A piezoelectric-driven microneedle platform for skin disease therapy.

With over a million cases detected each year, skin disease is a global public health problem that diminishes the quality of life due to its difficulty to eradicate, propensity for recurrence, and potential for post-treatment scarring. Photodynamic therapy (PDT) is a treatment with minimal invasiveness or scarring and few side effects, making it well tolerated by patients. However, this treatment requires further research and development to improve its effective clinical use. Here, a piezoelectric-driven microneedle (PDMN) platform that achieves high efficiency, safety, and non-invasiveness for enhanced PDT is proposed. This platform induces deep tissue cavitation, increasing the level of protoporphyrin IX and significantly enhancing drug penetration. A clinical trial involving 25 patients with skin disease was conducted to investigate the timeliness and efficacy of PDMN-assisted PDT (PDMN-PDT). Our findings suggested that PDMN-PDT boosted treatment effectiveness and reduced the required incubation time and drug concentration by 25% and 50%, respectively, without any anesthesia compared to traditional PDT. These findings suggest that PDMN-PDT is a safe and minimally invasive approach for skin disease treatment, which may improve the therapeutic efficacy of topical medications and enable translation for future clinical applications.

An optical aptasensor for real-time quantification of endotoxin: From ensemble to single-molecule resolution.

Endotoxin is a deadly pyrogen, rendering it crucial to monitor with high accuracy and efficiency. However, current endotoxin detection relies on multistep processes that are labor-intensive, time-consuming, and unsustainable. Here, we report an aptamer-based biosensor for the real-time optical detection of endotoxin. The endotoxin sensor exploits the distance-dependent scattering of gold nanoparticles (AuNPs) coupled to a gold nanofilm. This is enabled by the conformational changes of an endotoxin-specific aptamer upon target binding. The sensor can be used in an ensemble mode and single-particle mode under dark-field illumination. In the ensemble mode, the sensor is coupled with a microspectrometer and exhibits high specificity, reliability (i.e., linear concentration to signal profile in logarithmic scale), and reusability for repeated endotoxin measurements. Individual endotoxins can be detected by monitoring the color of single AuNPs via a color camera, achieving single-molecule resolution. This platform can potentially advance endotoxin detection to safeguard medical, food, and pharmaceutical products.

3D-Printed Integrated Ultrasonic Microneedle Array for Rapid Transdermal Drug Delivery.

Transdermal drug delivery (TDD) is an attractive alternative to oral and hypodermic injection drug administration, and is poised to increase its impact on medicine and pharmaceutical design. Microneedles (MNs) are a new minimally invasive TDD method widely used in medicine and cosmetology. MNs create a microscale channel from the stratum corneum to the dermis and enable drug delivery of hydrophilic and macromolecular into the skin. Although MNs allow different drugs to penetrate the stratum corneum, they cannot provide an extra driving force for drug transport in tissue. To overcome this limitation and achieve fast, controllable drug delivery, an integrated 3D-printed ultrasonic MN array (USMA) device consisting of hollow MNs and an ultrasonic transducer is proposed. The hollow MNs enable drug to penetrate the stratum corneum, and the ultrasound transmitted through the MNs provides the driving force for drug transportation in tissue. Using methylene blue and bovine serum albumin as model drugs, we tested the drug delivery performance of USMA on porcine skin; the results show that USMA significantly enhanced the delivery efficiency of model drugs. Besides, USMA obviously reduced MNs insertion force and tissue damage, which were well-tolerated and gentle. This study suggests that the integrated ultrasonic MN array has great potential for clinical drug delivery with high efficiency and lessening the suffering of patients.

Theoretical and experimental analyses of a legged piezoelectric bending actuator with shoe soles made of polyimide composites.

Friction materials form a critical component of piezoelectric actuators, and wear of the material affects output and service life of the actuator. This paper examines the influence of polyimide (PI) composites when used as a friction material on the performance of a legged piezoelectric bending actuator. We design and manufacture demountable shoe soles, made of a novel PI-based friction material, for an actuator. A Coulomb friction model is also established to determine the behavior resulting from contact-induced friction between the surface and the actuator. Reciprocating wear tests involving an insulation rubber pad against phosphor bronze and PI composites as friction materials yielded average friction coefficients of 0.21 and 0.28, respectively. We also found that PI composites have higher wear resistance than phosphor bronze, with a specific wear rate of 1.36 × 10-4 mm3/N m. The results of experiments and simulations indicate that the shoe soles made of PI composites reduced the actuator's driving frequency and vibrational amplitude, but they did not affect the principle of locomotion of the actuator. Furthermore, the operational stability of the actuator improved by 46.8% by using the demountable shoe soles made of PI composites, albeit at the cost of its velocity and load capacity. This work has guiding significance for the design and selection of friction materials for piezoelectric actuators.

Piezoelectric Single Crystal Ultrasonic Transducer for Endoscopic Drug Release in Gastric Mucosa.

