基于声镊子的细胞力学特性表征的理论和实验研究

项目来源

国家自然科学基金(NSFC)

项目主持人

刘晓宙

项目受资助机构

南京大学

项目编号

11774167

立项年度

2017

立项时间

未公开

研究期限

未知 / 未知

项目级别

国家级

受资助金额

66.00万元

学科

数理科学-声学-超声物理与技术

学科代码

A-A23-A2303

基金类别

面上项目

关键词

细胞表征 ; 声镊子 ; 力学特性 ; 弹性模量 ; 声辐射压力 ; acoustic tweezer ; acoustic radiation force ; cell characterization ; mechaical property ; elastic modulus

参与者

张古田;刘杰惠;何爱军;汪海宾;高莎;戚萌;罗本彪;陈珏光;崔骏

参与机构

南京大学;苏州大学

项目标书摘要:近年来生物细胞力学特性表征研究成为国际声学界研究的热点,它能揭示细胞力学特性变化与疾病的产生和发展的关系,因此是一个具有很强应用背景的基础性的研究课题。人们已经提出了一些理论和实验方法来获得生物细胞的力学响应,但对细胞的力学特性进行安全有效的表征仍然是一大挑战,迫切需要一个安全有效的表征方法。本项目拟采用声镊子来实现对细胞的力学特性进行安全有效的表征,我们将系统地研究肾小管上皮细胞在高频聚焦声场中的声辐射力特性,建立粘滞流体中声场中声辐射力模型,利用细胞力学模型对细胞的力学特性进行了理论预测、数值分析和实验验证。我们将研究肾小管上皮细胞在不同声压和渗透压条件下的力学特性,比较正常和病变细胞的粘弹性力学行为,为定量,无损进行生物细胞表征开辟一条新的途径,对这些问题的深入研究将有助于我们更深入地理解细胞的力学特性在生物组织中变化的物理本质,促进超声诊断技术的进一步发展。

Application Abstract: Biological cell mechanical property characterization has become an international hot topic in acoustic research in recent years,which can reveal the relationship between the change of the cell mechanical properties and the emergence and development of the diseases;therefore it is a basic research with strong background.People have provided a number of theoretical and experimental methods to get the mechanical response of cells,however,the safe and effective characterization of the mechanical properties of cells remains a major challenge,and there is an urgent need to get the method,which can come up with the safe and effective characterization of cells.In this project,the acoustic tweezer will be used to achieve the safe and effective characterization of the mechanical properties of cells.We will systematically study the characteristics of acoustic radiation force on renal tubular epithelial cells in high frequency focused ultrasonic field;establish the model of acoustic radiation force induced by sound field in viscous fluid.Using the model,the mechanical properties of cells will be theoretical predicted,numerical analyzed and experimental verified.We will research the mechanical characteristics of renal tubular epithelial cells at different sound pressures and different penetration pressures,and compare the viscous elastic behaviors between normal and biological cells,which will pave a new way to quantitative,nondestructive ultrasonic characterization of biological cells.The study will help us to deep understand the nature of the mechanical change of cells in biological tissues and promote the further development of ultrasound diagnosis technology.

项目受资助省

江苏省

项目结题报告(全文)

