基于纳米材料和核酸探针的生物传感方法研究
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摘要
生物传感是基于生物分子识别及其下游信号转换，进行目标物检测的一类分析方法，是分析化学与生命科学的交叉研究领域。比较其它分析方法，它有着不少的优势，特别是提高了分析速度和应用灵活性。随着电子、微电子和机械系统的进步，便携式、集成式传感元件的开发，生物传感方法研究有机会为医疗、环境保护、食品安全乃至公共安全等领域提供更多现场快速检测技术，为公共健康与公共安全建立第一道防线。近年来，纳米材料领域的研究不断突破，核酸识别、核酸信号放大新技术的持续发展，为构建高灵敏、高选择性、快速高效的新型生物传感器提供了更完美的设计思路，为生物传感器实现不同分析靶标的现场快速检测提供了更有力的平台。本论文则基于当前热点纳米材料-安全环保的碳、硅纳米材料发展了三个颇具医学诊断应用前景的生物传感器，其中有细胞信号通路重要蛋白酶-磷脂酶D的检测，活细胞及亚细胞器的示踪。首次报道非氧化石墨烯通过非共价生物功能化应用于生物传感器，也是首次展示利用无毒纳米材料对细胞能量工厂-线粒体的示踪研究效果能够堪比有机染料。同时涉及其中的纳米材料-非氧化石墨烯、硅量子点、碳量子点的生物功能化研究都各自有小小突破，为它们在生物传感领域的进一步发展奠定了良好的基础。本论文还基于核酸杂交技术和金属离子介导的核酸伪杂交技术分别发展了针对生物体重要的癌症标记物-小RNA（microRNA）和环境污染物-汞离子的检测技术，并且对这两种靶标都实现了高灵敏高选择性的分析。所有研究具体内容如下所述：
为了进一步拓宽非氧化石墨烯在生物传感领域的应用，在第2章中发展了一种新颖的双层磷脂膜修饰的非氧化石墨烯复合纳米材料，它是通过非氧化石墨烯大面积双面芳香环层和已合成的脂质体疏水烷烃夹层利用范德华力和疏水作用力形成的，并且这种非共价组装过程不会破坏石墨烯片层的电子大共轭结构，使得该复合纳米材料保留了非氧化石墨烯卓越的电学和光学性质，而表面修饰的磷脂膜层则能赋予非氧化石墨烯良好的生物相容性、亲水性以及表面可控修饰性，为石墨烯的生物功能化提供了一个新的实用平台，该复合纳米材料由磷脂双分子层和疏水的还原石墨烯片组成，类似细胞膜的结构，通过利用荧光素标记的磷脂掺杂在复合纳米材料中，发展出了一个检测磷脂酶D活性的荧光生物传感器。该生物传感器具有高灵敏和宽检测范围的特性，其检测下限低至0.010U/L，优于以往报道的磷脂酶D分析方法，而且基于该分析模式是一步均相法，该生物传感器有极好的适应性，操作简易性，以及进一步实现高通量分析和实时监测反应动力学的可能。
近年来，硅纳米材料凭借它出色的光学、电学、力学性质，以及表面可控修饰，可适应硅材料作为半导体材料的特殊应用吸引科学家们的关注，尤其是零维硅纳米材料-硅量子点，基于硅材料本身无毒、化学惰性、生物相容性极好，非常适合生物传感方法研究，特别是生物成像领域。在第3章中我们首先将电化学刻蚀法合成的硅点用双氧水氧化钝化，再用硅烷化试剂在有机相中进一步老化，转入水相后通过碳二亚胺/硫代琥珀酰亚胺法（EDC/Sulfo-NHS）进行表面水溶性改性获得最终的硅量子点，该硅量子点具有优良的水分散性，强荧光性（量子产率30%），合适的尺寸（约4nm），非常适合作为荧光成像探针。此方法合成的硅点表面保留了一定数目的伯胺基团，可以被进一步功能化。研究中我们分别选用线粒体定位试剂三苯基膦和溶酶体定位试剂吗啉通过EDC/Sulfo-NHS交联法进行功能化，并通过双光子荧光共聚焦成像证明其示踪效果，实验结果证明，通过和商品化的有机染料对比，硅量子点能准确、快速（约15min）对亚细胞器线粒体和溶酶体进行定位，且成像效果不逊于有机染料探针，此外线粒体会在细胞凋亡初期肿胀变圆，通过诱导剂引发细胞开始凋亡，实时成像图显示了我们合成的功能化硅量子点能很好的表现出线粒体形状变化，进行细胞早期凋亡的示踪，表明所得的硅量子点是有潜质的生物成像探针。
不光是石墨烯，碳纳米材料本身优异的光学、电学性质和无毒、化学惰性、容易代谢等特性促使科学家们不断开发其在生物、医学领域的应用。为了拓宽荧光碳纳米材料在生物成像领域的发展空间，在第4章中我们合成了一个双层脂质体共价修饰的新型碳量子点，因为传统一步法合成出的碳点往往光学性质差强人意（量子产率通常低于3%），很多相关研究都着力于表面改性提高量子产率，例如通过氨基修饰的低聚PEG（分子量约1500）进行表面钝化处理，实现光学性能提高（量子产率约10%），而我们则尝试用相似分子量的磷脂代替氨基修饰的低聚PEG对碳点进行表面钝化，首先通过传统的硝酸回流法合成出碳点前体，再通过超滤装置筛选出所需颗粒大小（小于10nm），同时合成好双分子层脂质体。利用碳二亚胺/硫代琥珀酰亚胺法将二棕榈酰磷脂酰乙醇胺的氨基末端和碳点表面因氧化产生的羧基官能团交联获得最终的碳量子点，该碳点荧光强度比同浓度的前体碳点高3倍，尺寸约5nm，表面包裹的脂质体双分子层能赋予碳点优异的生物相容性和表面可控修饰性。我们进一步探索了碳点在HeLa（宫颈癌）细胞中的双光子荧光共聚焦成像效果，实验证明碳点在细胞各个位置都有分布，说明该方法合成的碳点非常适合生物成像领域的应用。
汞是高毒的环境污染物，尤其是其具有高迁移性、持久性、甲基化作用性、生物富集性及食物链放大性等特点，即便是极微量的存在于环境中，对动植物及人类的健康也是极大的威胁。在第5章中我们设计了一个非常新颖的，基于T-Hg2+-T配位化学原理，能高灵敏性、高选择性的检测Hg2+的电化学传感器。这项技术的设计思路是邻近的聚T DNA链之间在Hg2+介导条件下产生的协同效应。先是在金电极表面，通过Au-S共价键，有序地组装上一层由8个碱基组成的全TDNA单链探针，且该探针末端标记了电活性物质二茂铁，当没有Hg2+存在时，电极表面的聚T DNA单链探针都各自柔软地趴在金盘表面，二茂铁离金表面很近，电子发生传递，可检测到二茂铁的氧化还原电流；当Hg2+存在条件下，最相邻的聚T DNA单链探针可以成对协同性地结合Hg2+，即电极表面的探针构象在Hg2+介导的T-T错配情况下可由柔软的单链结构变成相对刚性的类似双链的结构，这个构象变换导致了二茂铁远离电极表面，电子传递受阻，检测到的氧化还原电流大大减弱。通过电化学信号的变化可以判断Hg2+的存在及定量分析。这个检测机理已经得到毛细管电泳及一系列电化学方法的充分验证，并且实验结果表明这个传感器能在1nM-2μM之间高灵敏检测Hg2+，检测下限能到达0.5nM，优于本文中介绍的其它检测方法，并且这项技术表现出了优异的选择性，这是和传统的电化学方法（阳极溶出分析法ASV）检测Hg2+最大的区别，而且这个Hg2+传感器所需试剂非常少、操作步骤很简单又有着极好的再生性。如此经济高效的电化学传感器在实时现场监测环境中Hg2+将有很好的应用前景。
MicroRNA（miRNA）在生物体内发挥着至关重要的调控功能，不仅对细胞的生长、分化和凋亡有着重要的影响，而且还与许多疾病有着密切的关系，研究者发现在白血病、结肠直肠癌、乳腺癌和心血管障碍等疾病中，相关的miRNA都异常表达。由于miRNA具有核酸序列短、含量少以及相互之间序列相似性等特点，分析测试有一定的挑战性。传统的检测方法有印记杂交技术、微阵列检测技术、基于RCA信号放大的检测技术、阳离子聚合物等。本论文第6章中将向大家报道一种基于双重侵入式信号放大技术（Invader assay）高灵敏高选择性检测miRNA的方法。曾有研究小组基于侵入式信号放大技术检测miRNA，但是都是将目标miRNA作为模板探针，对相似序列的miRNA不能实现很好的区分，我们则是将miRNA设计成第一重循环放大的侵入式探针，并且miRNA的存在不会立即形成侵入位点重叠结构，我们借鉴缺口连接PCR的原理，设计出miRNA的3’端距侵入位点数个核苷酸距离。当加入嗜热性Taq聚合酶，和相应的核苷三磷酸，完全匹配的miRNA成为引物开始从3’端开始聚合延伸，当聚合延伸到达信号探针和模板探针杂交区的第一对核苷酸（即侵入位点），将距信号探针侵入位点核苷酸和后一位（靠近3’端）的核苷酸之间磷酸骨架断开，信号探针5’翘起一段离开，另一段也因杂交序列变短，与模板杂交稳定性减弱并脱离模板，遂成为第二重循环放大的引物探针。第二重循环放大类似第一重循环，也是需要借助聚合的作用才能形成侵入式结构，进一步消弱了非特异性切刻作用，第二重循环的信号探针是5’标记荧光团荧光素，中间标记淬灭基团的Taqman探针，但侵入式结构形成，信号探针5’翘起并带有荧光素修饰的“翼”离开，和信号探针中间标记的淬灭基团分开，荧光信号增强，并且与靶序列miRNA的浓度成正比。实验结果证明，该方法可以一步实现两重循环放大，检测灵敏度高，下限可达10fmol/L，尤其是能区分相似的miRNA序列，实现了难得的miRNA选择性检测。
Biosensor is based on the identification of biological molecules and theirdownstream signaling conversion, carried out a class of analytical methods to detectthe target, crossover study is to analyze the field of chemistry and the life sciences.Compared with other analysis methods, it has many advantages, especially toimprove the speed of analysis and application flexibility. With advances inelectronics, microelectronics and mechanical systems, portable, integrateddevelopment of the sensing element, biosensing methods have the opportunity tostudy medicine, environmental protection, food security,,and public safety and otherareas to provide more on-site rapid testing technology the establishment of the firstline of defense for the public health and public safety. In recent years, researcherscontinue to make breakthroughs in the field of nano-materials, nucleic acidrecognition, nucleic acid signal amplification continuous development of newtechnologies for building high sensitivity, high selectivity, fast and efficient novelbiosensor provides perfect design ideas, as biological sensors to achieve differenttarget site rapid testing analysis provides a more powerful platform. This paper isbased on the current hot spots of nanomaterials-environmentally safe carbon, siliconnanomaterials developed three medical diagnosis application prospects biosensors,including an important cell signaling pathway protease-phospholipase D testing, livecells and subcellular organelles tracer. It’s the first reported non-graphene oxidebiosensor applied by non-covalent biological function of the first to demonstrate theuse of non-toxic nanomaterials capablely traced of mitochondria-cellular energyfactory effectively comparable organic dyes. At the same time, which involvesnanomaterials-Non-graphene oxide, silicon quantum dots, bio-functional study ofcarbon quantum dots each have a small breakthrough, laid a better foundation fortheir further development in the field of bio-sensing. The paper is also based onnucleic acid hybridization technology and metal ion-mediated nucleic acidhybridization techniques, developed detection of important cancer markers-smallRNA (microRNA) of organisms and environmental pollutants-mercury ion, and thesetwo techniques are sensitive to target to achieve a high selectivity of the analysis.All research specific contents are as follows:
In order to further broaden the application of the non-oxidized graphene biosensor field, in Chapter2We developed a novel non-bilayer lipid membranesmodified graphene oxide nanocomposites, The nanoassembly can be prepared easilythrough noncovalent hydrophobic interactions between the lipid tails and thegraphene without destroying the electronic conjugation within the graphene sheet.This imparts the nanoassembly with desired electrical and optical properties withnonoxidative graphene. The phospholipid coating offers excellent biocompatibility,facile solubilization, and controlled surface modification for graphene, making thenanoassembly a useful platform for biofunctionalization of graphene. Thenanoassembly is revealed to comprise a bilayer of phospholipids with a reducedgraphene oxide sheet hosting in the hydrophobic interior, thus affording a uniqueplanar mimic of the cellular membrane. By using a fluorescein-labeled phospholipidin this nanoassembly, a fluorescence biosensor is developed for activity assay ofphospholipase D. The developed biosensor is demonstrated to have high sensitivity,wide dynamic range, and very low detection limit of0.010U/L. Moreover, becauseof its single-step homogeneous assay format it displays excellent robustness,improved assay simplicity and throughput, as well as intrinsic ability to real-timemonitor the reaction kinetics.
In recent years, silicon nanomaterials are a type of important semiconductornanomaterials with attractive properties including excellentoptical/electronic/mechanical properties, favorable biocompatibility, hugesurface-to-volume ratios, surface tailorability, improved multifunctionality, as wellas their compatibility with conventional silicon technology. Silicon materials ofvarious nanostructures have been developed, among which zero-dimensionalnanomaterials-silicon quantum dots (SiQDs) have been employed as an effectivenanomaterials for various sensing applications and fluorescent biological probes forin vitro and in vivo imaging because of their unique fluorescence properties,favorable biocompatibility, noncytotoxic property, fast response and goodreproducibility. In chapter3, we report a novel kind of SiQDs which simultaneouslypossess appropriate size (approximately4nm), excellent aqueous dispersibility, highphotoluminescent quantum yield (approximately30%), and excellent photostability.In brief, fluorescent SiQDs are facilely prepared via simple one-pot electrochemicaletching method, the as-prepared SiQDs can then be passivated by hydrogen peroxideoxidation, further aging using silane-coupling reagent in the organic phase prior tothe nanoparticles transfer to the aqueous phase, then the surface of the SiQDs aremodified with carbodiimide/sulfosuccinimidyl (EDC/Sulfo-NHS) to form final hydrophilic SiQDs. The decorated SiQDs retain a certain number of primary aminegroups, may be further functionalized with functional ligands, and they arewell-suited to fluorescence imaging. In this study, we have designed and synthesizedtwo high-friendly and brightly luminescent silicon quantum dots bioconjugates,silicon quantum dots-triphenylphosphonium (SiQDs-TPP) and silicon quantumdots-morpholine (SiQDs-MP), for subcellular mitochondrial/lysosomal imaging.Two-photon confocal imaging experiments establish that SiQDs-TPP and SiQDs-MPwere able to accurately and quickly localize to mitochondrias and lysosomesrespectively (approximately15min). Colocalization studies of the probe withcommercial colocalization reagents in cells demonstrated the specific localization ofthe probe in the mitochondrias or lysosomes with an extremely high colocalizationefficiency. Furthermore, SiQDs-TPP possesses high specificity to mitochondria,superior photostability, and appreciable tolerance to environmental change, allowingimaging and tracking of the mitochondrial morphological changes in a long period oftime, in early apoptosis, for example, swelling of mitochondria are clearly foundwhen the cells were treated with staurosporine(STS), a commonly used apoptosisinducer. The new imaging probe has a number of properties that far exceed those ofcommercial colocalization probes, including high mitochondrial/lysosomalselectivity, good fluorescence quantum yield, and, importantly, high photostability,high-friendly, all resulting in a superior figure of merit.
As the classical graphene, carbon-based nanomaterial offer several favorableattributes including excellent optical/electrical properties, non-toxic, chemicallyinert, easy metabolism and promise significant advantages in several imaging andbioanalytical applications. The aim of this work is to further extend the applicationof fluorescent carbon nanomaterials in the field of biochemistry to develop anfluorescent biological probes for cell imaging. In Chapter4, we synthesized a novelkind of carbon nanodots (C-dots), which specifically involves decorating thenanoparticles surface with liposome bilayer. Current synthetic methods of C-dots aremainly deficient in accurate control of uniform dimensions and the resulting surfacechemistry, as well as in obtaining fluorescent materials with low quantum yields(usually below3%). Most of these synthesis methods need post treatment withsurface passivating agents in order to improve their water solubility andluminescence property. Recently, for example, serious efforts have been made tosyntheses of amino-functionalized fluorescent C-dots (quantum yields wasapproximately10%) by amino-modified PEG (MW=1500). On the basis of the above, we first synthesis carbon precursor through conventional nitric acid reflux method,and obtain required uniform particle size (less than10nm) by ultrafiltration, andfurther tried a similar molecular weight phospholipids instead of amino-modifiedPEG for carbon surface passivation. The final C-dots were obtained via specialcoordination crosslinked interaction between dipalmitoyl phosphatidylethanolamine(DPPE) of the as-prepared liposome decorated C-dots and carboxyl functionalgroups that present in the surface of C-dots due to oxidation using the EDC andsulfo-NHS. The as-prepared liposome decorated C-dots have a uniform dispersionwithout apparent aggregation and particle diameters of5nm, excellentbiocompatibility, controllable surface modification and their fluorescence intensitythree times than carbon precursor at same concentration. We further explored thetracking and distribution of as-prepared liposome decorated C-dots in cells, Asexpected, after incubating with a C-dots-culture solution, two-photon confocalimaging experiments establish that the fluorescence in the Hela cells retained a highintensity, and distributed in various locations. This indicating the as-preparedliposome decorated C-dots ideally suited for applications in the field of biologicalimaging.
