Flexible surface acoustic wave technology for enhancing transdermal drug delivery.

Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.

Controlling bacterial growth and inactivation using thin film-based surface acoustic waves.

Formation of bacterial films on structural surfaces often leads to severe contamination of medical devices, hospital equipment, implant materials, etc., and antimicrobial resistance of microorganisms has indeed become a global health issue. Therefore, effective therapies for controlling infectious and pathogenic bacteria are urgently needed. Being a promising active method for this purpose, surface acoustic waves (SAWs) have merits such as nanoscale earthquake-like vibration/agitation/radiation, acoustic streaming induced circulations, and localised acoustic heating effect in liquids. However, only a few studies have explored controlling bacterial growth and inactivation behaviour using SAWs. In this study, we proposed utilising piezoelectric thin film-based SAW devices on a silicon substrate for controlling bacterial growth and inactivation with and without using ZnO micro/nanostructures. Effects of SAW powers on bacterial growth for two types of bacteria, i.e., E. coli and S. aureus, were evaluated. Varied concentrations of ZnO tetrapods were also added into the bacterial culture to study their effects and the combined antimicrobial effects along with SAW agitation. Our results showed that when the SAW power was below a threshold (e.g., about 2.55 W in this study), the bacterial growth was apparently enhanced, whereas the further increase of SAW power to a high power caused inactivation of bacteria. Combination of thin film SAWs with ZnO tetrapods led to significantly decreased growth or inactivation for both E. coli and S. aureus, revealing their effectiveness for antimicrobial treatment. Mechanisms and effects of SAW interactions with bacterial solutions and ZnO tetrapods have been systematically discussed.

Acoustofluidic Diversity Achieved by Multiple Modes of Acoustic Waves Generated on Piezoelectric-Film-Coated Aluminum Sheets.

Excitation of multiple acoustic wave modes on a single chip is beneficial to implement diversified acoustofluidic functions. Conventional acoustic wave devices made of bulk LiNbO3 substrates generally generate few acoustic wave modes once the crystal-cut and electrode pattern are defined, limiting the realization of acoustofluidic diversity. In this paper, we demonstrated diversity of acoustofluidic behaviors using multiple modes of acoustic waves generated on piezoelectric-thin-film-coated aluminum sheets. Multiple acoustic wave modes were excited by varying the ratios between IDT pitch/wavelength and substrate thickness. Through systematic investigation of fluidic actuation behaviors and performances using these acoustic wave modes, we demonstrated fluidic actuation diversities using various acoustic wave modes and showed that the Rayleigh mode, pseudo-Rayleigh mode, and A0 mode of Lamb wave generally have better fluidic actuation performance than those of Sezawa mode and higher-order modes of Lamb wave, providing guidance for high-performance acoustofluidic actuation platform design. Additionally, we demonstrated diversified particle patterning functions, either on two sides of acoustic wave device or on a glass sheet by coupling acoustic waves into the glass using the gel. The pattern formation mechanisms were investigated through finite element simulations of acoustic pressure fields under different experimental configurations.

Simple, and highly efficient edge-effect surface acoustic wave atomizer.

Conventional surface acoustic wave (SAW) atomizers require a direct water supply on the surface, which can be complex and cumbersome. This paper presents a novel SAW atomizer that uses lateral acoustic wetting to achieve atomization without a direct water supply. The device works by simply pressing a piece of wetted paper strip against the bottom of an excited piezoelectric transducer. The liquid then flows along the side to the unmodified surface edge, where it is atomized into a well-converging mist in a stable and sustainable manner. We identified this phenomenon as the edge effect, using numerical simulation results of surface displacement mode. The feasibility of the prototype design was demonstrated by observing and investigating the integrated process of liquid extraction, transport, and atomization. We further explored the hydrodynamic principles of the change and breakup in liquid film geometry under different input powers. Experiments demonstrate that our atomizer is capable of generating high-quality fine liquid particles stably and rapidly even at very high input power. Compared to conventional SAW atomizer, the dispersion of mist width can be scaled down by 70%, while the atomization rate can be increased by 37.5%. Combined with the advantages of easy installation and robustness, the edge effect-based atomizer offers an attractive alternative to current counterparts for applications requiring high efficiency and miniaturization, such as simultaneous synthesis and encapsulation of nanoparticles, pulmonary drug delivery and portable inhalation therapy.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Ultra-High Frequency Surface Acoustic Wave Sensors for Temperature Detection.