利用声辐射力对粒子的无损、非接触性操控作为一种新兴的粒子操控技术,是声学领域的研究热点之一。对声辐射力进行更深入全面地研究,可以使声辐射力操控技术在众多领域的应用得到实现,同时也能更好地实现相应器件和设备的微型化、集成化以及智能化。在此国家自然基金的资助下,该项目进展顺利。我们按预定计划进行了以下研究工作:(1)基于声波散射理论,研究了高斯驻波场中多层球粒子的声辐射力特性。(2)从声场散射入手,研究存在多个弹性粒子的高斯行波场中粒子受到的声辐射力。(3)针对阻抗边界附近粘弹性圆柱形粒子,在任意入射角传播的平面行波场所受的声辐射力和声辐射力矩进行了研究。(4)采用声辐射力方法,对人体泌尿系统的肾和膀胱两类正常与多组癌细胞进行了细胞变形的实验研究。(5)推导并给出了平面波以任意角入射到有界粘性流体中的自由圆柱形粒子的声辐射力。(6)对平面波入射时,粘性流体中自由球形粒子的声辐射力进行了推导,设计了相应的实验,以聚苯乙烯球形粒子为例,通过实验对其声辐射力进行了定量的测量,并将其与理论结果进行对比。(7)基于腹壁组织图像,利用k-Wave对超声波在腹壁组织区域传播时的声场进行数值模拟,获得了其声场分布,进而求得了组织中声辐射力分布情况。(8)从声波的散射理论出发,通过镜像原理和有限级数展开法等工具,研究单阻抗边界和双阻抗边界下柱形粒子和球形粒子的声辐射力特性,讨论了粒子本身特性、粒子与边界距离等因素对声辐射力函数的影响,并且在平面波入射的基础上讨论了以高斯波为代表的其他类型波束对粒子的声辐射力特性。(9)推导了任意阶X波照射下球形粒子上声辐射力的解析表达式,证明了非衍射波组合构造以X波为基波的远场声场的完整性和算法优越性。(10)研究两束艾利高斯波对圆柱形微粒子的声辐射力特性,详细推导了两束艾利高斯波的入射速度势,根据边界条件求得散射系数以及声辐射力表达式。本项目共发表论文29篇,其中SCI 24篇:包括刊物Scientific Reports,Ultrasonics,Wave Motion,New Journal of Physics,Physics of Fluid 和Physical Review Applied 等刊物上,出版专著1部,获得国家发明专利1项,另外申请6项国家发明专利。

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  • 1.基于水平可视图多元联合模体熵的多维EEG情感脑电信号识别

    • 关键词:
    • EEG;多路水平可视图;多元联合模体熵;情感识别;多维分析
    • 杨小冬;马志怡;任彦霖;陈梅辉;何爱军;王俊
    • 《中国科学:信息科学》
    • 2023年
    • 期刊

    目前,许多基于深度学习和神经网络的算法被应用于脑电(electroencephalogram, EEG)信号情感识别.然而,现有研究大多采用提取单维脑电信号特征的方法.随着多传感技术的更新,更具全面性和系统性的多维信号特征提取需求出现.本文尝试将复杂网络研究应用到多维情感脑电识别中,提出一种基于水平可视图多元联合模体熵的情感识别算法,该方法可以有效避免人工选取特征对实验结果的影响,保持原始序列的非线性动力学特征.首先利用水平可视图算法将多维情感脑电信号分别转换为多路可视图网络,提取模体熵特征识别情感脑电研究中的关键频带和关键通道.在此基础上,将水平可视图网络两两联合,提取多元水平联合模体熵向量,作为输入参数对情感脑电信号进行识别.由于情感脑电序列长度会对识别效果产生影响,我们将脑电信号切割成大小不一的窗口,对比不同窗口大小对分类准确率的影响.实验结果表明,当切割窗口大小为10 s时,多元水平联合模体熵对情感脑电信号的识别效果最佳,对积极脑电/消极脑电、积极脑电/中性脑电、消极脑电/中性脑电的分类准确率分别达到95.07%, 97.73%, 90.26%,优于其他二维连接参数.同时,三分类的准确率为93.67%,本文算法无论在识别复杂度和准确率上,与已有算法相比均有较大提高.

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  • 2.Acoustic radiation force on a rigid cylinder between two impedance boundaries in a viscous fluid

    • 关键词:
    • Acoustic emissions;Acoustic impedance;Acoustic radiators;Acoustic wave propagation;Acoustic wave scattering;Acoustic wave transmission;Cylinders (shapes);Microfluidics;Acoustic radiation force;Acoustic technology;Acoustics waves;Image theory;Impedance boundary;Microfluidics technology;Multiple-scattering;Particle manipulation;Rigid cylinder;Viscous fluids
    • Liu, Xinlei;Deng, Zhaoyu;Ma, Li;Liu, Xiaozhou
    • 《Nanotechnology and Precision Engineering》
    • 2022年
    • 5卷
    • 3期
    • 期刊

