Ultrasound Stimuli Research Articles

Corked Microcapsules Enabling Controlled Ultrasound-Mediated Protein Delivery.

While ultrasound represents a facile, portable, and noninvasive trigger for drug delivery vehicles, most reported ultrasound-triggered drug delivery vehicles predominately present "burst" release profiles that are hard to control after the initial activation stimulus. Herein, we report a submerged electrospraying technique to fabricate protein-loaded microcapsules in which silica "corks" are embedded within the microcapsule shell. Upon the application of an ultrasound trigger, the corks can be perturbed within the shell, allowing for the release of the protein payload through a phantom tissue mimic to a degree proportional to the number/time of pulses applied. Specifically, multiple ultrasound pulses were shown to enable a 15- to 23-fold increase in the rate of release of the model bovine serum albumin protein payload relative to no ultrasound being applied, with release returning to a lower level when the ultrasound stimulus was removed. Coupled with the low cytotoxicity of the vehicle components, the corked microcapsules show promise for expanding the potential to use ultrasound to facilitate both on-demand and pulsatile release profiles.

Doping-Engineered Piezoelectric Ultrathin Nanosheets for Synergistically Piezo-Chemocatalytic Antitumor and Antibacterial Therapies Against Cutaneous Melanoma.

The post-surgical melanoma recurrence and wound infections have persistently troubled clinical management. Piezocatalytic therapy features high efficiency in generating reactive oxygen species (ROS) for tumor therapy, but it faces limitations in piezoelectricity and redox-active site availability. Herein, Fe-doped ultrathin Bi4Ti3O12 nanosheets (designated as Fe-UBTO NSs) with synergistically piezo-chemocatalytic activity are engineered for antitumor and antibacterial treatment against cutaneous melanoma. The doping-engineered strategy induces oxygen vacancies and lattice distortions in Fe-UBTO NSs, which narrows bandgap to enhance piezocatalytic 1O2 and H2O2 generation by improving the electron-hole pairs separation, hindering their recombination, and increasing oxygen adsorption. Moreover, Fe doping establishes a piezo-chemocatalytic system, in which the piezocatalysis enables the self-supply of H2O2 and expedites electron transfer in Fenton reactions, inducing increased ·OH production. Besides, the atomic-level thickness and expanded surface area enhance the sensitivity to ultrasound stimuli and expose more redox-active sites, augmenting the piezo-chemocatalytic efficiency, and ultimately leading to abundant ROS generation. The Fe-UBTO-mediated piezo-chemocatalytic therapy causes intracellular oxidative stress, triggering apoptosis and excessive autophagy of tumor cells. Moreover, this strategy accelerates wound healing by facilitating sterilization, angiogenesis, and collagen deposition. This work provides distinct options to develop doping-engineered ultrathin nanosheets with augmented piezo-chemocatalytic activity for postoperative management of cutaneous melanoma.

Mechanical force-switchable aqueous organocatalysis

Control over the catalytic activity of artificial catalytic systems in aqueous media is of high interest for biomimetic artificial catalysts. The activity of catalytic systems can be controlled via introducing stimuli-responsive feature in the structure of the catalytic systems. However, temperature, pH or light have been predominantly used as stimulus. Aqueous catalytic system whose activity can be turned ‘ON/OFF’ employing mechanical force has not been demonstrated. Here we show how catalytic activity of an aqueous catalytic system can be switched ‘ON/OFF’ via the application/ceasing ultrasound stimulus. We demonstrate that the accessibility of imidazole, a catalyst moiety, can be modulated via the presence/absence of the ultrasound stimulus, resulting temporal control over the rate of ester hydrolysis reactions in aqueous buffer solution. This generic approach enables using a large range of organocatalysts for the preparation of molecules and/or materials in aqueous media for their application to material science, and in biomedical field.

