Search Results (197)

The motivation of this work is to enable the use of piezoelectric micromachined ultrasonic transducer (PMUT)-based implants within the human body for biomedical applications, particularly for power and data transfer for implanted medical devices. To protect surrounding tissue and ensure PMUT functionality over time, biocompatible and hermetic encapsulation is essential. This study investigates the impact of Parylene F-VT4 layers of various thicknesses as well as the effect of multilayer stacks of Parylene F-VT4 combined with atomic layer-deposited nanolayers of Al₂O₃ and HfO₂ on the mechanical and acoustic properties of PMUTs. PMUTs with various diameters (40 µm, 60 µm, and 80 µm) are fabricated and tested both as stand-alone devices and as arrays. The mechanical behavior of single stand-alone PMUT devices is characterized in air and in water using laser Doppler vibrometry (LDV), while the acoustic output of arrays is evaluated by pressure measurements in water. Experimental results reveal a non-monotonic change in resonance frequency as a function of increasing encapsulation thickness due to the competing effects of added mass and increased stiffness. The performance of PMUT arrays is clearly influenced by the encapsulation. For certain array designs, the encapsulation significantly improved the arrays’ pressure output, a change that is attributed to the change in the acoustic wavelength and inter-element coupling. These findings highlight the impact of encapsulation in modifying and potentially enhancing PMUT performance. Full article

The increasing demand for accurate and accessible medical imaging has driven efforts to develop technologies that overcome limitations associated with conventional imaging techniques, such as MRI and CT scans. This study presents the design and implementation of an electronic interface for acquiring signals from a piezoelectric ultrasound sensor with the aim of improving image reconstruction quality by addressing electromagnetic interference and speckle noise, two major factors that degrade image fidelity. The proposed interface is installed between the ultrasound transducer and acquisition system, allowing real-time signal capture without altering the medical equipment’s operation. Using a printed circuit board with 110-pin connectors, signals from individual piezoelectric elements were analyzed using an oscilloscope. Results show that noise amplitudes occasionally exceed those of the acoustic echoes, potentially compromising image quality. By enabling direct observation of these signals, the interface facilitates the future development of analog filtering solutions to mitigate high-frequency noise before digital processing. This approach reduces reliance on computationally expensive digital filtering, offering a low-cost, real-time alternative. The findings underscore the potential of the interface to enhance diagnostic accuracy and support further innovation in medical imaging technologies. Full article

Background: Organic anion transporter 3 (OAT3) in the kidney proximal tubule cells plays a critical role in renal clearance of numerous endogenous metabolites and exogenous drugs and toxins. In this study, we discovered that epidermal growth factor (EGF) regulates the expression and activity of OAT3 through palmitoylation, a novel mechanism that has never been described in the OAT field. Methods/Results: Our results showed that treatment of OAT3-expressing cells with EGF led to a ~40% increase in OAT3 expression and OAT3-mediated transport of estrone sulfate, a prototypical substrate for OAT3. EGF-stimulated OAT3 transport activity was abrogated by H-89, a protein kinase A (PKA) inhibitor, indicating that an EGF-PKA signaling pathway is involved in the regulation of OAT3. We also showed that treatment of OAT3-expressing cells with EGF resulted in an enhancement of OAT3 palmitoylation, a novel type of post-translational modification for OATs, and such an enhancement was blocked by H-89, suggesting that the EGF-PKA signaling pathway participated in the modulation of OAT3 palmitoylation. Palmitoylation was catalyzed by a group of palmitoyltransfereases, and we showed that OAT3 palmitoylation and expression were inhibited by 2-BP, a general inhibitor for palmitoyltransfereases. We also explored the relationship among EGF/PKA signaling, OAT palmitoylation, and OAT transport activity. We treated OAT3-expressing cells with EGF or Bt2-cAMP, a PKA activator, in the presence and absence of 2-BP, followed by the measurement of OAT3-mediated transport of estrone sulfate. We showed that both EGF- and Bt2-cAMP-stimulated OAT3 transport activity were abolished by 2-BP, suggesting that palmitoylation mediates the regulation of EGF/PKA on OAT3. Finally, we showed that osimertinib, an anti-cancer drug/EGFR inhibitor, blocked EGF-stimulated OAT3 transport activity. Conclusions: In summary, we provided the first evidence that palmitoylation transduces the EGF/PKA signaling pathway to the modulation of OAT3 expression and function. Our study also provided an important implication that during comorbidity therapies, EGFR inhibitor drugs could potentially decrease the transport activity of renal OAT3, which would subsequently alter the therapeutic efficacy and toxicity of many co-medications that are OAT3 substrates. Full article