    Acoustofluidic technology combines acoustic and microfluidic technologies to realize particle manipulation in microchannels driven by acoustic waves, and the acoustic radiation force (ARF) with boundaries is important for particle manipulation in an acoustofluidic device. In the work reported here, the ARF on a free cylinder immersed in a viscous fluid with an incident plane wave between two impedance boundaries is derived analytically and calculated numerically. The influence of multiple scattering between the particle and the impedance boundaries is described by means of image theory, the finite-series method, and the translational addition theorem, and multiple scattering is included partly in image theory. The ARF on a free rigid cylinder in a viscous fluid is analyzed by numerical calculation, with consideration given to the effects of the distances from cylinder edge to boundaries, fluid viscosity, cylinder size, and boundary reflectivity. The results show that the interaction between the two boundaries and the cylinder makes the ARF change more violently with different frequencies, while increasing the viscosity can reduce the amplitude of the ARF in boundary space. This study provides a theoretical basis for particle manipulation by the ARF in acoustofluidics. © 2022 Author(s).

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  • 3.Acoustic three-terminal controller with amplitude control for nonlinear seismic metamaterials

    • 关键词:
    • Controllers;Finite element method;Metamaterials;Perturbation techniques;Seismic design;Seismology;Acoustic metamaterial;Amplitude control;Finite elements simulation;Low bandgap;Nonlinear seismics;Perturbation method;Poincare;Resonant acoustics;Terminal controllers;Theoretical calculations
    • Li, Yuanyuan;Liu, Jiancheng;Deng, Zhaoyu;Gong, Menyang;Huang, Kunqi;Lai, Yun;Liu, Xiaozhou
    • 《AIP Advances》
    • 2022年
    • 12卷
    • 7期
    • 期刊

    To design and optimize seismic metamaterials, the impacts of nonlinearity in different locations of locally resonant acoustic metamaterials on the dispersions and the variation of amplitude-dependent bandgaps are investigated in this paper. The research used theoretical calculations, namely, Lindstedt-Poincaré perturbation method and prediction method, and combined finite-element simulation. Summarizing from our research, the lower bandgap is sensitive when exposed to amplitude stimulation, when there arise nonlinear characteristics between matrices; while nonlinearity appears within the interior oscillator, amplitudes obtain a more intense influence on the bandgap, introducing an enormous magnitude of deviation between the upper bandgap and the lower bandgap. Based on the peculiar frequency-shift characteristics, an acoustic three-terminal controller is proposed as a conventional subsize acoustical device and nonlinear seismic metamaterials component. This controller enables the realization of modulating the value of output signals by adjusting the quantitative loading on the control port, without changing the input signals and the parameters of the apparatus validated with the finite-element simulation. The work may offer potential applications in low-frequency vibration reduction and external-controllable multi-functional acoustical devices.
    © 2022 Author(s).

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  • 4.Realizing the second harmonic acoustic focusing based on an artificial bubble array

    • 关键词:
    • Acoustic field measurement;Acoustic wave scattering;Diagnosis;Focusing;Harmonic analysis;Medical imaging;Ultrasonic imaging;Acoustic focusing;Acoustic Scattering;Bubble arrays;Field model;Fundamental harmonic;Multi scatterings;Non-linear acoustics;Non-linear vibrations;Second harmonics;Ultrasonic imaging technology
    • Deng, Zhaoyu;Zeng, Longsheng;Zhu, Xue-Feng;Liu, Xiaozhou
    • 《AIP Advances》
    • 2022年
    • 12卷
    • 6期
    • 期刊

    Ultrasonic imaging technologies possess extensive applications in modern medical diagnosis and treatment. In this paper, a designed artificial bubble array is utilized to establish a multi-scattering sound field model to describe the nonlinear vibration of the artificial bubble array, combining nonlinear acoustics and multi-scattering theory. With the results of the effective medium model, the correctness and reliability of the multi-scattering model are verified. Furthermore, under different incident frequencies and different bubble array parameters, the distributions of fundamental and second harmonic sound pressure fields produced by nonlinear vibration of the artificial bubble array are investigated. Via a judicious design of structural parameters, both fundamental and second harmonic acoustic focusing at specific locations inside the bubble array and second harmonic acoustic focusing outside the array under a specific incident frequency are realized. © 2022 Author(s).

