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Conventional ultrasound probes have inherent limitations in some application scenarios. Because of their fixed shapes and sizes, they can hardly pass through small orifices to examine the target closely. With the recent development of micro-electro-mechanical systems (MEMS) and flexible electronic technologies, collapsible and self-assembling devices are being considered as a potential approach to address this problem. This paper presents an innovative transformable ultrasonic transducer (TUT), which can transform between a 1D linear array and a 2D planar array with the ability of switching between different functions including 2D/3D imaging and high-intensity focused ultrasound beamforming. The transforming process is accomplished with a specially designed flexible printed circuit board inspired by paper-folding mechanism. The electrical and acoustic properties of the developed transducer along with the acoustic field distribution in its different forms have been characterized. The 2D/3D imaging performances of the TUT have been also evaluated under 1D and 2D configurations, respectively. In addition, the performance of a focused concave transforming mode has been also discussed. The evaluation results suggest that TUT can maintain its performance under different structures with precise transforming control. The TUT device has the potential to considerably expand the applications of industrial and clinical ultrasound.

Objective: Traditional endoscopic ultrasonography (EUS), which uses one-dimensional (1-D) curvilinear or radial/circular transducers, cannot achieve dynamic elevational focusing, and the slice thickness is not sufficient. The purpose of this study was to design and fabricate a 1.5-dimensional (1.5-D) circular array transducer to achieve dynamic elevational focusing in EUS in vivo . Methods : An 84 × 5 element 1.5-D circular array transducer was successfully developed and characterized in this study. It was fabricated with PZT-5H 1-3 composite that attained a high-electromechanical coupling factor and low-acoustic impedance. The acoustic field distribution was measured with different transmission modes to validate the 1.5-D elevational beam focusing capability. The imaging performance of the 84 × 5 element 1.5-D circular array transducer was evaluated by two wire phantoms, an agar-based cyst phantom, an ex vivo swine pancreas, and an in vivo rhesus macaque rectum based on multifocal ray-line imaging method with five-row elevational beam steering. Results : It was demonstrated that the transducer exhibited a central frequency of 6.47 MHz with an average bandwidth of 50%, a two-way insertion loss of 23 dB, and crosstalk of Conclusion : Dynamic elevational focusing and the enhancement of the slice thickness in EUS were obtained with a 1.5-D circular array transducer. Significance : This study promotes the development of multirow and two-dimensional array EUS probes for a more precise clinical diagnosis and treatment.

Ultrasonic neuromodulation on large animals, like non-human primates, requires the array transducer to have a good steering ability to arbitrarily stimulate various brain locations. Moreover, due to the different sizes of the animal heads, the array is preferred to be conveniently adjustable to different aperture sizes. To meet these requirements, a scalable 2D plane array, which can consist of up to tens of 256-element square modules, has been designed and fabricated in this study. Arrays with large apertures, consisting of 12 and 48 modules (including 3072 and 12288 elements, respectively), have been assembled and tested. The square modules were driven at a center frequency of 1.04 MHz. The transcranial and steering abilities of the modules were verified in a water tank on an ex vivo macaque skull. A focused beam transmitted by single module could pass through the skull with its peak acoustic pressure reduced to 18.1% of that in the free-field, with an acceptable transverse steering range up to 10 mm. Moreover, a much smaller focal spot was obtained by simultaneous transmission using two vertical-placed modules. Compared to the single module, the focal zone axial size was reduced from 29.7 mm to 3.3 mm, and the "stripes" pattern in the focal zone caused by standing waves was eliminated using a difference-frequency transmitting strategy. Such scalable 2D plane array, which can provide a small-size focal spot and has a large steering range and an acceptable transcranial ability, can be useful in research on ultrasonic neuromodulation on non-human primates.

Acoustic vortex beams, which have both linear and angular momentum, can be used to make precise acoustic tweezers. Limited by the symmetry of a normal vortex beam, these tweezers are usually used for trapping or rotating particles in two dimensions. Here, the three-dimensional spiral motion of two soft particles of different sizes was realized using a vortex beam with a twisted focus, which was synthesized by a silicone binary-phase logarithmic-spiral zone plate. Numerical simulations and experimental measurements demonstrated that the beam had anisotropic focuses of crescent transverse intensity profiles and a screw phase dislocation with a singularity at the center. Experiments showed that a small particle (k0r ≈ 1.3) can follow the twisted intensity of the beam, but a large particle (k0r ≈ 4.7) spirals up away from the twisted field pattern. This is attributed to the dominant gradient force for the small particle, whereas the scattering effect induced a scattering force combined with a gradient force for the large particle. This focused twisted beam, which was generated with a structured silicone plate, and the three-dimensional spiral motion of microparticles, advance the development of simple, compact, and disposable acoustic devices for the precise and diverse manipulation of microparticles.

Neuromodulation is a fundamental method for obtaining basic information about neuronal circuits for use in treatments for neurological and psychiatric disorders. Ultrasound stimulation has become a promising approach for noninvasively inducing neuromodulation in animals and humans. However, the previous investigations were subject to substantial limitations, due to most of them involving anesthetized and fixed small-animal models. Studies of awake and freely moving animals are needed, but the currently used ultrasound devices are too bulky to be applied to a freely moving animal. This study is the first time to design and fabricate a miniature and lightweight head-mounted ultrasound stimulator for inducing neuromodulation in freely moving mice. The main components of the stimulator include a miniature piezoelectric ceramic, a concave epoxy acoustic lens, and housing and connection components. The device was able to induce action potentials recorded in situ and evoke head-turning behaviors by stimulating the primary somatosensory cortex barrel field of the mouse. These findings indicate that the proposed method can be used to induce noninvasive neuromodulation in freely moving mice. This novel method could potentially lead to the application of ultrasonic neuromodulation in more-extensive neuroscience investigations.

