超声联合微泡增强细胞内药物递送的研究进展

超声联合微泡介导的细胞内药物递送是通过微泡的声空化与细胞的相互作用而实现的.作为一种非侵入式的、非病毒的、具有靶向性的、可在成像技术引导下的药物递送技术,超声联合微泡在临床应用上具有独特的优势.该文围绕超声联合微泡实现药物递送的发生机理,从微泡的声学动态响应、细胞响应、细胞外物质进入细胞的动态过程及临床试验进展4方面对...     

组织内包膜微泡声空化动力学及其力学效应分析

声空化机械效应是聚焦超声治疗的重要物理机制.以脂类包膜微泡/纳米相变液滴为空化核可显著地增强空化效应,本文耦合空化动力学、组织和脂类包膜黏弹性模型,构建了组织内脂类包膜微泡声空化动力学模型,数值分析了微泡声空化动力学行为以及周围组织内机械应力的时空分布规律,并探究了包膜材料、组织黏弹性和驱动声压等关键参数的影响.包膜和组织黏弹性都将抑制微泡振动,但组织黏弹性的抑制作用更大.组织内机械应力在膨胀阶段为挤压应力,而在收缩阶段和反弹初始阶段为拉伸应力,且应力局部分布于微泡壁附近,随着距离增大而显著减小,其中拉伸应力衰减率明显更大.包膜黏弹性可减小应力,但声压较大时,应力减小可忽略不计.应力随着组织弹性增大而减小,随着组织黏度增大而先增大后减小,随着声压增大而增大.本研究可为进一步阐释聚焦超声治疗中组织机械损伤的内在机制奠定重要理论基础.     

超声脉冲长度与重复频率对流动微泡群稳态空化特性的影响

为了深入理解超声脉冲长度(PL)与重复频率(PRF)对流动微泡群稳态空化特性的影响,本研究自行制备仿体血管,利用注射泵推动微泡群在其中恒速流动,使用1 MHz的聚焦换能器激励微泡群产生稳态空化,另一个7.5 MHz的平面换能器接收声信号,经前置放大及高速采集后送至上位机存储。在定义临界重复频率(Critical PRF,CPRF)的基础上,通过深入的时频域分析,我们发现PL和PRF共同决定流动微泡群的稳态空化特性:当PRF低于CPRF时,流动微泡群的稳态空化剂量(Stable Cavitation Dose,SCD)与PL呈正相关,且时域分布均匀;而当PRF大于CPRF时,其稳态空化特性由PL决定,在长PL (＞100μs)下,SCD随着PL增加逐渐减小,且时域分布不均匀;在短PL (＜50μs)下,SCD和PRF无显著相关关系,且时域分布均匀。本研究结果深入阐明了流动微泡群的稳态空化特性,期望可用其获取可预测可控的生物效应,并应用于相关临床治疗。      

超声波声孔效应中气泡动力学的研究

在超声快速制取组织细胞病理切片的过程中，发现激励信号对切片制取效果有明显的影响.为了掌握超声激励信号对组织细胞的影响规律，达到快速制取病理切片的最佳状态，从气泡空化模型入手，通过改变激励信号频率、声压、气泡初始半径和液体黏滞系数等参量，研究了声孔效应中气泡动力学激励机制.数值计算表明：空化泡振动随激励声压增强而升高，随液体黏滞系数增强而减弱；一定频率范围内空化泡振动能保持在膨胀、收缩和振荡的稳定空化状态，存在空化泡稳态振动的最佳激励频率；一定初始半径能保证空化泡产生稳定的振动，存在空化泡稳态振动幅度最大的初始半径.实际操作中，在频率、声压、初始半径和黏滞系数综合作用的若干空化阈内，声孔效应使超声快速法制取细胞组织切片获得最佳效果. 关键词： 声孔效应 超声空化 气泡振动 稳态空化域     

超声造影剂微泡非线性动力学响应的机理及相关应用

随着生命科学及现代医学的发展, 一体化无创精准诊疗已经日益成为人们关注的焦点问题, 而关于超声造影剂微泡的非线性效应的相关机理、动力学建模及其在超声医学领域中的应用研究也得到了极大的推动. 本文对下列课题进行了总结和讨论, 包括: 1)基于Mie散射技术和流式细胞仪对造影剂微泡参数进行定征的一体化解决方案; 2)通过对微泡包膜的黏弹特性进行非线性修正, 构建新的包膜微泡动力学模型; 3)探索造影剂惯性空化阈值与其包膜参数之间的相关性; 以及4)研究超声联合造影剂微泡促进基因/药物转染效率并有效降低其生物毒性的相关机理.     