In recent years, implantable medical devices (IMDs) have introduced groundbreaking solutions for managing various health conditions. However, traditional implanted batteries necessitate periodic surgical replacement and tend to be relatively bulky, posing significant inconvenience to patients. To overcome these limitations, researchers have investigated various wireless power transfer (WPT) techniques, among which the ultrasonic wireless power transmission (UWPT) technique has distinct advantages. However, limited research has been conducted on ultrasonic power transfer at lower operating frequencies. Therefore, this study explores wireless power transfer using scandium-doped aluminum nitride (AlScN) piezoelectric micro-electromechanical transducers (PMUTs) in deionized (DI) water. Experimental results indicate that at an operating frequency of 14.075 kHz, the power transfer efficiency (PTE) can reach up to 2.68% under optimal load resistance conditions. Furthermore, a low-frequency UWPT system based on a AlScN PMUT has been developed, delivering a stable 3.3 V output for implantable medical devices and contributing to the advancement of a full-spectrum UWPT framework. Full article

An emerging alternative to conventional piezoelectric technologies, which continue to dominate the ultrasound medical imaging (US) market, is Capacitive Micromachined Ultrasonic Transducers (CMUTs). Ultrasound transducers based on this technology offer a wider frequency bandwidth, improved cost-effectiveness, miniaturized size and effective integration with electronics. These features have led to an increase in the commercialization of CMUTs in the last 10 years. We conducted a review to answer three main research questions: (1) What are the commercially available CMUT-based clinical sonographic devices in the medical imaging space? (2) What are the medical imaging applications of these devices? (3) What is the performance of the devices in these applications? We additionally reported on all the future work expressed by modern studies released in the past 2 years to predict the trend of development in future CMUT device developments and express gaps in current research. The search retrieved 19 commercially available sonographic CMUT products belonging to seven companies. Four of the products were clinically approved. Sonographic CMUT devices have established their niche in the medical US imaging market mainly through the Butterfly iQ and iQ+ for quick preliminary screening, emergency care in resource-limited settings, clinical training, teleguidance, and paramedical applications. There were no commercialized 3D CMUT probes. Full article

Background: Ultrasonography is commonly employed during thoracic regional anesthesia; however, its accuracy can be affected by factors such as obesity and poor penetration through the rib window. Needle-sized ultrasound transducers, known as intra-needle ultrasound (INUS) transducers, have been developed to detect the pleura and fascia using a one-dimensional radio frequency mode ultrasound signal. In this study, we aimed to use time-frequency analysis to characterize the pleural signal and develop an automated tool to identify the pleura during medical procedures. Methods: We developed an INUS system and investigated the pleural signal it measured by establishing a phantom study, and an in vivo animal study. Signals from the pleura, endothoracic fascia, and intercostal muscles were analyzed. Additionally, we conducted time- and frequency-domain analyses of the pleural and alveolar signals. Results: We identified the unique characteristics of the pleura, including a flickering phenomenon, speckle-like patterns, and highly variable multi-band spectra in the ultrasound signal during the breathing cycle. These characteristics are likely due to the multiple reflections from the sliding visceral pleura and alveoli. This automated identification of the pleura can enhance the safety for thoracic regional anesthesia, particularly in difficult cases. Conclusions: The unique flickering pleural signal based on INUS can be processed by time-frequency domain analysis and further tracked by an auto-identification algorithm. This technique has potential applications in thoracic regional anesthesia and other interventions. However, further studies are required to validate this hypothesis. Key Points Summary: Question: How can the ultrasound pleural signal be distinguished from other tissues during breathing? Findings: The frequency domain analysis of the pleural ultrasound signal showed fast variant and multi-band characteristics. We suggest this is due to ultrasound distortion caused by the interface of multiple moving alveoli. The multiple ultrasonic reflections from the sliding pleura and alveoli returned in variable and multi-banded frequency. Meaning: The distinguished pleural signal can be used for the auto-identification of the pleura for further clinical respiration monitoring and safety during regional anesthesia. Glossary of Terms: intra-needle ultrasound (INUS); radio frequency (RF); short-time Fourier transform (STFT); intercostal nerve block (ICNB); paravertebral block (PVB); pulse repetition frequency (PRF). Full article