Acoustic tweezers have great application prospects because they allow noncontact and noninvasive manipulation of microparticles in a wide range of media. However, the nontransparency and heterogeneity of media in practical applications complicate particle trapping and manipulation. In this study, we designed a 1.04 MHz 256-element 2D matrix array for 3D acoustic tweezers to guide and monitor the entire process using real-time 3D ultrasonic images, thereby enabling acoustic manipulation in nontransparent media. Furthermore, we successfully performed dynamic 3D manipulations on multiple microparticles using multifoci and vortex traps. We achieved 3D particle manipulation in heterogeneous media (through resin baffle and ex vivo macaque and human skulls) by introducing a method based on the time reversal principle to correct the phase and amplitude distortions of the acoustic waves. Our results suggest cutting-edge applications of acoustic tweezers such as acoustical drug delivery, controlled micromachine transfer, and precise treatment.

Endoscopic ultrasound (EUS), an interventional imaging technology, utilizes a circular array to delineate the cross-sectional morphology of internal organs through the gastrointestinal (GI) track. However, the performance of conventional EUS transducers has scope for improvement because of the ordinary piezoelectric parameters of Pb(Zr, Ti) $\text{O}_{{3}}$ (PZT) bulk ceramic as well as its inferior mechanical flexibility which can cause material cracks during the circular shaping process. To achieve both prominent imaging capabilities and high device reliability, a 128-element 6.8-MHz circular array transducer is developed using a Pb(Mg $_{\text {1/3}}$ Nb $_{\text {2/3}}$ ) $\text{O}_{{3}}$ -PbTiO3 (PMN-PT) 1–3 composite with a coefficient of high electromechanical coupling ( ${k}_{{\text {t}}} \sim 0.78$ ) and good mechanical flexibility. The characterization results exhibit a large average bandwidth of 58%, a high average sensitivity of 100 mVpp, and a crosstalk of less than −37 dB near the center frequency. Imaging performance of the PMN-PT composite-based array transducer is evaluated by a wire phantom, an anechoic cyst phantom, and an ex-vivo swine intestine. This work demonstrates the superior performance of the crucial ultrasonic device based on an advanced PMN-PT composite material and may lead to the development of next-generation biomedical ultrasonic devices for clinical diagnosis and treatment.

Brain ultrasound has attracted great attention recently due to its noninvasive treatment function for brain diseases. However, ultrasound is still difficult to pass through an intact skull. Phase correction is recognized as an effective method for skull compensation. Half-wavelength pitch transducer is important for the phase correction and, hence, thousands of elements array is required to cover large area human tissue. The clock synchronization between elements is crucial for the phase correction; however, the traditional clock scheme which is designed for 128- or 256-element system is not suitable for thousands of elements. In addition, the clock scheme needs to be magnetic resonance imaging (MRI) compatible since MRI-guided intervention is becoming a routine operation for the brain ultrasound. This study is the first to propose an optical fiber-based clock synchronization method for MRI-guided ultrasound array system. The optical fiber not only distributes the clock but also sets up a link to transmit the data for ultrasound beamformer. The link is full-duplex so both the clock and the data can be transmitted and received simultaneously. The precision of clock synchronization is less than 557 ps when using 50 MHz clock, and the period jitter of the clock is less than 10 ps (rms). Multiple 128- or 256-channel ultrasonic systems can be synchronized, and the error between the channels can be less than 10 ns when using 1-MHz ultrasound transducer. The system can work in an MRI scanning room and communicate with a console via only one fiber. In vivo primate animal study has been achieved, and it has been proven that the proposed clock scheme is suitable for MRI-guided large-scale ultrasound array system.

Mutant KRAS proto-oncogene GTPase (KRAS) serves an important role in predicting the development, diagnosis, treatment and efficacy of targeted drug therapies for colorectal cancer. To improve the detection efficacy of trace amount of mutant KRAS, the locked nucleic acid-based method was modified in the present study. Internal competitive amplification fragments were used to improve the inhibition of wild-type KRAS with a wild-type blocking (WTB) probe and specifically amplify the trace amounts of mutant KRAS. The modified method, quantitative clamp-based polymerase chain reaction technology using WTB coupled with internal competitive reference to enhance the amplification specificity, named WIRE-PCR, completely blocked the amplification of wild-type KRAS in 50–150 ng DNA templates. The added internal competitive amplified fragments were amplified together with the target gene, which were used to reduce base mismatch due to the high number of cycles in PCR and quantify the total amount of DNA. The results demonstrated that WIRE-PCR facilitated the detection of mutated alleles at a single molecular level. In the colorectal biopsies from 50 patients with suspected colorectal cancer, 18 cases (36%) contained mutant KRAS, and the amount of mutant DNA accounted for 18.6–64.2% of the total DNA. WIRE-PCR is a simple, rapid and low-cost quantitative analysis method for the detection of trace amounts of the mutant KRAS.

Focused ultrasound is important in clinical medical applications, to destroy tumor cells or treat a variety of neurological diseases, for example. The focused ultrasound field projected by a transducer array includes traditionally unavoidable side lobes, however, which may cause harmful heating in nontargeted regions. This work implements an active acoustic metasurface, comprising 16\ifmmode\times\else\texttimes\fi{}16 elements of subwavelength thickness, which can completely eliminate such side lobes. Experiments convincingly demonstrate that this active metasurface with programmable phase and amplitude distributions offers high performance in side-lobe-proof, steerable ultrasound focusing.