Wireless stimulation strategies are emerging as powerful tools for guiding neuronal activity and regeneration, yet most existing systems rely on rigid, inorganic materials that raise concerns regarding long-term biocompatibility and sustainability. Cellulose nanofibrils (CNF) are renewable and intrinsically piezoelectric, offering a fully organic alternative for ultrasound-driven neuromodulation. Here, we investigate phosphorylated cellulose nanofibrils (pCNF) as ultrasound-responsive piezoelectric interfaces for neuronal stimulation, including mechanistic interrogation via pharmacological inhibition assays. Phosphorylation enhances surface charge density and promotes fibril individualization and dispersion while preserving the crystalline structure and intrinsic piezoelectricity of cellulose. Nanoscale electromechanical activity was confirmed by piezoresponse force microscopy, and ultrasound stimulation generated intensity-dependent electrical outputs at the macroscopic level. pCNF exhibited excellent cytocompatibility and formed a tight interface with neuronal cells. Functionally, pCNF significantly amplified ultrasound-induced cellular responses, including reactive oxygen species production in SH-SY5Y cells and robust calcium transients in primary dorsal root ganglion neurons. Pharmacological inhibition studies revealed that these ultrasound-induced responses arise from a multimodal mechanism involving voltage-gated excitability, endoplasmic reticulum (ER)-associated intracellular Ca²⁺ release, and redox-sensitive processes. Together, these results establish phosphorylated cellulose nanofibrils as a sustainable, fully organic platform for wireless neuromodulation. By combining material renewability, mechanical compliance, and ultrasound-driven piezoelectricity, pCNF provides a foundation for organic nanobioelectronic interfaces and future ultrasound-responsive scaffolds for neural regeneration.
Noncontact actuation of small elastic structures is a challenging problem given the poor scaling of electronic actuators. Sound offers a convenient and steerable power source for actuation, but the direct conversion for actuation via primary acoustic forces is typically inefficient. We recently demonstrated that the secondary scattering forces between bubbles can be dramatically amplified by geometric patterning and used for precise actuation in a fluidic environment. Here, we build on this idea and introduce a dynamic metamaterial composed of trapped gas bubbles in a fluid. We show carefully designed structures that achieve wirelessly switchable mechanical motion via secondary acoustic radiation forces. We introduce a theoretical model of the system to describe the equilibrium configurations of the structures, and support this model with experimental results. Building on our model, we introduce design principles to achieve different actuation behaviors. Our results highlight the potential of such acousto-elastic actuators for applications in soft robotics, programmable matter, and smart materials capable of reconfigurable actuation.
Antibubbles are a novel carrier for precise, ultrasound-triggered delivery of fluid or nanoparticulate payloads. These structures combine the high acoustic contrast and strong acoustic response of conventional microbubbles with a significantly higher payload capacity thanks to their large fluid core. The release characteristics of antibubbles can be precisely tuned during fabrication to enable release across a range of pressures spanning a few kPa to several hundred kPa. Moreover, antibubbles can release these payloads either all at once, or incrementally across multiple ultrasonic pulses. This talk will illustrate how such characteristics make antibubbles unique reporters for ultrasonic pressure, and how the fabrication and design determine the antibubble’s response. We use high-speed microscopy to highlight the relationship between the antibubble and its released payload. Finally, it will be shown that by properly tailoring the payload, formulation, and supporting matrix, spatial maps of complex acoustic pressure fields can be produced and read out optically, providing real-time diagnostic information about spatially structured ultrasonic fields.
The ability to dynamically shape ultrasound fields is critical for emerging applications in therapeutic ultrasound, particle manipulation and tissue engineering. While existing phased arrays provide beam steering for imaging, these newer applications require higher intensities. This complicates the electrical driving and ultimately limits the array size and spatial complexity of the field. Here, we introduce a scalable architecture for driving phased arrays using a single power source and light-responsive analog phase shifters. Compared to conventional arrays, which drive each channel independently, our device only needs one amplifier. Moreover, the phase shift can be continuously varied between ±π based on light intensity. Using our phase shifter, we demonstrate dynamic, multi-focal ultrasound beams, fast beam steering, and spatially-complex beams including acoustic vortices. Because of its simple, analog design, optical addressing, and superior phase control, this architecture paves the way for very large transducer arrays and the generation of high-intensity, spatially-complex ultrasound fields.