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  • 5.Acoustic coding metamaterial based on non-uniform Mie resonators

    • 关键词:
    • ASYMMETRIC TRANSMISSION; REFLECTION; SOUND; MANIPULATION
    • Lan, Jun;Liu, Yunpeng;Wang, Tao;Li, Yifeng;Liu, Xiaozhou
    • 《APPLIED PHYSICS LETTERS》
    • 2022年
    • 120卷
    • 16期
    • 期刊

    Acoustic coding metamaterials have important applications in simplifying design procedure and providing a flexible approach to realize complicated functions. Here, we design a 1-bit coding metamaterial for flexibly manipulating the sound propagation path. The capability of subwavelength acoustic propagation control on coding metamaterial is attributed to the dipole-like characteristic of the Mie resonator. The Mie resonator with a subwavelength scale is constructed with a non-uniform structure, which can generate Mie resonance with dipole-like characteristic. Two kinds of coding elements are introduced by horizontally or vertically reversing the Mie resonator in each element. To verify the performance of the designed coding metamaterials, three specific metamaterial patterns are fabricated to give different trajectories of sound propagation. Our finding may open an avenue for designing acoustic metamaterials and is expected to design intelligent acoustic devices with exciting reconfigurable and programmable applications. Published under an exclusive license by AIP Publishing.

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  • 6.基于机器学习和超声成像的缺陷识别与分析

    • 关键词:
    • 超声相控阵;卷积神经网络;方向梯度直方图;支持向量机;机器学习
    • 李灏天;刘晓宙;何爱军
    • 《南京大学学报》
    • 2022年
    • 04期
    • 期刊

    为了量化分析样本中的缺陷,利用卷积神经网络(Convolutional Neural Network,CNN)结合阈值分割和深度优先搜索算法实现了对超声检测图像中样品内部缺陷的识别,将实际图像输入神经网络模型中,成功完成了对缺陷的标记,验证了模型的可靠性.利用Field Ⅱ对全矩阵捕获(Full Matrix Capture,FMC)过程及对数据以全聚焦成像方法(Total Focus Method,TFM)进行成像的过程进行了仿真模拟,获得了可用于机器学习的数据集.基于方向梯度直方图(Histogram of Oriented Gradient,HOG)提取了全聚焦成像结果图的图像特征,利用改进的支持向量机(Support Vector Machine,SVM)获得由图像预测缺陷半径的模型并对该模型进行了评价.结果表明,利用上述方法提取的缺陷半径信息精准度在0.1 mm,能够应用于缺陷半径的量化分析,预测误差主要来源于数据集两端,可以通过预处理算法进一步提升检测精度.

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  • 7.Realization of real-time directional radiation of acoustic wave with non-uniform Mie resonators

    • 关键词:
    • Acoustic metamaterial; directional sound radiation; non-uniform Mieresonator
    • Lan, Jun;Wang, Tao;Zhao, Ying;Liu, Xiaozhou;Wan, Xili;Liu, Yunpeng;Wang, Zixuan;Li, Yifeng
    • 《APPLIED PHYSICS EXPRESS》
    • 2022年
    • 15卷
    • 3期
    • 期刊

    In this study, we present a tunable metamaterial consisting of rotatable non-uniform Mie resonators (NMRs) with identical structures. The metamaterial can in real-time manipulate the direction of acoustic radiation and guarantee high transmission efficiency by simply changing the rotation angle of the NMR unit cells, which is induced by the anisotropic property of NMR. In addition, according to generalized Snell's law, the arbitrarily direction-scanning capability is realized by tuning the phase shift distribution along the metamaterial. Our proposed anisotropic metamaterial could contribute to designing a device for the emission and reception of acoustic waves in real-time.

