基于光镊技术的微细加工

光镊技术及其应用近年来有了很大的进步,目前已广泛应用于生物、医学、物理和化学等领域中,但在微细加工应用方面的研究国内外尚处于起步阶段.从光的力学效应出发,讨论了光镊的原理,提出了基于光镊技术实现磁加工的概念,接着分析了该微细加工方法的理论和加工机理,最后阐述了光镊在微细加工中的特点和巨大的发展前景.     

光镊技术及其在染色体研究中的应用

引入并介绍光镊的物理原理及其进展,结合详细的医学研究工作,总结了光镊技术在染色体中的具体应用情况。由于光镊具有无直接接触、无损伤等诸多优点,且光镊产生的力在皮牛顿量级,正好落在生物大分子相互作用力的范围,故用光镊捕获染色体的不同成分,可实现了DNA分子的扭转和打结,并实现了对人类染色体操控和鉴别。光镊技术有望成为在分子水平上对各种活细胞的检测、诊断的先进工具,具有非常广阔的前景。     

光镊驱动微转子

光镊技术已经成功应用于光学和微功能器件,但是,对光镊驱动复杂微转子所建模型尚不成熟。为了分析光镊的光驱动力和力矩,基于矩量法建立了一种新模型。基于此种模型的分析结果表明改变环境参量是提高光镊工作效率的方法之一,如微转子转动速率与光镊的激光功率成正比,与束腰半径成非线性关系。另一种可以大幅度提高光镊工作效率的方法是改变微转子的形状,数据表明"万字"形微转子的转动效率是相同尺寸的"十字"形转子转动效率的10^-7倍。此外,通过解析力场的分布状态,可得到光压力的主要作用面,为今后的微转子设计提供依据。新模型的另一个优点是耗费时间较少,对于模拟光镊驱动微功能器件具有通用性和柔性。     

利用单光纤光镊实现不同折射率的微粒分选

为解决在进行不同折射率的微粒分类时遇到的问题,本文提出了一种采用熔融法拉伸的抛物线型光纤探针,所得到的出射光场对于浸没在水溶液中的不同折射率的微粒具有不同的操作能力,可以达到微粒分类的目的。我们将波长为980 nm的激光通入光纤探针中,操控光纤在液体中实现对二氧化硅（SiO2）、聚苯乙烯（PS）和酵母菌细胞三种不同折射率的微粒及细胞的捕获和传输,进而实现不同微粒的分类。基本上实现了对三种微粒在1～10μm范围内的操控和分类。通过仿真验证了这种抛物线型光纤探针对三种微粒具有不同捕获能力,所得到的理论和实验结果保持一致。使用该方法对微粒进行分类,可以简化实验装置,并且在无标签混合光纤传感器的开发和传染病检测或细胞分类等方面有广泛应用。     

基于光纤光镊的长距离微粒可控操纵

在液体中灵活操纵微粒或细胞,特别是将细胞或微粒运输到指定位置,已经被证明在细胞分析、疾病诊断、药物递送等方面有着至关重要的作用。针对细胞或微粒非接触光学捕获的灵活性受限于光纤光镊操纵距离短的问题,提出了一种结构简单且具有长距离非接触可控操纵微粒的新型光纤光镊。利用加热和拉伸技术制作了类锥形平口光纤探针,980 nm的激光经过光纤探针后会对微粒产生大的散射力,将微粒逐渐推离光纤端口,同时借助反向流体阻力,在不移动光纤探针的情况下通过调节激光器光源的输出功率,对轴向位置上直径为6μm的聚苯乙烯微粒可以进行长达102.2μm的可控往返操纵,应用有限元法仿真了光镊的光场强度分布,并采用麦克斯韦应力张量法分析了光镊对微粒的作用力。实验和仿真结果表明,所提出的类锥形平口光镊是可行的。     

生命科学研究中的光镊技术

光镊诞生18年来,无论是技术本身还是它的应用都有了极大的进展.本文从光的力学效应出发,简要讨论了光镊的原理,介绍了光镊装置的基本结构,并对光镊的独特功能进行了分析,进而对光镊技术及其在生命科学中的应用现状和进一步发展作了评述和讨论.阐述了光镊在生命科学研究中的潜在地位和巨大的发展前景.     