Acoustic holograms have developed over the last 10 years as powerful tools for ultrasonic wavefront and field shaping. They can provide high-resolution control over wavefronts, allowing them to form much more spatially complex wavefronts than existing array transducers, and with significantly simpler hardware. However, unlike ultrasonic arrays, acoustic holograms are static: the fields they produce cannot be readily changed or adapted in real-time. To address this limitation, our group has developed different approaches to realize dynamic and interactive holograms over the past several years. In this talk, I will describe these recent efforts and highlight some of our latest work in this area, including the combination of holograms and transducer arrays, the integration of machine learning techniques in the hologram design process, and the development of remotely addressable electrical circuits for the dynamic updating of high-density ultrasonic arrays. Our work demonstrates different approaches that can be taken to expand the versatility of holograms. This talk highlights the opportunities for interactive holograms and the advantages of certain methods.
Acoustic metamaterials enhance traditional material properties through microstructure engineering, providing new opportunities to shape sound fields in applications ranging from biomedical imaging, clinical therapy to non-destructive testing. However, at the MHz frequency ranges, only a few metamaterial architectures exist. They are often highly attenuating or difficult to manufacture, and generally provide limited 3D control over sound propagation. Here, we introduce a MHz-frequency ultrasonic metamaterial based on laser-engraved glass. By structuring meta-voxels with different engraving patterns, we define a fully-3D, anisotropic metamaterial exhibiting local variations in the sound speed of up to 20
Antibubbles are an emerging carrier for low-intensity, ultrasound-triggered release that can carry large payloads in their liquid cores. As we have previously shown, antibubbles can release their payloads at adjustable pressures, ranging from as low as a few kPa (MI < 0.01) to above a few hundred kPa (MI > 0.2). The specific release threshold and behavior can be determined during fabrication, making it possible to realize either single-shot release or multi-stage dosing of a payload. These characteristics make antibubbles an attractive alternative to conventional microbubble delivery agents particularly in sensitive tissues where risks of ultrasound need to be kept to a minimum. In this talk, we discuss recent experiments in which we demonstrate triggered release from antibubbles in in vitro biological systems. We show that payload release can be controlled using patterned or focused ultrasound fields, and we characterize the distribution and cellular uptake of payloads inside cell-laden matrices. These results not only demonstrate the potential of antibubbles for therapeutic applications but also open the door to targeted delivery in complex tissue scaffolds for tissue engineering.
Combining cells, biomaterials and bioactive factors with biophysical cues to engineer cell and tissue constructs can address various applications, such as regenerative and personalized medicine, in addition to drug discovery and testing. However, challenges associated with the assembly of large, complex tissues integrating multiple cell types and functions require established technologies such as 3D printing to be combined with cell-assembly and cell-stimulation methods. Ultrasound is a potential tool for advancing tissue engineering, conferring the advantages of cytocompatibility and deep tissue penetration. In this Review, we discuss the application of ultrasound to the remote manipulation and assembly of biological building blocks, as well as the direct and indirect triggering of cellular processes, in combination with ultrasound-sensitive additives. Furthermore, we examine the role of ultrasound in tissue maturation, and in affecting the microenvironment and cell programming. Finally, we outline the challenges facing the technology and considerations for the widespread use of ultrasound in tissue engineering. Ultrasound is an emerging tool for tissue engineering with the distinct advantages of cytocompatibility and deep tissue penetration. This Review discusses the integration of ultrasound for cellular assembly and tissue maturation with tissue-engineering techniques to advance regenerative medicine.
Ultrasound offers promising applications in biology and chemistry, but quantifying local ultrasound conditions remains challenging due to the lack of non-invasive measurement tools. We introduce antibubbles as novel optical reporters of local ultrasound pressure. These liquid-core, air-shell structures encapsulate fluorescent payloads, releasing them upon exposure to low-intensity ultrasound. We demonstrate their versatility by fabricating antibubbles with hydrophilic and hydrophobic payloads, revealing payload-dependent encapsulation efficiency and release dynamics. Using acoustic holograms, we showcase precise spatial control of payload release, enabling visualization of complex ultrasound fields. High-speed fluorescence imaging reveals a gentle, single-shot release mechanism occurring within 20-50 ultrasound cycles. It is thus possible to determine via an optical fluorescence marker what the applied ultrasound pressure was. This work thereby introduces a non-invasive method for mapping ultrasound fields in complex environments, potentially accelerating research in ultrasound-based therapies and processes. The long-term stability and versatility of these antibubble reporters suggest broad applicability in studying and optimizing ultrasound effects across various biological and chemical systems.