Background/Objectives: The aim of the present study is to report an outbreak of bloodstream infections caused by Serratia marcescens in patients undergoing postoperational procedures in the Cardiothoracic Department and to describe the epidemiological investigations and control measures undertaken. A cluster of bacteremia due to Serratia marcescens was identified in blood cultures from postoperative patients in the Cardiothoracic Surgery Department in November 2023. Methods: Active surveillance by the hospital’s prevention and control team was initiated. Interviews with nurses and sanitary personnel and reviews of the most common procedures, such as hand washing, bladder catheterization, and intravenous catheter care, were performed. Culturing samples from hospital personnel, postoperative patients, and the environment, including pressure transducers, tap water, soap, therapeutic solutions, antiseptics, respirators, and various intravenous preparations, were drawn up. Overall, 225 samples were collected, including 149 blood cultures, and these were all sent to the Hospital’s Microbiology Laboratory. Results: Twenty-three out of forty-seven postoperative patients had positive blood cultures for Serratia marcescens. All the postoperative patients involved in the outbreak received cefepime according to antimicrobial susceptibility testing. Three pre-prepared flushing syringes were found to be positive for Serratia marcescens as well. The Cardiothoracic Department was kept under surveillance with hand hygiene measures, infusion preparation, medical device use, and cleaning procedures reviewed by the infection’s prevention and control team. Conclusions: Undoubtedly, nosocomial outbreaks represent an important health issue regarding morbidity, mortality, and costs. Timely interventions by the hospital’s infection prevention and control team may be life-saving under these circumstances. Full article

Non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations have brought great challenges to the medical treatment in the world. Current treatment strategies, such as EGFR tyrosine kinase inhibitors (TKIs), have reached certain achievements, however, patients inevitably experienced resistance after undergoing a period of treatment with these drugs. Hence, more novel therapy strategies need to be urgently developed. Natural compounds have become popular topics in drug development. α-Mangostin, which is derived from mangosteen, possesses multiple biological properties, yet the antitumor mechanism against NSCLC has not been further elucidated. In this study, an MTT assay, Western blotting, a colony formation assay, and flow cytometry were performed to detect the antitumor activity of α-Mangostin on NSCLC cell NCI-H1975. Molecular docking and molecular dynamics simulations were performed to analyze the interactions between α-Mangostin and the core target proteins. The results indicated that α-Mangostin exerts its antitumor activity by inhibiting cell proliferation and migration, reducing cell cycle arrest, promoting cell apoptosis, and regulating the phosphorylation expression levels of EGFR and signal transducer and activator of transcription 3 (STAT3). Moreover, the results of the molecular simulation study revealed the potential binding mode of α-Mangostin to EGFR and STAT3. In summary, we characterized that α-Mangostin may be used as a potent pro-drug against NSCLC via the EGFR/STAT3 pathway. Full article

Surface acoustic wave (SAW)-based microfluidics has emerged as a promising technology for precisely manipulating particles and cells at the micro- and nanoscales. Acoustofluidic devices offer advantages such as low energy consumption, high throughput, and label-free operation, making them suitable for particle manipulation tasks including pumping, mixing, sorting, and separation. In this review, we provide an overview and discussion of recent advancements in SAW-based microfluidic devices for micro- and nanoparticle manipulation. Through a thorough investigation of the literature, we explore interdigitated transducer designs, materials, fabrication techniques, microfluidic channel properties, and SAW operational modes of acoustofluidic devices. SAW-based actuators are mainly based on lithium niobate piezoelectric transducers, with a plethora of wavelengths, microfluidic dimensions, and transducer configurations, applied for different fluid manipulation methods: mixing, sorting, and separation. We observed the accuracy of particle sorting across different size ranges and discussed different alternative device configurations to enhance sensitivity. Additionally, the collected data show the successful implementation of SAW devices in real-world applications in medical diagnostics and environmental monitoring. By critically analyzing different approaches, we identified common trends, challenges, and potential areas for improvement in SAW-based microfluidics. Furthermore, we discuss the current state-of-the-art and opportunities for further research and development in this field. Full article

