重大工程结构智能传感网络与健康监测系统的研究与应用

本文重点介绍了我国,特别是哈尔滨工业大学近年来有关重大工程结\\r 构智能传感网络与健康监测系统的一些研究与应用成果。主要内容包括：光纤光栅应变和温 度传感器、压电薄膜（PVDF）应变和裂缝监测传感器、疲劳累积传感器、形状记忆合金传感 器等智能传感器研究与应用; 无线传感器网络与无线传输技术及其工程应用; 碳纤维筋式 传感器与纤维增强?光纤光栅复合筋式应变传感器研究开发与应用;碳纤维和(或)纳米粒子 添料 形成的自感知水泥砂浆及其混凝土标准应变传感器的研究与开发;智能健康监测系统及其在 海洋平台结构、混凝土坝面、大跨桥梁以及大跨空间结构等实际工程中的应用。最后,介绍 了我国在重大工程结构智能健康监测领域方面研究立项的情况,并指出了进一步值得研究的 一些问题。     

Optofluidic characterization of marine algae using a microflow cytometer

The effects of global warming, pollution in river effluents, and changing ocean currents can be studied by characterizing variations in phytoplankton populations. We demonstrate the design and fabrication of a Microflow Cytometer for characterization of phytoplankton. Guided by chevron-shaped grooves on the top and bottom of a microfluidic channel, two symmetric sheath streams wrap around a central sample stream and hydrodynamically focus it in the center of the channel. The lasers are carefully chosen to provide excitation light close to the maximum absorbance wavelengths for the intrinsic fluorophores chlorophyll and phycoerythrin, and the excitation light is coupled to the flow cytometer through the use of an optical fiber. Fluorescence and light scatter are collected using two multimode optical fibers placed at 90-degree angles with respect to the excitation fiber. Light emerging from these collection fibers is directed through optical bandpass filters into photomultiplier tubes. The cytometer measured the optical and side scatter properties of Karenia b., Synechococcus sp., Pseudo-Nitzchia, and Alexandrium. The effect of the sheath-to-sample flow-rate ratio on the light scatter and fluorescence of these marine microorganisms was investigated. Reducing the sample flow rate from 200 μL/min to 10 μL/min produced a more tightly focused sample stream and less heterogeneous signals.     

Self-assembly-induced luminescence of Eu3+-complexes and application in bioimaging

Design and engineering of highly efficient emitting materials with assembly-induced luminescence, such as room-temperature phosphorescence (RTP) and aggregation-induced emission (AIE), have stimulated extensive efforts. Here, we propose a new strategy to obtain size-controlled Eu³⁺-complex nanoparticles (Eu-NPs) with self-assembly-induced luminescence (SAIL) characteristics without encapsulation or hybridization. Compared with previous RTP or AIE materials, the SAIL phenomena of increased luminescence intensity and lifetime in aqueous solution for the proposed Eu-NPs are due to the combined effect of self-assembly in confining the molecular motion and shielding the water quenching. As proof of concept, we also show that this system can be further applied in bioimaging, temperature measurement and HClO sensing. The SAIL activity of the rare-earth (RE) system proposed here offers a further step forward on the roadmap for the development of RE light conversion systems and their integration in bioimaging and therapy applications.     

A method to integrate patterned electrospun fibers with microfluidic systems to generate complex microenvironments for cell culture applications