Biophysical stimuli for promoting bone repair and regeneration

Abstract Bone injuries and diseases are associated with profound changes in the biophysical properties of living bone tissues, particularly their electrical and mechanical properties. The biophysical properties of healthy bone are attributed to the complex network of interactions between its various cell types (i.e., osteocytes, osteoclast, immune cells and vascular endothelial cells) with the surrounding extracellular matrix (ECM) against the backdrop of a myriad of biomechanical and bioelectrical stimuli arising from daily physical activities. Understanding the pathophysiological changes in bone biophysical properties is critical to developing new therapeutic strategies and novel scaffold biomaterials for orthopedic surgery and tissue engineering, as well as provides a basis for the application of various biophysical stimuli as therapeutic agents to restore the physiological microenvironment of injured/diseased bone tissue, to facilitate its repair and regeneration. These include mechanical, electrical, magnetic, thermal and ultrasound stimuli, which will be critically examined in this review. A significant advantage of utilizing such biophysical stimuli to facilitate bone healing is that these may be applied non-invasively with minimal damage to surrounding tissues, unlike conventional orthopedic surgical procedures. Furthermore, the effects of such biophysical stimuli can be localized specifically at the bone defect site, unlike drugs or growth factors that tend to diffuse away after delivery, which may result in detrimental side effects at ectopic sites.

Nitric Oxide‐Actuated Titanium Dioxide Janus Nanoparticles for Enhanced Multimodal Disruption of Infectious Biofilms

AbstractSonodynamic therapy (SDT) is promising for combating deep‐seated infectious diseases by generating substantial reactive oxygen species (ROS) through the profound tissue penetration capabilities of ultrasound. However, the compact protective structures of bacterial biofilms present a formidable challenge, impeding ROS efficacy. Given that ROS have a limited diffusion range and current sonosensitizers struggle to infiltrate biofilms, complete eradication of pathogenic bacteria often remains unachieved. In this study, mesoporous titanium dioxide (TiO2) nanoparticles are engineered asymmetrically coated with a thin layer of Ag and loaded with L‐arginine (LA) to construct ultrasound‐propelled nanomotors. These Ag‐TiO2‐LA Janus nanoparticles demonstrate robust self‐propulsion upon ultrasonic activation, allowing for deeper penetration into biofilm matrices and enhancing localized biofilm disruption through improved SDT outcomes. Additionally, the incorporation of Ag not only broadens TiO2’s absorption spectrum but also confers photothermal capabilities upon NIR laser excitation at 808 nm. The Ag‐TiO2‐LA nanomotor amalgamates TiO2’s sonodynamic potential with Ag's photothermal properties, forging a versatile antimicrobial agent capable of efficient biofilm penetration and a synergistic antibacterial effect when subjected to dual NIR and ultrasound stimuli. This innovative, singularly‐structured nanoparticle stands out as an effective combatant against bacterial biofilms and accelerates the healing process of infected wounds, showcasing potential for multifaceted clinical applications.

The cochlear hook region detects harmonics beyond the canonical hearing range.

Ultrasound, or sound at frequencies exceeding the conventional range of human hearing, is not only audible to mice, microbats, and dolphins, but also creates an auditory sensation when delivered through bone conduction in humans. Although ultrasound is utilized for brain activation and in hearing aids, the physiological mechanism of ultrasonic hearing remains unknown. In guinea pigs, we found that ultrasound above the hearing range delivered through ossicles of the middle ear evokes an auditory brainstem response and a mechano-electrical transduction current through hair cells, as shown by the local field potential called the cochlear microphonic potential (CM). The CM synchronizes with ultrasound, and like the response to audible sounds is actively and nonlinearly amplified. In vivo optical nano-vibration analysis revealed that the sensory epithelium in the hook region, the basal extreme of the cochlear turns, resonates in response both to ultrasound within the hearing range and to harmonics beyond the hearing range. The results indicate that hair cells can respond to stimulation at the optimal frequency and its harmonics, and the hook region detects ultrasound stimuli with frequencies more than two octaves higher than the upper limit of the ordinary hearing range.