Highly sensitive surface acoustic wave (SAW) sensors have recently been recognized as a promising tool for various industrial and medical applications. However, existing SAW sensors generally suffer from a complex design, large size, and poor robustness. In this paper, we develop a simple and stable delay line ultra-high frequency (UHF) SAW sensor for highly sensitive detection of temperature. A Z-shaped delay line is specially designed on the piezoelectric substrate to improve the sensitivity and reduce the substrate size. Herein, the optimum design parameters of extremely short-pitch interdigital transducers (IDTs) are given by numerical simulations. The extremely short pitch gives the SAW sensor ultra-high operating frequency and consequently ultra-high sensitivity. Several experiments are conducted to demonstrate that the sensitivity of the Z-shaped SAW delay line sensor can reach up to 116.685°/°C for temperature detection. The results show that the sensor is an attractive alternative to current SAW sensing platforms in many applications.

Integrated Rayleigh wave streaming-enhanced sensitivity of shear horizontal surface acoustic wave biosensors.

Shear horizontal surface acoustic wave (SH-SAW) sensors are regarded as a promising alternative for label-free, sensitive, real time and low-cost detection. Nevertheless, achieving high sensitivity with SH-SAW has approached its limit imposed by the mass transport and probe-target affinity. We present here an SH-SAW biosensor accompanied by a unique Rayleigh wave-based actuator. The platform assembled on an ST-quartz substrate consists of dual-channel SH-SAW delay lines fabricated along a 90°-rotated direction, whilst another interdigital electrode (IDT) is orthogonally placed to generate Rayleigh waves so as to induce favourable streaming in the bio-chamber, enhancing the binding efficiency of the bio-target. Theoretical foundation and simulation have shown that Rayleigh acoustic streaming generates a level of agitation that accelerates the mass transport of the biomolecules to the surface. A fourfold improvement in sensitivity is achieved compared with conventional SH-SAW biosensors by means of complementary DNA hybridization with the aid of the Rayleigh wave device, giving a sensitivity level up to 6.15 Hz/(ng/mL) and a limit of detection of 0.617 ng/mL. This suggests that the proposed scheme could improve the sensitivity of SAW biosensors in real-time detection.

Clinical efficacy of breathing training combined with core stability training in chronic nonspecific low back pain.

Objective: The study aimed to assess the clinical efficacy of breathing training combined with core stability training in chronic nonspecific low back pain (CNLBP). Methods: This was a retrospective study. Of 60 included patients with CNLBP admitted by the Sichuan Province Orthopedic Hospital between December 2020 and February 2022. Random number table method was used to divide thirty patients to a control group, and the rest 30 to an observation group. The control group received core stability training, while the observation group underwent breathing training in addition to the exact treatment provided for the control group. To assess the utility of breathing and core stability training for CNLBP treatment, intergroup comparisons were made for clinical outcomes, the VAS, SF- 36, and SCODI scores before treatment and at three and seven weeks post-treatment, and static and dynamic low-back muscular endurance before and after treatment. Results: The observation group had an overall response rate (ORR) of 96.67%, significantly higher than that (73.33%) of the control group (p< 0.05). Following the intervention, the VAS and SCODI scores declined in both groups; The SF-36 score was elevated in both groups, and likewise. At the end of treatment, both groups exhibited improved static and dynamic muscular endurance of the low back, and the improvement was significantly more distinct in the observation group (p< 0.05). Conclusion: Compared with core stability training as a sole treatment, breathing training combined with core stability training can yield better outcomes, ameliorate lumbar spine function, relieve pain and enhance low-back muscular endurance in patients with CNLBP.

Elevated ZNF704 expression is associated with poor prognosis of uveal melanoma and promotes cancer cell growth by regulating AKT/mTOR signaling.