The properties of a cell’s microenvironment are one of the main driving forces in cellular fate processes and phenotype expression invivo. The ability to create controlled cell microenvironments invitro becomes increasingly important for studying or controlling phenotype expression in tissue engineering and drug discovery applications. This includes the capability to modify material surface properties within well-defined liquid environments in cell culture systems. One successful approach to mimic extra cellular matrix is with porous electrospun polymer fiber scaffolds, while microfluidic networks have been shown to efficiently generate spatially and temporally defined liquid microenvironments. Here, a method to integrate electrospun fibers with microfluidic networks was developed in order to form complex cell microenvironments with the capability to vary relevant parameters. Spatially defined regions of electrospun fibers of both aligned and random orientation were patterned on glass substrates that were irreversibly bonded to microfluidic networks produced in poly-dimethyl-siloxane. Concentration gradients obtained in the fiber containing channels were characterized experimentally and compared with values obtained by computational fluid dynamic simulations. Velocity and shear stress profiles, as well as vortex formation, were calculated to evaluate the influence of fiber pads on fluidic properties. The suitability of the system to support cell attachment and growth was demonstrated with a fibroblast cell line. The potential of the platform was further verified by a functional investigation of neural stem cell alignment in response to orientation of electrospun fibers versus a microfluidic generated chemoattractant gradient of stromal cell-derived factor 1 alpha. The described method is a competitive strategy to create complex microenvironments invitro that allow detailed studies on the interplay of topography, substrate surface properties, and soluble microenvironment on cellular fate processes.     

分子生物传感器与细胞内分子影像

分子生物传感器是由生物大分子通过基因重组或DNA合成所构成的传感器,能够实时、可视化探测活细胞及活体内关键分子事件。目前研究热度高、应用广的分子生物传感器包括分子信标(MB)、共振能量转移系统(荧光共振能量转移和生物发光共振能量转移)和分子荧光互补系统(如双分子荧光互补、三分子荧光互补等)。文章介绍了这几类分子生物传感器的原理和特点,重点强调了它们在活细胞分子影像学中的运用,如:研究细胞内蛋白之间的相互作用,探索生物大分子在细胞中的定位、运动和动力学等。此外,还讨论了分子生物传感器的局限性和面临的挑战,并展望了未来发展方向。"眼见为实",分子生物传感器在这方面发挥独特的作用,它使我们前所未有地深入到细胞内部去观察生物分子事件乃至生物学过程,从而解答更多的生物学难题。     

Modeling and validation of autoinducer-mediated bacterial gene expression in microfluidic environments

Biosensors exploiting communication within genetically engineered bacteria are becoming increasingly important for monitoring environmental changes. Currently, there are a variety of mathematical models for understanding and predicting how genetically engineered bacteria respond to molecular stimuli in these environments, but as sensors have miniaturized towards microfluidics and are subjected to complex time-varying inputs, the shortcomings of these models have become apparent. The effects of microfluidic environments such as low oxygen concentration, increased biofilm encapsulation, diffusion limited molecular distribution, and higher population densities strongly affect rate constants for gene expression not accounted for in previous models. We report a mathematical model that accurately predicts the biological response of the autoinducer N-acyl homoserine lactone-mediated green fluorescent protein expression in reporter bacteria in microfluidic environments by accommodating these rate constants. This generalized mass action model considers a chain of biomolecular events from input autoinducer chemical to fluorescent protein expression through a series of six chemical species. We have validated this model against experimental data from our own apparatus as well as prior published experimental results. Results indicate accurate prediction of dynamics (e.g., 14% peak time error from a pulse input) and with reduced mean-squared error with pulse or step inputs for a range of concentrations (10 μM–30 μM). This model can help advance the design of genetically engineered bacteria sensors and molecular communication devices.     

Integrated dynamic wet spinning of core-sheath hydrogel fibers for optical-to-brain/tissue communications

Hydrogel optical light-guides have received substantial interest for applications such as deep-tissue biosensors, optogenetic stimulation and photomedicine due to their biocompatibility, (micro)structure control and tissue-like Young''s modulus. However, despite recent developments, large-scale fabrication with a continuous synthetic methodology, which could produce core-sheath hydrogel fibers with the desired optical and mechanical properties suitable for deep-tissue applications, has yet to be achieved. In this study, we report a versatile concept of integrated light-triggered dynamic wet spinning capable of continuously producing core-sheath hydrogel optical fibers with tunable fiber diameters, and mechanical and optical propagation properties. Furthermore, this concept also exhibited versatility for various kinds of core-sheath functional fibers. The wet spinning synthetic procedure and fabrication process were optimized with the rational design of the core/sheath material interface compatibility [core = poly(ethylene glycol diacrylate-co-acrylamide); sheath = Ca-alginate], optical transparency, refractive index and spinning solution viscosity. The resulting hydrogel optical fibers exhibited desirable low optical attenuation (0.18 ± 0.01 dB cm⁻¹ with 650 nm laser light), excellent biocompatibility and tissue-like Young''s modulus (<2.60 MPa). The optical waveguide hydrogel fibers were successfully employed for deep-tissue cancer therapy and brain optogenetic stimulation, confirming that they could serve as an efficient versatile tool for diverse deep-tissue therapy and brain optogenetic applications.     