Mercury is highly toxic global environmental pollutants, especially its highmobility, persistence, the role of methylation, bioaccumulation and amplification ofthe characteristics of the food chain, even a very small amount present in theenvironment, for plants, animals and human health is also a great threat. In Chapter5, we have designed a very novel, based on T-Hg2+-T coordination chemistry, energysensitivity, high selectivity to detect Hg2+. This strategy exploited the cooperativityof proximate poly-T oligonucleotides in coordination with Hg2+. Ferrocene(Fc)-tagged poly-T oligonucleotides were immobilized on the electrode surface viaself-assembly of the terminal thiol moiety. In the presence of Hg2+, a pair of poly-Toligonucleotides could cooperatively coordinate with Hg2+, which triggered aconformational reorganization of the poly-T oligonucleotides from flexible singlestrands to relatively rigid duplexlike complexes, thus drawing the Fc tags away fromthe electrode with a substantially decreased redox current. The responsecharacteristics of the sensor were thoroughly investigated using capillaryelectrophoresis and electrochemical measurements. The results revealed that thesensor showed a sensitive response to Hg2+in a concentration range from1.0nM to2.0μM, with a detection limit of0.5nM. Also, this strategy afforded exquisiteselectivity for Hg2+against a reservoir of other environmentally related metal ions, compared to existinganodic stripping voltammetry (ASV) techniques. In addition,this sensor could be implemented using minimal reagents and working steps withexcellent reusability through mild regeneration procedure. It was expected that thiscost-effective electrochemical sensor might hold considerable potential in on-siteapplications of Hg2+detection.
MicroRNA (miRNA) plays a crucial regulatory function in vivo and importantimplications on not only for cell growth, differentiation and apoptosis, but alsorelated closely with many diseases. The researchers found that miRNA are related tothe abnormal expression in leukemia, colorectal cancer, breast cancer andcardiovascular disorders diseases. Since miRNA is very short, less content andsimilarity characteristics than other sequences, analytical testing has somechallenges. The traditional method included the mark detecting hybridization,microarray technology, based RCA signal amplification detection techniques, andcationic polymers. In Chapter6of this paper, we reported double-invasive signalamplification based on highly selective sensitive miRNA detection methods andtechniques (Invader assay). Other researchers had invasive signal amplificationtechnology to detect miRNA, but their template can not achieve a good distinctionwith similar miRNA sequences. We designed the first heavy sucked miRNA invasiveprobe amplification cycle, and there is not formed immediately invade miRNA locioverlapped structure, we can learn the principles of notches ligated PCR, design ofmiRNA3' end from the intrusion bit points nucleotides distance. When thethermophilic Taq polymerase was added, and the corresponding nucleosidetriphosphates, miRNA become fully matched primer extension to initiatepolymerization when the polymerization to the5' end of the signal probe and probehybridizing region of the template (invasion locus), Taq polymerase5'-3'exonuclease activity began to play a role in the invasion site nucleotide probe signala (near the3' end) of the disconnect between the nucleotide and the phosphatebackbone, the signal probe5' tilt leave, but also because of another section of shortersequences hybridize with a template from the template and hybrid stability weakened,became the second heavy cycle amplification primers probes. The second cycle ofamplification similar to the first heavy weight cycling, also needs the role ofpolymerization to form intrusive structure, and further weaken the role ofnon-specific nicking, the second re-circulation of the probe signal is5' fluorophorelabeled fluorescein, Taqman probes labeled quenching intermediate groups, butintrusive structure formation, the signal probe5' cocked and with fluorescein modified left, middle, and signal probes labeled quencher separate fluorescencesignal enhancement and is proportional to the concentration of the target miRNAsequence. Experimental results show that the method can achieve double loopamplification step, high detection sensitivity, the lower limit of up to10fmol/L, inparticular, can distinguish with similar miRNA sequences, achieved a rare miRNAselective detection.
为了进一步拓宽非氧化石墨烯在生物传感领域的应用，在第2章中发展了一种新颖的双层磷脂膜修饰的非氧化石墨烯复合纳米材料，它是通过非氧化石墨烯大面积双面芳香环层和已合成的脂质体疏水烷烃夹层利用范德华力和疏水作用力形成的，并且这种非共价组装过程不会破坏石墨烯片层的电子大共轭结构，使得该复合纳米材料保留了非氧化石墨烯卓越的电学和光学性质，而表面修饰的磷脂膜层则能赋予非氧化石墨烯良好的生物相容性、亲水性以及表面可控修饰性，为石墨烯的生物功能化提供了一个新的实用平台，该复合纳米材料由磷脂双分子层和疏水的还原石墨烯片组成，类似细胞膜的结构，通过利用荧光素标记的磷脂掺杂在复合纳米材料中，发展出了一个检测磷脂酶D活性的荧光生物传感器。该生物传感器具有高灵敏和宽检测范围的特性，其检测下限低至0.010U/L，优于以往报道的磷脂酶D分析方法，而且基于该分析模式是一步均相法，该生物传感器有极好的适应性，操作简易性，以及进一步实现高通量分析和实时监测反应动力学的可能。
近年来，硅纳米材料凭借它出色的光学、电学、力学性质，以及表面可控修饰，可适应硅材料作为半导体材料的特殊应用吸引科学家们的关注，尤其是零维硅纳米材料-硅量子点，基于硅材料本身无毒、化学惰性、生物相容性极好，非常适合生物传感方法研究，特别是生物成像领域。在第3章中我们首先将电化学刻蚀法合成的硅点用双氧水氧化钝化，再用硅烷化试剂在有机相中进一步老化，转入水相后通过碳二亚胺/硫代琥珀酰亚胺法（EDC/Sulfo-NHS）进行表面水溶性改性获得最终的硅量子点，该硅量子点具有优良的水分散性，强荧光性（量子产率30%），合适的尺寸（约4nm），非常适合作为荧光成像探针。此方法合成的硅点表面保留了一定数目的伯胺基团，可以被进一步功能化。研究中我们分别选用线粒体定位试剂三苯基膦和溶酶体定位试剂吗啉通过EDC/Sulfo-NHS交联法进行功能化，并通过双光子荧光共聚焦成像证明其示踪效果，实验结果证明，通过和商品化的有机染料对比，硅量子点能准确、快速（约15min）对亚细胞器线粒体和溶酶体进行定位，且成像效果不逊于有机染料探针，此外线粒体会在细胞凋亡初期肿胀变圆，通过诱导剂引发细胞开始凋亡，实时成像图显示了我们合成的功能化硅量子点能很好的表现出线粒体形状变化，进行细胞早期凋亡的示踪，表明所得的硅量子点是有潜质的生物成像探针。
不光是石墨烯，碳纳米材料本身优异的光学、电学性质和无毒、化学惰性、容易代谢等特性促使科学家们不断开发其在生物、医学领域的应用。为了拓宽荧光碳纳米材料在生物成像领域的发展空间，在第4章中我们合成了一个双层脂质体共价修饰的新型碳量子点，因为传统一步法合成出的碳点往往光学性质差强人意（量子产率通常低于3%），很多相关研究都着力于表面改性提高量子产率，例如通过氨基修饰的低聚PEG（分子量约1500）进行表面钝化处理，实现光学性能提高（量子产率约10%），而我们则尝试用相似分子量的磷脂代替氨基修饰的低聚PEG对碳点进行表面钝化，首先通过传统的硝酸回流法合成出碳点前体，再通过超滤装置筛选出所需颗粒大小（小于10nm），同时合成好双分子层脂质体。利用碳二亚胺/硫代琥珀酰亚胺法将二棕榈酰磷脂酰乙醇胺的氨基末端和碳点表面因氧化产生的羧基官能团交联获得最终的碳量子点，该碳点荧光强度比同浓度的前体碳点高3倍，尺寸约5nm，表面包裹的脂质体双分子层能赋予碳点优异的生物相容性和表面可控修饰性。我们进一步探索了碳点在HeLa（宫颈癌）细胞中的双光子荧光共聚焦成像效果，实验证明碳点在细胞各个位置都有分布，说明该方法合成的碳点非常适合生物成像领域的应用。
汞是高毒的环境污染物，尤其是其具有高迁移性、持久性、甲基化作用性、生物富集性及食物链放大性等特点，即便是极微量的存在于环境中，对动植物及人类的健康也是极大的威胁。在第5章中我们设计了一个非常新颖的，基于T-Hg2+-T配位化学原理，能高灵敏性、高选择性的检测Hg2+的电化学传感器。这项技术的设计思路是邻近的聚T DNA链之间在Hg2+介导条件下产生的协同效应。先是在金电极表面，通过Au-S共价键，有序地组装上一层由8个碱基组成的全TDNA单链探针，且该探针末端标记了电活性物质二茂铁，当没有Hg2+存在时，电极表面的聚T DNA单链探针都各自柔软地趴在金盘表面，二茂铁离金表面很近，电子发生传递，可检测到二茂铁的氧化还原电流；当Hg2+存在条件下，最相邻的聚T DNA单链探针可以成对协同性地结合Hg2+，即电极表面的探针构象在Hg2+介导的T-T错配情况下可由柔软的单链结构变成相对刚性的类似双链的结构，这个构象变换导致了二茂铁远离电极表面，电子传递受阻，检测到的氧化还原电流大大减弱。通过电化学信号的变化可以判断Hg2+的存在及定量分析。这个检测机理已经得到毛细管电泳及一系列电化学方法的充分验证，并且实验结果表明这个传感器能在1nM-2μM之间高灵敏检测Hg2+，检测下限能到达0.5nM，优于本文中介绍的其它检测方法，并且这项技术表现出了优异的选择性，这是和传统的电化学方法（阳极溶出分析法ASV）检测Hg2+最大的区别，而且这个Hg2+传感器所需试剂非常少、操作步骤很简单又有着极好的再生性。如此经济高效的电化学传感器在实时现场监测环境中Hg2+将有很好的应用前景。
MicroRNA（miRNA）在生物体内发挥着至关重要的调控功能，不仅对细胞的生长、分化和凋亡有着重要的影响，而且还与许多疾病有着密切的关系，研究者发现在白血病、结肠直肠癌、乳腺癌和心血管障碍等疾病中，相关的miRNA都异常表达。由于miRNA具有核酸序列短、含量少以及相互之间序列相似性等特点，分析测试有一定的挑战性。传统的检测方法有印记杂交技术、微阵列检测技术、基于RCA信号放大的检测技术、阳离子聚合物等。本论文第6章中将向大家报道一种基于双重侵入式信号放大技术（Invader assay）高灵敏高选择性检测miRNA的方法。曾有研究小组基于侵入式信号放大技术检测miRNA，但是都是将目标miRNA作为模板探针，对相似序列的miRNA不能实现很好的区分，我们则是将miRNA设计成第一重循环放大的侵入式探针，并且miRNA的存在不会立即形成侵入位点重叠结构，我们借鉴缺口连接PCR的原理，设计出miRNA的3’端距侵入位点数个核苷酸距离。当加入嗜热性Taq聚合酶，和相应的核苷三磷酸，完全匹配的miRNA成为引物开始从3’端开始聚合延伸，当聚合延伸到达信号探针和模板探针杂交区的第一对核苷酸（即侵入位点），将距信号探针侵入位点核苷酸和后一位（靠近3’端）的核苷酸之间磷酸骨架断开，信号探针5’翘起一段离开，另一段也因杂交序列变短，与模板杂交稳定性减弱并脱离模板，遂成为第二重循环放大的引物探针。第二重循环放大类似第一重循环，也是需要借助聚合的作用才能形成侵入式结构，进一步消弱了非特异性切刻作用，第二重循环的信号探针是5’标记荧光团荧光素，中间标记淬灭基团的Taqman探针，但侵入式结构形成，信号探针5’翘起并带有荧光素修饰的“翼”离开，和信号探针中间标记的淬灭基团分开，荧光信号增强，并且与靶序列miRNA的浓度成正比。实验结果证明，该方法可以一步实现两重循环放大，检测灵敏度高，下限可达10fmol/L，尤其是能区分相似的miRNA序列，实现了难得的miRNA选择性检测。
Biosensor is based on the identification of biological molecules and theirdownstream signaling conversion, carried out a class of analytical methods to detectthe target, crossover study is to analyze the field of chemistry and the life sciences.Compared with other analysis methods, it has many advantages, especially toimprove the speed of analysis and application flexibility. With advances inelectronics, microelectronics and mechanical systems, portable, integrateddevelopment of the sensing element, biosensing methods have the opportunity tostudy medicine, environmental protection, food security,,and public safety and otherareas to provide more on-site rapid testing technology the establishment of the firstline of defense for the public health and public safety. In recent years, researcherscontinue to make breakthroughs in the field of nano-materials, nucleic acidrecognition, nucleic acid signal amplification continuous development of newtechnologies for building high sensitivity, high selectivity, fast and efficient novelbiosensor provides perfect design ideas, as biological sensors to achieve differenttarget site rapid testing analysis provides a more powerful platform. This paper isbased on the current hot spots of nanomaterials-environmentally safe carbon, siliconnanomaterials developed three medical diagnosis application prospects biosensors,including an important cell signaling pathway protease-phospholipase D testing, livecells and subcellular organelles tracer. It’s the first reported non-graphene oxidebiosensor applied by non-covalent biological function of the first to demonstrate theuse of non-toxic nanomaterials capablely traced of mitochondria-cellular energyfactory effectively comparable organic dyes. At the same time, which involvesnanomaterials-Non-graphene oxide, silicon quantum dots, bio-functional study ofcarbon quantum dots each have a small breakthrough, laid a better foundation fortheir further development in the field of bio-sensing. The paper is also based onnucleic acid hybridization technology and metal ion-mediated nucleic acidhybridization techniques, developed detection of important cancer markers-smallRNA (microRNA) of organisms and environmental pollutants-mercury ion, and thesetwo techniques are sensitive to target to achieve a high selectivity of the analysis.All research specific contents are as follows:
In order to further broaden the application of the non-oxidized graphene biosensor field, in Chapter2We developed a novel non-bilayer lipid membranesmodified graphene oxide nanocomposites, The nanoassembly can be prepared easilythrough noncovalent hydrophobic interactions between the lipid tails and thegraphene without destroying the electronic conjugation within the graphene sheet.This imparts the nanoassembly with desired electrical and optical properties withnonoxidative graphene. The phospholipid coating offers excellent biocompatibility,facile solubilization, and controlled surface modification for graphene, making thenanoassembly a useful platform for biofunctionalization of graphene. Thenanoassembly is revealed to comprise a bilayer of phospholipids with a reducedgraphene oxide sheet hosting in the hydrophobic interior, thus affording a uniqueplanar mimic of the cellular membrane. By using a fluorescein-labeled phospholipidin this nanoassembly, a fluorescence biosensor is developed for activity assay ofphospholipase D. The developed biosensor is demonstrated to have high sensitivity,wide dynamic range, and very low detection limit of0.010U/L. Moreover, becauseof its single-step homogeneous assay format it displays excellent robustness,improved assay simplicity and throughput, as well as intrinsic ability to real-timemonitor the reaction kinetics.
In recent years, silicon nanomaterials are a type of important semiconductornanomaterials with attractive properties including excellentoptical/electronic/mechanical properties, favorable biocompatibility, hugesurface-to-volume ratios, surface tailorability, improved multifunctionality, as wellas their compatibility with conventional silicon technology. Silicon materials ofvarious nanostructures have been developed, among which zero-dimensionalnanomaterials-silicon quantum dots (SiQDs) have been employed as an effectivenanomaterials for various sensing applications and fluorescent biological probes forin vitro and in vivo imaging because of their unique fluorescence properties,favorable biocompatibility, noncytotoxic property, fast response and goodreproducibility. In chapter3, we report a novel kind of SiQDs which simultaneouslypossess appropriate size (approximately4nm), excellent aqueous dispersibility, highphotoluminescent quantum yield (approximately30%), and excellent photostability.In brief, fluorescent SiQDs are facilely prepared via simple one-pot electrochemicaletching method, the as-prepared SiQDs can then be passivated by hydrogen peroxideoxidation, further aging using silane-coupling reagent in the organic phase prior tothe nanoparticles transfer to the aqueous phase, then the surface of the SiQDs aremodified with carbodiimide/sulfosuccinimidyl (EDC/Sulfo-NHS) to form final hydrophilic SiQDs. The decorated SiQDs retain a certain number of primary aminegroups, may be further functionalized with functional ligands, and they arewell-suited to fluorescence imaging. In this study, we have designed and synthesizedtwo high-friendly and brightly luminescent silicon quantum dots bioconjugates,silicon quantum dots-triphenylphosphonium (SiQDs-TPP) and silicon quantumdots-morpholine (SiQDs-MP), for subcellular mitochondrial/lysosomal imaging.Two-photon confocal imaging experiments establish that SiQDs-TPP and SiQDs-MPwere able to accurately and quickly localize to mitochondrias and lysosomesrespectively (approximately15min). Colocalization studies of the probe withcommercial colocalization reagents in cells demonstrated the specific localization ofthe probe in the mitochondrias or lysosomes with an extremely high colocalizationefficiency. Furthermore, SiQDs-TPP possesses high specificity to mitochondria,superior photostability, and appreciable tolerance to environmental change, allowingimaging and tracking of the mitochondrial morphological changes in a long period oftime, in early apoptosis, for example, swelling of mitochondria are clearly foundwhen the cells were treated with staurosporine(STS), a commonly used apoptosisinducer. The new imaging probe has a number of properties that far exceed those ofcommercial colocalization probes, including high mitochondrial/lysosomalselectivity, good fluorescence quantum yield, and, importantly, high photostability,high-friendly, all resulting in a superior figure of merit.
