Periodic Reporting for period 4 - HOLOMAN (Holographic acoustic assembly and manipulation)
Reporting period: 2023-08-01 to 2025-07-31
Acoustic waves in the form of ultrasound are used for sensing and detection, for instance as distance sensors in a car or for medical imaging. However, ultrasound can also exert forces and interact with materials. Examples include ultrasonic cleaning baths, ultrasonic welding setups, as well as devices to destroy kidney stones and ablate biological tissue, particularly in transcranial ultrasound applications. Recent developments also show the promise of well-controlled and shaped ultrasound fields for neuromodulation. The latter are important applications in medicine. Ultrasound can also exert small forces to move particulate matter and even living cells. The aforementioned applications would all benefit from technologies that can precisely shape an ultrasonic wave. For instance, it would be a major advance, if it were possible to project ultrasound to form well-controlled pressure zones in a defined volume. In medical ultrasound it would, for instance, be beneficial if one could match the focal volume of the ultrasound to the precise shape of a tumor. This has thus far not been possible with high resolution. This ERC project HOLOMAN has the goals of developing technologies, computational models and applications that are based on our invention of the acoustic hologram, which permits sophisticated sound patterns to be formed. The hologram is used to control the phase and amplitude across an ultrasound beam with a specially designed mask, such that pressure images can be formed in space. A stated goal is to develop the tools to compute the holograms that will yield pressure distributions (images) in 2D and 3D. These pressure distributions can exert forces on microparticles and/or cells, and a major goal of the ERC project is to realize the contactless, parallel assembly of an object from particulate matter “in one shot”. Another goal is to develop technologies that allow the dynamic projection of ultrasound patterns and images, i.e. a projector for ultrasound (pressure) movies. We will use our tools to investigate the interaction of ultrasound microrobotic systems and biological matter.
The results of the ERC AdG HOLOMAN show that the stated goals have been realized. Computational tools have been developed that permit the determination of the wavefronts that are needed to form a desired intensity distribution in space. It was also possible to experimentally demonstrate this in the form of the first connected 3D hologram image that was formed with ultrasound waves. The use of the pressure ‘images’ in 2D or ‘objects’ in 3D for the assembly of matter, including biological cells from suspension could also be successfully demonstrated. One major benefit of this rapid form of contactless assembly is that the cell density is much higher than what can be realized in conventional bioprinting. Within the grant, new technologies have been developed that permit the realization of dynamic ultrasound fields, both using the new concept of an ultrasound modulator, as well as a novel way of controlling a phase array using light. We could also demonstrate a way to amplify acoustic forces, which is promising for micromanipulation. Using the secondary Bjerknes force we realized a way to assemble objects with great positional accuracy at a fluid interface. In the interaction of ultrasound with matter, a system of antibubbles could be advanced that is promising for targeted delivery and potential applications in the opening of the blood-brain-barrier. Overall, the grant has advanced the capabilities of generating sophisticated ultrasound fields as well as applications of shaped ultrasound.
The results of the ERC AdG HOLOMAN show that the stated goals have been realized. Computational tools have been developed that permit the determination of the wavefronts that are needed to form a desired intensity distribution in space. It was also possible to experimentally demonstrate this in the form of the first connected 3D hologram image that was formed with ultrasound waves. The use of the pressure ‘images’ in 2D or ‘objects’ in 3D for the assembly of matter, including biological cells from suspension could also be successfully demonstrated. One major benefit of this rapid form of contactless assembly is that the cell density is much higher than what can be realized in conventional bioprinting. Within the grant, new technologies have been developed that permit the realization of dynamic ultrasound fields, both using the new concept of an ultrasound modulator, as well as a novel way of controlling a phase array using light. We could also demonstrate a way to amplify acoustic forces, which is promising for micromanipulation. Using the secondary Bjerknes force we realized a way to assemble objects with great positional accuracy at a fluid interface. In the interaction of ultrasound with matter, a system of antibubbles could be advanced that is promising for targeted delivery and potential applications in the opening of the blood-brain-barrier. Overall, the grant has advanced the capabilities of generating sophisticated ultrasound fields as well as applications of shaped ultrasound.
The ERC AdG project HOLOMAN has been multifaceted with work on technology development, theory and computation, as well as experimental demonstrations with applications in the biomedical sciences. We have shown that we can assemble living cells into shapes defined by the hologram. The acoustic images generated by the hologram are ‘line drawings’ in solution, where the lines represent regions of high (or low) pressure. Cells in suspension experience forces because of the pressure gradients and will move to assemble along the patterns defined by the pressure image. The assembly of cells is promising for tissue engineering, especially as the method is benign to the cells and achieves higher cell densities than what is possible in bioprinting. The development of efficient computational tools has allowed the demonstration of the first three-dimensional hologram-formed pressure patterns. These could be used for ‘one-shot’ assembly into entire objects. Another major advance is a technology that permits us to update the hologram that shapes the ultrasound wave. Utilizing a CMOS chip with 10,000 electrodes that generate microbubble patterns, it was possible to modulate the ultrasound wave and generate amplitude holograms. This spatial ultrasound modulator can thus be used to project dynamic ultrasound patterns. Another implementation utilizes light to generate the bubble patterns that in turn form amplitude holograms. Finally, light could be used to tune the phase of each transducer in an array, only requiring one amplifier. This significantly simplifies the architecture needed for phase arrays and promises the scalability of phase array transducers (PATs). We also described a way to amplify acoustic fields to realize micro-actuators that are promising for micromanipulation and microrobotics, and found ways to realize hybrid particle-based systems that are promising for targeted delivery in the form of antibubbles. We also found ways to advance the generation of low-energy, scalable neural networks, and exploited the power of machine learning to simplify the computation of acoustic holograms. We have built setups and undertaken work to identify the biophysical mechanisms that underlie ultrasound-cell interactions.
The results have led to a number of scientific papers published in leading journals. The work has also been disseminated at conferences, summer schools, and scientific meetings.
The results have led to a number of scientific papers published in leading journals. The work has also been disseminated at conferences, summer schools, and scientific meetings.
The project has been concluded and the results have been described in this report.