反射式光纤电流传感器信号处理仿真研究

反射式电流传感器比一般的光纤电流传感器的灵敏度提高了4倍,并且集中了光纤电流传感器的优点,逐渐成为人们普遍关注的新型的电流传感器。但是光纤电流传感器的输出信号较小,一般都会被噪声淹没,因此对其的信号的后期处理是反射式光纤电流传感器必须解决的问题。介绍了反射式电流传感器系统组成,针对其输出信号特点进行处理,并在MATLAB中进行了信号处理仿真,取得了很好的效果。     

Bromo-oxidation reaction in enzyme-entrapped alginate hollow microfibers

In this article, the authors present the fabrication of an enzyme-entrapped alginate hollow fiber using a microfluidic device. Further use of enzyme-entrapped alginate hollow fibers as a biocatalytic microchemical reactor for chemical synthesis is also deliberated in this article. To ensure that there is no enzyme leaching from the fiber, fiber surfaces were coated with chitosan. To confine the mobility of reactants and products within the porous hollow fibers the entire fibers were embedded into a transparent polydimethylsiloxane (PDMS) matrix which also works as a support matrix. A vanadium-containing bromoperoxidase enzyme isolated from Corallina confusa was used as a model enzyme to demonstrate the use of these alginate hollow-fiber reactors in bromo-oxidation of phenol red to bromophenol blue at different dye flow rates. Stability of the entrapped enzyme at different temperatures and the effect of the chitosan coating on the reaction conversion were also studied. It was observed that molecules as big as 27 kDa can be retained in the matrix after coating with chitosan while molecules with molecular-weight of around 378 Da can still diffuse in and out of the matrix. The kinetic conversion rate in this microfluidic bioreactor was more than 41-fold faster when compared with the standard test-tube procedure.     

基于四波混频效应的光纤参量放大器的设计

利用一组非线性耦合方程,在理论上推导出了双泵浦、级联结构光纤参量放大器的增益表达式。研究表明,在双泵浦情况下,光纤参量放大器的增益与光纤长度、非线性系数以及泵浦光功率呈指数关系。采用多段光纤级联的结构,可以均衡光纤参量放大器增益的不平坦性,理论上得到了带宽达160nm、起伏小于1．5dB的理想增益。     

Enhanced electrohydrodynamic collapse of DNA due to dilute polymers

We experimentally demonstrate that addition of small, charge-neutral polymers to a buffer solution can promote compression of dilute solutions of single electrophoresing DNA. This phenomenon contrasts with the observed extension of DNA during capillary electrophoresis in dilute solutions of high molecular weight polymers. We propose these discrepancies in micron-scale DNA configurations arise from different nano-scale DNA-polymer collision events, controlled by solute polymer properties. We build upon theories previously proposed for intermolecular DNA aggregation in polymer-free solutions to develop scaling theories that describe trends seen in our data for intramolecular DNA compaction in dilute polymer solutions.     

Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor

Detection of proteins and nucleic acids is dominantly performed using optical fluorescence based techniques, which are more costly and timely than electrical detection due to the need for expensive and bulky optical equipment and the process of fluorescent tagging. In this paper, we discuss our study of the electrical properties of nucleic acids and proteins at the nanoscale using a nanoelectronic probe we have developed, which we refer to as the Nanoneedle biosensor. The nanoneedle consists of four thin film layers: a conductive layer at the bottom acting as an electrode, an oxide layer on top, and another conductive layer on top of that, with a protective oxide above. The presence of proteins and nucleic acids near the tip results in a decrease in impedance across the sensing electrodes. There are three basic mechanisms behind the electrical response of DNA and protein molecules in solution under an applied alternating electrical field. The first change stems from modulation of the relative permittivity at the interface. The second mechanism is the formation and relaxation of the induced dipole moment. The third mechanism is the tunneling of electrons through the biomolecules. The results presented in this paper can be extended to develop low cost point-of-care diagnostic assays for the clinical setting.     