As the classical graphene, carbon-based nanomaterial offer several favorableattributes including excellent optical/electrical properties, non-toxic, chemicallyinert, easy metabolism and promise significant advantages in several imaging andbioanalytical applications. The aim of this work is to further extend the applicationof fluorescent carbon nanomaterials in the field of biochemistry to develop anfluorescent biological probes for cell imaging. In Chapter4, we synthesized a novelkind of carbon nanodots (C-dots), which specifically involves decorating thenanoparticles surface with liposome bilayer. Current synthetic methods of C-dots aremainly deficient in accurate control of uniform dimensions and the resulting surfacechemistry, as well as in obtaining fluorescent materials with low quantum yields(usually below3%). Most of these synthesis methods need post treatment withsurface passivating agents in order to improve their water solubility andluminescence property. Recently, for example, serious efforts have been made tosyntheses of amino-functionalized fluorescent C-dots (quantum yields wasapproximately10%) by amino-modified PEG (MW=1500). On the basis of the above, we first synthesis carbon precursor through conventional nitric acid reflux method,and obtain required uniform particle size (less than10nm) by ultrafiltration, andfurther tried a similar molecular weight phospholipids instead of amino-modifiedPEG for carbon surface passivation. The final C-dots were obtained via specialcoordination crosslinked interaction between dipalmitoyl phosphatidylethanolamine(DPPE) of the as-prepared liposome decorated C-dots and carboxyl functionalgroups that present in the surface of C-dots due to oxidation using the EDC andsulfo-NHS. The as-prepared liposome decorated C-dots have a uniform dispersionwithout apparent aggregation and particle diameters of5nm, excellentbiocompatibility, controllable surface modification and their fluorescence intensitythree times than carbon precursor at same concentration. We further explored thetracking and distribution of as-prepared liposome decorated C-dots in cells, Asexpected, after incubating with a C-dots-culture solution, two-photon confocalimaging experiments establish that the fluorescence in the Hela cells retained a highintensity, and distributed in various locations. This indicating the as-preparedliposome decorated C-dots ideally suited for applications in the field of biologicalimaging.
Mercury is highly toxic global environmental pollutants, especially its highmobility, persistence, the role of methylation, bioaccumulation and amplification ofthe characteristics of the food chain, even a very small amount present in theenvironment, for plants, animals and human health is also a great threat. In Chapter5, we have designed a very novel, based on T-Hg2+-T coordination chemistry, energysensitivity, high selectivity to detect Hg2+. This strategy exploited the cooperativityof proximate poly-T oligonucleotides in coordination with Hg2+. Ferrocene(Fc)-tagged poly-T oligonucleotides were immobilized on the electrode surface viaself-assembly of the terminal thiol moiety. In the presence of Hg2+, a pair of poly-Toligonucleotides could cooperatively coordinate with Hg2+, which triggered aconformational reorganization of the poly-T oligonucleotides from flexible singlestrands to relatively rigid duplexlike complexes, thus drawing the Fc tags away fromthe electrode with a substantially decreased redox current. The responsecharacteristics of the sensor were thoroughly investigated using capillaryelectrophoresis and electrochemical measurements. The results revealed that thesensor showed a sensitive response to Hg2+in a concentration range from1.0nM to2.0μM, with a detection limit of0.5nM. Also, this strategy afforded exquisiteselectivity for Hg2+against a reservoir of other environmentally related metal ions, compared to existinganodic stripping voltammetry (ASV) techniques. In addition,this sensor could be implemented using minimal reagents and working steps withexcellent reusability through mild regeneration procedure. It was expected that thiscost-effective electrochemical sensor might hold considerable potential in on-siteapplications of Hg2+detection.
MicroRNA (miRNA) plays a crucial regulatory function in vivo and importantimplications on not only for cell growth, differentiation and apoptosis, but alsorelated closely with many diseases. The researchers found that miRNA are related tothe abnormal expression in leukemia, colorectal cancer, breast cancer andcardiovascular disorders diseases. Since miRNA is very short, less content andsimilarity characteristics than other sequences, analytical testing has somechallenges. The traditional method included the mark detecting hybridization,microarray technology, based RCA signal amplification detection techniques, andcationic polymers. In Chapter6of this paper, we reported double-invasive signalamplification based on highly selective sensitive miRNA detection methods andtechniques (Invader assay). Other researchers had invasive signal amplificationtechnology to detect miRNA, but their template can not achieve a good distinctionwith similar miRNA sequences. We designed the first heavy sucked miRNA invasiveprobe amplification cycle, and there is not formed immediately invade miRNA locioverlapped structure, we can learn the principles of notches ligated PCR, design ofmiRNA3' end from the intrusion bit points nucleotides distance. When thethermophilic Taq polymerase was added, and the corresponding nucleosidetriphosphates, miRNA become fully matched primer extension to initiatepolymerization when the polymerization to the5' end of the signal probe and probehybridizing region of the template (invasion locus), Taq polymerase5'-3'exonuclease activity began to play a role in the invasion site nucleotide probe signala (near the3' end) of the disconnect between the nucleotide and the phosphatebackbone, the signal probe5' tilt leave, but also because of another section of shortersequences hybridize with a template from the template and hybrid stability weakened,became the second heavy cycle amplification primers probes. The second cycle ofamplification similar to the first heavy weight cycling, also needs the role ofpolymerization to form intrusive structure, and further weaken the role ofnon-specific nicking, the second re-circulation of the probe signal is5' fluorophorelabeled fluorescein, Taqman probes labeled quenching intermediate groups, butintrusive structure formation, the signal probe5' cocked and with fluorescein modified left, middle, and signal probes labeled quencher separate fluorescencesignal enhancement and is proportional to the concentration of the target miRNAsequence. Experimental results show that the method can achieve double loopamplification step, high detection sensitivity, the lower limit of up to10fmol/L, inparticular, can distinguish with similar miRNA sequences, achieved a rare miRNAselective detection.
引文
[1] Clark L C, Lyons C. Electrode systems for continuous monitoring incardiovascular surgery. Annals of the New York Academy of Sciences,1962,102(1):29-45
[2] Mascini M, Tombelli S. Biosensors for biomarkers in medical diagnostics.Biomarkers,2008,13(7-8):637-657
[3] Cammann K. Bio-sensors based on ion-selective electrodes. Fresenius'Zeitschrift Für Analytische Chemie,1977,287(1):1-9
[4] Turner A P F, Karube I, Wilson G S, et al. Biosensors: fundamentals andapplications. Oxford: Oxford University Press,1987
[5] Eggins B R. Chemical sensors and biosensors. West Sussex: John Wiley&Sons, Ltd,2002
[6] Chaubey A, Malhotra B D. Mediated biosensors. Biosensors&Bioelectronics,2002,17(6):441-456
[7] D’Orazio P. Biosensors in clinical chemistry. Clinica Chimica Acta,2003,334(1):41-69
[8] Schoning M J, Poghossian A. Recent advances in biologically sensitivefield-effect transistors (BioFETs). Analyst,2002,127(9):1137-1151
[9] Mirsky V M, Riepl M, Wolfbeis O S. Capacitive monitoring of proteinimmobilization and antigen-antibody reactions on monomolecular alkylthiolfilms on gold electrodes. Biosensors&Bioelectronics,1997,12(9):977-989
[10] Guiseppi-Elie A, Lingerfelt L. Impedimetric detection of DNA hybridization:towards near-patient DNA diagnostics. In: Immobilisation of DNA on Chips I.Springer Berlin Heidelberg,2005:161-186
[11] Thevenot D R, Toth K, Durst R A, et al. Electrochemical biosensors:recommended definitions and classification. Biosensors&Bioelectronics,2001,16(1):121-131
[12] Jameson D M, Croney J C, Moens P D J. Fluorescence: Basic concepts,practical aspects, and some anecdotes. Methods in Enzymology,2003,360:1-43
[13] Markov D A, Swinney K, Bornhop D J. Label-free molecular interactiondeterminations with nanoscale interferometry. Journal of the AmericanChemical Society,2004,126(50):16659-16664
[14] Bornhop D J, Latham J C, Kussrow A, et al. Free-solution, label-freemolecular interactions studied by back-scattering interferometry. Science,2007,317(5845):1732-1736
[15] Magrez A, Kasas S, Salicio V, et al. Cellular toxicity of carbon-basednanomaterials. Nano Letters,2006,6(6):1121-1125
[16] Dumortier H, Lacotte S, Pastorin G, et al. Functionalized carbon nanotubes arenon-cytotoxic and preserve the functionality of primary immune cells. NanoLetters,2006,6(7):3003-3003
[17] Liu Z, Fan A C, Rakhra K, et al. Supramolecular stacking of doxorubicin oncarbon nanotubes for in vivo cancer therapy. Angewandte ChemieInternational Edition,2009,48(41):7668-7672
[18] Liu Z, Cai W B, He L, et al. In vivo biodistribution and highly efficienttumour targeting of carbon nanotubes in mice. Nature Nanotechnology,2007,2(1):47-52
[19] Bianco A, Prato M. Can carbon nanotubes be considered useful tools forbiological applications? Advanced Materials,2003,15(20):1765-1768
[20] Cherukuri P, Bachilo S M, Litovsky S H, et al. Near-infrared fluorescencemicroscopy of single-walled carbon nanotubes in phagocytic cells. Journal ofAmerican Chemical Society,2004,126(48):15638-15639
[21] Sun X M, Liu Z, Welsher K, et al. Nano-graphene oxide for cellular imagingand drug delivery. Nano Research,2008,1(3):203-212
[22] Cao L, Wang X, Meziani M J, et al. Carbon dots for multiphoton bioimaging.Journal of the American Chemical Society,2007,129(37):11318-11319
[23] Liu Z, Robinson J T, Sun X M, et al. PEGylated nanographene oxide fordelivery of water-insoluble cancer drugs. Journal of American ChemicalSociety,2008,130(33):10876-10877
[24] Yang K, Zhang S, Zhang G X. Graphene in mice: ultrahigh in vivo tumoruptake and efficient photothermal therapy. Nano Letters,2010,10(9):3318-3323
[25] Zanello L P, Zhao B, Hu H, et al. Bone cell proliferation on carbonnanotubes. Nano Letters,2006,6(3):562-567
[26] Kratschrner W, Lamb L D, Fostiropoulous K, et al. Solid C60: a new form ofcarbon. Nature,1990,347(6291):354-358
[27] Friedman S H, DeCamp D L, Sijbesma R P, et al. Inhibition of the HIV-1protease by fullerene derivatives: model building studies and experimentalverification. Journal of American Chemical Society,1993,115(15):6506-6509
[28] Sijbesma R, Srdanov G, Wudif F, et a1. Synthesis of a fullerene derivative forthe inhibition of HIV enzymes. Journal of American Chemical Society,1993,115(15):6510-6512
[29] Friedman S H, Ganapathi P S, Rubin Y, et al. Optimizing the binding offullerene inhibitors of the HIV-1protease through predicted increases inhydrophobic desolvation. Journal of Medicinal Chemistry,1998,41(13):2424-2429
[30] Useng T H, Kang J J, Wang H W, et a1. Suppression of microsomalcytochrome P450-dependent monooxygenases and mitochondrial oxidativepolyhydroxylated by fullerenol, a polyhydroxylated fullerene C60. ToxicologyLetters,1997,93(1):29-37
[31] Wolff D J, Papoiu A D P, Mialkowski K, et a1. Inhibition of nitric oxidesynthase isoforms by tris-malonyl-C60-fullerene adducts. Archives ofBiochemistry and Biophysics,2000,378(2):216-223
[32] Wolif D J, Barbieri C M, Richardson C F, et a1. Trisamine C60-fullereneadducts inhibit neuronal nitric oxide synthase by acting as highly potentcalmodulin antagonists. Archives of Biochemistry and Biophysics,2002,399(2):130-141
[33] Iijima S. Helical microtubules of graphitic carbon. Nature,1991,354(6348):56-58
[34] Kam N W S, Liu Z, Dai H J. Functionalization of carbon nanotubes viacleavable disulfide bonds for efficient intracellular delivery of siRNA andpotent gene silencing. Journal of American Chemical Society,2005,127(36):12492-12493
[35] Richard C, Balavoine F, Schultz P, et al. Supramolecular self-assembly oflipid derivatives on carbon nanotubes. Science,2003,300(5620):775-778
[36] Wong S S, Joselevich E, Woolley A T, et al. Covalently functionalizednanotubes as nanometre-sized crobes in chemistry and biology. Nature,1998,394(6688):52-55
[37] Baughman R H, Zakhidov A A, DeHeer W A. Carbon nanotubes-the routetoward applications. Science,2002,297(5582):787-792
[38] Lu F S, Gu L, Meziani M J, et a1. Advances in bioapplications of carbonnanotubes. Advanced Materials,2009,21(2):139-152
[39] Kim S N, Rusling J F, Papadimitrakopoulos F. Carbon nanotubes forelectronic and electrochemical detection of biomolecules. Advanced Materials,2007,19(20):3214-3228
[40] McCreery R L. Advanced carbon electrode materials for molecularelectrochemistry. Chemical Reviews,2008,108(7):2646-2687
[41] Viswanathan S, Wu L C, Huang M R, et al. Electrochemical immunosensor forcholera toxin using liposomes and poly(3,4-ethylenedioxythiophene)-coatedcarbon nanotubes. Analytical Chemistry,2006,78(4):1115-1121
[42] Gong K, Chakrabart S, Da L. Electrochemistry at carbon nanotube electrodes:is the nanotube tip more active than the sidewall? Angewandte ChemieInternational Edition,2008,47(29):5446-5450
[43] Vainrub A, Pettitt B M. Sensitive quantitative nucleic acid detection usingoligonucleotide microarrays. Journal of the American Chemical Society,2003,125(26):7798-7799
[44] Gooding J J, Wibowo R, Liu J, et al. Protein electrochemistry using alignedcarbon nanotube arrays. Journal of American Chemical Society,2003,125(30):9006-9007
[45] Star A, Gabriel J C P, Bradley K, et al. Electronic detection of specific proteinbinding using nanotube FET devices. Nano Letters,2003,3(4):459-463
[46] Byon H R, Choil H C. Network single-walled Ccarbon nanotube-field effecttransistors (SWNT-FETs) with increased schottky contact area for highlysensitive biosensor applications. Journal of American Chemical Society,2006,128(7):2188-2189
[47] Nie H G, Liu S J, Yu R Q, et al. Phospholipid-coated carbon nanotubes assensitive electrochemical labels with controlled assembly mediated signaltransduction for magnetic separation immunoassay. Angewandte ChemieInternational Edition,2009,48(52):9862-9866
[48] Wang J, Liu G D, Jan M R. Ultrasensitive electrical biosensing of proteins andDNA: carbon-nanotube derived amplification of the recognition andtransduction events. Journal of American Chemical Society,2004,126(10):3010-3011
[49] Yu X, Munge B, Patel V, et al. Carbon nanotube amplification strategies forhighly sensitive immunodetection of cancer biomarkers. Journal of AmericanChemical Society,2006,128(34):11199-11205
[50] Yun Y H, Bange A, Heineman W R, et a1. A nanotube array immunosensor fordirect electrochemical detection of antigen-antibody binding. Sensors andActuators B,2007,123(1):177-182
[51] Novoselov K S, Geim A K, Morozov S V, et al. Electric field effect inatomically thin carbon films. Science,2004,306(5696):666-669
[52] Latil S, Henrard L. Charge carriers in few-layer graphene films. PhysicalReview Letters,2006,97(3):036803
[53] Nair R R, Blake P, Grigorenko A N, et al. Fine structure constant definesvisual transparency of graphene. Science,2008,320(5881):1308-1308
[54] Park S, Ruoff R S. Chemical methods for the production of graphenes. NatureNanotechnology,2009,4(4):217-224
[55] Du X, Skachko I, Barker A, et al. Approaching ballistic transport in suspendedgraphene. Nature Nanotechnology,2008,3(8):491-495
[56] Balandin A A, Ghosh S, Bao W, et al. Superior thermal conductivity ofsingle-layer graphene. Nano Letters,2008,8(3):902-907
[57] Hu J N, Ruan X L, Chen Y P. Thermal conductivity and thermal rectificationin graphene nanoribbons: a molecular dynamics study. Nano Letters,2009,9(7):2730-2735
[58] Jung I, Dikin D A, Piner R D, et al. Tunable electrical conductivity ofindividual graphene oxide sheets reduced at “low” temperatures. Nano Letters,2008,8(12):4283-4287
[59] Petit C, Bandosz T J. MOF-graphite oxide composites: combining theuniqueness of graphene layers and metal–organic frameworks. AdvancedMaterials,2009,21(46):4753-4757