BP神经网络用于光镊力的非线性修正研究

光镊是测量微小力的有效工具,力的测量范围和测量精度是光镊系统的重要指标。本研究提出运用BP神经网络方法对光镊系统的力的测量和标定进行非线性修正,并通过实际应用检验,证明BP神经网络方法对光镊系统力的测量进行非线性修正,不仅扩大了光镊系统力的测量范围,而且与多项式拟合方法相比,该方法的精度更高,从而有效提高了光镊系统的性能指标。     

光镊系统随机漂移建模和误差补偿

针对光镊系统本身噪声对测量精度的影响,提出了一种光镊系统随机漂移误差的有效补偿方法。首先,介绍了时间序列分析法和卡尔曼滤波技术,基于时间序列分析法建立了光镊的随机漂移误差模型;然后,用基于时间序列模型的卡尔曼滤波方法来减小该漂移误差。采用提出的方法对光镊设备实测数据的误差进行了补偿,结果表明：数据的误差方差由补偿前的188.90 nm²减小为8.41 nm²。计算补偿前后的艾伦方差可知,系统在平均时间为1 s时可使最小位移误差从 0.7 nm降低到0.1 nm。得到的结果显示：提出的滤波方法有效地抑制了光镊系统的漂移误差,将其用于双光镊对准可提高捕获光和探测光的对准精度,进而提高光镊系统的性能指标。     

采用玻尔兹曼统计法分析光阱刚度的测量精度

考虑高精度的光阱刚度测量是光阱力测量的关键,本文提出了采用玻尔兹曼统计法来分析光阱刚度的测量精度。首先,描述了实验室搭建的近红外光镊系统,并将其搭建在暗室中的气垫平台上,以便隔离光干扰和振动干扰。然后,用四象限光电探测器探测被光镊捕获的微球向后散射的光,并选用与溶液黏度无关的玻尔兹曼统计法计算样品池底面附近的光阱刚度。最后,分析和讨论了溶液温度的变化、四象限光电探测器的灵敏度、采样频率以及采样时间对光阱刚度测量精度的影响。理论分析及实验计算显示:溶液温度的变化对光阱刚度的测量影响很小,但四象限光电探测器的灵敏度对光阱刚度测量精度影响较大。考虑采样的完整性和数据处理速度,采样频率通常取为被捕获颗粒拐角频率的5~10倍。对于本文搭建的近红外光镊测量系统,采样时间取为1~7s时,可以保证高精度地测量光阱刚度。     

利用光镊系统实现纳米加工的理论和实验研究

阐述光镊形成的基本原理,利用几何光学和动量守恒定律对激光势阱中约10μm大小的高强度微粒子(如:金刚石、碳化硅、石英等)受力进行分析。同时建立了实验装置,通过操纵微粒子的运动,实现对硅表面的纳米加工,并通过实验比较,定性分析最佳加工条件(如:激光功率和加工基底参数)。     

The influence of lateral forces on the cell stiffness measurement by optical tweezers vertical indentation

We studied the lateral forces arising during the vertical indentation of the cell membrane by an optically trapped microbead, using back focal plane interferometry to determine force components in all directions. We analyzed the cell-microbead interaction and showed that indeed the force had also lateral components. Using the Hertz model, we calculated and compared the elastic moduli resulting from the total and vertical forces, showing that the differences are important and the total force should be considered. To confirm our results we analyzed cells from two breast cancer cell lines: MDA-MB-231 and HBL-100, known to have different cancer aggressiveness and hence stiffness.     