BACKGROUND: Uveal melanoma (UM) is the most common intraocular malignancy in adults, with a poor survival prognosis. To date, limited understanding of UM's molecular mechanisms constitutes an obstacle to developing effective therapy. In this study, we examined key regulators mediating UM progression and their clinical relevance. METHODS: Transcriptomics of UM patients and cells were analyzed via RNA sequencing and bioinformatic analysis. Zinc finger protein 704 (ZNF704) was identified as prognosis-related biomarker for UM based on clinical characteristics and RNA-seq data from The Cancer Genome Atlas (TCGA). Gene expression was knocked down by specific shRNAs/siRNAs and overexpressed by transfection with plasmids inserted with investigated gene cDNA. Cell proliferation, viability and invasion abilities were determined by CCK8, colony formation and transwell assays, respectively. For cell cycle and apoptosis, cells were PI or PI/Annexin V-APC stained and analyzed by flow cytometry. Standard immunoblotting and quantitative RT-PCR were employed to assess the mRNA and protein abundance. To determine tumor growth in vivo, 4-week-old BALB/c-nu immune-deficient nude mice were inoculated with tumor cells. RESULTS: Analysis of differential expressed genes (DEGs) and survival analysis identified ZNF704 as a novel biomarker of UM. Prognostic analysis indicated ZNF704 as an independent predictor of UM overall survival. Expression of ZNF704 is elevated in UM tissues relative to adjacent normal choroid tissues. Knockdown of ZNF704 suppressed the growth and migration of UM cells and vice versa. In addition, expression of ZNF704 arrest UM cells at G0/G1 phase and inhibit cell apoptosis. RNA sequencing analysis indicated that SORBS3 were dysregulated after ZNF704 downregulation. Gene Set Enrichment Analysis (GSEA) revealed that upon ZNF704 knowndown, genes related with PI3K/AKT/mTOR, EMT and metastasis are enriched. Mechanistically, ZNF704 activates AKT/mTOR/glycolysis signaling pathway in UM cells. Moreover, expression of SORBS3 is downregulated by ZNF704 and knockdown of SORBS3 restored tumor cell viability in ZNF704 silenced cells. CONCLUSIONS: ZNF704 predicts poor prognosis of UM and exhibit pro-oncogenic effect in UM progression in vivo and in vitro, mediated through AKT/mTOR signaling pathway and suppression of SORBS3 expression.

Regional chemotherapy for uveal melanoma liver metastases.

Chemotherapy remains an important approach for the treatment of liver metastases from uveal melanoma (UM). Compared with systemic chemotherapy, regional chemotherapy has similar efficacy and fewer systemic adverse effects. Regional chemotherapy for UM liver metastases includes hepatic artery infusion (HAI), transarterial chemoembolization (TACE), and isolated hepatic perfusion (IHP). In this review, we aim to examine the efficacy of regional chemotherapy and compare HAI, TACE, and IHP in terms of overall survival (OS). The three approaches showed no obvious difference in OS results.

Superior Performances of Self-Driven Near-Infrared Photodetectors Based on the SnTe:Si/Si Heterostructure Boosted by Bulk Photovoltaic Effect.

The upsurge of new materials that can be used for near-infrared (NIR) photodetectors operated without cooling is crucial. As a novel material with a small bandgap of ≈0.28 eV, the topological crystalline insulator SnTe has attracted considerable attention. Herein, this work demonstrates self-driven NIR photodetectors based on SnTe/Si and SnTe:Si/Si heterostructures. The SnTe/Si heterostructure has a high detectivity D* of 3.3 × 1012 Jones. By Si doping, the SnTe:Si/Si heterostructure reduces the dark current density and increases the photocurrent by ≈1 order of magnitude simultaneously, which improves the detectivity D* by ≈2 orders of magnitude up to 1.59 × 1014 Jones. Further theoretical analysis indicates that the improved device performance may be ascribed to the bulk photovoltaic effect (BPVE), in which doped Si atoms break the inversion symmetry and thus enable the generation of additional photocurrents beyond the heterostructure. In addition, the external quantum efficiency (EQE) measured at room temperature at 850 nm increases by a factor of 7.5 times, from 38.5% to 289%. A high responsivity of 1979 mA W-1 without bias and fast rising time of 8 µs are also observed. The significantly improved photodetection achieved by the Si doping is of great interest and may provide a novel strategy for superior photodetectors.

High-Performance Ppb Level NO2 Gas Sensor Based on Colloidal SnO2 Quantum Wires/Ti3C2Tx MXene Composite.