[60] Su Q, Pang S P, Alijani V, et al. Composites of graphene with large aromaticmolecules. Advanced Materials,2009,21(31):3191-3195
[61] Tang Z W, Wu H, Cort Z R, et al. Constraint of DNA on functionalizedgraphene improves its biostability and specificity. Small,2010,6(11):1205-1209
[62] Lu C H, Zhu C L, Li J, et al. Using graphene to protect DNA from cleavageduring cellular delivery. Chemical Communications,2010,46:3116-3118
[63] Lu C H, Yang H H, Zhu C L, et al. A graphene platform for sensingbiomolecules. Angewandte Chemie International Edition,2009,48(26):4785-4787
[64] He S J, Song B, Li D, et al. A graphene nanoprobe for rapid, sensitive, andmulticolor fluorescent DNA analysis. Advanced Functional Materials,2010,20(3):453-459
[65] Wang H B, Zhang Q, Chu X, et al. Graphene oxide-peptide conjugate as anintracellular protease sensor for caspase-3activation imaging in live cells.Angewandte Chemie International Edition,2011,50(31):7065-7069
[66] Leutwyler W K, Burgi S L, Burgl H B. Semiconductor clusters, nanocrystals,and quantum dots. Science,1996,271:933-937
[67] Kastner M A. Artificial atoms. Physics Today,1993,46:24-31
[68] Guyot-Sionnest P, Hines M A. Intraband transitions in semiconductornanocrystals. Applied Physics Letters,1998,72(6):686-688
[69] Chan W C W, Nie S M. Quantum dot bioconjugates for ultrasensitivenonisotopic detection. Science,1998,281(5385):2016-2018
[70] Chan W C W, Maxwell D J, Gao X H, et al. Luminescent QDs for multiplexedbiological detection and imaging. Current Opinion in Biotechnology,2002,13(1):40-46
[71] Xu X Y, Ray R, Gu Y L, et al. Electrophoretic analysis and purification offluorescent single-walled carbon nanotube fragments. Journal of AmericanChemical Society,2004,126(40):12736-12737
[72] Bourlinos A B, Stassinopoulos A, Anglos D, et al. Photoluminescentcarbogenic dots. Chemistry of Materials,2008,20:4539-4541
[73] Liu H P, Ye T, Mao C D. Fluorescent carbon nanoparticles derived fromcandle soot. Angewandte Chemie International Edition,2007,46(34):6473-6475
[74] Liu R L, Wu D Q, Liu S H, et al. An aqueous route to multicolorphotoluminescent carbon dots using silica spheres as carriers. AngewandteChemie International Edition,2009,48(25):4598-4601
[75] Sun Y P, Zhou B, Lin Y, et al. Quantum-sized carbon dots for bright andcolorful photoluminescence. Journal of American Chemical Society,2006,128(24):7756-7757
[76] Zhao Q L, Zhang Z L, Huang B H, et al. Facile preparation of low cytotoxicityfluorescent carbon nanocrystals by electrooxidation of graphite. ChemicalCommunications,2008,41,5116-5118
[77] Zheng Y L, Chi Y W, Dong Y Q, et al. Electrochemiluminescence ofwater-soluble carbon nanocrystals released electrochemically from graphite.Journal of American Chemical Society,2009,131(13):4564-4565
[78] Zhu H, Wang X L, Li Y L, et al. Microwave synthesis offluorescent carbon nanoparticles with electrochemiluminescence properties.Chemical Communications,2009,34,5118-5120
[79] Baker S N, Baker G A. Luminescent carbon nanodots: emergent nanolights.Angewandte Chemie International Edition,2010,49(38):6726-6744
[80] Huang W J, Fernando S, Allard L F, et al. Solubilization of single-walledcarbon nanotubes with diamine-terminated oligomeric poly(ethylene glycol) indifferent functionalization reactions. Nano Letters,2003,3(4):565-568
[81] Larson D R, Zipfe W R, Williams R M, et al. Water-soluble quantum dots formultiphoton fluorescence imaging in vivo. Science,2003,300(5624):1434-1436
[82] Yang S T, Wang X, Wang H F, et al. Carbon dots as nontoxic andhigh-performance fluorescence imaging agents. The Journal of PhysicalChemistry C,2009,113(42),18110-18114
[83] Yang S T, Cao L, Luo P G, et al. Carbon dots for optical imaging in vivo.Journal of the American Chemical Society,2009,131(32):11308-11309
[84] Luo X, Zhang S B, Wei S H. Chemical design of direct-gap light-emittingsilicon. Physical Review Letters,2002,89(7),076802
[85] Mayne A H, Bayliss S C, Barr P, et al. Biologically interfaced porous silicondevices. Physica Status Solidi A,2000,182(1):505-513
[86] Pierotti R A, Rouquerol J. Reporting physisorption data for gas/solid systemswith special reference to the determination of surface area and porosity. Pureand Applied Chemistry,1985,57(4):603-619
[87] Weiss S M, Fauchet P M. Porous silicon one-dimensional photonic crystals foroptical signal modulation, IEEE J. Selected Topics in Quantum Electronics,2006,12(6):1514-1519
[88] Sailor M J. Biological nanosensors, AFOSR annual program reviewnanoelectronics, negative index materials and superconducting electronics,2005, July26-28
[89] Jaffer F A, Weisslender R. Seeing within-molecular imaging of cardiovascularsystem. Circulation Research,2004,94(4):433-445
[90] Perez J M, Josephson L, Weissleder R. Use of magnetic nanoparticles asnanosensors to probe for molecular interactions. ChembioChem,2004,5(3):261-264
[91] Vo-Dinh T. Biosensors, nanosensors and biochips: frontiers in environmentaland medical diagnosis. In: Proceedings of the First International Symposiumon Micro&Nano Technology. Hawaii,2004,1-6
[92] Lin V S Y, Motesharei K, Dancil K P S, et al. A porous silicon-based opticalinterferometric biosensor. Science,1997,278(5339):840-843
[93] De S L, Moretti L, Rendina I, et al. Time-resolved sensing of chemical speciesin porous silicon optical microcavity. Sensors and Actuators B: Chemical,2004,100(1):168-172
[94] Mulloni V, Pavesi L. Porous Silicon microcavities as optical chemical sensors.Applied Physics Letters,2000,76(18):2523-2525
[95] Benson T M, Arrand H F, Sewell P, et al. Progress towards achievingintegrated circuit functionality using porous silicon optoelectroniccomponents. Materials Science and Engineering: B,2000,69:92-99
[96] Wongmanered C, Zangooie S, Arwin H. Determination of pore sizedistribution and surface area of this porous silicon layer by spectroscopicellipsometry. Applied Surface Science,2001,172(1):117-125
[97] Canham L. Properties of porous silicon. EMIS Datareviews, ed. B. Wiess,1997,18
[98] Singh S, Sharma S N, Shivaprasad S M, et al. Nanostructured porous silicon asfunctionalized material for biosensor application. Journal of MaterialsSciencel: Materials in Medicine,2009,20(1):81-187
[99] Francia G D, Ferrara V L, Manzo S, et al. Towards a label-free optical poroussilicon DNA sensor. Biosensors&Bioelectronics,2005,21(4):661-665
[100] Santos H A, Salonel J, Riikonen J, et al. Size-dependent in vitro toxicity ofporous silicon micro-and nanoparticles. In: Proc of the Nanotech Conf&Expo.Houston,2009,3-7
[101] Ouyang H, Striemer C C, Fauchet P M. Quantitative analysis of the sensitivityof porous silicon optical biosensors. Applied Physics Letters,2006,88(16):163108-163108
[102] Anglin E J, Cheng L, Freeman W R, et al. Porous silicon in drug deliverydevices and materials. Advanced Drug Delivery Reviews,2008,60(11):1266-1277
[103] Bonanno L M, DeLouise L A. Whole blood optical biosensor. Biosensors&Bioelectronics,2007,23(3):444-448
[104] Tasciotti E, Chiappini C, Martinez J, et al. Multistage mesoporous siliconparticles for biomedical applications. In: Proc of the11th Int Conf on AdvanceMaterials. Brazil,2009,20-25
[105] Kovalev D, Diener J, Heckler H, et al. Optical absorption cross sections of Sinanocrystals. Physical Review B,2000,61(7):4485-4487
[106] Kovalev D, Heckler H, Polisski G, et al. Optical properties of Si nanocrystals.Physica Status Solidi B,1999,215(2):871-932
[107] Allan G, Delerue C, Lannoo M. Excitons in silicon nanostructures. Journal ofLuminescence,1993,57(1),239-242
[108] Allan G, Delerue C, Lannoo M. Nature of luminescent surface states ofsemiconductor nanocrystallites. Physical Review Letters,1996,76(16):2961-2964
[109] Delerue C, Allan G, Lannoo M. Optical band gap of Si nanoclusters. Journalof Luminescence,1998,80(1):65-73
[110] Wolkin M V, Jorne J, Fauchet P M, et al. Electronic states and luminescencein porous silicon quantum dots: the role of oxygen. Physical Review Letters,1999,82(1):197-200
[111] Vasiliev I, Martin R M. Optical properties of hydrogenated silicon clusterswith reconstructed surfaces. Physica Status Solidi B,2002,233(1):5-9
[112] He Y, Su Y, Yang X, et al. Photo and pH stable, highly-luminescent siliconnanospheres and their bioconjugates for immunofluorescent cell imaging.Journal of the American Chemical Society,2009,131(12):4434-4438
[113] Warner J H, Hoshino A, Yamamoto K, et al. Water-soluble photoluminescentsilicon quantum dots. Angewandte Chemie International Edition,2005,44(29):4550-4554
[114] Li Z F, Ruckenstein E. Water-soluble poly (acrylic acid) grafted luminescentsilicon nanoparticles and their use as fluorescent biological staining labels.Nano Letters,2004,4(8):1463-1467
[115] Erogbogbo F, Yong K T, Roy I, et al. Biocompatible luminescent siliconquantum dots for imaging of cancer cells. ACS Nano,2008,2(5):873-878
[116] Zhong Y, Peng F, Bao F, et al. Large-scale aqueous synthesis of fluorescentand biocompatible silicon nanoparticles and their use as highly photostablebiological probes. Journal of the American Chemical Society,2013,135(22):8350-8356
[117] Prodi L, Bargossi C, Montalti M, et al. An effective fluorescent chemosensorfor mercury ions. Journal of the American Chemical Society,2000,122(28):6769-6770
[118] Ono A, Cao S, Togashi H, et al. Specific interactions between silver (I) ionsand cytosine-cytosine pairs in DNA duplexes. Chemical Communications,2008,39:4825-4827
[119] Wang K, Tang Z, Yang C J, et al. Molecular engineering of DNA: molecularbeacons. Angewandte Chemie International Edition,2009,48(5):856-870
[120] Wang C M, Zhu Z, Song Y L, et al. Caged molecular beacons: controllingnucleic acid hybridization with light. Chemical Communications,2011,47(20),5708-5710
[121] Kong W, Zhao J J, He L, et al. Strategies for profiling microRNA expression.Journal of Cellular Physiology,2009,218(1):22-25
[122] stergaard M E, Cheguru P, Papasani M R, et al. Glowing locked nucleicacids: brightly fluorescent probes for detection of nucleic acids in cells.Journal of the American Chemical Society,2010,132(40):14221-14228
[123] Zanoli L M, Licciardello M, D’Agata R, et al. Peptide nucleic acid molecularbeacons for the detection of PCR amplicons in droplet-based microfluidicdevices. Analytical and Bioanalytical Chemistry,2013,405(2-3):615-624
[124] Kolpashchikov D M. Binary probes for nucleic acid analysis. ChemicalReviews,2010,110(8):4709-4723
[125] Johnson R P, Richardson J A, Brown T, et al. A label-free, electrochemicalSERS-based assay for detection of DNA hybridization and discrimination ofmutations. Journal of the American Chemical Society,2012,134(34):14099-14107
[126] Xiao Y, Lou X, Uzawa T, et al. An electrochemical sensor for singlenucleotide polymorphism detection in serum based on a triple-stem DNAprobe. Journal of the American Chemical Society,2009,131(42):15311-15316
[127] Genot A J, Zhang D Y, Bath J, et al. Remote toehold: a mechanism for flexiblecontrol of DNA hybridization kinetics. Journal of the American ChemicalSociety,2011,133(7):2177-2182
[128] Wang F, Elbaz J, Teller C, et al. Amplified detection of DNA through anautocatalytic and catabolic DNAzyme-mediated process. Angewandte ChemieInternational Edition,2011,50(1):295-299
[129] Gadkar V J, Filion M. New developments in quantitative real-time polymerasechain reaction technology. Current Issues in Molecular Biology,2013,16(1):1-6
[130] Curtis Saunders D, Holst G L, Phaneuf C R, et al. Rapid, quantitative, reversetranscription PCR in a polymer microfluidic chip. Biosensors&Bioelectronics,2013,44,222-228
[131] Shin G W, Chung B, Jung G Y, et al. Multiplex ligase-based genotypingmethods combined with CE. Electrophoresis,2013
[132] Murakami T, Sumaoka J, Komiyama M. Sensitive isothermal detection ofnucleic-acid sequence by primer generation-rolling circle amplification.Nucleic Acids Research,2009,37(3): e19-e19
[133] Harcourt E M, Kool E T. Amplified microRNA detection by templatedchemistry. Nucleic Acids Research,2012,40(9): e65-e65
[134] Kong R M, Zhang X B, Zhang L L, et al. Molecular beacon-based junctionprobes for efficient detection of nucleic acids via a true target-triggeredenzymatic recycling amplification. Analytical Chemistry,2010,83(1):14-17
[135] Yan C Y, Jiang C, Jiang J H, et al. Simple, colorimetric detection ofmicroRNA based on target amplification and DNAzyme. Analytical Sciences,2013,29(6),605-609
[136] Zhou H, Xie S J, Zhang S B, et al. Isothermal amplification system based ontemplate-dependent extension. Chemical Communications,2013,49,2448-2450
[137] Nakayama S, Yan L, Sintim H O. Junction probes-sequence specific detectionof nucleic acids via template enhanced hybridization processes. Journal of theAmerican Chemical Society,2008,130(38):12560-12561
[138] Wang F, Freage L, Orbach R, et al. Autonomous replication of nucleic acidsby polymerization/nicking enzyme/DNAzyme cascades for the amplifieddetection of DNA and the aptamer-cocaine complex. Analytical Chemistry,2013,85(17):8196-8203
[139] Zuo X, Xia F, Xiao Y, et al. Sensitive and selective amplified fluorescenceDNA detection based on exonuclease III-aided target recycling. Journal of theAmerican Chemical Society,2010,132(6):1816-1818
[140] Lee H J, Li Y, Wark A W, et al. Enzymatically amplified surface plasmonresonance imaging detection of DNA by exonuclease III digestion of DNAmicroarrays. Analytical Chemistry,2005,77(16):5096-5100
[141] Weizmann Y, Cheglakov Z, Willner I. A Fok I/DNA machine that duplicatesits analyte gene sequence. Journal of the American Chemical Society,2008,130(51):17224-17225
[142] Gerasimova Y V, Peck S, Kolpashchikov D M. Enzyme-assisted binary probefor sensitive detection of RNA and DNA. Chemical Communications,2010,46:8761-8763
[143] Yin B C, Liu Y Q, Ye B C. One-Step, Multiplexed fluorescence detection ofmicroRNAs based on duplex-specific nuclease signal amplification. Journal ofthe American Chemical Society,2012,134(11):5064-5067
[144] Lee J S, Han M S, Mirkin C A. Colorimetricdetection of mercuricion (Hg2+) inaqueous media using DNA-functionalized gold nanoparticles. AngewandteChemie International Edition,2007,46(22),4093-4096
[145] Li D, Wieckowska A, Willner I. Optical analysis of Hg2+ions byoligonucleotide-gold-nanoparticle hybrids and DNA-based machines.Angewandte Chemie International Edition,2008,47(21),3927-3931
[146] Ono A, Togashi H. Highly selective oligonucleotide-based sensor formercury(II) in aqueous solutions. Angewandte Chemie International Edition,2004,43(33),4300-4302
[147] Chiang C K, Huang C C, Liu C W, et al. Oligonucleotide-based fluorescenceprobe for sensitive and selective detection of mercury (II) in aqueous solution.Analytical Chemistry,2008,80(10):3716-3721
[148] Li T, Shi L, Wang E, et al. Silver-ion-mediated DNAzyme switch for theultrasensitive and selective colorimetric detection of aqueous Ag+and cysteine.Chemistry-A European Journal,2009,15(14):3347-3350
[149] Wu C, Xiong C, Wang L, et al. Sensitive and selective localized surfaceplasmon resonance light-scattering sensor for Ag+with unmodified goldnanoparticles. Analyst,2010,135(10):2682-2687
[150] Bolger P M, Schwetz B A. Mercury and health. The New England Journal ofMedicine,2002,347(22):1735-1736
[151] Clarkson T W, Magos L, Myers G J. The toxicology of mercury-currentexposures and clinical manifestations. The New England Journal of Medicine,2003,349(18):1731-1737
[152] Boening D W. Ecological effects, transport, and fate of mercury: a generalreview. Chemosphere,2000,40(12):1335-1351
[153] Kim S, Choi J E, Choi J, et al. Oxidative stress-dependent toxicity of silvernanoparticles in human hepatoma cells. Toxicology in Vitro,2009,23(6):1076-1084
[154] Rümmeli M H, Rocha C G, Ortmann F, et al. Graphene: piecing it together.Advanced Materials,2011,23(39):4471-4490
[155] Wang Y, Li Z, Wang J, et al. Graphene and graphene oxide: bio-functionalization and applications in biotechnology. Trends in Biotechnology,2011,29(5):205-212
[156] Liu Z, Robinson J T, Sun X, et al. PEGylated nanographene oxide for deliveryof water-insoluble cancer drugs. Journal of the American Chemical Society,2008,130(33):10876-10877
[157] Gulbakan B, Yasun E, Shukoor M I, et al. A dual platform for selectiveanalyte enrichment and ionization in mass spectrometry usingaptamer-conjugated graphene oxide. Journal of the American ChemicalSociety,2010,132(49):17408-17410
[158] Wang H, Zhang Q, Chu X, et al. Graphene oxide-peptide conjugate as anintracellular protease sensor for caspase-3activation imaging in live cells.Angewandte Chemie International Edition,2011,50(31):7065-7069