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  • 8.Adjustable Magnetic-Control Design of a Metasurface for Sound Insulation

    • 关键词:
    • Acoustic properties;Metamaterials;Sound insulation;Active acoustic metamaterials;Adjustable;Contact control;Magnetic control;Magnetic-field;Magnetorheological;Magnetorheological metasurface;Metasurface;Non-contact;Performance
    • Xia, Pu;Lai, Yun;Liu, Xiaozhou
    • 《Frontiers in Mechanical Engineering》
    • 2022年
    • 7卷
    • 期刊

    Magnetic field is one efficient approach to realize non-contact control of materials. Here, we propose a type of membrane-based metasurface consisting of several parts of magnetorheological films embedded with magnetic particles, which enable non-contact control of sound insulation through magnetic field. The abundant degree of freedoms in membrane-type metamaterials are explored by considering composite structures. Through numerical calculations, we have investigated the effect of magnetic field excitation and film composition on the acoustic properties and the performance for sound insulation. We find an optimized model for better adjustability, wider acoustic band, and more balanced performance. Copyright © 2022 Xia, Lai and Liu.

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  • 9.Synergy of hypoxia relief and heat shock protein inhibition for phototherapy enhancement

    • 关键词:
    • Irradiation;Tumors;Diseases;Photosensitizers;Chemotherapy;Hyperthermia therapy;Proteins;Hydrophobicity;Infrared devices;Nanoparticles ;Heat resistance;Manganese oxide;Albumin nanoparticles;Anti-tumor efficacy;Clinical application;Hydrophobic interactions;Photodynamic therapy (PDT);Photothermal therapy;Therapeutic efficacy;Tumor microenvironment
    • Zhang, Gutian;Cheng, Wenting;Du, Lin;Xu, Chuanjun;Li, Jinlong
    • 《Journal of Nanobiotechnology》
    • 2021年
    • 19卷
    • 1期
    • 期刊

    Background: Phototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). However, the therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). In this study, we developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement. Results: Near-infrared photosensitizer (IR780) and gambogic acid (GA, Hsp90 inhibitor) were encapsulated into albumin nanoparticles via hydrophobic interaction, which was further deposited MnO2 on the surface to form IGM nanoparticles. Both in vitro and in vivo studies demonstrated that IGM could catalyze overexpress of hydrogen peroxide to relive hypoxic tumor microenvironment. With near infrared irradiation, the ROS generation was significantly increase for PDT enhancement. In addition, the release of GA was promoted by irradiation to bind with Hsp90, which could reduce cell tolerance to heat for PTT enhancement. As a result, IGM could achieve better antitumor efficacy with enhanced PDT and PTT. Conclusion: This study develops a facile approach to co-deliver IR780 and GA with self-assembled albumin nanoparticles, which could relive hypoxia and suppress Hsp for clinical application of cancer phototherapy. [Figure not available: see fulltext.].
    © 2020, The Author(s).

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  • 10.基于多路可视图的健康与心梗患者ECG信号复杂网络识别

    • 《物理学报》
    • 2021年
    • 期刊

    可视图(Visibility Graph, VG)算法已被证明是将时间序列转换为复杂网络的简单且高效的方法,其构成的复杂网络在拓扑结构中继承了原始时间序列的动力学特性。目前,单维时间序列的可视图分析已趋于成熟,但应用于复杂系统时,单变量往往无法描述系统的全局特征。本文提出一种新的多元时间序列分析方法,将心梗和健康人的12导联心电图(Electrocardiograph, ECG)信号转换为多路可视图,以每个导联为一个节点,两个导联构成可视图的层间互信息为连边权重,将其映射到复杂网络。由于不同人群的全连通网络表现为完全相同的拓扑结构,无法唯一表征不同个体的动力学特征,根据层间互信息大小重构网络,提取权重度和加权聚类系数,实现对不同人群12导联ECG信号的识别。为判断序列长度对识别效果的影响,引入多尺度权重度分布熵。由于健康受试者拥有更高的平均权重度和平均加权聚类系数,其映射网络表现为更加规则的结构、更高的复杂性和连接性,可以与心梗患者进行区分,两个参数的识别准确率均达到93.3%。

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