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OBJECTIVE: To demonstrate the feasibility of using a ring array ultrasound (US) transducer, guided by ultrasound tomography (UST), for generating and monitoring mild hyperthermia (MHTh). METHODS: In silico and in vitro experiments were designed to evaluate the efficacy of a ring array US transducer for generating MHTh and monitoring changes in temperature. In a series of in silico studies, we compared the acoustic focal profiles produced by a ring array US transducer transmitting at different frequencies and further investigated the effectiveness of UST-guidance in implementing aberration correction to enhance the focal profile. In vitro experiments evaluated the capability of using a ring array US transducer to generate and maintain MHTh and the accuracy of using UST to monitor temperature changes. RESULTS: The simulations demonstrated that a ring array US transducer achieves symmetrical and localized acoustic focusing. In a heterogenous tissue model, a ring array US transducer achieved a superior acoustic focus by implementing aberration correction with guidance from UST. In vitro experiments demonstrated the capability of a ring array US transducer to generate MHTh in a tissue-mimicking phantom in an average of 117 ± 18 s and subsequently maintain MHTh. Lastly, a ring array US transducer utilized UST to track temperature changes in a preheated water-filled inclusion while it passively cooled from 45 °C to 25 °C, with a maximum error of 0.58 °C. CONCLUSION: A ring array US transducer can noninvasively generate and monitor MHTh, overcoming many limitations of current clinical systems. The closed geometry of the transducer is optimal for acoustic focusing and UST-guidance allows for improved aberration correction in a heterogenous medium. Utilizing UST thermometry with the same ring array US transducer will allow for implementing an image-guided, temperature-controlled, all-acoustic MHTh system.

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The exponential growth of therapeutic ultrasound applications demonstrates the power of the technology to leverage the combinations of transducer technology and treatment monitoring techniques to effectively control the preferred bioeffect to elicit the desired clinical effect.Objective: This review provides an overview of the most commonly used bioeffects in therapeutic ultrasound and describes existing transducer technologies and monitoring techniques to ensure treatment safety and efficacy.Methods and materials: Literature reviews were conducted to identify key choices that essential in terms of transducer design, treatment parameters and procedure monitoring for therapeutic ultrasound applications. Effective combinations of these options are illustrated through descriptions of several clinical indications, including uterine fibroids, prostate disease, liver cancer, and brain cancer, that have been successful in leveraging therapeutic ultrasound to provide effective patient treatments.Results: Despite technological constraints, there are multiple ways to achieve a desired bioeffect with therapeutic ultrasound in a target tissue. Visualizations of the interplay of monitoring modality, bioeffect, and applied acoustic parameters are presented that demonstrate the interconnectedness of the field of therapeutic ultrasound. While the clinical indications explored in this review are at different points in the clinical evaluation path, based on the ever expanding research being conducted in preclinical realms, it is clear that additional clinical applications of therapeutic ultrasound that utilize a myriad of bioeffects will continue to grow and improve in the coming years.Conclusions: Therapeutic ultrasound will continue to improve in the next decades as the combination of transducer technology and treatment monitoring techniques will continue to evolve and be translated in clinical settings, leading to more personalized and efficient therapeutic ultrasound mediated therapies.

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Micro-sensors, such as pressure and flow sensors, are usually adopted to attain actual fluid information around swimming biomimetic robotic fish for hydrodynamic analysis and control. However, most of the reported micro-sensors are mounted discretely on body surfaces of robotic fish and it is impossible to analyzed the hydrodynamics between the caudal fin and the fluid. In this work, a biomimetic caudal fin integrated with a resistive pressure sensor is designed and fabricated by laser machined conductive carbon fibre composites. To analyze the pressure exerted on the caudal fin during underwater oscillation, the pressure on the caudal fin is measured under different oscillating frequencies and angles. Then a model developed from Bernoulli equation indicates that the maximum pressure difference is linear to the quadratic power of the oscillating frequency and the maximum oscillating angle. The fluid disturbance generated by caudal fin oscillating increases with an increase of oscillating frequency, resulting in the decrease of the efficiency of converting the kinetic energy of the caudal fin oscillation into the pressure difference on both sides of the caudal fin. However, perhaps due to the longer stability time of the disturbed fluid, this conversion efficiency increases with the increase of the maximum oscillating angle. Additionally, the pressure variation of the caudal fin oscillating with continuous different oscillating angles is also demonstrated to be detected effectively. It is suggested that the caudal fin integrated with the pressure sensor could be used for sensing thein situflow field in real time and analyzing the hydrodynamics of biomimetic robotic fish.