Model-based correction of rapid thermal confounds in fluorescence neuroimaging of targeted perturbation.

An array of techniques for targeted neuromodulation is emerging, with high potential in brain research and therapy. Calcium imaging or other forms of functional fluorescence imaging are central solutions for monitoring cortical neural responses to targeted neuromodulation, but often are confounded by thermal effects that are inter-mixed with neural responses. Here, we develop and demonstrate a method for effectively suppressing fluorescent thermal transients from calcium responses. We use high precision phased-array 3MHz focused ultrasound delivery integrated with fiberscope-based widefield fluorescence to monitor cortex-wide calcium changes. Our approach for detecting the neural activation first takes advantage of the high inter-hemispheric correlation of resting state dynamics and then removes the ultrasound-induced thermal effect by subtracting its simulated spatio-temporal signature from the processed profile. The focused -sized ultrasound stimulus triggered rapid localized activation events dominated by transient thermal responses produced by ultrasound. By employing bioheat equation to model the ultrasound heat deposition, we can recover putative neural responses to ultrasound. The developed method for canceling transient thermal fluorescence quenching could also find applications with optical stimulation techniques to monitor thermal effects and disentangle them from neural responses. This approach may help deepen our understanding of the mechanisms and macroscopic effects of ultrasound neuromodulation, further paving the way for tailoring the stimulation regimes toward specific applications.

Low-intensity ultrasound activates transmembrane chloride flow through CFTR

Ultrasound has been demonstrated to activate mechanosensitive channels, which is considered the main mechanism of ultrasound neuromodulation. Currently, all channels that have been shown to be sensitive to ultrasound are cation channels. In addition to cation channels, anion channels also play indispensable roles in neural function. However, there have been no research on ultrasound regulation of anion channels until now. If anion channels can be activated by ultrasound as well, they will inevitably lead to more versatility in ultrasound neuromodulation. Cystic fibrosis transmembrane transduction regulator (CFTR) has been demonstrated to be a mechanically sensitive channel, mediating anionic transmembrane flow. To identify that CFTR is sensitive to ultrasound, CFTR was exogenously expressed in HEK293T cells and was stimulated by low intensity ultrasound. Outward currents in CFTR-expressed HEK293T cells were observed by using whole-cell patch clamp when ultrasound (0.8 MHz, 0.20 MPa) was delivered to these cells. These currents were abolished when the CFTR inhibitor (GlyH101) was applied to the solution or chloride ions was cleared from the solution. Meanwhile, the amplitude of these currents increased when the CFTR agonist (Forskolin) was applied. These results suggest that ultrasound stimuli can activate the CFTR to mediate transmembrane flowing of chloride ions at the single cell level. These findings may expand the application of ultrasound in the neuromodulation field.

In Vitro Prototyping of a Nano-Organogel for Thermo-Sonic Intra-Cervical Delivery of 5-Fluorouracil-Loaded Solid Lipid Nanoparticles for Cervical Cancer

Solid lipid nanoparticles (SLNs) are used extensively to achieve site-specific drug delivery with improved bioavailability and reduced toxicity. This work focused on a new approach to provide site-specific stimuli-responsive delivery of SLNs loaded within thermo-sonic nano-organogel (TNO) variants to deliver the model chemotherapeutic agent 5-FU in treating cervical cancer. Pharmaceutically stable nanospherical SLNs comprising poly-L-lactic acid (PLA), palmitic acid (PA), and polyvinyl alcohol (PVA) were prepared and incorporated into TNO variants augmented by external thermal and ultrasound stimuli for release of 5-FU in the cervix. Results revealed that rate-modulated 5-FU release was achieved from SLNs (particle size =450.9 nm; PDI =0.541; zeta potential =−23.2 mV; %DL =33%) within an organogel upon exposure to either a single (thermo-) and/or both (thermo-sonic) stimuli. 5FU was released from all TNO variants with an initial burst on day 1 followed by sustained release over 14 days. TNO 1 provided desirable release over 15 days (44.29% vs. 67.13% under single (T) or combined (TU) stimuli, respectively). Release rates were primarily influenced by the SLN:TO ratio in tandem with biodegradation and hydrodynamic influx. Biodegradation by day 7 revealed that variant TNO 1 (1:5) released 5FU (46.8%) analogous to its initial mass than the other TNO variants (i.e., ratios of 2:5 and 3:5). FT-IR spectra revealed assimilation of the system components and corroborative with the DSC and XRD analysis (i.e., in ratios of PA:PLA 1:1 and 2:1). In conclusion, the TNO variants produced may be used as a potential stimuli-responsive platform for the site-specific delivery of chemotherapeutic agents such as 5-FU to treat cervical cancer.

