some extent when pressed and released, while water flows when a force is applied.
Hydrogels possess both properties to some degree.

G' and G''

• G' (Storage Modulus): Represents elastic properties.
  A larger G' signifies a stronger tendency to return to original shape.
• G'' (Loss Modulus): Represents viscous properties.
  A larger G'' indicates a stronger tendency to flow.

Generally, if G' > G'' it is interpreted that elasticity predominates, while G'' > G' indicates that viscosity is predominant.

Caution

Stating "G' is 100 Pa" is far less accurate than stating "G' measured under specific conditions is 100 Pa."
This is because results can vary based on measurement temperature, frequency, strain, and sample preparation methods.

Is a higher G' always better for fillers?

Not necessarily.
Fillers and hydrogels require different properties depending on their intended use.
For products where shape retention is critical, elasticity is important; however, for products where injectability is key, too high a modulus may actually hinder usability.

The core issue is not simply whether "G' is high," but rather whether it has properties suitable for the product's intended use.

Key Points to Remember

• Particle Size Analysis: Do not look solely at D50; consider D10 and D90 as well.
• Rheometer: Look at G' and G'' numbers, but also consider measurement conditions.
• For both tests, "How was the measurement conducted?" is just as important as "What results were obtained?"

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In the next article, we will take a step further.
"What is necessary for using these analytical results as regulatory documentation?" We will examine analysis method validation, repeat testing, the significance of n=3, inter-batch variation, and comparisons before and after sterilization from a regulatory perspective.

Frequently asked questions

How many times should particle size analysis be repeated?

There is no single official number that applies to every test.
Repeating a measurement on the same sample, testing independently collected samples, and comparing batches involve different types of repetition.
Design the study around the test objective and product characteristics.