超声药物释放空化动力学行为研究

以直径1 μm的脂质体为空化研究对象,从修正的Rayleigh空化方程入手,研究机械系数(MI)对300 kHz和1 MHz超声作用时空化效应的影响。脂质体的药物释放以超声作用前后脂质体中钙黄绿素的荧光强度为量度。模拟结果表明:在微泡振荡过程中,由超声波驱动产生的负向最大泡壁运动速度促使微泡半径从最大快速减小接近于零,微泡积聚到最大能量。对于300 kHz和1 MHz的激励超声,存在一个拐点(MI)值,当MI小于接近0.4时,1 MHz微泡半径变化幅度强于300 kHz;当MI>0.4时,300 kHz微泡半径变化幅度强于1 MHz。这一结果预示在此范围内,300 kHz的药物释放效果好于1 MHz。本研究为超声空化效应研究及超声药物释放应用提供了理论依据。     

超声微泡低频动力学特性及其生物效应

理论上利用有耗散函数的Lagrange方程,建立了有壳微泡的R(t)运动方程,开展了自由空间中有壳微泡动力学特性的研究,表明微泡内外半径增量随声压的增大、超声频率的降低、初始内径的增大及壳厚的减薄而迅速增大。实验上,利用Mie散射技术在80°散射角和前向Mie散射检测新技术实验测量了微泡R(t)曲线;利用体视显微镜,实时观察了超声微泡对动物活体微血管损伤,开展了超声微泡生物效应的动物和细胞试验研究。结果表明:(1)超声作用下,微泡引起肿瘤中微血管壁周期性膨胀收缩而发生管壁破裂,形成血栓和微血管栓塞,抑制了肿瘤生长;(2)超声联合微泡可以破坏微血管内皮生长因子(VEGF)和肝癌细胞,可以减少肿瘤血管和癌细胞再生,因此,低频超声联合微泡技术是一种值得探索抑制肿瘤生长的新技术。     

激光协同聚焦超声辐照生物样品增强热效应的实验和理论研究

对中等强度聚焦超声在生物样品中产生的热效应以及激光协同超声增强热效应进行了实验和理论研究。实验上,对生物和仿生样品在超声作用和激光协同超声作用下加热情况进行测量,通过对比表明,激光协同超声作用于生物样品,引起空化效应以及温度升高更为明显。同时,理论上对聚焦超声在生物样品中衰减产生的热效应、超声空化以及激光协同超声增强空化及其产生热效应进行机理分析。通过对机理的分析表明,激光引起的光致核化使超声空化更易于产生,有效的增强空化效应,进而增强热效应。为对具体实验给出量化分析和估算,通过理论与实验结果相拟合,对超声传播引起的温度升高进行计算,并估算超声和激光协同超声产生空化微泡对加热效应的不同贡献,为空化效应在超声治疗中的贡献提供参考数据。      

超声振动珩磨作用下空化泡动力学及影响参数

为了合理利用超声振动珩磨作用下的空化效应,以磨削区单个空化泡为研究对象,考虑珩磨头合成扰动速度和珩磨压力的作用建立了磨削区空化泡的动力学模型。数值模拟了空化泡初始半径,珩磨压力,液体静压力和超声声压幅值对磨削区空化效应的影响。研究表明考虑超声振动珩磨作用时,空化泡膨胀的幅值会受到抑制,其溃灭时间也会缩短,而且较容易出现稳态空化。珩磨压力和液体静压力对磨削区空化主要起抑制作用,超声波声压幅值在一定范围内能够促进磨削区空化效果的提升。本文的研究为进一步理解超声振动珩磨的空化机理提供了理论支持。     

