Ultrasonic Crystallization and Precipitation

Ultrasound initiates and promotes the nucleation and crystallization of organic molecules. Having control over this process is vital to make sure the final product is of high quality. The advantages of using sonication for crystallization and making solids from liquids are that it makes the process much faster, uses less material, and lets you manage the final crystals size. Hielscher provides reliable and easy-to-use sonicators for successful crystallization and solid-formation, whether in batch, inline, or in-situ during a reaction.

Sono-Crystallization and Sono-Precipitation

The application of ultrasonic waves during crystallization and precipitation have various positive effects on the process.
Power ultrasound helps to

  • form oversaturated/ supersaturated solutions
  • initiate a fast nucleation
  • control the rate of crystal growth
  • control the precipitation
  • control polymorphs
  • reduce impurities
  • obtain an uniform crystal size distribution
  • obtain an even morphology
  • prevent unwanted deposition on surfaces
  • initiate secondary nucleation
  • ameliorate solid-liquid separation


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Sono-crystallization of crystals such as pharmceuticals, fine chemicals etc.

Sonicator UIP2000hdT with batch reactor for sono-crystallization

Difference between Crystallization and Precipitation

Both crystallization and precipitation are solubility-driven processes, wherein a solid phase, be it a crystal or precipitate, emerges from a solution that has surpassed its saturation point. The distinction between crystallization and precipitation hinges on the mechanism of formation and the nature of the final product.

In crystallization, a methodical and gradual development of a crystalline lattice occurs, selectively assembled from organic molecules, ultimately yielding a pure and well-defined crystalline or polymorphic compound. Conversely, precipitation entails the swift generation of solid phases from an oversaturated solution, resulting in the formation of either crystalline or amorphous solids. It is important to note that distinguishing between crystallization and precipitation can be challenging, as many organic substances initially manifest as amorphous, non-crystalline solids, which subsequently undergo a transition to become truly crystalline. In such instances, the delineation between nucleation and the formation of an amorphous solid during precipitation becomes intricate.

The crystallization and precipitation processes are dictated by two fundamental steps: nucleation and crystal growth. Nucleation commences when solute molecules in an oversaturated solution accumulate, forming clusters or nuclei, which then serve as the foundation for the subsequent growth of solid phases.

Common Problems with Crystallization and Precipitation Processes

Crystallization and precipitation are normally either very selectively or very rapidly propagating processes and thereby hardly to control. The result is that in general, nucleation occurs randomly, so that the quality of the resulting crystals (precipitants) is uncontrolled. Accordingly, the outcoming crystals have a untailored crystal size, are unevenly distributed and non-uniformly shaped. Such randomly precipitated crystals cause major quality problems since crystal size, crystal distribution and morphology are crucial quality criteria of the precipitated particles. An uncontrolled crystallization and precipitation means a poor product.

Solution: Crystallization and Precipitation under Sonication

An ultrasonically assisted crystallization (sonocrystallization) and precipitation (sonoprecipitation) allows for the precise control over the process conditions. All important parameters of the ultrasonic crystallization can be precisely influenced – resulting in a controlled nucleation and crystallization. The ultrasonically precipitated crystals feature have a more uniform size and more cubic morphology. The controlled conditions of sono-crystallization and sono-precipitation allow for high reproducibility and a continuous crystal quality. All results achieved in small scale, can be up-scaled completely linear. Ultrasonic crystallization and precipitation enable for the sophisticated production of crystalline nano-particles – on both, lab and industrial scale.

TEM image of ultrasonically synthesized perovskite nanocrystals

TEM image of ultrasonically synthesized perovskite nanocrystals: CH3NH3PbBr3 QDs (a) with and (b) without ultrasonic treatment.
(Picture and study: ©Chen et al., 2007)