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Bladder volume measurement is critical for early detection and management of lower urinary tract dysfunctions. Current gold standard is invasive, and alternative technologies either require trained personnel or do not offer medical grade information. Here, we report an integrated wearable ultrasonic bladder volume monitoring device for accurate and autonomous continuous monitoring of the bladder volume. The device incorporates flexible and air-backed ultrasonic transducers and miniaturized control electronics with wireless data transmission capability. We demonstrate the real-life application of the device on healthy volunteers with various bladder shapes and sizes with high accuracy. Apart from the lower urinary tract dysfunctions, the proposed technology could also be adapted for various wearable ultrasonic applications.

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Low-frequency sonophoresis has emerged as a promising minimally invasive transdermal drug delivery method. However, effectively inducing cavitation on the skin surface with a compact, low-frequency ultrasound transducer poses a significant challenge. This paper presents a modified design of a low-frequency ultrasound transducer capable of generating ultrasound cavitation on the skin surfaces. The transducer comprises a piezoelectric ceramic disk and a bowl-shaped acoustic resonator. A conical slit structure was incorporated into the modified transducer design to amplify vibration displacement and enhance the maximum sound pressure. The FEM-based simulation results confirmed that the maximum sound pressure at the resonance frequency of 78 kHz was increased by 1.9 times that of the previous design. Ultrasound cavitation could be experimentally observed on the gel surface. Moreover, 3 min of ultrasound treatment significantly improved the caffeine permeability across an artificial membrane. These results demonstrated that this transducer holds promise for enhancing drug permeation by generating ultrasound cavitation on the skin surface.

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Tracking and controlling microbubble (MB) dynamics in the human brain through acoustic emission (AE) monitoring during transcranial focused ultrasound (tFUS) therapy are critical for attaining safe and effective treatments. The low-amplitude MB emissions have harmonic and ultra-harmonic components, necessitating a broad bandwidth and low-noise system for monitoring transcranial MB activity. Capacitive micromachined ultrasonic transducers (CMUTs) offer high sensitivity and low noise over a broad bandwidth, especially when they are tightly integrated with electronics, making them a good candidate technology for monitoring the MB activity through human skull. In this study, we designed a 16-channel analog front-end (AFE) electronics with a low-noise transimpedance amplifier (TIA), a band-gap reference circuit, and an output buffer stage. To assess AFE performance and ability to detect MB AE, we combined it with a commercial CMUT array. The integrated system has 12.3 - [Formula: see text] receive sensitivity with 0.085 - [Formula: see text] minimum detectable pressure (MDP) up to 3 MHz for a single element CMUT with 3.78 [Formula: see text] area. Experiments with free MBs in a microfluidic channel demonstrate that our system is able to capture key spectral components of MBs' harmonics when sonicated at clinically relevant frequencies (0.5 MHz) and pressures (250 kPa). Together our results demonstrate that the proposed CMUT system can support the development of novel passive cavitation detectors (PCD) to track MB activity for attaining safe and effective focused ultrasound (FUS) treatments.

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Over the past few decades, early osteoporosis detection using ultrasonic bone quality evaluation has gained prominence. Specifically, various studies focused on axial transmission using ultrasonic guided waves and have highlighted this technique's sensitivity to intrinsic properties of long cortical bones. This work aims to demonstrate the potential of low-frequency ultrasonic guided waves to infer the properties of the bone inside which they are propagating. A proprietary ultrasonic transducer, tailored to transmit ultrasonic guided waves under 500 kHz, was used for the data collection. The gathered data underwent two-dimensional fast Fourier transform processing to extract experimental dispersion curves. The proposed inversion scheme compares experimental dispersion curves with simulated dispersion curves calculated through the semi-analytical iso-geometric analysis (SAIGA) method. The numerical model integrates a bone phantom plate coupled with a soft tissue layer on its top surface, mimicking the experimental bone phantom plates. Subsequently, the mechanical properties of the bone phantom plates were estimated by reducing the misfit between the experimental and simulated dispersion curves. This inversion leaned heavily on the dispersive trajectories and amplitudes of ultrasonic guided wave modes. Results indicate a marginal discrepancy under 5% between the mechanical properties ascertained using the SAIGA-based inversion and those measured using bulk wave pulse-echo measurements.