More is different: how aggregation turns on the light

The reductionist approach to science seeks to understand the behaviour of systems by studying their individual components. It has been an enormously productive approach, but it is also widely acknowledged now that in some systems the behaviour of interest is an emergent property that cannot be discerned in the separate parts. Biology is replete with such examples, from the flocking of birds to the way metabolic processes in cells rely on a dynamic interplay of proteins and other components.Yet molecular systems do not have to be particularly complex before their properties become more than the sum of the parts. A classic example is the appearance of bulk-like metallic behaviour in small clusters of metal atoms only once they exceed a certain critical size. One of the most striking instances became apparent in 2001, when Ben Zhong Tang of the Hong Kong University of Science and Technology and his co-workers found that heterocyclic silicon-containing molecules called siloles become luminescent as nanoscopic aggregates even though the individual molecules in dilute solution do not emit light [1]. This looked like the opposite of the well-known phenomenon of concentration quenching, in which energy transfer between fluorescent (generally organic) molecules quenches the emission, an effect explained in 1955 [2]. Aggregation-induced ‘switching off’ is intuitively understandable, but ‘switching on’ due to aggregation was more surprising.Yet this effect of ‘aggregation-induced emission’ (AIE), as Tang and colleagues called it, was apparently seen, but not understood, much earlier [3]. In the 1850s, George Stokes noted that some inorganic complexes were fluorescent in the condensed, solid state but not in solution. At first, AIE was seen as a curiosity and deemed likely to be rare. However, subsequent research has shown not only that it is a rather common effect but also that it can be considered just one manifestation of a wide range of behaviours that arise from aggregation—leading to the proposed field of ‘aggregate science’, manifesting at the supramolecular level of small clusters or groups of molecules held together by relatively weak interactions. The field might be considered to illustrate George Whitesides’ notion of a chemistry ‘beyond the molecule’ [4], which bridges disciplines ranging from colloid science to crystal growth, nanotechnology, liquid crystals, photochemistry and molecular biology. At the same time, it echoes the famous insight of physicist Philip Anderson about emergent phenomena and the hierarchical nature of science: ‘More is different’ [5]. An ability to switch properties on and off by controlling intermolecular interactions and aggregation suggests various applications, from optical device technologies to targeted drugs for cancer therapy [6].NSR spoke to Ben Zhong Tang about the origins and possibilities of the field.

NSR: It seems you noticed AIE in 2001 by accident. How did it come about? Tang: Yes, it was serendipity. Development of new light emitters for the fabrication of organic light-emitting diodes was a hot topic at that time. We were trying to make new luminophores [light-emitting molecules] with high efficiencies and novel structures. Attracted by the aesthetically pleasing molecular structures of siloles, I asked my students to prepare various silole compounds. One day, a student told me that he could not see any luminescence when he used a UV lamp to excite the solution of the silole compound he had made. This surprised me, because I myself prepared a silole compound when I was a PhD student and I remember that its crystal was luminescent. I sensed something strange and immediately rushed to the lab. After careful verification and discussion with the student, we concluded that both of us were correct: the silole solution was not luminescent (his observation was right) but the silole powder was emissive (my memory was right). The non-luminescent molecular species in the dilute solution were induced to emit light through formation of aggregates in the solid state. We termed the process aggregation-induced emission or AIE.