The Effects of Ultrasonic Cavitation on Crystallization and Precipitation

When highly energetic ultrasonic waves are coupled into liquids, alternating high pressure/ low pressure cycles create bubbles or voids in the liquid. Those bubbles grow over several cycles until they cannot absorp more energy so that they collapse violently during a high pressure cycle. The phenomenon of such violent bubble implosions is known as acoustic cavitation and is characterized by local extreme conditions such as very high temperatures, high cooling rates, high pressure differentials, shock waves and liquid jets.
The effects of ultrasonic cavitation promote crystallization and precipitation providing a very homogeneous mixing of the precursors. Ultrasonic dissolving is a well-eastblished method to produce oversaturated/ supersaturated solutions. The intense mixing and the thereby improved mass transfer improves the seeding of the nuclei. The ultrasonic shockwaves assist the formation of the nuclei. The more nuclei are seeded, the finer and faster will occur the crystal growth. As ultrasonic cavitation can be very precisely controlled, it is possible to control the crystallization process. Naturally existing barriers for nucleation are easily overcome due to the ultrasonic forces.
Additionally, sonication assists during so-called secondary nucleation since the powerful ultrasonic shear forces break and deagglomerate larger crystals or agglomerates.
With ultrasound, a pre-treatment of the precursors can be avoided since sonication enhances the reaction kinetics.

Acoustic or ultrasonic cavitation: bubble growth and implosion

Ultrasonic cavitation creates highly intense forces that promotes the crystallization and precipitation processes

Influencing Crystal Size by Sonication

Ultrasound enables for the production of crystals tailored to requirements. Three general options of sonication have important effects on the output:

  • Initial Sonication:
    The short application of ultrasound waves to a supersaturated solution can initiate the seeding and formation of nuclei. As sonication is only applied during the initial stage, the subsequent crystal growth proceeds unimpeded resulting in larger crystals.
  • Continuous Sonication:
    The continuous irradiation of the supersaturated solution results in small crystals since the unpaused ultrasonication creates a lot of nuclei resulting in the growth of many small crystals.

  • Pulsed Sonication:
    Pulsed ultrasound means the application of ultrasound in determined intervals. A precisely controlled input of ultrasonic energy allows to influence the crystal growth in order to obtain a tailored crystal size.

Sonicators for Improved Crystallization and Precipitation Processes

Sono-crystallization and sono-precipitation processes can be carried out in batches or closed reactors, as continuous inline process or as in-situ reaction. Hielscher Ultrasonics supplies you the perfectly suitable sonicator for your specific sono-crystallization and sono-precipitation process – whether in research purpose on lab and bench-top scale or in industrial production. Our broad product range covers your needs. All ultrasonicators can be set to ultrasonic pulsation cycles – a feature that allows to influence a tailored crystal size.
To ameliorate the benefits ultrasonic crystallization even more, the use of the Hielscher flow cell insert MultiPhaseCavitator is recommended. This special insert provides the injection of the precursor through 48 fine cannulas improving the initial seeding of the nuclei. The precursors can be exactly dosed resulting in a high controllability over the crystallization process.

Multi-Phase-Cavitator MPC48Insert for improved emulsification and crystallization processes using sonication

MultiPhaseCavitator for enhanced crystallization processes

Ultrasonic Crystallization


  • fast
  • efficient
  • exactly reproducible
  • high quality output
  • high yields
  • controllable
  • reliable
  • various setup options
  • safe
  • easy operation
  • easy to clean (CIP/ SIP)
  • low maintenance


The table below gives you an indication of the approximate processing capacity of our ultrasonicators:

Batch VolumeFlow RateRecommended Devices
0.5 to 1.5mLn.a.VialTweeter
1 to 500mL10 to 200mL/minUP100H
10 to 2000mL20 to 400mL/minUP200Ht, UP400St
0.1 to 20L0.2 to 4L/minUIP2000hdT
10 to 100L2 to 10L/minUIP4000hdT
15 to 150L3 to 15L/minUIP6000hdT
n.a.10 to 100L/minUIP16000
n.a.largercluster of UIP16000

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Ultrasonic flow cell for dispersion and dissolving

Ultrasonic glass reactor for inline crystallization and precipitation

Literature / References

Facts Worth Knowing

The application of intense ultrasound waves to liquids, liquid-solid and liquid-gas mixtures contributes to manifold processes in materials science, chemistry, biology and biotechnology. Similar to its manifold applications, the coupling of ultrasonic waves into liquids or slurries is named with various terms that describe the sonication process. Common terms are: sonication, ultrasonication, sonification, ultrasonic irradiation, insonation, sonorisation, and insonification.

High performance ultrasonics! The Hielscher product range covers the full spectrum from the compact lab ultrasonicator over bench-top units to full-industrial ultrasonic systems.

Hielscher Ultrasonics manufactures high-performance ultrasonic homogenizers from lab to industrial size.

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