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Innovative intraoral ultrasound devices with smart artificial intelligence-based identification for dento-anatomy could provide crucial information for oral health diagnosis and treatment and shed light on real-time detection of developmental dentistry. However, the grand challenge is that the current ultrasound technologies are meant for external use due to their bulkiness and low frequency. We report a compact versatile ultrasound intraoral device that consists of a rotational probe head robustly pivoted around a hand-held and portable handle for real-time imaging of intraoral anatomy using high-frequency ultrasonography (up to 25 MHz). The intraoral ultrasound device that could be adjusted for various orientations of the imaging planes by rotating the head provides real-time, high-resolution ultrasonograms of intraoral structures, including dento-periodontium of most tooth types and maxillary palate. Machine learning-based algorithms are integrated to automate the identification of important structures, including alveolar bone and cementum-enamel junction. The intraoral ultrasound device smartened with artificial intelligence could innovate oral health diagnosis and treatment plans toward precision health and patient care.

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The equivalent electrical circuit approach is explored to improve a bioimpedance-based transducer for measuring the bioavailability of synthetic insulin already presented in previous studies. In particular, the electrical parameter most sensitive to the variation of insulin amount injected was identified. Eggplants were used to emulate human electrical behavior under a quasi-static assumption guaranteed by a very low measurement time compared to the estimated insulin absorption time. Measurements were conducted with the EVAL-AD5940BIOZ by applying a sinusoidal voltage signal with an amplitude of 100 mV and acquiring impedance spectra in the range [1-100] kHz. 14 units of insulin were gradually administered using a Lilly's Insulin Pen having a 0.4 cm long needle. Modified Hayden's model was adopted as a reference circuit and the electrical component modeling the extracellular fluids was found to be the most insulin-sensitive parameter. The trnasducer achieves a state-of-the-art sensitivity of 225.90 ml1. An improvement of 223 % in sensitivity, 44 % in deterministic error, 7 % in nonlinearity, and 42 % in reproducibility was achieved compared to previous experimental studies. The clinical impact of the transducer was evaluated by projecting its impact on a Smart Insulin Pen for real-time measurement of insulin bioavailability. The wide gain in sensitivity of the bioimpedance-based transducer results in a significant reduction of the uncertainty of the Smart Insulin Pen. Considering the same improvement in in-vivo applications, the uncertainty of the Smart Insulin Pen is decreased from [Formula: see text]l to [Formula: see text]l.Clinical and Translational Impact Statement: A Smart Insulin Pen based on impedance spectroscopy and equivalent electrical circuit approach could be an effective solution for the non-invasive and real-time measurement of synthetic insulin uptake after subcutaneous administration.

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The Tendo Unit (TU) and GymAware (GA) are the two most frequently used linear transducers for assessing muscle power in older adults via the sit-to-stand (STS) test. Unlike TU, GA incorporates a sensor mechanism to correct for non-vertical movements, which may lead to systematic differences between devices. The aim of this study therefore was to compare GA to TU for measuring STS power in community-dwelling older adults. Community-dwelling adults (n = 51, aged ≥65 years, 61% female) completed a single chair stand, with peak power measured simultaneously using GA and TU. Participants also completed the pneumatic leg press, 8-Foot Up and Go (TUG) test, Short Physical Performance Battery (SPPB), and self-reported measures of physical function. Intraclass correlations (ICC) were used to assess agreement, and Pearson's correlations were used to assess correlations. The study protocol was prospectively registered on the Open Science Framework. In alignment with our pre-registered hypothesis, peak power demonstrated an ICC of 0.93 (95% CI: 0.88, 0.96). For secondary aims, both transducers showed a correlation greater than 0.8 compared to pneumatic leg press power. For physical performance outcomes, both TU and GA showed similar correlations, as hypothesized: SPPB (r = 0.29 for TU vs. 0.33 for GA), Chair Stands (r = -0.41 vs. -0.38), TUG Fast (r = -0.53 vs. -0.52), mobility questionnaire (r = 0.52 vs. 0.52) and physical function questionnaire (r = 0.44 vs. 0.43). GA and TU peak power showed a high degree of agreement and similar correlations with physical and self-reported performance measures, suggesting that both methods can be used for assessing STS power in older adults.