A mesoscopic aggregate can have a property that its molecular species does not exhibit at all.—Ben Zhong Tang

Open in a separate windowBen Zhong Tang of the Hong Kong University of Science and Technology, China (Courtesy of Ben Zhong Tang). NSR: The phenomenon seemed to defy conventional expectations. Did you have trouble persuading others—or yourselves!—that it was real? Tang: I initially thought the student might have done something wrong, for the phenomenon he observed was totally unexpected. The common belief in the community of photophysics research is that luminescence from an organic dye generally weakens when its molecules are aggregated, an effect often referred to as aggregation-caused quenching or ACQ. I was shocked when I realized that the silole luminogen was showing an anti-ACQ effect. Still, I felt lucky to encounter something ‘abnormal’. No matter how odd a phenomenon seems, if it can be repeatedly observed, it must be real. We repeated our experiments many times and we were eventually convinced that the AIE effect was true. We had trouble, however, to understand why the silole luminogen behaved in such a way that was diametrically opposed to conventional ACQ. NSR: Are there any historical precedents—experiments in which this effect might have been glimpsed previously, but not recognized as such? Tang: When we published our first AIE paper in 2001, we thought the photophysical effect was unprecedented. However, we gradually found out that similar phenomena had been previously observed by other scientists. For example, in 1853 George Stokes reported in a paper that some inorganic platinocyanide salts ‘are sensitive’ (meaning luminescent in modern terminology) ‘only in the solid state’ but ‘their solutions look like mere water’. Sadly, he didn’t follow it up. Other people have made similar observations in different dye systems, which were, however, not recognized as AIE processes. Partially because of this, we had great difficulty in finding relevant reference papers. As a matter of fact, Stokes’ report, published in the mid-19th century, was not known to us until the middle of 2018. However, we are not surprised by those early works, for we understand that science progresses not in an abrupt but in a continuous way. George Smith articulated this: ‘Very few research breakthroughs are novel. Virtually all of them build on what went on before.’ A discovery is often a happenstance. We happened to have ‘rediscovered’ a very old but largely unnoticed phenomenon. Luckily, we grasped the opportunity to see more and farther by standing on the shoulders of giants.     

Sulfation modification of dopamine in brain regulates aggregative behavior of animals

Behavioral plasticity and the underlying neuronal plasticity represent a fundamental capacity of animals to cope with environmental stimuli. Behavioral plasticity is controlled by complex molecular networks that act under different layers of regulation. While various molecules have been found to be involved in the regulation of plastic behaviors across species, less is known about how organisms orchestrate the activity of these molecules as part of a coherent behavioral response to varying environments. Here we discover a mechanism for the regulation of animal behavioral plasticity involving molecular sulfation in the brain, a modification of substrate molecules by sulfotransferase (ST)-catalyzed addition of a sulfonate group (SO₃) from an obligate donor, 3^′-phosphoadenosine 5^′-phosphosulfate (PAPS) to the substrates. We investigated aggregation behaviors of migratory locusts, which are well-known for extreme phase change plasticity triggered by population density. The processes of PAPS biosynthesis acted efficiently on induction of locust behavioral transition: Inhibition of PAPS synthesis solicited a behavioral shift from gregarious to solitarious states; external PAPS dosage, by contrast, promoted aggregation in solitarious locusts. Genetic or pharmacological intervention in the sulfation catalyzation resulted into pronounced solitarizing effects. Analysis of substrate-specific STs suggests a widespread involvement of sulfated neurotransmitters in the behavioral response. Dopamine in the brain was finally identified to be actively sulfate conjugated, and the sulfate conjugation enhanced the free DA-mediated behavioral aggregation. Similar results in Caenorhabditis elegans and mice indicate that sulfation may be involved more broadly in the modulation of animal aggregation. These findings reveal a general mechanism that effectively regulates animal social-like behavioral plasticity, possibly through sulfation-mediated modification of neural networks.     