Skeletal Muscle Assessment Using Quantitative Ultrasound: A Narrative Review.

Ultrasound (US) is an important imaging tool for skeletal muscle analysis. The advantages of US include point-of-care access, real-time imaging, cost-effectiveness, and absence of ionizing radiation. However, US can be highly dependent on the operator and/or US system, and a portion of the potentially useful information carried by raw sonographic data is discarded in image formation for routine qualitative US. Quantitative ultrasound (QUS) methods provide analysis of the raw or post-processed data, revealing additional information about normal tissue structure and disease status. There are four QUS categories that can be used on muscle and are important to review. First, quantitative data derived from B-mode images can help determine the macrostructural anatomy and microstructural morphology of muscle tissues. Second, US elastography can provide information about muscle elasticity or stiffness through strain elastography or shear wave elastography (SWE). Strain elastography measures the induced tissue strain caused either by internal or external compression by tracking tissue displacement with detectable speckle in B-mode images of the examined tissue. SWE measures the speed of induced shear waves traveling through the tissue to estimate the tissue elasticity. These shear waves may be produced using external mechanical vibrations or internal "push pulse" ultrasound stimuli. Third, raw radiofrequency signal analyses provide estimates of fundamental tissue parameters, such as the speed of sound, attenuation coefficient, and backscatter coefficient, which correspond to information about muscle tissue microstructure and composition. Lastly, envelope statistical analyses apply various probability distributions to estimate the number density of scatterers and quantify coherent to incoherent signals, thus providing information about microstructural properties of muscle tissue. This review will examine these QUS techniques, published results on QUS evaluation of skeletal muscles, and the strengths and limitations of QUS in skeletal muscle analysis.

GSH-activated Porphyrin Sonosensitizer Prodrug for Fluorescence Imaging-guided Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which uses ultrasound to trigger a sonosensitizer to generate reactive oxygen species (ROS), is a promising form of cancer therapy with outstanding tissue penetration depth. However, the sonosensitizer may inevitably spread to surrounding healthy tissue beyond the tumor, resulting in undesired side effects under an ultrasound stimulus. Herein, as glutathione (GSH) is overexpressed in the tumor microenvironment, a GSH-activatable sonosensitizer prodrug was designed by attaching a quencher to tetraphydroxy porphyrin for tumor therapy. The prodrug exhibited poor fluorescence and low ROS generation capacity under ultrasound irradiation but it can be activated by GSH to simultaneously switch on fluorescence emission and ROS generation in tumor site. Compared with the non-quenched sonosensitizer, the designed prodrug exhibited significantly higher tumor/healthy organ fluorescence ratios, due to the specific fluorescence and ROS activation by overexpressed GSH in the tumor. Finally, the prodrug exhibited efficient tumor growth inhibition under ultrasound irradiation, further demonstrating its promise as a GSH-activated sonosensitizer prodrug for highly effective cancer treatment.