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PURPOSE: Clinical audiologists typically assume that headphones and insert phones will produce comparable results when they are used to conduct speech-in-noise or other audiological tests; however, this may not always be the case. Here, we show that there are significant differences in the scores that previous studies have reported for headphone and insert-phone transducers on the Words-in-Noise (WIN) Test, and discuss the possibility that the variations in high-frequency output that are allowable under the speech source specifications of American National Standards Institute S3.6 might be contributing to transducer-dependent differences in performance for the WIN and other tests that are presented through the auxiliary input channels of clinical audiometers. METHOD: A literature review was conducted to identify articles that reported WIN Test results for both listeners with normal hearing and with hearing impairment and specified the type of transducer (insert or TDH-50) used for the data collection. RESULTS: Among the 19 included studies, participants with normal hearing using inserts exhibited systematically worse WIN Test scores compared to those using TDH-50 headphones, while participants with hearing loss showed comparable average scores across transducer types. CONCLUSIONS: The results highlight the importance of considering transducer type when interpreting WIN Test outcomes, particularly when comparing to normative scores obtained from individuals with normal hearing. Although further research is needed to elucidate the underlying mechanisms driving differences in test performance across transducer types, these findings underscore the need for standardized test administration protocols and careful documentation of transducer type when administering speech-in-noise tests for clinical or research applications.

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Ultrasound velocimetry has been widely used for blood flow imaging. However, the flow measurements are constrained to resolve the in-plane 2D flow components when using a 1D transducer array. In this work, an ultrasound speckle decorrelation analysis-based velocimetry (3C-vUS) is proposed for 3D velocity components measurement using a 1D transducer array. The 3C-vUS theory is first derived and validated with numerical simulations and phantom experiments. The in vivo testing results show that 3C-vUS can accurately measure the blood flow 3D-velocity-components of the human carotid artery at arbitrary probe-to-vessel angles throughout the cardiac cycle. With such capability, the 3C-vUS will alleviate the requirement of operators and promote disease screening for blood flow-related disorders.

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In recent years, personalized diagnosis and treatment have gained significant recognition and rapid development in the biomedicine and healthcare. Due to the flexibility, portability and excellent compatibility, wearable ultrasound (WUS) devices have become emerging personalized medical devices with great potential for development. Currently, with the development of the ongoing advancements in materials and structural design of the ultrasound transducers, WUS devices have improved performance and are increasingly applied in the medical field. In this review, we provide an overview of the design and structure of WUS devices, focusing on their application for diagnosis and treatment of various diseases from a clinical application perspective, and then explore the issues that need to be addressed before clinical translation. Finally, we summarize the progress made in the development of WUS devices, and discuss the current challenges and the future direction of their development. In conclusion, WUS devices usher an emerging era for biomedicine with great clinical promise.

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The selection of an appropriate transducer is a key element in biosensor development. Currently, a wide variety of substrates and working electrode materials utilizing different fabrication techniques are used in the field of biosensors. In the frame of this study, the following three specific material configurations with gold-finish layers were investigated regarding their efficacy to be used as electrochemical (EC) biosensors: (I) a silicone-based sensor substrate with a layer configuration of 50 nm SiO/50 nm SiN/100 nm Au/30-50 nm WTi/140 nm SiO/bulk Si); (II) polyethylene naphthalate (PEN) with a gold inkjet-printed layer; and (III) polyethylene terephthalate (PET) with a screen-printed gold layer. Electrodes were characterized using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) to evaluate their performance as electrochemical transducers in an aptamer-based biosensor for the detection of cardiac troponin I using the redox molecule hexacyanoferrade/hexacyaniferrade (K3[Fe (CN)6]/K4[Fe (CN)6]. Baseline signals were obtained from clean electrodes after a specific cleaning procedure and after functionalization with the thiolate cardiac troponin I aptamers "Tro4" and "Tro6". With the goal of improving the PEN-based and PET-based performance, sintered PEN-based samples and PET-based samples with a carbon or silver layer under the gold were studied. The effect of a high number of immobilized aptamers will be tested in further work using the PEN-based sample. In this study, the charge-transfer resistance (Rct), anodic peak height (Ipa), cathodic peak height (Ipc) and peak separation (∆E) were determined. The PEN-based electrodes demonstrated better biosensor properties such as lower initial Rct values, a greater change in Rct after the immobilization of the Tro4 aptamer on its surface, higher Ipc and Ipa values and lower ∆E, which correlated with a higher number of immobilized aptamers compared with the other two types of samples functionalized using the same procedure.

