Development of exosome membrane materials-fused microbubbles for enhanced stability and efficient drug delivery of ultrasound contrast agent.

Lipid-coated microbubbles are widely used as an ultrasound contrast agent, as well as drug delivery carriers. However, the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system, and the difficulty of surface modification of microbubbles for active targeting. The exosome, a type of extracellular vesicle, has a preferentially targeting ability for its original cell. In this study, exosome-fused microbubbles (Exo-MBs) were developed by embedding the exosome membrane proteins into microbubbles. As a result, the stability of Exo-MBs is improved over the conventional microbubbles. On the same principle that under the exposure of ultrasound, microbubbles are cavitated and self-assembled into nano-sized particles, and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles (Exo-NPs). The Exo-NPs showed favorable targeting properties to their original cells. A photosensitizer, chlorin e6, was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier. Much higher therapeutic efficacy of photodynamic therapy was confirmed, followed by cancer immunotherapy from immunogenic cell death. We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.

Polymer link breakage of polyimide-film-surface using hydrolysis reaction accelerator for enhancing chemical-mechanical-planarization polishing-rate.

In this study, the chemical decomposition of a polyimide-film (i.e., a PI-film)-surface into a soft-film-surface containing negatively charged pyromellitic dianhydride (PMDA) and neutral 4,4'-oxydianiline (ODA) was successfully performed. The chemical decomposition was conducted by designing the slurry containing 350 nm colloidal silica abrasive and small molecules with amine functional groups (i.e., ethylenediamine: EDA) for chemical-mechanical planarization (CMP). This chemical decomposition was performed through two types of hydrolysis reactions, that is, a hydrolysis reaction between OH- ions or R-NH3+ (i.e., EDA with a positively charged amine groups) and oxygen atoms covalently bonded with pyromellitimide on the PI-film-surface. In particular, the degree of slurry adsorption of the PI-film-surface was determined by the EDA concentration in the slurry because of the presence of R-NH3+, that is, a higher EDA concentration resulted in a higher degree of slurry adsorption. In addition, during CMP, the chemical decomposition degree of the PI-film-surface was principally determined by the EDA concentration; that is, the degree of chemical composition was increased noticeably and linearly with the EDA concentration. Thus, the polishing-rate of the PI-film-surface increased notably with the EDA concentration in the CMP slurry.

Super fine cerium hydroxide abrasives for SiO2 film chemical mechanical planarization performing scratch free.

Face-centered-cubic crystallized super-fine (~ 2 nm in size) wet-ceria-abrasives are synthesized using a novel wet precipitation process that comprises a Ce4+ precursor, C3H4N2 catalyst, and NaOH titrant for a synthesized termination process at temperature of at temperature of 25 °C. This process overcomes the limitations of chemical-mechanical-planarization (CMP)-induced scratches from conventional dry ceria abrasives with irregular surfaces or wet ceria abrasives with crystalline facets in nanoscale semiconductor devices. The chemical composition of super-fine wet ceria abrasives depends on the synthesis termination pH, that is, Ce(OH)4 abrasives at a pH of 4.0-5.0 and a mixture of CeO2 and Ce(OH)4 abrasives at a pH of 5.5-6.5. The Ce(OH)4 abrasives demonstrate better abrasive stability in the SiO2-film CMP slurry than the CeO2 abrasives and produce a minimum abrasive zeta potential (~ 12 mV) and a minimum secondary abrasive size (~ 130 nm) at the synthesis termination pH of 5.0. Additionally, the abrasive stability of the SiO2-film CMP slurry that includes super-fine wet ceria abrasives is notably sensitive to the CMP slurry pH; the best abrasive stability (i.e., a minimum secondary abrasive size of ~ 130 nm) is observed at a specific pH (6.0). As a result, a maximum SiO2-film polishing rate (~ 524 nm/min) is achieved at pH 6.0, and the surface is free of stick-and-slip type scratches.

A new frequency domain passive acoustic mapping method using passive Hilbert beamforming to reduce the computational complexity of fast Fourier transform.

Passive acoustic mapping (PAM) is the current state-of-the-art imaging tool for monitoring cavitation activity during focused ultrasound therapy such as blood-brain barrier opening. However, PAM incurs huge computational complexity. To address this issue, frequency-domain PAM (FD-PAM) was proposed. Nevertheless, FD-PAM still requires a large number of fast Fourier transforms (FFTs) to produce the frequency components utilized for cavitation monitoring with PAM. Hence, in this paper, we proposes a frequency domain PAM method using passive Hilbert beamforming (PHB-PAM), which can significantly reduce the number of input samples for FFT by down-sampling the analytic signal of the received RF samples at each channel at a rate equal to the bandwidth of the frequency components of interest. The experimental results show that the proposed PHB-PAM provides comparable image quality to that of FD-PAM (correlation coefficient > 0.98). Additionally, the study experimentally verifies that the pre-processing block for generating the decimated analytic signal and FFT in PHB-PAM can be realized using lesser logic resources than FFT in FD-PAM when implemented in an FPGA. Especially, with 128-fold decimation, PHB-PAM reduces the amount of LUTs and DSP slices to implement the pre-processing block by 72.16% and 53.4%, respectively, compared to those of FD-PAM, which allows the 64-channel implementation of the pre-processing block in a low-cost single FPGA. Finally, a hardware-efficient architecture for the pre-processing block of PHB-PAM is described, which can be implemented by replacing the two lowpass filters of an off-the-shelf analog front-end component for ultrasound imaging with a pair of band-pass filters. If PHB-PAM is realized using such a component, it can truly minimize the computational complexity of FD-PAM.

Comparison study of passive acoustic mapping and high-speed photography for monitoring in situ cavitation bubbles.

The spatiotemporal accuracy of passive acoustic mapping (PAM) for monitoring in situ cavitation bubbles has not been assessed directly via optical means. Here, the cavitation bubbles are monitored from two image sequences obtained simultaneously with PAM and high-speed photography (HSP). The temporal accuracy of PAM for detecting cavitation nucleation and the spatial resolution for cavitation localization are compared with those measured from HSP. The results show that PAM has a temporal accuracy of 20 µs. Mean differences in the spatial locations of PAM and HSP are as small as 10.0 and 30.5 µm along the lateral and axial directions, respectively.

Ultrasonic sector imaging using plane wave synthetic focusing with a convex array transducer.

Synthetic transmit focusing (STF) methods using unfocused waves or plane waves (PWs) have recently been investigated extensively. However, STF using PWs with a convex array (PWSTF-CA) has not been rigorously studied for high-resolution sector imaging. In this paper, the authors suggest an analytical model for accurate characterization of the spatial beam patterns of PWSTF-CA using a large range of either uniformly or non-uniformly distributed PW angles. On the basis of the model, a frame-based PWSTF-CA approach with non-uniform PW angles is suggested to achieve superior image quality at a higher frame rate than conventional transmit focusing (CTF). The analytical model can also be used for optimal selection of a set of PW angles to scan the entire sectorial field of view and its subsets employed for STF at each imaging point. The authors also investigate how to select transmit subarrays for each of the PWs to obtain the best spatial resolution. A theoretical analysis and simulations are conducted for the verification of the analytical model and the optimal utilization strategy of PWSTF-CA. The results indicate that the PWSTF-CA improves not only the frame rate but also the contrast, signal-to-noise ratio, and resolution compared with the CTF, as in the case of PWSTF with linear arrays.