脉冲超声激励下SonoVue微泡的瞬态空化特性

将SonoVue微泡从临床疾病诊断拓展至治疗引起了诸多研究人员的兴趣。为了平衡治疗效率和生物安全性,深入理解声学参数和SonoVue微泡瞬态空化的关系至关重要。本研究自行制备仿体容器放置SonoVue微泡,使用1 MHz发射换能器激励其产生空化效应,另一个7.5 MHz的聚焦换能器接收声信号,经放大及高速数据采集后送上位机处理。通过深入分析信号的时频域特征,我们提出以宽带信号的能量及其随时间变化曲线的半高宽来表征瞬态空化的剂量(ICD)和相对持续时间(ICP),并确定:瞬态空化的发生和ICD依赖于峰值负声压,但ICP随峰值负声压的增加而减小;脉冲重复频率和脉冲持续时间都和ICD及ICP正相关;且脉冲持续时间的影响较大。这些结果有望为SonoVue微泡的治疗应用提供理论支持。      

Guided-Wave Two-Dimensional Acousto-Optic Scanner Using Proton-Exchanged Lithium Niobate Waveguide

Two-dimensional scanning of a 0.6328 mum guided-light beam has been realized using noncolinear acousto-optic (AO) coplanar Bragg diffraction together with colinear AO guided-mode to substrate radiation-mode conversion in a Z-cut Xpropagation LiNbO3 proton-exchanged (PE) waveguide. The two surface acoustic (SAW) waves utilized are at the center frequencies of 500 and 200 MHz, propagating in the Y and X axes, respectively. Two-dimensional scanning of approximately 720 resolvable light beam spots, namely, 18 40 (horizontal vertical) scanning, has been demonstrated using a light beam of 1.0 mm aperture. The total number of resolvable beam spots can be greatly increased from 720 by simply utilizing SAW transducers of larger bandwidth and a light beam of greater aperture. It should also be possible to significantly increase the diffraction efficiency from 3 % by optimizing the parameters of the PE waveguide and the SAWs.     

Hybrid Wavelength and Code Division Multiple Access in Optical Networks

A review of schemes for multiple access in fiber optic networks shows that a hybrid of wavelength and code division multiple access (WCDMA) combines the best features of both. In particular, the hybrid scheme retains the large information carrying capacity of wavelength division multiple access (WDMA) and flexibility of code division multiple access (CDMA). In this paper WDMA, optical CDMA (OCDMA), and WCDMA networks are discussed. In OCDMA networks, concept of incoherent and coherent coding including inverse decoding and matched filter is introduced. The delay performance of both WDMA and WCDMA networks, under the simple suboptimum access protocols based on cyclic search, is computed. It has been shown quantitatively that tuning delay significantly affects the delay performance of both WDMA and WCDMA networks. Futhermore, delay performance of WCDMA networks is always better than the WDMA networks for the same tuning delay, load, and number of users.     

Effect ofγ-radiation on the spectral luminescence characteristics of impure cadmium tungstate crystals

Results of a study of the effect of γ-radiation on the spectral luminescence properties of cadmium tungstate crystals doped with silver, bismuth, and molybdenum cations are presented. Spectral characteristics of the nondnnnoped crystals are briefly described. Absorption and photo and X-ray luminescence spectra of the crystals taken before and after exposure to γ-radiation (5.5·10⁴ Gy) are compared. It is found that the spectral characteristics of the crystals doped with silver, bismuth, and molybdenum cations do not change markedly after the exposure. The relation between the type of impurity-induced defects, individual characteristics of the impurity cations, and the character of the effect of γ-radiation on the spectral luminescence properties of impure crystals is analyzed (preliminarily). Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 64, No. 1, pp. 55–60, January–February, 1997.     