Low-intensity ultrasound directly modulates neural activity of the cerebellar cortex

BackgroundLow-intensity ultrasound is a noninvasive neuromodulation technique with the potential to focally manipulate deep brain activity at millimeter-scale resolution. However, there have been controversies over the direct influence of ultrasound on neurons, due to an indirect auditory activation. Besides, the capacity of ultrasound to stimulate the cerebellum remains underestimated. ObjectiveTo validate the direct neuromodulation effects of ultrasound on the cerebellar cortex from both cellular and behavioral levels. MethodsTwo-photon calcium imaging were used to measure the neuronal responses of cerebellar granule cells (GrCs) and Purkinje cells (PCs) to ultrasound application in awake mice. And a mouse model of paroxysmal kinesigenic dyskinesia (PKD), in which direct activation of the cerebellar cortex leads to dyskinetic movements, was used to assess the ultrasound-induced behavioral responses. ResultsLow-intensity ultrasound stimulus (0.1 W/cm2) evoked rapidly increased and sustained neural activity in GrCs and PCs at targeted region, while no significant changes in calcium signals were observed responding to off-target stimulus. The efficacy of ultrasonic neuromodulation relies on acoustic dose modified by ultrasonic duration and intensity. In addition, transcranial ultrasound reliably triggered dyskinesia attacks in proline-rich transmembrane protein 2 (Prrt2) mutant mice, suggesting that the intact cerebellar cortex were activated by ultrasound. ConclusionLow-intensity ultrasound directly activates the cerebellar cortex in a dose-dependent manner, and thus serves as a promising tool for cerebellar manipulation.

Combined photothermal and sonodynamic therapy using a 2D black phosphorus nanosheets loaded coating for efficient bacterial inhibition and bone-implant integration

Surgical site infection (SSI) remains a major threat for implant failure in orthopedics. Herein, we report a dual-functional coating on Ti implants (named Ti/PDA/BP) with the integration of two-dimensional (2D) photo-sono sensitive black phosphorus nanosheets (BPNSs) and polydopamine (PDA) for efficient bacterial inhibition and bone-implant integration. For the first time, we employ BPNSs as generators of reactive radicals (ROS) under ultrasound (US) stimuli for implant associated infection. Additionally, the application of PDA improves the stability of BPNSs, the biocompatibility and photothermal performance of this hybrid coating. The as-prepared Ti/PDA/BP coating exhibits superior biocompatibility, bioactivity, photothermal and sonodynamic conversion abilities. Owing to the synergistic effect of hyperthermia and ·OH, Ti/PDA/BP damages the membrane and antioxidant system of Staphylococcus aureus, reaching a high antibacterial activity of 96.6% in vitro and 97.3% in vivo with rapid 10 min NIR irradiation and 20 min US treatment. In addition, we firstly unveil the significant effect of Ti/PDA/BP-based sonodynamic therapy (SDT) on bacterial membrane and oxidative stress at the transcriptome level. Moreover, the Ti/PDA/BP coating remarkably promotes osteogenesis in vitro and bone-implant osseointegration in vivo. Overall, development of Ti/PDA/BP bioactive coating provides a new strategy for combating the implant associated infection.

An Intelligent Cell-Derived Nanorobot Bridges Synergistic Crosstalk Between Sonodynamic Therapy and Cuproptosis to Promote Cancer Treatment.

Recent progress in cuproptosis sheds light on the development of treatment approaches for advancing sonodynamic therapy (SDT) due to its unique cell death mechanism. Herein, we elaborately developed an intelligent cell-derived nanorobot (SonoCu), composed of macrophage-membrane-camouflaged nanocarrier encapsulating copper-doped zeolitic imidazolate framework-8 (ZIF-8), perfluorocarbon, and sonosensitizer Ce6, for synergistically triggering cuproptosis-augmented SDT. SonoCu not only improved tumor accumulation and cancer-cell uptake through cell-membrane camouflaging but responded to ultrasound stimuli to enhance intratumor blood flow and oxygen supply, which consequently overcame treatment barriers and activated sonodynamic cuproptosis. Importantly, the SDT effectiveness could be further amplified by cuproptosis through multiple mechanisms, including reactive oxygen species accumulation, proteotoxic stress, and metabolic regulation, which synergistically sensitized cancer cell death. Particularly, SonoCu exhibited ultrasound-responsive cytotoxicity against cancer cells but not healthy cells, endowing it with good biosafety. Therefore, we present the first anticancer combination of SDT and cuproptosis, which may inspire studies pursuing a rational multimodal treatment strategy.