[159] Lu C H, Yang H H, Zhu C L, et al. A graphene platform for sensingbiomolecules. Angewandte Chemie International Edition,2009,48(26):4785-4787
[160] Jang H J, Kim Y K, Kwon H M, et al. A grapheme-based platform for theassay of duplex-DNA unwinding by helicase. Angewandte ChemieInternational Edition,2010,49(33):5703-5707
[161] Tang L, Wang Y, Liu Y, et al. DNA-directed self-assembly of graphene oxidewith applications to ultrasensitive oligonucleotide assay. ACS Nano,2011,5(5):3817-3822
[162] Dong H, Gao W, Yan F, et al. Fluorescence resonance energy transfer betweenquantum dots and graphene oxide for sensing biomolecules. AnalyticalChemistry,2010,82(13):5511-5517
[163] Lin L, Liu Y, Zhao X, et al. Sensitive and rapid screening of T4polynucleotide kinase activity and inhibition based on coupled exonucleasereaction and graphene oxide platform. Analytical Chemistry,2011,83(22):8396-8402
[164] Tang L A L, Wang J, Loh K P. Graphene-based SELDI probe with ultrahighextraction and sensitivity for DNA oligomer. Journal of the AmericanChemical Society,2010,132(32):10976-10977
[165] Cui Y, Kim S N, Jones S E, et al. Chemical functionalization of grapheneenabled by phage displayed peptides. Nano Letters,2010,10(11):4559-4565
[166] Artyukhin A B, Shestakov A, Harper J, et al. Functional one-dimensional lipidbilayers on carbon nanotube templates. Journal of the American ChemicalSociety,2005,127(20):7538-7542
[167] Richard C, Balavoine F, Schultz P, et al. Supramolecular self-assembly oflipid derivatives on carbon nanotubes. Science,2003,300(5620):775-778
[168] Nie H G, Liu S J, Yu R Q, et al. Phospholipid-coated carbon nanotubes assensitive electrochemical labels with controlled-assembly-mediated signaltransduction for magnetic separation immunoassay. Angewandte ChemieInternational Edition,2009,48(52):9862-9866
[169] Loh K P, Bao Q, Eda G, et al. Graphene oxide as a chemically tunableplatform for optical applications. Nature Chemistry,2010,2(12):1015-1024
[170] Schultz C. Challenges in studying phospholipid signaling. Nature ChemicalBiology,2010,6(7):473-475
[171] Hannun Y A, Obeid L M. Principles of bioactive lipid signalling: lessons fromsphingolipids. Nature Reviews Molecular Cell Biology,2008,9(2):139-150
[172] Li D, Li G, Li P, et al. The enhancement of transfection efficiency of cationicliposomes by didodecyldimethylammonium bromide coated gold nanoparticles.Biomaterials,2010,31(7):1850-1857
[173] Song J, Cheng L, Liu A, et al. Plasmonic vesicles of amphiphilic goldnanocrystals: self-assembly and external-stimuli-triggered destruction. Journalof the American Chemical Society,2011,133(28):10760-10763
[174] Dubertret B, Skourides P, Norris D J, et al. In vivo imaging of quantum dotsencapsulated in phospholipid micelles. Science,2002,298(5599):1759-1762
[175] Jamal W T, Jamal K T, Cakebread A, et al. Blood circulation and tissuebiodistribution of lipid-quantum dot (L-QD) hybrid vesicles intravenouslyadministered in mice. Bioconjugate Chemistry,2009,20(9):1696-1702
[176] Gopalakrishnan G, Danelon C, Izewska P, et al. Multifunctional lipid/quantumdot hybrid nanocontainers for controlled targeting of live cells. AngewandteChemie International Edition,2006,45(33):5478-5483
[177] Eun C, Berkowitz M L. Molecular dynamics simulation study of interactionbetween model rough hydrophobic surfaces. The Journal of PhysicalChemistry A,2011,115(23):6059-6067
[178] Eun C, Berkowitz M L. Origin of the hydration force: water-mediatedinteraction between two hydrophilic plates. The Journal of Physical ChemistryB,2009,113(40):13222-13228
[179] Ang P K, Jaiswal M, Lim C H Y X, et al. A bioelectronic platform using agrapheme-lipid bilayer interface. ACS Nano,2010,4(12):7387-7394
[180] Athenstaedt K, Daum G. Phosphatidic acid, a key intermediate in lipidmetabolism. European Journal of Biochemistry,1999,266(1):1-16
[181] Hornberger T A, Chu W K, Mak Y W, et al. The role of phospholipase D andphosphatidic acid in the mechanical activation of mTOR signaling in skeletalmuscle. Proceedings of the National Academy of Sciences of the United Statesof America,2006,103(12):4741-4746
[182] Fezza F, Gasperi V, Mazzei C, et al. Radiochromatographic assay ofN-acyl-phosphatidylethanolamine-specific phospholipase D activity.Analytical Biochemistry,2005,339(1):113-120
[183] Ferguson C G, Bigman C S, Richardson R D, et al. Fluorogenic phospholipidsubstrate to detect lysophospholipase D/autotaxin activity. Organic Letters,2006,8(10):2023-2026
[184] Lee J, Kim Y K, Min D H. Laser desorption/ionization mass spectrometricassay for phospholipase activity based on graphene oxide/carbon nanotubedouble-layer films. Journal of the American Chemical Society,2010,132(42):14714-14717
[185] Majd S, Yusko E C, MacBriar A D, et al. Gramicidin pores report the activityof membrane-active enzymes. Journal of the American Chemical Society,2009,131(44):16119-16126
[186] Ho J A, Hsu H W. Procedures for preparing escherichia coli O157:H7immunoliposome and its application in liposome immunoassay. AnalyticalChemistry,2003,75(16):4330-4334
[187] Hummers Jr W S, Offeman R E. Preparation of graphitic oxide. Journal of theAmerican Chemical Society,1958,80(6):1339-1339
[188] Park S, An J, Jung I, et al. Colloidal suspensions of highly reduced grapheneoxide in a wide variety of organic solvents. Nano Letters,2009,9(4):1593-1597
[189] Wei Z, Wang D, Kim S, et al. Nanoscale tunable reduction of graphene oxidefor graphene electronics. Science,2010,328(5984):1373-1376
[190] Stankovich S, Dikin D A, Dommett G H B, et al. Graphene-based compositematerials. Nature,2006,442(7100):282-286
[191] Dong X, Cheng J, Li J, et al. Graphene as a novel matrix for the analysis ofsmall molecules by MALDI-TOF MS. Analytical Chemistry,2010,82(14):6208-6214
[192] Geng D, Chura J, Roberts M F. Activation of phospholipase D by phosphatidicacid enhanced vesicle binding, phosphatidic acid-Ca2+interaction, or anallosteric effect? Journal of Biological Chemistry,1998,273(20):12195-12202
[193] Estrela-Lopis I, Brezesinski G, M hwald H. Dipalmitoyl-phosphatidylcholine/phospholipase D interactions investigated with polarization-modulatedinfrared reflection absorption spectroscopy. Biophysical Journal,2001,80(2):749-754
[194] Li Z F, Ruckenstein E. Water-soluble poly (acrylic acid) grafted luminescentsilicon nanoparticles and their use as fluorescent biological staining labels.Nano Letters,2004,4(8):1463-1467
[195] Warner J H, Hoshino A, Yamamoto K, et al. Water-soluble photoluminescentsilicon quantum dots. Angewandte Chemie International Edition,2005,44(29):4550-4554
[196] Erogbogbo F, Yong K T, Roy I, et al. Biocompatible luminescent siliconquantum dots for imaging of cancer cells. ACS Nano,2008,2(5):873-878
[197] Erogbogbo F, Yong K T, Roy I, et al. In vivo targeted cancer imaging, sentinellymph node mapping and multi-channel imaging with biocompatible siliconnanocrystals. ACS Nano,2010,5(1):413-423
[198] Shiohara A, Hanada S, Prabakar S, et al. Chemical reactions on surfacemolecules attached to silicon quantum dots. Journal of the American ChemicalSociety,2009,132(1):248-253
[199] Atkins T M, Thibert A, Larsen D S, et al. Femtosecond ligand/core dynamicsof microwave-assisted synthesized silicon quantum dots in aqueous solution.Journal of the American Chemical Society,2011,133(51):20664-20667
[200] Sato K, Yokosuka S, Takigami Y, et al. Size-tunable silicon/iron oxide hybridnanoparticles with fluorescence, superparamagnetism, and biocompatibility.Journal of the American Chemical Society,2011,133(46):18626-18633
[201] Mastronardi M L, Maier-Flaig F, Faulkner D, et al. Size-dependent absolutequantum yields for size-separated colloidally-stable silicon nanocrystals. NanoLetters,2011,12(1):337-342
[202] Guan M, Wang W, Henderson E J, et al. Assembling photoluminescent siliconnanocrystals into periodic mesoporous organosilica. Journal of the AmericanChemical Society,2012,134(20):8439-8446
[203] Belomoin G, Therrien J, Smith A, et al. Observation of a magic discrete familyof ultrabright Si nanoparticles. Applied Physics Letters,2002,80(5):841-843
[204] English D S, Pell L E, Yu Z, et al. Size tunable visible luminescence fromindividual organic monolayer stabilized silicon nanocrystal quantum dots.Nano Letters,2002,2(7):681-685
[205] Schuppler S, Friedman S L, Marcus M A, et al. Size, shape, and compositionof luminescent species in oxidized Si nanocrystals and H-passivated porous Si.Physical Review B,1995,52(7):4910-4925
[206] Rogozhina E, Belomoin G, Smith A, et al. Si-N linkage in ultrabright,ultrasmall Si nanoparticles. Applied Physics Letters,2001,78(23):3711-3713
[207] Warner J H, Hoshino A, Yamamoto K, et al. Water-soluble photoluminescentsilicon quantum dots. Angewandte Chemie International Edition,2005,44(29),4450-4454
[208] Zou J, Baldwin R K, Pettigrew K A, et al. Solution synthesis of ultrastableluminescent siloxane-coated silicon nanoparticles. Nano Letters,2004,4(7):1181-1186
[209] Mayne A H, Bayliss S C, Barr P, et al. Biologically interfaced porous silicondevices. Physica Status Solidi A,2000,182(1):505-513
[210] Kirchner C, Liedl T, Kudera S, et al. Cytotoxicity of colloidal CdSe andCdSe/ZnS nanoparticles. Nano Letters,2005,5(2):331-338
[211] Miller D A. Optoelectronics-silicon sees the light. Nature,1995,378(6554):238-238
[212] Nilsson J R. How cytotoxic is zinc? A study on effects of zinc on cellproliferation, endocytosis, and fine structure of the ciliate Tetrahymena. ActaProtozoologica,2003,42(1):19-29
[213] Zhang Y, Chen W, Zhang J, et al. In vitro and in vivo toxicity of CdTenanoparticles. Journal of Nanoscience and Nanotechnology,2007,7(2):497-503
[214] Miller D A. Optoelectronics-silicon sees the light. Nature,1995,378(6554):238-238
[215] Zhang H L, Liu T C, Wang J H, et al. Development of quantum dots inBioimaging. Chinese Journal of Analytical Chemistry,2006,34(10):1491-1495
[216] Zhang Y, Kaji N, Tokeshi M, et al. Nanobiotechnology: quantum dots inbioimaging. Expert Review of Proteomics,2007,4(4):565-572
[217] Kang Z, Liu Y, Tsang C H A, et al. Water-soluble silicon quantum dots withwavelength-tunable photoluminescence. Advanced Materials,2009,21(6):661-664
[218] Hua F, Erogbogbo F, Swihart M T, et al. Organically capped siliconnanoparticles with blue photoluminescence prepared by hydrosilylationfollowed by oxidation. Langmuir,2006,22(9):4363-4370
[219] Hua F, Swihart M T, Ruckenstein E. Efficient surface grafting of luminescentsilicon quantum dots by photoinitiated hydrosilylation. Langmuir,2005,21(13):6054-6062
[220] Li X, He Y, Swihart M T. Surface functionalization of silicon nanoparticlesproduced by laser-driven pyrolysis of silane followed by HF-HNO3etching.Langmuir,2004,20(11):4720-4727
[221] Li X, He Y, Talukdar S S, et al. Process for preparing macroscopic quantitiesof brightly photoluminescent silicon nanoparticles with emission spanning thevisible spectrum. Langmuir,2003,19(20):8490-8496
[222] Holmes J D, Ziegler K J, Doty R C, et al. Highly luminescent siliconnanocrystals with discrete optical transitions. Journal of the AmericanChemical Society,2001,123(16):3743-3748
[223] Pettigrew K A, Liu Q, Power P P, et al. Solution synthesis of alkyl-andalkyl/alkoxy-capped silicon nanoparticles via oxidation of Mg2Si. Chemistryof Materials,2003,15(21):4005-4011
[224] Zhang X, Neiner D, Wang S, et al. A new solution route tohydrogen-terminated silicon nanoparticles: synthesis, functionalization andwater stability. Nanotechnology,2007,18(9):095601-095606
[225] Neiner D, Chiu H W, Kauzlarich S M. Low-temperature solution route tomacroscopic amounts of hydrogen terminated silicon nanoparticles. Journal ofthe American Chemical Society,2006,128(34):11016-11017
[226] Zou J, Sanelle P, Pettigrew K A, et al. Size and spectroscopy of siliconnanoparticles prepared via reduction of SiCl4. Journal of Cluster Science,2006,17(4):565-578
[227] Wilcoxon J P, Samara G A. Tailorable, visible light emission from siliconnanocrystals. Applied Physics Letters,1999,74(21):3164-3166
[228] Wilcoxon J P, Samara G A, Provencio P N. Optical and electronic propertiesof Si nanoclusters synthesized in inverse micelles. Physical Review B,1999,60(4):2704-2714
[229] Tilley R D, Warner J H, Yamamoto K, et al. Micro-emulsion synthesis ofmonodisperse surface stabilized silicon nanocrystals. ChemicalCommunications,2005(14):1833-1835
[230] Mayeri D, Phillips B L, Augustine M P, et al. NMR study of the synthesis ofalkyl-terminated silicon nanoparticles from the reaction of SiCl4with the zintlsalt, NaSi. Chemistry of Materials,2001,13(3):765-770
[231] Rogozhina E V, Eckhoff D A, Gratton E, et al. Carboxyl functionalization ofultrasmall luminescent silicon nanoparticles through thermal hydrosilylation.Journal of Materials Chemistry,2006,16(15):1421-1430
[232] Sato S, Swihart M T. Propionic-acid-terminated silicon nanoparticles:synthesis and optical characterization. Chemistry of Materials,2006,18(17):4083-4088
[233] Sa'Ar A, Reichman Y, Dovrat M, et al. Resonant coupling between surfacevibrations and electronic states in silicon nanocrystals at the strongconfinement regime. Nano Letters,2005,5(12):2443-2447
[234] Veinot J G C. Synthesis, surface functionalization, and properties offreestanding silicon nanocrystals. Chemical Communications,2006(40):4160-4168
[235] Sun Q Y, De Smet L C P M, van Lagen B, et al. Covalently attachedmonolayers on crystalline hydrogen-terminated silicon: extremely mildattachment by visible light. Journal of the American Chemical Society,2005,127(8):2514-2523
[236] Buriak J M, Stewart M P, Geders T W, et al. Lewis acid mediatedhydrosilylation on porous silicon surfaces. Journal of the American ChemicalSociety,1999,121(49):11491-11502
[237] Rosso-asic M, Spruijt E, van Lagen B, et al. Alkyl-unctionalized oxide-freesilicon nanoparticles: synthesis and optical properties. Small,2008,4(10):1835-1841
[238] Nelles J, Sendor D, Ebbers A, et al. Functionalization of silicon nanoparticlesvia hydrosilylation with1-alkenes. Colloid and Polymer Science,2007,285(7):729-736
[239] Canham L T. Silicon quantum wire array fabrication by electrochemical andchemical dissolution of wafers. Applied Physics Letters,1990,57:1046-1048
[240] Godefroo S, Hayne M, Jivanescu M, et al. Classification and control of theorigin of photoluminescence from Si nanocrystals. Nature Nanotechnology,2008,3(3):174-178
[241] Landes C, Burda C, Braun M, et al. Photoluminescence of CdSe nanoparticlesin the presence of a hole acceptor: n-butylamine. The Journal of PhysicalChemistry B,2001,105(15):2981-2986
[242] Landes C F, Braun M, El-Sayed M A. On the nanoparticle to molecular sizetransition: fluorescence quenching studies. The Journal of Physical ChemistryB,2001,105(43):10554-10558
[243] Bruchez M, Moronne M, Gin P, et al. Semiconductor nanocrystals asfluorescent biological labels. Science,1998,281(5385):2013-2016
[244] Michalet X, Pinaud F F, Bentolila L A, et al. Quantum dots for live cells, invivo imaging, and diagnostics. Science,2005,307(5709):538-544
[245] Alivisatos P. The use of nanocrystals in biological detection. NatureBiotechnology,2003,22(1):47-52
[246] Michalet X, Pinaud F, Lacoste T D, et al. Properties of fluorescentsemiconductor nanocrystals and their application to biological labeling. SingleMolecules,2001,2(4):261-276
[247] Gerion D, Pinaud F, Williams S C, et al. Synthesis and properties ofbiocompatible water-soluble silica-coated CdSe/ZnS semiconductor quantumdots. The Journal of Physical Chemistry B,2001,105(37):8861-8871
[248] Dabbousi B O, Rodriguez-Viejo J, Mikulec F V, et al.(CdSe) ZnS core-shellquantum dots: synthesis and characterization of a size series of highlyluminescent nanocrystallites. The Journal of Physical Chemistry B,1997,101(46):9463-9475
[249] He Y, Su Y, Yang X, et al. Photo and pH stable, highly-luminescent siliconnanospheres and their bioconjugates for immunofluorescent cell imaging.Journal of the American Chemical Society,2009,131(12):4434-4438
[250] He Y, Kang Z H, Li Q S, et al. Ultrastable, highly fluorescent, andwater-dispersed silicon-based nanospheres as cellular probes. AngewandteChemie International Edition,2009,48(1),128-132
[251] He Y, Zhong Y, Peng F, et al. Highly luminescent water-dispersible siliconnanowires for long-term immunofluorescent cellular imaging. AngewandteChemie International Edition,2011,50(13),30803083
[252] He Y, Zhong Y, Peng F, et al. One-pot microwave synthesis ofwater-dispersible, ultraphoto-and pH-stable, and highly fluorescent siliconquantum dots. Journal of the American Chemical Society,2011,133(36):14192-14195