A hybrid total internal reflection fluorescence and optical tweezers microscope to study cell adhesion and membrane protein dynamics of single living cells

The dynamics of cell surface membrane proteins plays an important role in cell–cell interactions. The onset of the interaction is typically not precisely controlled by current techniques, making especially difficult the visualization of early-stage dynamics. We have developed a novel method where optical tweezers are used to trap cells and precisely control in space and time the initiation of interactions between a cell and a functionalized surface. This approach is combined with total internal reflection fluorescence microscopy to monitor dynamics of membrane bound proteins. We demonstrate an accuracy of ∼2 s in determining the onset of the interaction. Furthermore, we developed a data analysis method to determine the dynamics of cell adhesion and the organization of membrane molecules at the contact area. We demonstrate and validate this approach by studying the dynamics of the green fluorescent protein tagged membrane protein activated leukocyte cell adhesion molecule expressed in K562 cells upon interaction with its ligand CD6 immobilized on a coated substrate. The measured cell spreading is in excellent agreement with existing theoretical models. Active redistribution of activated leukocyte cell adhesion molecule is observed from a clustered to a more homogenous distribution upon contact initiation. This redistribution follows exponential decay behaviour with a characteristic time of 35 s.     

Kinetics of TmHU binding to DNA as observed by optical tweezers

The kinetics of binding for the histone-like protein TmHU (from Thermotoga maritima) to DNA is analyzed on a single molecule level by use of optical tweezers. For the reaction rate a pronounced concentration-dependence is found with an "all or nothing"-limit which suggests the cooperative nature of the binding-reaction. By analyzing the statistics of mechanically induced dissociation-events of TmHU from DNA multiple reaction sites are observed to become more likely with increasing TmHU concentration. This is interpreted as a hint for a secondary organizational level of the TmHU/DNA complex. The reaction rate of TmHU binding to DNA is remarkably higher than that of the HU protein from Escherichia coli which will be discussed.     

钙离子光时标守时技术研究

近年来光学频率标准(光钟)技术快速发展,国际时间频率咨询委员会计划于 2030 年用光钟重新定义“秒”,并提出了 技术路线,光时标的研究也成为时间频率领域的研究热点。 利用钙离子光钟驾驭微波氢钟,开展高精度光时标信号 TS(Ca + )产 生技术研究。 结果表明,钙离子光钟准连续稳定运行率可达 87% ,稳定度达 8×10 -17 / day。 对光钟和氢钟的频率比对测量分别 采用微波频率锁定方案(上转换)和光生超稳微波方案(下转换),上转换方案引入了并放大了噪声,测量数据比氢钟稳定度差, 而下转换方案产生超稳微波,测量数据频率稳定度与氢钟几乎重合,实现了光钟对氢钟的准确测量。 将测量得到的频差数据直 接置入相位微跃计,产生光时标 TS(Ca + ),独立运行的光时标 TS(Ca + )在一个月内与 UTC 偏差保持在 0. 6 ns 以内。 研究成果 为报送秒定义数据和驾驭自由原子时 TAI 提供技术基础,为提升我国光时标守时能力提供了宝贵的技术支持和工程经验。     

Shear force near-field optical microscope based on Q-controlled bimorph sensor for biological imaging in liquid

Shear force near‐field microscopy on biological samples in their physiological environment loses considerable sensitivity and resolution as a result of liquid viscous damping. Using a bimorph‐based cantilever sensor incorporating force feedback, as recently developed by us, gives an alternative force detection scheme for biological imaging in liquid. The dynamics and sensitivity of this sensor were theoretically and experimentally discussed. Driving the bimorph cantilever close to its resonance frequency with appropriate force feedback allows us to obtain a quality factor (Q‐factor) of up to 10³ in water, without changing its intrinsic resonance frequency and spring constant. Thus, the force detection sensitivity is improved. Shear force imaging on mouse brain sections and human skin tissues in liquid with an enhanced Q‐factor of 410 have shown a high sensitivity and stability. A resolution of about 50 nm has been obtained. The experimental results suggest that the system is reliable and particularly suitable for biological cell imaging in a liquid environment.     