The Fifth Bioelectronic Medicine Summit Hosted by the Feinstein Institutes for Medical Research (Manhasset, NY) and Columbia Engineering (NY, NY) at The Garden City Hotel, Garden City, NY 11530 on October 11-12th, 2022- Bioelectronic Medicine: Today’s Tools, Tomorrow’s Therapies

The Fifth Bioelectronic Medicine Summit Hosted by the Feinstein Institutes for Medical Research (Manhasset, NY) and Columbia Engineering (NY, NY) at The Garden City Hotel, Garden City, NY 11530 on October 11-12th, 2022- Bioelectronic Medicine: Today’s Tools, Tomorrow’s Therapies

Defect-Rich Glassy IrTe2 with Dual Enzyme-Mimic Activities for Sono-Photosynergistic-Enhanced Oncotherapy.

The complexity, diversity, and heterogeneity of malignant tumors pose a formidable challenge for antitumor therapy. To achieve the goal of significantly enhancing the antitumor effect, nanomedicine-based synergistic therapy is one of the important strategies. Herein, we innovatively report a defect-rich glassy IrTe2 (G-IrTe2) with weak Ir-Te bond strength for synergistic sonodynamic therapy (SDT), chemodynamic therapy (CDT), and mild photothermal therapy (PTT). G-IrTe2 sonosensitizer under ultrasound (US) stimuli exhibits excellent reactive oxygen species (ROS) production performance. Besides, catalase (CAT)-like activity of G-IrTe2 can provide abundant oxygen to enhance the SDT effect. Then, the theoretical calculation verifies that US stimuli can easily make the irregular Ir-Te bond to be broken in amorphous IrTe2 and free electrons will be released to combine with the oxygen and further form singlet oxygen (1O2). Meanwhile, G-IrTe2 with peroxidase (POD)-like activity can also catalyze endogenous H2O2 to produce more ROS for chemodynamic therapy (CDT), which is conducive to better tumor ablation. Furthermore, the ROS produced by sono-/chemodynamic processes can cause mitochondrial dysfunction and further give rise to heat shock protein (HSP) downregulated expression, maximizing the efficiency of mild PTT. Therefore, such glassy IrTe2 with rich defect could be significantly involved in synergistic oncotherapy and then effectively achieve outstanding antitumor efficacy. This study provides a new research idea for expanding the application of inorganic glassy nanomaterials in promoting the therapeutic effect of tumors.

First-in-human noninvasive left ventricular ultrasound pacing: A potential screening tool for cardiac resynchronization therapy.

A screening tool to predict response to cardiac resynchronization therapy (CRT) could improve patient selection and outcomes. The purpose of this study was to investigate the feasibility and safety of noninvasive CRT via transcutaneous ultrasonic left ventricular (LV) pacing applied as a screening test before CRT implants. P-wave-triggered ultrasound stimuli were delivered during bolus dosing of an echocardiographic contrast agent to simulate CRT noninvasively. Ultrasound pacing was delivered at a variety of LV locations with a range of atrioventricular delays to achieve fusion with intrinsic ventricular activation. Three-dimensional cardiac activation maps were acquired via the Medtronic CardioInsight 252-electrode mapping vest during baseline, ultrasound pacing, and after CRT implantation. A separate control group received only the CRT implants. Ultrasound pacing was achieved in 10 patients with a mean of 81.2 ± 50.8 ultrasound paced beats per patient and up to 20 consecutive beats of ultrasound pacing. QRS width at baseline (168.2 ± 17.8 ms) decreased significantly to 117.3 ± 21.5 ms (P<.001) in the best ultrasound paced beat and to 125.8 ± 13.3 ms (P <.001) in the best CRT beat. Electrical activation patterns were similar between CRT pacing and ultrasound pacing with stimulation from the same area of the LV. Troponin results were similar between the ultrasound pacing and the control groups (P = .96), confirming safety. Noninvasive ultrasound pacing before CRT is safe and feasible, and it estimates the degree of electrical resynchronization achievable with CRT. Further study of this promising technique to guide CRT patient selection is warranted.