[253] Zhong Y, Peng F, Wei X, et al. Microwave-assisted synthesis of biofunctionaland fluorescent silicon nanoparticles using proteins as hydrophilic ligands.Angewandte Chemie International Edition,2012,51(34):8485-8489
[254] Sreenivasan V K A, Zvyagin A V, Goldys E M. Luminescent nanoparticles andtheir applications in the life sciences. Journal of Physics: Condensed Matter,2013,25(19):194101
[255] Choi Y, Cho Y, Kim M, et al. Fluorogenic quantum dot-gold nanoparticleassembly for beta secretase inhibitor screening in live cell. AnalyticalChemistry,2012,84(20):8595-8601
[256] Baker S N, Baker G A. Luminescent carbon nanodots: emergent nanolights.Angewandte Chemie International Edition,2010,49(38):6726-6744
[257] Korzeniowska B, Nooney R, Wencel D, et al. Silica nanoparticles for cellimaging and intracellular sensing. Nanotechnology,2013,24(44):442002
[258] Yang S T, Wang X, Wang H, et al. Carbon dots as nontoxic andhigh-performance fluorescence imaging agents. The Journal of PhysicalChemistry C,2009,113(42):18110-18114
[259] Mulder W J M, Koole R, Brandwijk R J, et al. Quantum dots with aparamagnetic coating as a bimodal molecular imaging probe. Nano Letters,2006,6(1):1-6
[260] Yu H, Xiao Y, Jin L. A Lysosome-targetable and two-photon fluorescentprobe for monitoring endogenous and exogenous nitric oxide in living cells.Journal of the American Chemical Society,2012,134(42):17486-17489
[261] Dickinson B C, Chang C J. A targetable fluorescent probe for imaginghydrogen peroxide in the mitochondria of living cells. Journal of the AmericanChemical Society,2008,130(30):9638-9639
[262] Karunakaran S C, Babu P S S, Madhuri B, et al. In vitro demonstration ofapoptosis mediated photodynamic activity and NIR nucleus imaging through anovel porphyrin. ACS Chemical Biology,2012,8(1):127-132
[263] Kuo C W, Chueh D Y, Singh N, et al. Targeted nuclear delivery usingpeptide-coated quantum dots. Bioconjugate Chemistry,2011,22(6):1073-1080
[264] Tan S J, Jana N R, Gao S, et al. Surface-ligand-dependent cellular interaction,subcellular localization, and cytotoxicity of polymer-coated quantum dots.Chemistry of Materials,2010,22(7):2239-2247
[265] Huang D, Su L, Peng X, et al. Quantum dot-based quantification revealeddifferences in subcellular localization of EGFR and E-cadherin betweenEGFR-TKI sensitive and insensitive cancer cells. Nanotechnology,2009,20(22):225102
[266] Du F, Min Y, Zeng F, et al. A targeted and FRET-based ratiometricfluorescent nanoprobe for imaging mitochondrial hydrogen peroxide in livingcells. Small,2013
[267] Nan X, Sims P A, Chen P, et al. Observation of individual microtubule motorsteps in living cells with endocytosed quantum dots. Journal of PhysicalChemistry B,2005,109(51):24220-24224
[268] Courty S, Luccardini C, Bellaiche Y, et al. Tracking individual kinesin motorsin living cells using single quantum-dot imaging. Nano Letters,2006,6(7):1491-1495
[269] Cao L, Wang X, Meziani M J, et al. Carbon dots for multiphoton bioimaging.Journal of the American Chemical Society,2007,129(37):11318-11319
[270] Yang S T, Cao L, Luo P G, et al. Carbon dots for optical imaging in vivo.Journal of the American Chemical Society,2009,131(32):11308-11309
[271] Sun Y P, Zhou B, Lin Y, et al. Quantum-sized carbon dots for bright andcolorful photoluminescence. Journal of the American Chemical Society,2006,128(24):7756-7757
[272] Yang S T, Wang X, Wang H, et al. Carbon dots as nontoxic andhigh-performance fluorescence imaging agents. The Journal of PhysicalChemistry C,2009,113(42):18110-18114
[273] Ray S C, Saha A, Jana N R, et al. Fluorescent carbon nanoparticles: synthesis,characterization, and bioimaging application. The Journal of PhysicalChemistry C,2009,113(43):18546-18551
[274] Zhao Q L, Zhang Z L, Huang B H, et al. Facile preparation of low cytotoxicityfluorescent carbon nanocrystals by electrooxidation of graphite. ChemicalCommunications,2008,41:5116-5118
[275] Sun Y P, Wang X, Lu F, et al. Doped carbon nanoparticles as a new platformfor highly photoluminescent dots. The Journal of Physical Chemistry C,2008,112(47):18295-18298
[276] Xu X, Ray R, Gu Y, et al. Electrophoretic analysis and purification offluorescent single-walled carbon nanotube fragments. Journal of the AmericanChemical Society,2004,126(40):12736-12737
[277] Wang X, Cao L, Lu F, et al. Photoinduced electron transfers with carbon dots.Chemical Communications,2009,25:3774-3776
[278] Peng H, Travas-Sejdic J. Simple aqueous solution route to luminescentcarbogenic dots from carbohydrates. Chemistry of Materials,2009,21(23):5563-5565
[279] Baker S N, Baker G A. Luminescent carbon nanodots: emergent nanolights.Angewandte Chemie International Edition,2010,49(38):6726-6744
[280] Wang X, Qu K, Xu B, et al. Multicolor luminescent carbon nanoparticles:synthesis, supramolecular assembly with porphyrin, intrinsic peroxidase-likecatalytic activity and applications. Nano Research,2011,4(9):908-920
[281] Ravindran S, Chaudhary S, Colburn B, et al. Covalent coupling of quantumdots to multiwalled carbon nanotubes for electronic device applications.Nano Letters,2003,3(4):447-453
[282] Dong Y, Zhou N, Lin X, et al. Extraction of electrochemiluminescent oxidizedcarbon quantum dots from activated carbon. Chemistry of Materials,2010,22(21):5895-5899
[283] Tian L, Ghosh D, Chen W, et al. Nanosized carbon particles from natural gassoot. Chemistry of Materials,2009,21(13):2803-2809
[284] Qiao Z A, Wang Y, Gao Y, et al. Commercially activated carbon as the sourcefor producing multicolor photoluminescent carbon dots by chemical oxidation.Chemical Communications,2010,46:8812-8814
[285] Zhou J, Booker C, Li R, et al. An electrochemical avenue to blue luminescentnanocrystals from multiwalled carbon nanotubes (MWCNTs). Journal of theAmerican Chemical Society,2007,129(4):744-745
[286] Lu J, Yang J, Wang J, et al. One-pot synthesis of fluorescent carbonnanoribbons, nanoparticles, and graphene by the exfoliation of graphite inionic liquids. ACS Nano,2009,3(8):2367-2375
[287] Hu S L, Niu K Y, Sun J, et al. One-step synthesis of fluorescent carbonnanoparticles by laser irradiation. Journal of Materials Chemistry,2009,19(4):484-488
[288] Li H, He X, Kang Z, et al. Water-soluble fluorescent carbon quantum dots andphotocatalyst design. Angewandte Chemie International Edition,2010,49(26):4430-4434
[289] Bourlinos A B, Stassinopoulos A, Anglos D, et al. Surface functionalizedcarbogenic quantum dots. Small,2008,4(4):455-458
[290] Zhu H, Wang X, Li Y, et al. Microwave synthesis of fluorescent carbonnanoparticles with electrochemiluminescence properties. ChemicalCommunications,2009,34:5118-5120
[291] Bourlinos A B, Stassinopoulos A, Anglos D, et al. Photoluminescentcarbogenic dots. Chemistry of Materials,2008,20(14):4539-4541
[292] Chandra S, Das P, Bag S, et al. Synthesis, functionalization and bioimagingapplications of highly fluorescent carbon nanoparticles. Nanoscale,2011,3(4):1533-1540
[293] Mitra S, Chandra S, Patra P, et al. Novel fluorescent matrix embedded carbonquantum dots for the production of stable gold and silver hydrosols. Journal ofMaterials Chemistry,2011,21(44):17638-17641
[294] Liu H, Ye T, Mao C. Fluorescent carbon nanoparticles derived from candlesoot. Angewandte Chemie International Edition,2007,46(34):6473-6475
[295] Zhang H, Huang H, Ming H, et al. Carbon quantum dots/Ag3PO4complexphotocatalysts with enhanced photocatalytic activity and stability undervisible light. Journal of Materials Chemistry,2012,22(21):10501-10506
[296] Chandra S, Mitra S, Laha D, et al. Fabrication of multi-structure nanocarbonsfrom carbon xerogel: a unique scaffold towards bioimaging. ChemicalCommunications,2011,47(30):8587-8589
[297] Yu S J, Kang M W, Chang H C, et al. Bright fluorescent nanodiamonds: nophotobleaching and low cytotoxicity. Journal of the American ChemicalSociety,2005,127(50):17604-17605
[298] Bharali D J, Lucey D W, Jayakumar H, et al. Folate-receptor-mediateddelivery of InP quantum dots for bioimaging using confocal and two-photonmicroscopy. Journal of the American Chemical Society,2005,127(32):11364-11371
[299] Zhu S, Zhang J, Qiao C, et al. Strongly green-photoluminescent graphenequantum dots for bioimaging applications. Chemical Communications,2011,47:6858-6860
[300] Zhao Q L, Zhang Z L, Huang B H, et al. Facile preparation of low cytotoxicityfluorescent carbon nanocrystals by electrooxidation of graphite. ChemicalCommunications,2008,41:5116-5118
[301] Yang Y, Cui J, Zheng M, et al. One-step synthesis of amino-functionalizedfluorescent carbon nanoparticles by hydrothermal carbonization of chitosan.Chemical Communications,2012,48(3):380-382
[302] Yang Z C, Wang M, Yong A M, et al. Intrinsically fluorescent carbon dotswith tunable emission derived from hydrothermal treatment of glucose in thepresence of monopotassium phosphate. Chemical Communications,2011,47:11615-11617
[303] Sun Y P, Zhou B, Lin Y, et al. Quantum-sized carbon dots for bright andcolorful photoluminescence. Journal of the American Chemical Society,2006,128(24):7756-7757
[304] Wang F, Xie Z, Zhang H, et al. Highly luminescentorganosilane-functionalized carbon dots. Advanced Functional Materials,2011,21(6):1027-1031
[305] Li Q, Ohulchanskyy T Y, Liu R, et al. Photoluminescent carbon dots asbiocompatible nanoprobes for targeting cancer cells in vitro. The Journal ofPhysical Chemistry C,2010,114(28):12062-12068
[306] Esteves da Silva J C G, Gon alves H M R. Analytical and bioanalyticalapplications of carbon dots. TrAC Trends in Analytical Chemistry,2011,30(8):1327-1336
[307] Mao X J, Zheng H Z, Long Y J, et al. Study on the fluorescence characteristicsof carbon dots. Spectrochimica Acta Part A: Molecular and BiomolecularSpectroscopy,2010,75(2):553-557
[308] Bolger P M, Schwetz B A. Mercury and health. The New England Journal ofMedicine,2002,347(22):1735
[309] Stern A H. A review of the studies of the cardiovascular health effects ofmethylmercury with consideration of their suitability for risk assessment.Environmental Research,2005,98(1):133-142
[310] Morel F M M, Kraepiel A M L, Amyot M. The chemical cycle andbioaccumulation of mercury. Annual Review of Ecology and Systematics,1998:543-566
[311] Onyido I, Norris A R, Buncel E. Biomolecule-mercury interactions: modalitiesof DNA base-mercury binding mechanisms. Remediation strategies. ChemicalReviews,2004,104(12):5911-5930
[312] Prodi L, Bargossi C, Montalti M, et al. An effective fluorescent chemosensorfor mercury ions. Journal of the American Chemical Society,2000,122(28):6769-6770
[313] Nolan E M, Lippard S J. A “turn-on” fluorescent sensor for the selectivedetection of mercuric ion in aqueous media. Journal of the American ChemicalSociety,2003,125(47):14270-14271
[314] Zhu X J, Fu S T, Wong W K, et al. A near-infrared-fluorescentchemodosimeter for mercuric ion based on an expanded porphyrin.Angewandte Chemie International Edition,2006,45(19):3150-3154
[315] Yang Y K, Yook K J, Tae J. A rhodamine-based fluorescent and colorimetricchemodosimeter for the rapid detection of Hg2+ions in aqueous media. Journalof the American Chemical Society,2005,127(48):16760-16761
[316] Nolan E M, Lippard S J. Turn-on and ratiometric mercury sensing in waterwith a red-emitting probe. Journal of the American Chemical Society,2007,129(18):5910-5918
[317] Zhu C, Li L, Fang F, et al. Functional InP nanocrystals as novel near-infraredfluorescent sensors for mercury ions. Chemistry Letters,2005,34(7):898-899
[318] Huang C C, Chang H T. Selective gold-nanoparticle-based “turn-on”fluorescent sensors for detection of mercury (II) in aqueous solution.Analytical Chemistry,2006,78(24):8332-8338
[319] Kim I B, Bunz U H F. Modulating the sensory response of a conjugatedpolymer by proteins: an agglutination assay for mercury ions in water. Journalof the American Chemical Society,2006,128(9):2818-2819
[320] Liu X, Tang Y, Wang L, et al. Optical detection of mercury (II) in aqueoussolutions by using conjugated polymers and label-free oligonucleotides.Advanced Materials,2007,19(11):1471-1474
[321] Nolan M A, Kounaves S P. Microfabricated array of iridium microdisks as asubstrate for direct determination of Cu2+or Hg2+using square-wave anodicstripping voltammetry. Analytical Chemistry,1999,71(16):3567-3573
[322] Wang S, Forzani E S, Tao N. Detection of heavy metal ions in water byhigh-resolution surface plasmon resonance spectroscopy combined with anodicstripping voltammetry. Analytical Chemistry,2007,79(12):4427-4432
[323] Hollenstein M, Hipolito C, Lam C, et al. A highly selective DNAzyme sensorfor mercuric ions. Angewandte Chemie International Edition,2008,47(23):4346-4350
[324] Chen P, He C. A general strategy to convert the merR family proteins intohighly sensitive and selective fluorescent biosensors for metal ions. Journal ofthe American Chemical Society,2004,126(3):728-729
[325] Miyake Y, Togashi H, Tashiro M, et al. Mercury(II)-mediated formation ofthymine-Hg(II)-thymine base pairs in DNA duplexes. Journal of the AmericanChemical Society,2006,128(7):2172-2173
[326] Tanaka Y, Oda S, Yamaguchi H, et al.15N-15N J-coupling across Hg(II): directobservation of Hg(II)-mediated TT base pairs in a DNA duplex. Journal of theAmerican Chemical Society,2007,129(2):244-245
[327] Lee J S, Han M S, Mirkin C A. Colorimetric detection of mercuric ion (Hg2+)in aqueous media using DNA-functionalized gold nanoparticles. AngewandteChemie International Edition,2007,46(22):4093-4096
[328] Xue X, Wang F, Liu X. One-step, room temperature, colorimetric detection ofmercury (Hg2+) using DNA/nanoparticle conjugates. Journal of the AmericanChemical Society,2008,130(11):3244-3245
[329] Liu C W, Hsieh Y T, Huang C C, et al. Detection of mercury (II) based onHg2+-DNA complexes inducing the aggregation of gold nanoparticles.Chemical Communications,2008(19):2242-2244
[330] Li D, Wieckowska A, Willner I. Optical analysis of Hg2+ions byoligonucleotide-gold-nanoparticle hybrids and DNA-based machines.Angewandte Chemie International Edition,2008,47(21):3927-3931
[331] Ono A, Togashi H. Highly selective oligonucleotide-based sensor for mercury(II) in aqueous solutions. Angewandte Chemie International Edition,2004,43(33):4300-4302
[332] Liu J, Lu Y. Rational design of “Turn-On” allosteric DNAzyme catalyticbeacons for aqueous mercury ions with ultrahigh sensitivity and selectivity.Angewandte Chemie International Edition,2007,46(40):7587-7590
[333] Chiang C K, Huang C C, Liu C W, et al. Oligonucleotide-based fluorescenceprobe for sensitive and selective detection of mercury (II) in aqueous solution.Analytical Chemistry,2008,80(10):3716-3721
[334] Wang J, Liu B. Highly sensitive and selective detection of Hg2+in aqueoussolution with mercury-specific DNA and sybr green I. ChemicalCommunications,2008(39):4759-4761
[335] Fan C, Plaxco K W, Heeger A J. Electrochemical interrogation ofconformational changes as a reagentless method for the sequence-specificdetection of DNA. Proceedings of the National Academy of Sciences,2003,100(16):9134-9137
[336] Xiao Y, Lubin A A, Heeger A J, et al. Label-free electronic detection ofthrombin in blood serum by using an aptamer-based sensor. AngewandteChemie International Edition,2005,44(34):5456-5459
[337] Radi A E, Acero Sánchez J L, Baldrich E, et al. Reagentless, reusable,ultrasensitive electrochemical molecular beacon aptasensor. Journal of theAmerican Chemical Society,2006,128(1):117-124
[338] Xiao Y, Rowe A A, Plaxco K W. Electrochemical detection of parts-per-billionlead via an electrode-bound DNAzyme assembly. Journal of the AmericanChemical Society,2007,129(2):262-263
[339] Willner I, Zayats M. Electronic aptamer-based sensors. Angewandte ChemieInternational Edition,2007,46(34):6408-6418
[340] Wu Z S, Guo M M, Zhang S B, et al. Reusable electrochemical sensingplatform for highly sensitive detection of small molecules based onstructure-switching signaling aptamers. Analytical Chemistry,2007,79(7):2933-2939
[341] Zhang Y L, Huang Y, Jiang J H, et al. Electrochemical aptasensor based onproximity-dependent surface hybridization assay for single-step, reusable,sensitive protein detection. Journal of the American Chemical Society,2007,129(50):15448-15449
[342] Huang Y, Zhang Y L, Xu X, et al. Highly specific and sensitiveelectrochemical genotyping via gap ligation reaction and surface hybridizationdetection. Journal of the American Chemical Society,2009,131(7):2478-2480
[343] Zhang Y, Wang Y, Wang H, et al. Electrochemical DNA biosensor based onthe proximity-dependent surface hybridization assay. Analytical Chemistry,2009,81(5):1982-1987