Nitrogen dioxide is one origin of air pollution from fossil fuels with the potential to cause great harm to human health in low concentrations. Therefore, low-cost, low-power-consumption sensors for low-concentration NO2 detection are essential. Herein, heterojunction by SnO2 quantum wires, a traditional metal oxide NO2 sensing material, and Ti3C2Tx MXene, a novel type of 2D layered material, was synthesized using a simple solvothermal method for enhancing gas-sensing performance and reducing operating temperature. The operating temperature was reduced to 80 °C, with a best performance of 27.8 and a fast response and recovery time (11 s and 23 s, respectively). The SnO2 and Ti3C2Tx MXene composite exhibits high speed and low detection limit due to the construction of the heterojunction with high conductive Ti3C2Tx MXene. The selectivity and stability of gas sensors are carried out. This could enable the realization of fast response, high-sensitivity, and selective NO2 sensing under low operating temperatures.

Flexible multifunctional platform based on piezoelectric acoustics for human-machine interaction and environmental perception.

Flexible human-machine interfaces show broad prospects for next-generation flexible or wearable electronics compared with their currently available bulky and rigid counterparts. However, compared to their rigid counterparts, most reported flexible devices (e.g., flexible loudspeakers and microphones) show inferior performance, mainly due to the nature of their flexibility. Therefore, it is of great significance to improve their performance by developing and optimizing new materials, structures and design methodologies. In this paper, a flexible acoustic platform based on a zinc oxide (ZnO) thin film on an aluminum foil substrate is developed and optimized; this platform can be applied as a loudspeaker, a microphone, or an ambient sensor depending on the selection of its excitation frequencies. When used as a speaker, the proposed structure shows a high sound pressure level (SPL) of ~90 dB (with a standard deviation of ~3.6 dB), a low total harmonic distortion of ~1.41%, and a uniform directivity (with a standard deviation of ~4 dB). Its normalized SPL is higher than those of similar devices reported in the recent literature. When used as a microphone, the proposed device shows a precision of 98% for speech recognition, and the measured audio signals show a strong similarity to the original audio signals, demonstrating its equivalent performance compared to a rigid commercial microphone. As a flexible sensor, this device shows a high temperature coefficient of frequency of -289 ppm/K and good performance for respiratory monitoring.

Dynamic Mitigation Mechanisms of Rime Icing with Propagating Surface Acoustic Waves.

Ice accretion on economically valuable and strategically important surfaces poses significant challenges. Current anti-/de-icing techniques often have critical issues regarding their efficiency, convenience, long-term stability, or sustainability. As an emerging ice mitigation strategy, the thin-film surface acoustic wave (SAW) has great potentials due to its high energy efficiency and effective integration on structural surfaces. However, anti-/de-icing processes activated by SAWs involve complex interfacial evolution and phase changes, and it is crucial to understand the nature of dynamic solid-liquid-vapor phase changes and ice nucleation, growth, and melting events under SAW agitation. In this study, we systematically investigated the accretion and removal of porous rime ice from structural surfaces activated by SAWs. We found that icing and de-icing processes are strongly linked with the dynamical interfacial phase and structure changes of rime ice under SAW activation and the acousto-thermally induced localized heating that facilitate the melting of ice crystals. Subsequently, interactions of SAWs with the formed thin water layer at the ice/structure interface result in significant streaming effects that lead to further damage and melting of ice, liquid pumping, jetting, or nebulization.

Characteristics, Treatments, and Survival of Uveal Melanoma: A Comparison between Chinese and American Cohorts.

Uveal melanoma (UM) is the most common intraocular malignant carcinoma. This study aimed to compare the clinical features, treatment modalities, and prognosis of UM patients in China with those in America over a 15-year period. In the study, 4088 American patients with primary UM from the Surveillance, Epidemiology, and End Results (SEER) database and 1508 Chinese patients from Tongren-ophthalmology Research Association of Clinical Evaluation (TRACE) were included. Univariable and multivariable analyses were performed to determine prognostic factors and propensity score matching (PSM) and sensitivity analyses were applied to adjust for confounders and identify independent prognostic factors. Chinese patients were diagnosed at a younger age (mean ± SD, 47.3 ± 12.5 years vs. 59.7 ± 14.8 years) and tumors at diagnosis were larger (diameter: 12.0 ± 3.54 mm vs. 11.3 ± 8.27 mm; thickness: 7.13 ± 3.28 mm vs. 4.91 ± 3.01 mm). Chinese patients were more likely to undergo brachytherapy than American patients. Chinese patients had better overall survival than American patients while no significant differences exhibited after adjusting for age through PSM. In conclusion, compared with American patients, Chinese patients had younger onset age, larger tumors at diagnosis and better prognosis, mainly because of their younger age.