This paper investigates the symmetrical layout effect in ultrasonic cleaning via acoustic solid coupling simulation, with emphasis on how the symmetrical arrangement of transducers influences sound pressure distribution. Two specific transducer layout methods are examined: uniform arrangement at the bottom and symmetrical arrangement along the sides. The findings indicate that when the tank length is an integer multiple of one-quarter of the acoustic wavelength, the symmetrical side arrangement markedly enhances the sound pressure level within the tank and optimizes the propagation and reflection of acoustic waves. In megasonic cleaning, focusing is achieved through a 7 × 7 transducer array by precisely controlling the phase, and the symmetrical arrangement ensures uniform sound pressure distribution. By integrating 1 MHz megasonic sources from both focused and unfocused configurations, the overall sound pressure distribution and peak sound pressure at the focal point are calculated using multi-physics field coupling simulations. A comparative analysis of the sound fields generated by focused and unfocused sources reveals that the focused source can produce significantly higher sound pressure in specific regions. Leveraging the enhanced cleaning capability of the focused acoustic wave in targeted areas while maintaining broad coverage with the unfocused acoustic wave significantly improves the overall cleaning efficiency. Ultrasonic cleaning finds extensive applications in industries such as electronic component manufacturing, medical device sterilization, and automotive parts cleaning. Its efficiency and environmental friendliness make it highly significant for both daily life and industrial production. Full article

An ultra-low-power implantable body temperature sensor with a power consumption of 40.9 nW is presented. Deep body temperature measurement can be utilized for diseases such as inflammatory response due to implantable devices, treatment of traumatic brain injury, early monitoring of rejection after kidney transplantation, and monitoring of frictional heat in artificial joints, as well as health management such as ovulation cycles. Since it is implanted in the body and operated by a battery, it is very important to minimize power consumption. For low power consumption, we propose a dynamic virtual Wheatstone bridge technology for low-power transducer driving, and the simplified architecture is designed to operate at 0.6 V. The chip fabricated in a 180 nm CMOS process meets the ASTM E1112-00 specification for medical thermometers. That is, it can measure from 34 °C to 43 °C and meets the accuracy of ±0.1 °C between 37 °C and 39 °C. The measured power consumption at 37 °C is 40.9 nW. To verify practical application, a temperature sensor was implanted in a rat and body temperature changes before and after anesthesia were observed. Full article

Lentiviral vector-transduced T cells were approved by the FDA as gene therapy anti-cancer medications. Little is known about the effects of host genetic variation on the safety and efficacy of the lentiviral vector gene delivery system. To narrow this knowledge gap, we characterized hepatic gene delivery by lentiviral vectors across the Collaborative Cross (CC) mouse genetic reference population. For 24 weeks, we periodically measured hepatic luciferase expression from lentiviral vectors in 41 CC mouse strains. Hepatic and splenic vector copy numbers were determined. We report that the CC mouse strains showed highly diverse outcomes following lentiviral gene delivery. For the first time, a moderate correlation between mouse-strain-specific sleeping patterns and transduction efficiency was observed. We associated two quantitative trait loci (QTLs) with intrastrain variations in transduction phenotypes, which mechanistically relates to the phenomenon of metastable epialleles. An additional QTL was associated with the kinetics of hepatic transgene expression. Genes found in the above QTLs are potential targets for personalized gene therapy protocols. Importantly, we identified two mouse strains that open new directions for characterizing continuous viral vector silencing and HIV latency. Our findings suggest that wide-range patient-specific outcomes of viral vector-based gene therapy should be expected. Thus, novel clinical protocols should be considered for non-fatal diseases. Full article

Biosensors, which combine physical transducers with biorecognition elements, have seen significant advancement due to the heightened interest in rapid diagnostic technologies across a number of fields, including medical diagnostics, environmental monitoring, and food safety. In particular, polydiacetylene (PDA) is gaining attention as an ideal material for label-free colorimetric biosensor development due to its unique color-changing properties in response to external stimuli. PDA forms through the self-assembly of diacetylene monomers, with color change occurring as its conjugated backbone twists in response to stimuli such as temperature, pH, and chemical interactions. This color change enables the detection of biomarkers, metal ions, and toxic compounds. Moreover, the combination of PDA with polymeric structures including hydrogels further enhances the sensitivity and structural stability of PDA-based biosensors, making them reliable and effective in complex biological and environmental conditions. This review comprehensively examines recent research trends and applications of PDA–polymeric structure hybrid biosensors, while discussing future directions and potential advancements in this field. Full article