[344] Fahlman R P, Sen D. DNA conformational switches as sensitive electronicsensors of analytes. Journal of the American Chemical Society,2002,124(17):4610-4616
[345] Salaün P, van den Berg C M G. Voltammetric detection of mercury and copperin seawater using a gold microwire electrode. Analytical Chemistry,2006,78(14):5052-5060
[346] Steel A B, Levicky R L, Herne T M, et al. Immobilization of nucleic acids atsolid surfaces: effect of oligonucleotide length on layer assembly. BiophysicalJournal,2000,79(2):975-981
[347] Demers L M, Mirkin C A, Mucic R C, et al. A fluorescence-based method fordetermining the surface coverage and hybridization efficiency of thiol-cappedoligonucleotides bound to gold thin films and nanoparticles. AnalyticalChemistry,2000,72(22):5535-5541
[348] Hirst J, Duff J L C, Jameson G N L, et al. Kinetics and mechanism ofredox-coupled, long-range proton transfer in an iron-sulfur protein.Investigation by fast-scan protein-film voltammetry. Journal of the AmericanChemical Society,1998,120(28):7085-7094
[349] Anne A, Bouchardon A, Moiroux J.3'-ferrocene-labeled oligonucleotidechains end-tethered to gold electrode surfaces: novel model systems forexploring flexibility of short DNA using cyclic voltammetry. Journal of theAmerican Chemical Society,2003,125(5):1112-1113
[350] Patolsky F, Lichtenstein A, Willner I. Electronic transduction of DNA sensingprocesses on surfaces: amplification of DNA detection and analysis ofsingle-base mismatches by tagged liposomes. Journal of the AmericanChemical Society,2001,123(22):5194-5205
[351] Bonfil Y, Brand M, Kirowa-Eisner E. Trace determination of mercury byanodic stripping voltammetry at the rotating gold electrode. Analytica ChimicaActa,2000,424(1):65-76
[352] Xiao L, Dietze W, Nyasulu F, et al. Ultramicroband array electrode.1. analysisof mercury in contaminated soils and flue gas exposed samples using agold-plated iridium portable system by anodic stripping voltammetry.Analytical Chemistry,2006,78(14):5172-5178
[353] Griffiths-Jones S, Saini H K, van Dongen S, et al. MiRBase: tools formicroRNA genomics. Nucleic Acids Research,2008,36(suppl1): D154-D158
[354] Johnson S M, Grosshans H, Shingara J, et al. RAS is regulated by the let-7microRNA fimily. Cell,2005,120:635-647
[355] Stahlhut E C E, Slack F J. The role of microRNAs in cancer. The Yale Journalof Biology and Medicine,2006,79(3-4),131-140
[356] Reinhart B J, Slack F J, Basson M, et al. The21-nucleotide let-7RNAregulates developmental timing in caenorhabditis elegans. Nature,2000,403(6772):901-906
[357] Lee R C, Ambros V. An extensive class of small RNAs in caenorhabditiselegans. Science,2001,294(5543):862-864
[358] Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identification of novelgenes coding for small expressed RNAs. Science,2001,294(5543):853-858
[359] Calin G A, Dumitru C D, Shimizu M, et al. Frequent deletions and down-regulation of microRNA genes miR15and miR16at13q14in chroniclymphocyticleukemia. Proceedings of the National Academy of Sciences,2002,99(24):15524-15529
[360] Yan J, Li Z, Liu C, et al. Simple and sensitive detection of microRNAs withligase chain reaction. Chemical Communications,2010,46(14):2432-2434
[361] Zhang Y, Li Z, Cheng Y, et al. Colorimetric detection of microRNA andRNase H activity in homogeneous solution with cationic polythiophenederivative. Chemical Communications,2009,22:3172-3174
[362] Allawi H T, Dahlberg J E, Olson S, et al. Quantitation of microRNAs using amodified invader assay. RNA,2004,10(7):1153-1161
[363] Hartig J S, Grüne I, Najafi-Shoushtari S H, et al. Sequence-specific detectionof microRNAs by signal-amplifying ribozymes. Journal of the AmericanChemical Society,2004,126(3):722-723
[364] Maroney P A, Chamnongpol S, Souret F, et al. A rapid, quantitative assay fordirect detection of microRNAs and other small RNAs using splinted ligation.RNA,2007,13(6):930-936
[365] Matthew M L, Samuel J L, Bennett E, et al. Characterization of the5' to3'exonuclease associated with Therrmus aquaticus DNA polymerase. NucleicAcids Research,1990,18(24):7317-7322
[2] Mascini M, Tombelli S. Biosensors for biomarkers in medical diagnostics.Biomarkers,2008,13(7-8):637-657
[3] Cammann K. Bio-sensors based on ion-selective electrodes. Fresenius'Zeitschrift Für Analytische Chemie,1977,287(1):1-9
[4] Turner A P F, Karube I, Wilson G S, et al. Biosensors: fundamentals andapplications. Oxford: Oxford University Press,1987
[5] Eggins B R. Chemical sensors and biosensors. West Sussex: John Wiley&Sons, Ltd,2002
[6] Chaubey A, Malhotra B D. Mediated biosensors. Biosensors&Bioelectronics,2002,17(6):441-456
[7] D’Orazio P. Biosensors in clinical chemistry. Clinica Chimica Acta,2003,334(1):41-69
[8] Schoning M J, Poghossian A. Recent advances in biologically sensitivefield-effect transistors (BioFETs). Analyst,2002,127(9):1137-1151
[9] Mirsky V M, Riepl M, Wolfbeis O S. Capacitive monitoring of proteinimmobilization and antigen-antibody reactions on monomolecular alkylthiolfilms on gold electrodes. Biosensors&Bioelectronics,1997,12(9):977-989
[10] Guiseppi-Elie A, Lingerfelt L. Impedimetric detection of DNA hybridization:towards near-patient DNA diagnostics. In: Immobilisation of DNA on Chips I.Springer Berlin Heidelberg,2005:161-186
[11] Thevenot D R, Toth K, Durst R A, et al. Electrochemical biosensors:recommended definitions and classification. Biosensors&Bioelectronics,2001,16(1):121-131
[12] Jameson D M, Croney J C, Moens P D J. Fluorescence: Basic concepts,practical aspects, and some anecdotes. Methods in Enzymology,2003,360:1-43
[13] Markov D A, Swinney K, Bornhop D J. Label-free molecular interactiondeterminations with nanoscale interferometry. Journal of the AmericanChemical Society,2004,126(50):16659-16664
[14] Bornhop D J, Latham J C, Kussrow A, et al. Free-solution, label-freemolecular interactions studied by back-scattering interferometry. Science,2007,317(5845):1732-1736
[15] Magrez A, Kasas S, Salicio V, et al. Cellular toxicity of carbon-basednanomaterials. Nano Letters,2006,6(6):1121-1125
[16] Dumortier H, Lacotte S, Pastorin G, et al. Functionalized carbon nanotubes arenon-cytotoxic and preserve the functionality of primary immune cells. NanoLetters,2006,6(7):3003-3003
[17] Liu Z, Fan A C, Rakhra K, et al. Supramolecular stacking of doxorubicin oncarbon nanotubes for in vivo cancer therapy. Angewandte ChemieInternational Edition,2009,48(41):7668-7672
[18] Liu Z, Cai W B, He L, et al. In vivo biodistribution and highly efficienttumour targeting of carbon nanotubes in mice. Nature Nanotechnology,2007,2(1):47-52
[19] Bianco A, Prato M. Can carbon nanotubes be considered useful tools forbiological applications? Advanced Materials,2003,15(20):1765-1768
[20] Cherukuri P, Bachilo S M, Litovsky S H, et al. Near-infrared fluorescencemicroscopy of single-walled carbon nanotubes in phagocytic cells. Journal ofAmerican Chemical Society,2004,126(48):15638-15639
[21] Sun X M, Liu Z, Welsher K, et al. Nano-graphene oxide for cellular imagingand drug delivery. Nano Research,2008,1(3):203-212
[22] Cao L, Wang X, Meziani M J, et al. Carbon dots for multiphoton bioimaging.Journal of the American Chemical Society,2007,129(37):11318-11319
[23] Liu Z, Robinson J T, Sun X M, et al. PEGylated nanographene oxide fordelivery of water-insoluble cancer drugs. Journal of American ChemicalSociety,2008,130(33):10876-10877
[24] Yang K, Zhang S, Zhang G X. Graphene in mice: ultrahigh in vivo tumoruptake and efficient photothermal therapy. Nano Letters,2010,10(9):3318-3323
[25] Zanello L P, Zhao B, Hu H, et al. Bone cell proliferation on carbonnanotubes. Nano Letters,2006,6(3):562-567
[26] Kratschrner W, Lamb L D, Fostiropoulous K, et al. Solid C60: a new form ofcarbon. Nature,1990,347(6291):354-358
[27] Friedman S H, DeCamp D L, Sijbesma R P, et al. Inhibition of the HIV-1protease by fullerene derivatives: model building studies and experimentalverification. Journal of American Chemical Society,1993,115(15):6506-6509
[28] Sijbesma R, Srdanov G, Wudif F, et a1. Synthesis of a fullerene derivative forthe inhibition of HIV enzymes. Journal of American Chemical Society,1993,115(15):6510-6512
[29] Friedman S H, Ganapathi P S, Rubin Y, et al. Optimizing the binding offullerene inhibitors of the HIV-1protease through predicted increases inhydrophobic desolvation. Journal of Medicinal Chemistry,1998,41(13):2424-2429
[30] Useng T H, Kang J J, Wang H W, et a1. Suppression of microsomalcytochrome P450-dependent monooxygenases and mitochondrial oxidativepolyhydroxylated by fullerenol, a polyhydroxylated fullerene C60. ToxicologyLetters,1997,93(1):29-37
[31] Wolff D J, Papoiu A D P, Mialkowski K, et a1. Inhibition of nitric oxidesynthase isoforms by tris-malonyl-C60-fullerene adducts. Archives ofBiochemistry and Biophysics,2000,378(2):216-223
[32] Wolif D J, Barbieri C M, Richardson C F, et a1. Trisamine C60-fullereneadducts inhibit neuronal nitric oxide synthase by acting as highly potentcalmodulin antagonists. Archives of Biochemistry and Biophysics,2002,399(2):130-141
[33] Iijima S. Helical microtubules of graphitic carbon. Nature,1991,354(6348):56-58
[34] Kam N W S, Liu Z, Dai H J. Functionalization of carbon nanotubes viacleavable disulfide bonds for efficient intracellular delivery of siRNA andpotent gene silencing. Journal of American Chemical Society,2005,127(36):12492-12493
[35] Richard C, Balavoine F, Schultz P, et al. Supramolecular self-assembly oflipid derivatives on carbon nanotubes. Science,2003,300(5620):775-778
[36] Wong S S, Joselevich E, Woolley A T, et al. Covalently functionalizednanotubes as nanometre-sized crobes in chemistry and biology. Nature,1998,394(6688):52-55
[37] Baughman R H, Zakhidov A A, DeHeer W A. Carbon nanotubes-the routetoward applications. Science,2002,297(5582):787-792
[38] Lu F S, Gu L, Meziani M J, et a1. Advances in bioapplications of carbonnanotubes. Advanced Materials,2009,21(2):139-152
[39] Kim S N, Rusling J F, Papadimitrakopoulos F. Carbon nanotubes forelectronic and electrochemical detection of biomolecules. Advanced Materials,2007,19(20):3214-3228
[40] McCreery R L. Advanced carbon electrode materials for molecularelectrochemistry. Chemical Reviews,2008,108(7):2646-2687
[41] Viswanathan S, Wu L C, Huang M R, et al. Electrochemical immunosensor forcholera toxin using liposomes and poly(3,4-ethylenedioxythiophene)-coatedcarbon nanotubes. Analytical Chemistry,2006,78(4):1115-1121
[42] Gong K, Chakrabart S, Da L. Electrochemistry at carbon nanotube electrodes:is the nanotube tip more active than the sidewall? Angewandte ChemieInternational Edition,2008,47(29):5446-5450
[43] Vainrub A, Pettitt B M. Sensitive quantitative nucleic acid detection usingoligonucleotide microarrays. Journal of the American Chemical Society,2003,125(26):7798-7799
[44] Gooding J J, Wibowo R, Liu J, et al. Protein electrochemistry using alignedcarbon nanotube arrays. Journal of American Chemical Society,2003,125(30):9006-9007
[45] Star A, Gabriel J C P, Bradley K, et al. Electronic detection of specific proteinbinding using nanotube FET devices. Nano Letters,2003,3(4):459-463
[46] Byon H R, Choil H C. Network single-walled Ccarbon nanotube-field effecttransistors (SWNT-FETs) with increased schottky contact area for highlysensitive biosensor applications. Journal of American Chemical Society,2006,128(7):2188-2189
[47] Nie H G, Liu S J, Yu R Q, et al. Phospholipid-coated carbon nanotubes assensitive electrochemical labels with controlled assembly mediated signaltransduction for magnetic separation immunoassay. Angewandte ChemieInternational Edition,2009,48(52):9862-9866
[48] Wang J, Liu G D, Jan M R. Ultrasensitive electrical biosensing of proteins andDNA: carbon-nanotube derived amplification of the recognition andtransduction events. Journal of American Chemical Society,2004,126(10):3010-3011
[49] Yu X, Munge B, Patel V, et al. Carbon nanotube amplification strategies forhighly sensitive immunodetection of cancer biomarkers. Journal of AmericanChemical Society,2006,128(34):11199-11205
[50] Yun Y H, Bange A, Heineman W R, et a1. A nanotube array immunosensor fordirect electrochemical detection of antigen-antibody binding. Sensors andActuators B,2007,123(1):177-182
[51] Novoselov K S, Geim A K, Morozov S V, et al. Electric field effect inatomically thin carbon films. Science,2004,306(5696):666-669
[52] Latil S, Henrard L. Charge carriers in few-layer graphene films. PhysicalReview Letters,2006,97(3):036803
[53] Nair R R, Blake P, Grigorenko A N, et al. Fine structure constant definesvisual transparency of graphene. Science,2008,320(5881):1308-1308
[54] Park S, Ruoff R S. Chemical methods for the production of graphenes. NatureNanotechnology,2009,4(4):217-224
[55] Du X, Skachko I, Barker A, et al. Approaching ballistic transport in suspendedgraphene. Nature Nanotechnology,2008,3(8):491-495
[56] Balandin A A, Ghosh S, Bao W, et al. Superior thermal conductivity ofsingle-layer graphene. Nano Letters,2008,8(3):902-907
[57] Hu J N, Ruan X L, Chen Y P. Thermal conductivity and thermal rectificationin graphene nanoribbons: a molecular dynamics study. Nano Letters,2009,9(7):2730-2735
[58] Jung I, Dikin D A, Piner R D, et al. Tunable electrical conductivity ofindividual graphene oxide sheets reduced at “low” temperatures. Nano Letters,2008,8(12):4283-4287
[59] Petit C, Bandosz T J. MOF-graphite oxide composites: combining theuniqueness of graphene layers and metal–organic frameworks. AdvancedMaterials,2009,21(46):4753-4757
[60] Su Q, Pang S P, Alijani V, et al. Composites of graphene with large aromaticmolecules. Advanced Materials,2009,21(31):3191-3195
[61] Tang Z W, Wu H, Cort Z R, et al. Constraint of DNA on functionalizedgraphene improves its biostability and specificity. Small,2010,6(11):1205-1209
[62] Lu C H, Zhu C L, Li J, et al. Using graphene to protect DNA from cleavageduring cellular delivery. Chemical Communications,2010,46:3116-3118
[63] Lu C H, Yang H H, Zhu C L, et al. A graphene platform for sensingbiomolecules. Angewandte Chemie International Edition,2009,48(26):4785-4787
[64] He S J, Song B, Li D, et al. A graphene nanoprobe for rapid, sensitive, andmulticolor fluorescent DNA analysis. Advanced Functional Materials,2010,20(3):453-459
[65] Wang H B, Zhang Q, Chu X, et al. Graphene oxide-peptide conjugate as anintracellular protease sensor for caspase-3activation imaging in live cells.Angewandte Chemie International Edition,2011,50(31):7065-7069
[66] Leutwyler W K, Burgi S L, Burgl H B. Semiconductor clusters, nanocrystals,and quantum dots. Science,1996,271:933-937
[67] Kastner M A. Artificial atoms. Physics Today,1993,46:24-31
[68] Guyot-Sionnest P, Hines M A. Intraband transitions in semiconductornanocrystals. Applied Physics Letters,1998,72(6):686-688
[69] Chan W C W, Nie S M. Quantum dot bioconjugates for ultrasensitivenonisotopic detection. Science,1998,281(5385):2016-2018
[70] Chan W C W, Maxwell D J, Gao X H, et al. Luminescent QDs for multiplexedbiological detection and imaging. Current Opinion in Biotechnology,2002,13(1):40-46
[71] Xu X Y, Ray R, Gu Y L, et al. Electrophoretic analysis and purification offluorescent single-walled carbon nanotube fragments. Journal of AmericanChemical Society,2004,126(40):12736-12737
[72] Bourlinos A B, Stassinopoulos A, Anglos D, et al. Photoluminescentcarbogenic dots. Chemistry of Materials,2008,20:4539-4541
[73] Liu H P, Ye T, Mao C D. Fluorescent carbon nanoparticles derived fromcandle soot. Angewandte Chemie International Edition,2007,46(34):6473-6475
[74] Liu R L, Wu D Q, Liu S H, et al. An aqueous route to multicolorphotoluminescent carbon dots using silica spheres as carriers. AngewandteChemie International Edition,2009,48(25):4598-4601
[75] Sun Y P, Zhou B, Lin Y, et al. Quantum-sized carbon dots for bright andcolorful photoluminescence. Journal of American Chemical Society,2006,128(24):7756-7757
[76] Zhao Q L, Zhang Z L, Huang B H, et al. Facile preparation of low cytotoxicityfluorescent carbon nanocrystals by electrooxidation of graphite. ChemicalCommunications,2008,41,5116-5118
[77] Zheng Y L, Chi Y W, Dong Y Q, et al. Electrochemiluminescence ofwater-soluble carbon nanocrystals released electrochemically from graphite.Journal of American Chemical Society,2009,131(13):4564-4565
[78] Zhu H, Wang X L, Li Y L, et al. Microwave synthesis offluorescent carbon nanoparticles with electrochemiluminescence properties.Chemical Communications,2009,34,5118-5120
[79] Baker S N, Baker G A. Luminescent carbon nanodots: emergent nanolights.Angewandte Chemie International Edition,2010,49(38):6726-6744
