Using an Ultrasonic Homogenizer to Process Substances for Human Consum

By Aimee O'Driscoll, 08 July 2021

An ultrasonic homogenizer is a highly useful tool for many applications, including nanoparticle creation, emulsification, particle size reduction, and cell lysis. However, it doesn’t come without its downsides. One of those is that trace amounts of titanium alloy (the material the probe is constructed from) can end up in the sample or product that is being processed.

For many applications, this isn't a concern. However, if the final product is intended for human consumption, this would be reason to question the safety implications of this process. While titanium is generally considered inert and biocompatible—indeed, it’s used for medical and dental implants and as a whitener in products such as many toothpastes—there is evidence that titanium and its by-products could be harmful to humans.

Here, we look at the issue of trace amounts of titanium in samples and what you can do to limit risks.

Ultrasonic Homogenization and Titanium Migration

Ultrasonic homogenizer probes are typically constructed of a titanium alloy, Ti-6Al-4V. During ultrasonic homogenization, the probe (horn) vibrates rapidly. As the probe vibrates, it’s expected that trace amounts of the probe material will migrate to the sample. Indeed, several reports note the presence of trace amounts of titanium and aluminum in samples post-sonication, including:

As noted in the latter report by the National Institute of Standards and Technology (NIST):

“Tip erosion is an unavoidable side effect in direct sonication. When the tip erodes, microscopic tip residues (typically titanium metal) are released from the tip into the sonicated suspension, introducing impurities and potentially contaminating the suspension.”

While there have not been conclusive studies to determine how much of the probe material migrates to the samples, it’s expected  that the level will depend on several factors including the time period over which homogenization takes place and the amplitude of probe vibrations.

Another varying factor is the amount of wear on the horn. As noted in this report titled Effect of sonication conditions: solvent, time, temperature and reactor type on the preparation of micron sized vermiculite particles

“The main difference in the elemental analysis of the raw samples and the sonicated samples (Table 1) is the increase of the amount of Ti after sonication due to the erosion of the Titanium probe. Inferred from Table 1, the Ti impurities content in the vermiculites sonicated for 5h in water medium is in the range 0.6-1 weight %.”

Again, the expected levels are not well-studied or documented so it would be improper to draw conclusive figures from this isolated anecdotal evidence, but it does serve as a very rough estimation of what you might observe.

How to Remove Titanium from Products

Depending on the intended use for the sample you are processing, there is often little concern regarding low levels of titanium and other probe material contaminants in the product. However, in other cases, it can be an issue. This is especially true if products are intended for human consumption:

If you deem it necessary to remove the trace materials, you have two main options:

  1. Filtration: One option is to filter the particles out of the sample. Andrea Coppola of Qsonica suggests that sterilizing grade filtration (0.2 or 0.45 micron pore size) is appropriate as the titanium particulate from ultrasonic processing is 0.5 micron or greater.
  2. Centrifugation: Coppola says that centrifugation is also an option to concentrate the particles. Using a centrifuge with the appropriate parameters should force the titanium particles into the bottom of the vessel such that they can be easily separated from the sample.

How to Limit the Migration of Probe Material

As mentioned, there are likely several determining factors affecting how much titanium ends up in your product. Assuming tweaks would not affect your process outcome, you could try limiting the processing time or using a unit with lower amplitude. However, there are likely limits to the changes you can make here, particularly if your process has been optimized for the desired outcome.

One parameter that is arguably more controllable is the wear on the horn. NIST suggests inspecting any daily-use probes on at least a weekly basis. You should be able to spot tip erosion as the usually lustrous appearance of the tip will look gray and matte. With more extensive erosion, it will appear pitted.


Stages of tip erosion.

Source: NIST

In some cases, if the tip is simply matted, it can be buffed using carbide paper or an emery cloth. However, if you’re concerned about material migration into your product, it’s probably best to replace the tip at the first sign of erosion.

Note that the type of sample you’re processing can impact the speed with which the probe tip wears. For example, gritty solids can induce wear quite quickly and will require that tips are replaced more often.

If you anticipate needing to replace tips regularly, when deciding on a probe, you may want to select one with replaceable tips such as select standard probes for the Q500 and Q700 Sonicators (below). It should be noted, however, that replaceable tips are not suitable for organic solvents or other solvents with low surface tension.


Replaceable tips.