Modern advanced minimally invasive surgery has been implemented for most of the significant gastrointestinal diseases. However, patients with coagulopathy or unresectable tumors cannot be cured by current treatment methods. Moreover, other existing medical devices for targeted drug release are too large to be applied in gastric endoscope because the diameter of the biopsy channel is smaller than 3 mm. To address it, in this work, we developed a piezoelectric single crystal ultrasonic transducer (the diameter was only 2.2 mm and the mass was 0.076 g) to produce acoustic waves, which could promote the drug release in the designed position of the digestive tract through an endoscope. It exhibited the electromechanical coupling coefficient of 0.36 and the center frequency of 6.9 MHz with the -6-dB bandwidth of 23%. In in vitro sonophoresis experiment, the gastric mucosa permeability to Bovine Serum Albumin increased about 5.6 times when the ultrasonic transducer was activated at 40 [Formula: see text] and 60% duty ratio, proving that employment of this transducer could facilitate drug penetration in the gastric mucosa. Meanwhile, the permeability could be adjusted by tuning the duty ratio of the ultrasonic transducer. The corresponding sonophoresis mechanism was related to the acoustic streaming and the thermal effect produced by the transducer. In addition, the measured maximum power density was 128 mW/cm2 and the mechanical index of the ultrasonic transducer was 0.02. The results held a great implication for applications of the transducer for targeted drug release in the gastrointestinal tract.

Ultrafast Growth and Locomotion of Dandelion-Like Microswarms with Tubular Micromotors.

Dynamic assembly and cooperation represent future frontiers for next generations of advanced micro/nano robots, but the required local interaction and communication cannot be directly translated from macroscale robots through the minimization because of tremendous technological challenges. Here, an ultrafast growth and locomotion methodology is presented for dandelion-like microswarms assembled from catalytic tubular micromotors. With ultrasound oscillation of self-generated bubbles, such microswarms could overcome the tremendous and chaotic drag force from extensive and disordered bubble generation in single units. Tubular MnO2 micromotor individuals headed by self-generated oxygen bubbles are ultrasonically driven to swim rapidly in surfactant-free H2 O2 solutions. A large bubble core fused from multiple microbubbles is excited to oscillate and the resultant local intensified acoustic field attracts the individual micromotors to school around it, leading to a simultaneous growth of dandelion-like microswarms. The bubble-carried micromotor groups driven by ultrasound could swarm at a zigzag pattern with an average speed of up to 50 mm s-1 , which is validated in low H2 O2 concentrations. Additionally, such superfast locomotion could be ultrasonically modulated on demand. The ultrafast microswarm growth and locomotion strategy offers a new paradigm for constructing distinct dynamic assemblies and rapid transmission of artificial microrobots, paving the way to a myriad of promising applications.

Acoustic Energy Controlled Nanoparticle Aggregation for Nanotherapy.

Patients with unresectable or nonablatable tumors are difficult to cure, but nanotherapy combining targeted nanoparticles has many severe side effects due to the toxicities of anticancer drugs. We found that acoustic energy can produce a local region with high concentration from a low concentration suspended liquid of nano-SiO2 particles at 2.5 MHz. Our calculated results show that the main reason for aggregation is the synthesized effect of the potential well of acoustic energy and streaming to trap them. In addition, the aggregated region can be manipulated to a targeted position in the vessel phantom by moving the ultrasound transducer external to the body. This noninvasive manipulation of suspended nanoparticles can rapidly increase the local drug concentration, but reduce the total dosage of anticancer drugs, which has the potential to be used for patients with advanced tumors by improving the physiological effects and reducing the side effects.

A Human Microrobot Interface Based on Acoustic Manipulation.

Micro/nanorobotic systems capable of targeted transporting and releasing hold considerable promise for drug delivery, cellular surgery, biosensing, nano assembling, etc. However, on-demand precise control of the micro/nanorobot movement remains a major challenge. In particular, a practical interface to realize instant and customized interactions between human and micro/nanorobots, which is quite essential for developing next generation intelligent micro/nanorobots, has seldom been explored. Here, we present a human-microrobot user interface to perform direct and agile recognition of user commands and signal conversion for driving the microrobot. The microrobot platform is built based on locally enhanced acoustic streaming which could precisely transport microparticles and cells along a given pathway, while the interface is enabled by tuning the actuation frequency and time with different instructions and inputs. Our numerical simulations and experimental demonstrations illustrate that microparticles can be readily transported along the path by the acoustic robotic system, due to the vibration-induced locally enhanced acoustic streaming and resultant propulsion force. The acoustic robotic platform allows large-scale parallel transportation for microparticles and cells along given paths. The human microrobot interface enables the micromanipulator to response promptly to the users' commands input by typing or music playing for accurate transport. For example, the music tone of a playing melody is used for manipulating a cancer cell to a targeted position. The interface offers several attractive capabilities, including tunable speed and orientation, quick response, considerable delivery capacities, high precision and favorable controllability. We expect that such interface will work as a compelling and versatile platform for myriad potential scenarios in transportation units of microrobots, single cell analysis instruments, lab-on-chip systems, microfactories, etc.