Acoustic holograms are able to control pressure fields with high spatial resolution, enabling complex fields to be projected with minimal hardware. This capability has made holograms attractive tools for applications, including manipulation, fabrication, cellular assembly, and ultrasound therapy. However, the performance benefits of acoustic holograms have traditionally come at the cost of temporal control. Once a hologram is fabricated, the field it produces is static and cannot be reconfigured. Here, we introduce a technique to project time-dynamic pressure fields by combining an input transducer array with a multiplane hologram, which is represented computationally as a diffractive acoustic network (DAN). By exciting different input elements in the array, we can project distinct and spatially complex amplitude fields to an output plane. We numerically show that the multiplane DAN outperforms a single-plane hologram, while using fewer total pixels. More generally, we show that adding more planes can increase the output quality of the DAN for a fixed number of degrees of freedom (DoFs; pixels). Finally, we leverage the pixel efficiency of the DAN to introduce a combinatorial projector that can project more output fields than there are transducer inputs. We experimentally demonstrate that a multiplane DAN could be used to realize such a projector.
The benefits of ultrasound are its ease-of-use and its ability to precisely deliver energy in opaque and complex media. However, most materials responsive to ultrasound show a weak response, requiring the use of high powers, which are associated with undesirable streaming, cavitation, or temperature rise. These effects hinder response control and may even cause damage to the medium where the ultrasound is applied. Moreover, materials that are currently in use rely on all-or-nothing effects, limiting the ability to fine-tune the response of the material on the fly. For these reasons, there is a need for materials that can respond to low intensity ultrasound with programmable responses. Here it is demonstrated that antibubbles are a low-intensity-ultrasound-responsive material system that can controllably release a payload using acoustic pressures in the kPa range. Varying their size and composition tunes the release pressure, and the response can be switched between a single release and stepwise release across multiple ultrasound pulses. Observations using confocal and high-speed microscopy revealed different ways that can lead to release. These findings lay the groundwork to design antibubbles that controllably respond to low-intensity ultrasound, opening a wide range of applications ranging from ultrasound-responsive material systems to carriers for targeted delivery.
One approach to ultrasound therapy is to use therapeutic agents that can be activated by focused ultrasound when they reach a specific site in the body. Commonly, such agents are loaded on the surfaces of microbubbles, which respond strongly to ultrasound and shed the payload. However, microbubbles require high pressures and mechanical indices to burst (typically above 200 kPa, MI > 0.2). Moreover, the quantity and types of therapeutic payload that can be delivered by microbubbles are limited because payloads must be attached to the microbubble surface. Here, we show how these limitations can be overcome by using stabilized antibubbles as an ultrasound-responsive carrier. Antibubbles are liquid droplets encased within an air bubble. Because therapeutic payloads can be encapsulated in the core, larger volumes can be carried per antibubble. Additionally, by carrying payloads in the volume rather than on the surface, a wider variety of payloads can be carried. Through experiments we demonstrate that antibubbles respond strongly to ultrasound and can release payloads with pressures below 50 kPa (MI = 0.05) for certain formulations. By modifying the formulation, we show that the release pressure and temporal release profile can be tuned. Finally, we show that the bursting is highly selective in space, demonstrating that antibubbles can be used for precise delivery of payloads using shaped, low-intensity ultrasound fields.
Manipulation of macroscale objects by sound is fundamentally limited by the wavelength and object size. Resonant subwavelength scatterers such as bubbles can decouple these requirements, but typically the forces are weak. Here we show that patterning bubbles into arrays leads to geometric amplification of the scattering forces, enabling the precise assembly and manipulation of cm-scale objects. We rotate a 1 cm object continuously or position it with 15 μm accuracy, using sound with a 50 cm wavelength. The results are described well by a theoretical model. Our results lay the foundation for using secondary Bjerknes forces in the controlled organization and manipulation of macroscale structures.
Smart materials can respond to stimuli and adapt their responses based on external cues from their environments. Such behavior requires a way to transport energy efficiently and then convert it for use in applications such as actuation, sensing, or signaling. Ultrasound can carry energy safely and with low losses through complex and opaque media. It can be localized to small regions of space and couple to systems over a wide range of time scales. However, the same characteristics that allow ultrasound to propagate efficiently through materials make it difficult to convert acoustic energy into other useful forms. Recent work across diverse fields has begun to address this challenge, demonstrating ultrasonic effects that provide control over physical and chemical systems with surprisingly high specificity. Here, we review recent progress in ultrasound-matter interactions, focusing on effects that can be incorporated as components in smart materials. These techniques build on fundamental phenomena such as cavitation, microstreaming, scattering, and acoustic radiation forces to enable capabilities such as actuation, sensing, payload delivery, and the initiation of chemical or biological processes. The diversity of emerging techniques holds great promise for a wide range of smart capabilities supported by ultrasound and poses interesting questions for further investigations.