Background/Objectives: Endothelial hyperpermeability is the hallmark of severe disease, including sepsis and acute respiratory syndrome (ARDS). The development of medical countermeasures to treat the corresponding illness is of utmost importance. Synthetic somatostatin analogs (SSA) are FDA-approved drugs prescribed in patients with neuroendocrine tumors, and they act via growth hormone (GH) suppression. Preclinical investigations suggest that Octreotide (OCT) alleviates Lipopolysaccharide (LPS)-induced injury. The aim of the study is to investigate the involvement of activating transcription factor 6 (ATF6) in the protective effects of OCT in endothelial dysfunction. To the best of our knowledge, the available information on that topic is limited. Methods: Human lung microvascular endothelial cells (HULEC-5a) and bovine pulmonary artery endothelial cells (BPAEC) which expressed elevated levels of ATF6 due to AA147 were exposed to OCT or vehicle. Protein expression, endothelial permeability, and reactive oxygen species (ROS) generation were assessed utilizing Western blot analysis, Fluorescein isothiocyanate (FITC)-Dextran assay, and Dichlorofluorescein diacetate measurements, respectively. Results: Our observations suggest that ATF6 activation significantly improves OCT-induced endothelial barrier enhancement. This combination led to increased expression of binding immunoglobulin protein (BiP) and glucose-regulated protein 94 (Grp94), which are downstream unfolded protein response (UPR) targets. Moreover, ATF6 activation prior to OCT treatment resulted in decreased activation of myosin light chain 2 (MLC2) and cofilin; and reduced reactive oxygen species (ROS) generation. ATF6 activation enhanced the anti-inflammatory effects of OCT, as reflected in the suppression of transducer and activator of transcription (STAT) 1, STAT3, and P38 phosphorylation. Conclusions: Our findings suggest that ATF6 activation prior to OCT treatment enhances the beneficial effects of OCT in the endothelium. Full article

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, and although the diagnosis is primarily based on clinical criteria, ENMG, as the “gold standard”, does not always show detectable changes. Therefore, our study suggests that alterations in echogenicity and heterogeneity of the phrenic nerve (PN) may serve as potential additional diagnostic tools for ALS. Methods: Our study included 32 patients in the ALS group and 64 individuals in the control group. Each participant underwent an interview and completed questionnaires to collect clinical and demographic data, including age, gender, height, body mass index (BMI), hip and waist circumference, duration of illness, ALS-FRS-R score, comorbidities, and medication use. Ultrasound examinations of the PN were performed by two authors using a high-resolution “Philips EPIQ 7” ultrasound machine equipped with a linear 4–18 MHz transducer. The ALS group participants underwent PN sonography and conduction examinations, arterial blood gas (ABG) analysis, respiratory function tests (RFT), and electroneuromyography (ENMG). Results: The study demonstrated that the phrenic nerve is significantly smaller on both sides in patients with ALS compared to the control group (p < 0.01). Changes in the homogeneity and echogenicity of the PN were also observed on both sides. On the right side, 43.8% of the nerves showed heterogeneity, 40.6% were isoechoic, and 21.9% were hyperechoic. On the left side, 59.4% of the nerves exhibited heterogeneity, 34.4% were isoechoic, and 28.1% were hyperechoic. Moreover, sonography on both sides showed significant correlation with ALS-FRS-R, COMPASS-31, and ENMG results. Conclusions: Our study highlights the importance of phrenic nerve ultrasound as a promising supplementary diagnostic tool for ALS. The significant differences in phrenic nerve size, echogenicity, and homogeneity between patients with ALS and the control group demonstrate that ultrasound imaging can detect morphological changes in the phrenic nerve. Incorporating phrenic nerve ultrasound into routine diagnostic protocols could improve early detection, enhance disease monitoring, and offer a more comprehensive understanding of the neurodegenerative processes in ALS. Full article