Highly Sensitive Love Mode Acoustic Wave Platform with SiO2 Wave-Guiding Layer and Gold Nanoparticles for Detection of Carcinoembryonic Antigens.

A highly sensitive and precise Love wave mode surface acoustic wave (SAW) immunosensor based on an ST-cut 90°X quartz substrate and an SiO2 wave-guiding layer was developed to detect cancer-related biomarkers of carcinoembryonic antigens (CEAs). A delay line structure of the SAW device with a resonant frequency of 196 MHz was designed/fabricated, and its surface was functionalized through CEA antibody immobilization. The CEA antibodies were bound with gold nanoparticles and CEA antibodies to form a sandwich structure, which significantly amplified the mass loading effect and enhanced the maximum responses by 30 times. The center frequency of the Love wave immunosensor showed a linear response as a function of the CEA concentration in the range of 0.2-5 ng/mL. It showed a limit of detection of 0.2 ng/mL, and its coefficient of determination was 0.983. The sensor also showed minimal interference from nonspecific adsorptions, thus demonstrating its promise for point-of-care applications for cancer biomarkers.

Surface potential-determined performance of Ti3C2T2 (T = O, F, OH) and Zr3C2T2 (T = O, F, OH, S) MXenes as anode materials of sodium ion batteries.

Sodium ion batteries (SIBs) have attracted increasing attention due to their low cost and abundant reserves of sodium, but their ideal anode materials still need to be explored. MXenes could be candidate electrode materials due to their excellent electrical conductivity and large specific surface area. In this work, the theoretical performance of Ti- and Zr-containing MXenes Ti3C2T2 (T = O, F, OH) and Zr3C2T2 (T = O, F, OH, S) as SIB anode materials is investigated. The influence of the Hubbard U correction is discussed, and the behaviour at the MXene surface with the partial occupation of sodium atoms is considered. Including the weight and volume of adsorbed sodium atoms, Ti3C2O2 presents the best performance among the seven MXenes studied. Its mass and volumetric capacities are 299 mA h g-1 and 993 mA h cm-3 respectively, and the migration barrier and open circuit voltage are 0.138 eV and 0.421 V. Both Zr3C2O2 and Zr3C2S2 can adsorb double layers of sodium atoms on both sides, and the former shows a higher capacity because of its lower weight and smaller volume. The mass and volumetric capacities of Zr3C2O2 are 254 mA h g-1 and 913 mA h cm-3 respectively. More importantly, the surface potential is determined to be an effective descriptor for selecting electrode materials. The migration barrier is proportional to the fluctuation amplitude of the surface potential. A low surface potential generally implies a high capacity. A large open circuit voltage is prone to appear in the structure with a large fluctuation amplitude and a low average value of its surface potential.

A Biodegradable and Recyclable Piezoelectric Sensor Based on a Molecular Ferroelectric Embedded in a Bacterial Cellulose Hydrogel.

Currently, various electronic devices make our life more and more safe, healthy, and comfortable, but at the same time, they produce a large amount of nondegradable and nonrecyclable electronic waste that threatens our environment. In this work, we explore an environmentally friendly and flexible mechanical sensor that is biodegradable and recyclable. The sensor consists of a bacterial cellulose (BC) hydrogel as the matrix and imidazolium perchlorate (ImClO4) molecular ferroelectric as the functional element, the hybrid of which possesses a high sensitivity of 4 mV kPa-1 and a wide operational range from 0.2 to 31.25 kPa, outperforming those of most devices based on conventional functional biomaterials. Moreover, the BC hydrogel can be fully degraded into glucose and oligosaccharides, while ImClO4 can be recyclable and reused for the same devices, leaving no environmentally hazardous electronic waste.