基于声卡和Adobe Audition的动弹性模量测试方法研究

弹性模量是表征材料弹性性质的特征物理量,在工程应用中具有重要的作用。设计了基于声卡和Adobe Audition的材料动弹性模量测定的测试系统,基于声卡的数据采集系统由传感器、调理装置、计算机组成。对不同长度的等强度悬臂梁进行实验,利用Matlab软件进行实验数据分析,得到悬臂梁的固有频率,从而根据理论公式计算出材料的动弹性模量,并与有限元分析结果进行比较。实验结果表明该测试系统测量精度较高,该试验方法简单易行,具有较强的实用性。     

Impairment of cytoskeleton-dependent vesicle and organelle translocation in green algae: combined use of a microfocused infrared laser as microbeam and optical tweezers

A Nd‐YAG laser at 1064 nm is used as optical tweezers to move intracellular objects and a laser microbeam to cause impairment of cytoskeleton tracks and influence intracellular motions in desmidiaceaen green algae. Naturally occurring migrations of large nuclei are inhibited in Micrasterias denticulata and Pleurenterium tumidum when the responsible microtubules are targeted with a laser microbeam generating 180 mW power in the focal plane. Impairment of the microtubule tracks appears to be irreversible, as the nucleus cannot pass the former irradiated area in Pleurenterium or remains abnormally dislocated in Micrasterias. The actin filament‐dependent movement of secretory vesicles and smaller particles can be manipulated by the same IR‐laser at 90 mW when functioning as optical tweezers. In Closterium lunula particles are displaced from their cytoplasmic tracks for up to 10 µm but return to their tracks immediately after removing the light pressure gained by the optical tweezers. The cytoplasmic tracks consist of actin filament cables running parallel to the longitudinal axis of Closterium cells as depicted by Alexa phalloidin staining and confocal laser scanning microscopy. Dynamics and extensibility of the cytoplasmic strands connecting particles to the tracks are also demonstrated in the area of large vacuoles which are surrounded by actin filament bundles. In Micrasterias trapping of secretory vesicles by the optical tweezers causes irreversible malformations of the cell shape. The vesicle accumulation itself dissipates within 30 s after removing the optical tweezers, also indicating reversibility of the effects induced, in the case of actin filament‐mediated processes.     

Dynamic simulation of particles in optoelectronic tweezers based on the monte carlo method

Optoelectronic tweezers to manipulate cells and particles into a desirable arrangement have contributed to the concentration, separation, and transportation for biological investigations and applications. In this article, a novel numeric model is presented based on the Monte Carlo method for understanding the behavior of polystyrene beads. The polarization effects between an electric field and the dielectric particles are determined, obeying both random events and the energy reduction rule. The manipulated forces such as dipole-dipole electrostatic attraction forces and light-induced dielectrophoretic forces are analyzed in uniform and nonuniform electric fields. In addition to steady analysis, the dynamic behavior of the particles experiencing negative dielectrophoresis has been described so that this model may be used to solve for the particle transport in the time domain. The particle distribution in the optoelectronic tweezer chip is in good agreement with experimental results. The numerical model is expected to provide simulation software to predict the behavior of particles in future experiments.     

基于低相干光干涉的液体折射率测量

液体折射率是液体一个重要指标,介质中折射率的变化会影响光程,提出一种用低相干光干涉测量光程变化,进而测得折射率的方法。通过调节两束低相干光使它们之间的光程差在相干长度之内,将被测液体放入一束光路中,根据光电探测器得到的干涉信号可求得相应的光程变化量,进而得到待测液体的折射率。利用低相干光干涉测量折射率的方法,其测量和计算过程方便快捷,受外界限制因素小,在810nm波长下,对折射率的测量精度可以达到10-4量级以上,是测量各种液体折射率的有效方法。     

基于时间戳技术的光纤长度精确测量方法

本文提出了一种基于时间戳技术的光纤长度测量方法.利用IEEE1588精密时间同步协议的线路时延不对称导致同步时间偏差的原理,测量同步时间偏差,反推线路时延差.并通过一路已知长度的参考光纤,计算得到被测光纤的长度.同时利用时间同步协议的同步信号和延时请求信号测量机理对称的特点,交换来回两线路上的光纤,来均衡此两线路上光脉冲色散和光电探测器性能的不对称性.将客户端和服务器至于同一时基,来消除同步时间偏差中客户端和服务器时钟不一致的影响.最后利用该方法测量了两根长度为3 227.722m和25 491.522m的单模光纤,不确定度分别为0.578m和0.758m.故此测量方法精度高且范围大.