DNA combing on low-pressure oxygen plasma modified polysilsesquioxane substrates for single-molecule studies

Molecular combing and flow-induced stretching are the most commonly used methods to immobilize and stretch DNA molecules. While both approaches require functionalization steps for the substrate surface and the molecules, conventionally the former does not take advantage of, as the latter, the versatility of microfluidics regarding robustness, buffer exchange capability, and molecule manipulation using external forces for single molecule studies. Here, we demonstrate a simple one-step combing process involving only low-pressure oxygen (O₂) plasma modified polysilsesquioxane (PSQ) polymer layer to facilitate both room temperature microfluidic device bonding and immobilization of stretched single DNA molecules without molecular functionalization step. Atomic force microscopy and Kelvin probe force microscopy experiments revealed a significant increase in surface roughness and surface potential on low-pressure O₂ plasma treated PSQ, in contrast to that with high-pressure O₂ plasma treatment, which are proposed to be responsible for enabling effective DNA immobilization. We further demonstrate the use of our platform to observe DNA-RNA polymerase complexes and cancer drug cisplatin induced DNA condensation using wide-field fluorescence imaging.     

测定条件对旋光方向的影响

有些光学活性分子因测定条件不同而改变旋光方向,因为不同条件下,分子构象发生了变化。构象改变后,分子结构内的螺旋方向改变,其旋光方向随之改变。测定条件变化,若不影响化合物构象,则其旋光方向不改变。     

Trapping endoplasmic reticulum with amphiphilic AIE-active sensor via specific interaction of ATP-sensitive potassium (KATP)

The current aggregation-induced emission luminogens (AIEgens) sometimes suffer from poor targeting selectivity due to undesirable aggregation in the hydrophilic biosystem with ‘always-on’ fluorescence or unspecific aggregation in the lipophilic organelle with prematurely activated fluorescence. Herein, we report an unprecedented ‘amphiphilic AIEgen’ sensor QM-SO₃-ER based on the AIE building block of quinoline-malononitrile (QM). The introduced hydrophilic sulfonate group can well control the specific solubility in a hydrophilic system with desirable initial ‘fluorescence-off’ state. Moreover, the incorporated p-toluenesulfonamide group plays two roles: enhancing the lipophilic dispersity, and behaving as binding receptor to the adenosine triphosphate (ATP)-sensitive potassium (K_ATP) on the endoplasmic reticulum (ER) membrane to generate the docking assay confinement effect with targetable AIE signal. The amphiphilic AIEgen has for the first time settled down the predicament of unexpected ‘always-on’ fluorescence in the aqueous system and the untargetable aggregation signal in the lipophilic organelle before binding to ER, thus successfully overcoming the bottleneck of AIEgens'' targetability.     

湿敏元件及湿度传感器常用的测量装置

介绍了湿敏元件及湿度传感器常用的测量装置及基本原理。论述了各种测量装置所能达到的测量精度及适用范围。同时指出正确使用双压法、双温法、分流法及饱和盐法湿度发生装置对于保证湿敏元件及湿度传感器测量至关重要。     

Sub-nanomolar detection of thrombin activity on a microfluidic chip

Bioluminescence resonance energy transfer (BRET) is a form of Förster resonance energy transfer. BRET has been shown to support lower limits of detection than fluorescence resonance energy transfer (FRET) but, unlike FRET, has not been widely implemented on microfluidic devices for bioanalytical sensing. We recently reported a microscope-based microfluidic system for BRET-based biosensing, using a hybrid, high quantum-efficiency, form of BRET chemistry. This paper reports the first optical fiber-based system for BRET detection on a microfluidic chip, capable of quantifying photon emissions from the low quantum-efficiency BRET² system. We investigated the effects of varying core diameter and numerical aperture of optical fibers, as well as varying microfluidic channel design and measurement conditions. We optimized the set-up in order to maximize photon counts and minimize the response time. The optimized conditions supported measurement of thrombin activity, with a limit of detection of 20 pM, which is lower than the microscope-based system and more than 20 times lower than concentrations reported to occur in plasma clots.     

基于偏振特性的液晶光开关原理研究

根据液晶响应速度快,对光的吸收少的特性,研究了液晶光开关的工作原理,并与其它光开关相比较,分析了液晶光开关在光纤通讯方面的应用前景,建立了三种液晶光开关的物理模型。