Ultrasound modulates neuronal potassium currents via ionotropic glutamate receptors

BackgroundFocused ultrasound stimulation (FUS) has the potential to provide non-invasive neuromodulation of deep brain regions with unparalleled spatial precision. However, the cellular and molecular consequences of ultrasound stimulation on neurons remains poorly understood. We previously reported that ultrasound stimulation induces increases in neuronal excitability that persist for hours following stimulation in vitro. In the present study we sought to further elucidate the molecular mechanisms by which ultrasound regulates neuronal excitability and synaptic function. ObjectivesTo determine the effect of ultrasound stimulation on voltage-gated ion channel function and synaptic plasticity. MethodsPrimary rat cortical neurons were exposed to a 40 s, 200 kHz pulsed ultrasound stimulus or sham-stimulus. Whole-cell patch clamp electrophysiology, quantitative proteomics and high-resolution confocal microscopy were employed to determine the effects of ultrasound stimulation on molecular regulators of neuronal excitability and synaptic function. ResultsWe find that ultrasound exposure elicits sustained but reversible increases in whole-cell potassium currents. In addition, we find that ultrasound exposure activates synaptic signalling cascades that result in marked increases in excitatory synaptic transmission. Finally, we demonstrate the requirement of ionotropic glutamate receptor (AMPAR/NMDAR) activation for ultrasound-induced modulation of neuronal potassium currents. ConclusionThese results suggest specific patterns of pulsed ultrasound can induce contemporaneous enhancement of both neuronal excitability and synaptic function, with implications for the application of FUS in experimental and therapeutic settings. Further study is now required to deduce the precise molecular mechanisms through which these changes occur.

Gap Detection in Pairs of Ultrasound Mid-air Vibrotactile Stimuli

Ultrasound mid-air haptic (UMH) devices are a novel tool for haptic feedback, capable of providing localized vibrotactile stimuli to users at a distance. UMH applications largely rely on generating tactile shape outlines on the users’ skin. Here we investigate how to achieve sensations of continuity or gaps within such two-dimensional curves by studying the perception of pairs of amplitude-modulated focused ultrasound stimuli. On the one hand, we aim to investigate perceptual effects that may arise from providing simultaneous UMH stimuli. On the other hand, we wish to provide perception-based rendering guidelines for generating continuous or discontinuous sensations of tactile shapes. Finally, we hope to contribute toward a measure of the perceptually achievable resolution of UMH interfaces. We performed a user study to identify how far apart two focal points need to be to elicit a perceptual experience of two distinct stimuli separated by a gap. Mean gap detection thresholds were found at 32.3-mm spacing between focal points, but a high within- and between-subject variability was observed. Pairs spaced below 15 mm were consistently (&gt;95%) perceived as a single stimulus, while pairs spaced 45 mm apart were consistently (84%) perceived as two separate stimuli. To investigate the observed variability, we resort to acoustic simulations of the resulting pressure fields. These show a non-linear evolution of actual peak pressure spacing as a function of nominal focal point spacing. Beyond an initial threshold in spacing (between 15 and 18 mm), which we believe to be related to the perceived size of a focal point, the probability of detecting a gap between focal points appears to linearly increase with spacing. Our work highlights physical interactions and perceptual effects to consider when designing or investigating the perception of UMH shapes.

Imaging-guided gene delivery: seeing is delivering

Imaging-guided gene delivery: seeing is delivering