Micro-/Nanomachines Driven by Ultrasonic Power Sources.

Autonomous micro-/nanomachines that can convert diverse energy sources into effective locomotion under the constraint of low Reynolds numbers hold considerable promise for a variety of applications, such as cargo delivery, localized biosensing, nanosurgery, and detoxification. In this Minireview, we briefly overview recent advances in the development of micro-/nanomachines that are specifically powered by ultrasound, in particular new concept design, their working principles, and their fabrication and manipulation strategies. Finally, the exclusive biocompatibility and sustainability of ultrasound-powered micro-/nanomachines, as well as the critical challenges that face their in vivo application, are discussed to provide insight for the next phase of micro-/nanomachines with versatile functionalities and enhanced capabilities.

Design of PVDF sensor array for determining airflow direction and velocity.

An airflow sensor comprised of an array of piezoelectric polyvinylidene fluoride (PVDF) cantilever sensors mounted on a sensor ring is fabricated. A fluid-solid-electric coupling model based on the finite element method is presented to obtain the mathematical relationship between the normal airflow velocity and the response voltage. According to the response voltages from all pieces of PVDF cantilevers in the array, the values of the airflow direction and the velocity can be calculated. Furthermore, to find a suitable algorithm for error calculations and to achieve high accuracy, a method of reducing the flow angle error ( Eαn,cal¯ ) and flow velocity error ( Δvn,cal¯ ) by extracting Um of the effective cantilevers can be established. The experimental results show that the maximum value of Eαn,cal¯ is 1.2° (at 270° with 11.1 m/s) and the minimum value of Eαn,cal¯ is 0.3° (at 135° with 11.1 m/s) based on the PVDF sensor array with eight cantilevers. Meanwhile, the maximum value of Evn,cal¯ is 3% (at 315° with 11.1 m/s), and the minimum value of Evn,cal¯ is 1.5% (at 360° with 11.1 m/s). In addition, under 20 random airflow angles at 8 m/s, the error range in airflow velocity is from 1.27% to 2.67%, the error range in airflow angle is from 0.34° to 1.24°, and the response time is 20 ms. Therefore, the proposed design for an airflow sensory ring array can be used to determine the airflow direction and velocity, and the airflow sensor can be miniaturized as a bionic antennae, which is mounted on the skin of a piezoelectric autonomous mobile robot for sensing and escaping from an attack of the natural enemy.

Thermal analyses of in vitro low frequency sonophoresis.

As a type of transdermal drug delivery method, low frequency sonophoresis (LFS) has been investigated during the last twenty years and is currently being attempted in a clinical setting. However, the safety of low frequency ultrasound on humans has not been completely guaranteed with high-intensity ultrasound. Thermal damage, one of the challenges in the LFS process, e.g., burns, epidermal detachment and necrosis of tissues, hinders its widespread applications. To predict and impede the overheating problems in LFS, an acoustic-flow-thermal finite element method (FEM) based on COMSOL Multiphysics software is proposed in this paper to achieve thermal analyses. The temperature distribution and its rising curves in in vitro LFS are obtained by the FEM method and experimental measurements. Both simulated and experimental maximum temperatures are larger than the safety value (e.g., 42°C on human tissues) when the driving voltage is higher than 40V (5.5W input electric power), which proves that the overheating problem really exists in high-intensity ultrasound. Furthermore, the results show that the calculated temperature rising curves in in vitro LFS correspond to the experimental results, proving the effectiveness of this FEM method. In addition, several potential thermal influence factors have been studied, including a duty ratio and amplitude of the driving voltage, and liquid height in the donor, which may be helpful in restraining the temperature increase to limit thermal damage. According to the calculated and experimental results, the former two factors are sensitive to the rise in temperature, but a small scale of liquid volume increase can enhance the permeation of Calcein without obvious temperature change. Hence, the above factors can be synthetically utilized to restrain the rise in temperature with little sacrifice of permeation ability. So this acoustic-flow-thermal FEM method could be applied to an optimized LFS system design and simulating the thermal analyses of LFS in healthy human body in terms of safe thermal limits.

A new topological structure for the Langevin-type ultrasonic transducer.

In this paper, a new topological structure for the Langevin-type ultrasonic transducer is proposed and investigated. The two cylindrical terminal blocks are conically shaped with four supporting plates each, and two cooling fins are disposed at the bottom of terminal blocks, adjacent to the piezoelectric rings. Experimental results show that it has larger vibration velocity, lower temperature rise and higher electroacoustic energy efficiency than the conventional Langevin transducer. The reasons for the phenomena can be well explained by the change of mass, heat dissipation surface and force factor of the transducer. The proposed design may effectively improve the performance of ultrasonic transducers, in terms of the working effect, energy consumption and working life.