Acoustic waves, capable of transmitting through optically opaque objects, have been widely used in biomedical imaging, industrial sensing and particle manipulation. High-fidelity wave front shaping is essential to further improve performance in these applications. An acoustic analog to the successful spatial light modulator (SLM) in optics would be highly desirable. To date there have been no techniques shown that provide effective and dynamic modulation of a sound wave and which also support scale-up to a high number of individually addressable pixels. In the present study, we introduce a dynamic spatial ultrasound modulator (SUM), which dynamically reshapes incident plane waves into complex acoustic images. Its transmission function is set with a digitally generated pattern of microbubbles controlled by a complementary metal-oxide-semiconductor (CMOS) chip, which results in a binary amplitude acoustic hologram. We employ this device to project sequentially changing acoustic images and demonstrate the first dynamic parallel assembly of microparticles using a SUM.
When asymmetric Janus micromotors are immobilized on a surface, they act as chemically powered micropumps, turning chemical energy from the fluid into a bulk flow. However, such pumps have previously produced only localized recirculating flows, which cannot be used to pump fluid in one direction. Here, we demonstrate that an array of three-dimensional, photochemically active Au/TiO2 Janus pillars can pump water. Upon UV illumination, a water-splitting reaction rapidly creates a directional bulk flow above the active surface. By lining a 2D microchannel with such active surfaces, various flow profiles are created within the channels. Analytical and numerical models of a channel with active surfaces predict flow profiles that agree very well with the experimental results. The light-driven active surfaces provide a way to wirelessly pump fluids at small scales and could be used for real-time, localized flow control in complex microfluidic networks.
Acoustic holograms are a simple yet powerful tool to project structured pressure fields for applications including acoustic manipulation, ultrasonic therapy, and compressed sensing. However current holographic projectors lack the ability to dynamically change the pressure field, which is necessary for real-time manipulation and control of acoustically excited systems. A promising solution is to use hybrid projectors: multi-element phased arrays combined with high-resolution static holograms. Such a system was recently built to dynamically translate high-resolution pressure fields for particle manipulation in water. Here, we extend this paradigm and introduce a more general hybrid acoustic projector capable of projecting distinct high-resolution pressure fields using arrays with only a few elements. Each input element excites a distinct output field through a multi-plane hologram, whose phase delays are calculated by representing pixels in each phase plate as neurons in a diffractive neural network. This representation allows us to efficiently multiplex the holograms so that all of the input-output transformations are performed by a single set of static phase plates. We experimentally characterize the output of our device and show that by cycling through the different inputs, the projected acoustic field can be changed in real time, creating an “acoustic animation.”
Optical breakdown of water is used as a sound source to excite a broadband set of leaky Lamb waves in submerged aluminum plates. The source is shown to simultaneously excite guided modes spanning 0.1-5 MHz in frequency and 0-0.8 mm-1 in wavenumber. The measured response overlaps well with dispersion curves for Lamb waves in the plates, revealing strong coupling to both symmetric and antisymmetric modes. The strongest responses arise when a mode's phase velocity approximately equals the plate's compressional wave velocity. These results are shown to arise from an interplay of the sensing geometry, guided wave speeds, and signal processing. Finally, implications for non-contact sensing are discussed.
When a high-power laser is focused to a small spot in a fluid, nonlinear interactions at the focus can excite a plasma that evolves and glows according to the properties of the breakdown medium. This phenomenon—optical breakdown—is commonly used for underwater chemical measurements in a technique called Laser-Induced Breakdown Spectroscopy (LIBS). However, LIBS generally operates at short ranges and only leverages the optical emission of the plasma for sensing. If instead, the laser systems were tuned to amplify the mechanical effects of optical breakdown, then it could be deployed as a versatile source for broadband acoustic sensing. The optical breakdown acoustic source is simultaneously compact (mm-scale), loud (MPa peak pressures), ultra-broadband (10 kHz–4 MHz), and geometrically reconfigurable. Here, I will describe the physics governing optical breakdown transduction and then show how can this be tuned to enable new single-vehicle sensing strategies in the ocean.