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Coronary artery disease (CAD) is one of the leading causes of death globally. Currently, diagnosis and intervention in CAD are typically performed via minimally invasive cardiac catheterization procedures. Using current diagnostic technology, such as angiography and fractional flow reserve (FFR), interventional cardiologists must decide which patients require intervention and which can be deferred; 10% of patients with stable CAD are incorrectly deferred using current diagnostic best practices. By developing a forward-viewing intravascular ultrasound (FV-IVUS) 2-D array capable of simultaneously evaluating morphology, hemodynamics, and plaque composition, physicians would be better able to stratify risk of major adverse cardiac events in patients with intermediate stenosis. For this application, a forward-viewing, 16-MHz 2-D array transducer was designed and fabricated. A 2-mm-diameter aperture consisting of 140 elements, with element dimensions of 98×98×70 µ m ( w×h×t ) and a nominal interelement spacing of 120 µ m, was designed for this application based on simulations. The acoustic stack for this array was developed with a designed center frequency of 16 MHz. A novel via-less interconnect was developed to enable electrical connections to fan-out from a 140-element 2-D array with 120- µ m interelement spacing. The fabricated array transducer had 96/140 functioning elements operating at a center frequency of 16 MHz with a -6-dB fractional bandwidth of 62% ± 7 %. Single-element SNR was 23 ± 3 dB, and the measured electrical crosstalk was - 33 ± 3 dB. In imaging experiments, the measured lateral resolution was 0.231 mm and the measured axial resolution was 0.244 mm at a depth of 5 mm. Finally, the transducer was used to perform 3-D B-mode imaging of a 3-mm-diameter spring and 3-D B-mode and power Doppler imaging of a tissue-mimicking phantom.

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Secreted metabolites are an important class of bio-process analytical technology (PAT) targets that can correlate to cell conditions. However, current strategies for measuring metabolites are limited to discrete measurements, resulting in limited understanding and ability for feedback control strategies. Herein, a continuous metabolite monitoring strategy is demonstrated using a single-use metabolite absorbing resonant transducer (SMART) to correlate with cell growth. Polyacrylate is shown to absorb secreted metabolites from living cells containing hydroxyl and alkenyl groups such as terpenoids, that act as a plasticizer. Upon softening, the polyacrylate irreversibly conformed into engineered voids above a resonant sensor, changing the local permittivity which is interrogated, contact-free, with a vector network analyzer. Compared to sensing using the intrinsic permittivity of cells, the SMART approach yields a 20-fold improvement in sensitivity. Tracking growth of many cell types such as Chinese hamster ovary, HEK293, K562, HeLa, and E. coli cells as well as perturbations in cell proliferation during drug screening assays are demonstrated. The sensor is benchmarked to show continuous measurement over six days, ability to track different growth conditions, selectivity to transducing active cell growth metabolites against other components found in the media, and feasibility to scale out for high throughput campaigns.

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Focused ultrasound (FUS) combined with microbubbles (MBs) has emerged as a promising strategy for transiently opening the blood-brain barrier (BBB) to enhance drug permeability in the brain. Current FUS systems for BBB opening use piezoelectric transducers as transmitters and receivers. While capacitive micromachined ultrasonic transducers (CMUTs) have been suggested as an FUS receiver alternative due to their broad bandwidth, their capabilities as transmitters have not been investigated. This is mainly due to the intrinsic nonlinear behavior of CMUTs, which complicates the detection of MB generated harmonic signals and their low-pressure output at FUS frequencies. Various methods have been proposed to mitigate CMUT nonlinearity; however, these approaches have primarily targeted contrast enhanced ultrasound imaging. In this study, we propose the use of polyphase modulation (PM) technique to isolate MB emissions when CMUTs are employed as transmitters for BBB opening. Our calculations for a human scale FUS system with multiple CMUT transmitters show that 10-kPa peak negative pressure (PNP) at 150-mm focal distance will be sufficient for MB excitation for BBB opening. Experimental findings indicate that this pressure level can be easily generated at 400-800 kHz using a readily available CMUT. Furthermore, more than 50-dB suppression of the fundamental harmonic signal is obtained in free field and transcranial hydrophone measurements by processing receive signals in response to phase-modulated transmit waveforms. In vitro validation of PM is also conducted using Definity MB flowing through a tube phantom. MB-filled tube phantoms show adequate nonlinear signal isolation and SNR for MB harmonic detection. Together our findings indicate that PM can effectively mitigate CMUT harmonic generation, thereby creating new opportunities for wideband transmission and receive operation for BBB opening in clinical and preclinical applications.

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