Femtosecond Transform-Limited Pulse Generation by Compensating for the Linear Chirp of SPM Spectra in Dispersion Shifted Fibers

A simple technique of pulse compression, based on the linear chirp compensation of self-phase modulation (SPM) spectra in dispersion shifted fibers, is demonstrated. The optimization procedure is carried out, for a short span of a single-mode fiber, using a parabolic law, which describes the behavior of the squared output pulse width versus the pump peak power in the case of Gaussian pulses. The experimental results give a minimum pulse duration of 233 fs, which is in good agreement with the model. Shorter and coherent pulses, down to 90 fs, have been obtained by inserting an interference filter at the optical output.     

Sorting of bending magnets for the SSRF booster

The Shanghai Synchrotron Radiation Facility(SSRF)booster ring,a full energy injector for the storage ring,is deigned to accelerate the electron beam energy from 150MeV to 3.5GeV that demands high extraction efficiency at the extraction energy with low beam loss rate when electrons are ramping.Closed orbit distortion(COD)caused by bending magnet field uniformity errors which affects the machine performance harmfully could be effectively reduced by bending magnet location sorting.Considering the affections of random errors in measurement,both ideal sorting and realistic sorting are studied based on measured bending magnet field uniformity errors and one reasonable combination of bending magnets which can reduce the horizontal COD by a factor of 5is given as the final installation sequence of the booster bending magnets in this paper.     

Measurement of nonlinear coefficient of optical fiber based on small chirped soliton transmission

We measure the waveform and phase curves of short optical pulses before and after transmission over different lengths of fibers by use of the pulse analyzer with the frequency-resolved optical gating (FROG),and numerically simulate pulse evolution under the experimental conditions.The nonlinear coefficient of the fiber is given by comparing the experimental results with the numerical ones.Difference between the experiment and numerical simulation is analyzed.     

Resonance scattering of canonical elastic shells in absorbing fluid medium

Resonance scattering of elastic spherical shell and cylindrical shell while the surrounding fluid medium has absorption is studied. The normal mode solution derived using exact elastic theory and the separation of variables is still applicable. However, the scattering form function has to be modified for the absorbing medium, otherwise the unreasonable result would be obtained. The backscattering form function in the absorbing medium is redefined, and the form function of elastic spherical and cylindrical shell with vacuum or solid matter filled is calculated in various absorption conditions. The results show that the absorption of surrounding fluid leads to notable attenuation of the coincidence resonances in the mid-frequency, but it has a little influence on the low-frequency resonance scattering induced by the filler inside the shell.     

Single-beam self-referenced phase-sensitive surface plasmon resonance sensor with high detection resolution

A versatile and low-cost single-beam self-referenced phase-sensitive surface plasmon resonance(SPR)sensing system with ultra-high resolution performance is presented.The system exhibits a root-mean-square phase fluctuation of ±0.0028.over a period of 45 min.i.e.a resolution of±5.2×10-9 refractive index units.The enhanced performance has been achieved through the incorporation of three design elements:a true single-beam configuration enabling complete self-referencing so that only the phase change associated with SPR gets detected,a differential measurement scheme to eliminate spurious signals not related to the sensor response,and the elimination of retardation drifts by incorporating temperature stabilization in the liquid crystal phase modulato .Our design should bring the detection sensitivity of non-labeling SPR biosensing closer to that achievable by conventional fluorescence-based techniques.     

Influences of SiO2 protective layers and annealing on the laser-induced damage threshold of Ta2O5 films

Ta2O5 films are prepared on BK7 substrates with conventional electron beam evaporation deposition.The effects of SiO2 protective layers and annealing on the laser-induced damage threshold (LIDT) of the films are investigated.The results show that SiO2 protective layers exert little influence on the electric field intensity(EFI)distribution,microstructure and microdefect density but increase the absorption slightly.Annealing iS effective on decreasing the microdefect density and the absorption of the films.Both SiO2 protective layers and annealing are beneficial to the damage resistance of the films and the latter is more effective to improve the LIDT.Moreover,the maximal LIDT of Ta2O5 films is achieved by the combination of SiO2 protective layers and annealing.