[80] Huang W J, Fernando S, Allard L F, et al. Solubilization of single-walledcarbon nanotubes with diamine-terminated oligomeric poly(ethylene glycol) indifferent functionalization reactions. Nano Letters,2003,3(4):565-568
[81] Larson D R, Zipfe W R, Williams R M, et al. Water-soluble quantum dots formultiphoton fluorescence imaging in vivo. Science,2003,300(5624):1434-1436
[82] Yang S T, Wang X, Wang H F, et al. Carbon dots as nontoxic andhigh-performance fluorescence imaging agents. The Journal of PhysicalChemistry C,2009,113(42),18110-18114
[83] Yang S T, Cao L, Luo P G, et al. Carbon dots for optical imaging in vivo.Journal of the American Chemical Society,2009,131(32):11308-11309
[84] Luo X, Zhang S B, Wei S H. Chemical design of direct-gap light-emittingsilicon. Physical Review Letters,2002,89(7),076802
[85] Mayne A H, Bayliss S C, Barr P, et al. Biologically interfaced porous silicondevices. Physica Status Solidi A,2000,182(1):505-513
[86] Pierotti R A, Rouquerol J. Reporting physisorption data for gas/solid systemswith special reference to the determination of surface area and porosity. Pureand Applied Chemistry,1985,57(4):603-619
[87] Weiss S M, Fauchet P M. Porous silicon one-dimensional photonic crystals foroptical signal modulation, IEEE J. Selected Topics in Quantum Electronics,2006,12(6):1514-1519
[88] Sailor M J. Biological nanosensors, AFOSR annual program reviewnanoelectronics, negative index materials and superconducting electronics,2005, July26-28
[89] Jaffer F A, Weisslender R. Seeing within-molecular imaging of cardiovascularsystem. Circulation Research,2004,94(4):433-445
[90] Perez J M, Josephson L, Weissleder R. Use of magnetic nanoparticles asnanosensors to probe for molecular interactions. ChembioChem,2004,5(3):261-264
[91] Vo-Dinh T. Biosensors, nanosensors and biochips: frontiers in environmentaland medical diagnosis. In: Proceedings of the First International Symposiumon Micro&Nano Technology. Hawaii,2004,1-6
[92] Lin V S Y, Motesharei K, Dancil K P S, et al. A porous silicon-based opticalinterferometric biosensor. Science,1997,278(5339):840-843
[93] De S L, Moretti L, Rendina I, et al. Time-resolved sensing of chemical speciesin porous silicon optical microcavity. Sensors and Actuators B: Chemical,2004,100(1):168-172
[94] Mulloni V, Pavesi L. Porous Silicon microcavities as optical chemical sensors.Applied Physics Letters,2000,76(18):2523-2525
[95] Benson T M, Arrand H F, Sewell P, et al. Progress towards achievingintegrated circuit functionality using porous silicon optoelectroniccomponents. Materials Science and Engineering: B,2000,69:92-99
[96] Wongmanered C, Zangooie S, Arwin H. Determination of pore sizedistribution and surface area of this porous silicon layer by spectroscopicellipsometry. Applied Surface Science,2001,172(1):117-125
[97] Canham L. Properties of porous silicon. EMIS Datareviews, ed. B. Wiess,1997,18
[98] Singh S, Sharma S N, Shivaprasad S M, et al. Nanostructured porous silicon asfunctionalized material for biosensor application. Journal of MaterialsSciencel: Materials in Medicine,2009,20(1):81-187
[99] Francia G D, Ferrara V L, Manzo S, et al. Towards a label-free optical poroussilicon DNA sensor. Biosensors&Bioelectronics,2005,21(4):661-665
[100] Santos H A, Salonel J, Riikonen J, et al. Size-dependent in vitro toxicity ofporous silicon micro-and nanoparticles. In: Proc of the Nanotech Conf&Expo.Houston,2009,3-7
[101] Ouyang H, Striemer C C, Fauchet P M. Quantitative analysis of the sensitivityof porous silicon optical biosensors. Applied Physics Letters,2006,88(16):163108-163108
[102] Anglin E J, Cheng L, Freeman W R, et al. Porous silicon in drug deliverydevices and materials. Advanced Drug Delivery Reviews,2008,60(11):1266-1277
[103] Bonanno L M, DeLouise L A. Whole blood optical biosensor. Biosensors&Bioelectronics,2007,23(3):444-448
[104] Tasciotti E, Chiappini C, Martinez J, et al. Multistage mesoporous siliconparticles for biomedical applications. In: Proc of the11th Int Conf on AdvanceMaterials. Brazil,2009,20-25
[105] Kovalev D, Diener J, Heckler H, et al. Optical absorption cross sections of Sinanocrystals. Physical Review B,2000,61(7):4485-4487
[106] Kovalev D, Heckler H, Polisski G, et al. Optical properties of Si nanocrystals.Physica Status Solidi B,1999,215(2):871-932
[107] Allan G, Delerue C, Lannoo M. Excitons in silicon nanostructures. Journal ofLuminescence,1993,57(1),239-242
[108] Allan G, Delerue C, Lannoo M. Nature of luminescent surface states ofsemiconductor nanocrystallites. Physical Review Letters,1996,76(16):2961-2964
[109] Delerue C, Allan G, Lannoo M. Optical band gap of Si nanoclusters. Journalof Luminescence,1998,80(1):65-73
[110] Wolkin M V, Jorne J, Fauchet P M, et al. Electronic states and luminescencein porous silicon quantum dots: the role of oxygen. Physical Review Letters,1999,82(1):197-200
[111] Vasiliev I, Martin R M. Optical properties of hydrogenated silicon clusterswith reconstructed surfaces. Physica Status Solidi B,2002,233(1):5-9
[112] He Y, Su Y, Yang X, et al. Photo and pH stable, highly-luminescent siliconnanospheres and their bioconjugates for immunofluorescent cell imaging.Journal of the American Chemical Society,2009,131(12):4434-4438
[113] Warner J H, Hoshino A, Yamamoto K, et al. Water-soluble photoluminescentsilicon quantum dots. Angewandte Chemie International Edition,2005,44(29):4550-4554
[114] Li Z F, Ruckenstein E. Water-soluble poly (acrylic acid) grafted luminescentsilicon nanoparticles and their use as fluorescent biological staining labels.Nano Letters,2004,4(8):1463-1467
[115] Erogbogbo F, Yong K T, Roy I, et al. Biocompatible luminescent siliconquantum dots for imaging of cancer cells. ACS Nano,2008,2(5):873-878
[116] Zhong Y, Peng F, Bao F, et al. Large-scale aqueous synthesis of fluorescentand biocompatible silicon nanoparticles and their use as highly photostablebiological probes. Journal of the American Chemical Society,2013,135(22):8350-8356
[117] Prodi L, Bargossi C, Montalti M, et al. An effective fluorescent chemosensorfor mercury ions. Journal of the American Chemical Society,2000,122(28):6769-6770
[118] Ono A, Cao S, Togashi H, et al. Specific interactions between silver (I) ionsand cytosine-cytosine pairs in DNA duplexes. Chemical Communications,2008,39:4825-4827
[119] Wang K, Tang Z, Yang C J, et al. Molecular engineering of DNA: molecularbeacons. Angewandte Chemie International Edition,2009,48(5):856-870
[120] Wang C M, Zhu Z, Song Y L, et al. Caged molecular beacons: controllingnucleic acid hybridization with light. Chemical Communications,2011,47(20),5708-5710
[121] Kong W, Zhao J J, He L, et al. Strategies for profiling microRNA expression.Journal of Cellular Physiology,2009,218(1):22-25
[122] stergaard M E, Cheguru P, Papasani M R, et al. Glowing locked nucleicacids: brightly fluorescent probes for detection of nucleic acids in cells.Journal of the American Chemical Society,2010,132(40):14221-14228
[123] Zanoli L M, Licciardello M, D’Agata R, et al. Peptide nucleic acid molecularbeacons for the detection of PCR amplicons in droplet-based microfluidicdevices. Analytical and Bioanalytical Chemistry,2013,405(2-3):615-624
[124] Kolpashchikov D M. Binary probes for nucleic acid analysis. ChemicalReviews,2010,110(8):4709-4723
[125] Johnson R P, Richardson J A, Brown T, et al. A label-free, electrochemicalSERS-based assay for detection of DNA hybridization and discrimination ofmutations. Journal of the American Chemical Society,2012,134(34):14099-14107
[126] Xiao Y, Lou X, Uzawa T, et al. An electrochemical sensor for singlenucleotide polymorphism detection in serum based on a triple-stem DNAprobe. Journal of the American Chemical Society,2009,131(42):15311-15316
[127] Genot A J, Zhang D Y, Bath J, et al. Remote toehold: a mechanism for flexiblecontrol of DNA hybridization kinetics. Journal of the American ChemicalSociety,2011,133(7):2177-2182
[128] Wang F, Elbaz J, Teller C, et al. Amplified detection of DNA through anautocatalytic and catabolic DNAzyme-mediated process. Angewandte ChemieInternational Edition,2011,50(1):295-299
[129] Gadkar V J, Filion M. New developments in quantitative real-time polymerasechain reaction technology. Current Issues in Molecular Biology,2013,16(1):1-6
[130] Curtis Saunders D, Holst G L, Phaneuf C R, et al. Rapid, quantitative, reversetranscription PCR in a polymer microfluidic chip. Biosensors&Bioelectronics,2013,44,222-228
[131] Shin G W, Chung B, Jung G Y, et al. Multiplex ligase-based genotypingmethods combined with CE. Electrophoresis,2013
[132] Murakami T, Sumaoka J, Komiyama M. Sensitive isothermal detection ofnucleic-acid sequence by primer generation-rolling circle amplification.Nucleic Acids Research,2009,37(3): e19-e19
[133] Harcourt E M, Kool E T. Amplified microRNA detection by templatedchemistry. Nucleic Acids Research,2012,40(9): e65-e65
[134] Kong R M, Zhang X B, Zhang L L, et al. Molecular beacon-based junctionprobes for efficient detection of nucleic acids via a true target-triggeredenzymatic recycling amplification. Analytical Chemistry,2010,83(1):14-17
[135] Yan C Y, Jiang C, Jiang J H, et al. Simple, colorimetric detection ofmicroRNA based on target amplification and DNAzyme. Analytical Sciences,2013,29(6),605-609
[136] Zhou H, Xie S J, Zhang S B, et al. Isothermal amplification system based ontemplate-dependent extension. Chemical Communications,2013,49,2448-2450
[137] Nakayama S, Yan L, Sintim H O. Junction probes-sequence specific detectionof nucleic acids via template enhanced hybridization processes. Journal of theAmerican Chemical Society,2008,130(38):12560-12561
[138] Wang F, Freage L, Orbach R, et al. Autonomous replication of nucleic acidsby polymerization/nicking enzyme/DNAzyme cascades for the amplifieddetection of DNA and the aptamer-cocaine complex. Analytical Chemistry,2013,85(17):8196-8203
[139] Zuo X, Xia F, Xiao Y, et al. Sensitive and selective amplified fluorescenceDNA detection based on exonuclease III-aided target recycling. Journal of theAmerican Chemical Society,2010,132(6):1816-1818
[140] Lee H J, Li Y, Wark A W, et al. Enzymatically amplified surface plasmonresonance imaging detection of DNA by exonuclease III digestion of DNAmicroarrays. Analytical Chemistry,2005,77(16):5096-5100
[141] Weizmann Y, Cheglakov Z, Willner I. A Fok I/DNA machine that duplicatesits analyte gene sequence. Journal of the American Chemical Society,2008,130(51):17224-17225
[142] Gerasimova Y V, Peck S, Kolpashchikov D M. Enzyme-assisted binary probefor sensitive detection of RNA and DNA. Chemical Communications,2010,46:8761-8763
[143] Yin B C, Liu Y Q, Ye B C. One-Step, Multiplexed fluorescence detection ofmicroRNAs based on duplex-specific nuclease signal amplification. Journal ofthe American Chemical Society,2012,134(11):5064-5067
[144] Lee J S, Han M S, Mirkin C A. Colorimetricdetection of mercuricion (Hg2+) inaqueous media using DNA-functionalized gold nanoparticles. AngewandteChemie International Edition,2007,46(22),4093-4096
[145] Li D, Wieckowska A, Willner I. Optical analysis of Hg2+ions byoligonucleotide-gold-nanoparticle hybrids and DNA-based machines.Angewandte Chemie International Edition,2008,47(21),3927-3931
[146] Ono A, Togashi H. Highly selective oligonucleotide-based sensor formercury(II) in aqueous solutions. Angewandte Chemie International Edition,2004,43(33),4300-4302
[147] Chiang C K, Huang C C, Liu C W, et al. Oligonucleotide-based fluorescenceprobe for sensitive and selective detection of mercury (II) in aqueous solution.Analytical Chemistry,2008,80(10):3716-3721
[148] Li T, Shi L, Wang E, et al. Silver-ion-mediated DNAzyme switch for theultrasensitive and selective colorimetric detection of aqueous Ag+and cysteine.Chemistry-A European Journal,2009,15(14):3347-3350
[149] Wu C, Xiong C, Wang L, et al. Sensitive and selective localized surfaceplasmon resonance light-scattering sensor for Ag+with unmodified goldnanoparticles. Analyst,2010,135(10):2682-2687
[150] Bolger P M, Schwetz B A. Mercury and health. The New England Journal ofMedicine,2002,347(22):1735-1736
[151] Clarkson T W, Magos L, Myers G J. The toxicology of mercury-currentexposures and clinical manifestations. The New England Journal of Medicine,2003,349(18):1731-1737
[152] Boening D W. Ecological effects, transport, and fate of mercury: a generalreview. Chemosphere,2000,40(12):1335-1351
[153] Kim S, Choi J E, Choi J, et al. Oxidative stress-dependent toxicity of silvernanoparticles in human hepatoma cells. Toxicology in Vitro,2009,23(6):1076-1084
[154] Rümmeli M H, Rocha C G, Ortmann F, et al. Graphene: piecing it together.Advanced Materials,2011,23(39):4471-4490
[155] Wang Y, Li Z, Wang J, et al. Graphene and graphene oxide: bio-functionalization and applications in biotechnology. Trends in Biotechnology,2011,29(5):205-212
[156] Liu Z, Robinson J T, Sun X, et al. PEGylated nanographene oxide for deliveryof water-insoluble cancer drugs. Journal of the American Chemical Society,2008,130(33):10876-10877
[157] Gulbakan B, Yasun E, Shukoor M I, et al. A dual platform for selectiveanalyte enrichment and ionization in mass spectrometry usingaptamer-conjugated graphene oxide. Journal of the American ChemicalSociety,2010,132(49):17408-17410
[158] Wang H, Zhang Q, Chu X, et al. Graphene oxide-peptide conjugate as anintracellular protease sensor for caspase-3activation imaging in live cells.Angewandte Chemie International Edition,2011,50(31):7065-7069
[159] Lu C H, Yang H H, Zhu C L, et al. A graphene platform for sensingbiomolecules. Angewandte Chemie International Edition,2009,48(26):4785-4787
[160] Jang H J, Kim Y K, Kwon H M, et al. A grapheme-based platform for theassay of duplex-DNA unwinding by helicase. Angewandte ChemieInternational Edition,2010,49(33):5703-5707
[161] Tang L, Wang Y, Liu Y, et al. DNA-directed self-assembly of graphene oxidewith applications to ultrasensitive oligonucleotide assay. ACS Nano,2011,5(5):3817-3822
[162] Dong H, Gao W, Yan F, et al. Fluorescence resonance energy transfer betweenquantum dots and graphene oxide for sensing biomolecules. AnalyticalChemistry,2010,82(13):5511-5517
[163] Lin L, Liu Y, Zhao X, et al. Sensitive and rapid screening of T4polynucleotide kinase activity and inhibition based on coupled exonucleasereaction and graphene oxide platform. Analytical Chemistry,2011,83(22):8396-8402
[164] Tang L A L, Wang J, Loh K P. Graphene-based SELDI probe with ultrahighextraction and sensitivity for DNA oligomer. Journal of the AmericanChemical Society,2010,132(32):10976-10977
[165] Cui Y, Kim S N, Jones S E, et al. Chemical functionalization of grapheneenabled by phage displayed peptides. Nano Letters,2010,10(11):4559-4565
[166] Artyukhin A B, Shestakov A, Harper J, et al. Functional one-dimensional lipidbilayers on carbon nanotube templates. Journal of the American ChemicalSociety,2005,127(20):7538-7542
[167] Richard C, Balavoine F, Schultz P, et al. Supramolecular self-assembly oflipid derivatives on carbon nanotubes. Science,2003,300(5620):775-778
[168] Nie H G, Liu S J, Yu R Q, et al. Phospholipid-coated carbon nanotubes assensitive electrochemical labels with controlled-assembly-mediated signaltransduction for magnetic separation immunoassay. Angewandte ChemieInternational Edition,2009,48(52):9862-9866
[169] Loh K P, Bao Q, Eda G, et al. Graphene oxide as a chemically tunableplatform for optical applications. Nature Chemistry,2010,2(12):1015-1024
[170] Schultz C. Challenges in studying phospholipid signaling. Nature ChemicalBiology,2010,6(7):473-475
[171] Hannun Y A, Obeid L M. Principles of bioactive lipid signalling: lessons fromsphingolipids. Nature Reviews Molecular Cell Biology,2008,9(2):139-150
[172] Li D, Li G, Li P, et al. The enhancement of transfection efficiency of cationicliposomes by didodecyldimethylammonium bromide coated gold nanoparticles.Biomaterials,2010,31(7):1850-1857
[173] Song J, Cheng L, Liu A, et al. Plasmonic vesicles of amphiphilic goldnanocrystals: self-assembly and external-stimuli-triggered destruction. Journalof the American Chemical Society,2011,133(28):10760-10763
[174] Dubertret B, Skourides P, Norris D J, et al. In vivo imaging of quantum dotsencapsulated in phospholipid micelles. Science,2002,298(5599):1759-1762
[175] Jamal W T, Jamal K T, Cakebread A, et al. Blood circulation and tissuebiodistribution of lipid-quantum dot (L-QD) hybrid vesicles intravenouslyadministered in mice. Bioconjugate Chemistry,2009,20(9):1696-1702
[176] Gopalakrishnan G, Danelon C, Izewska P, et al. Multifunctional lipid/quantumdot hybrid nanocontainers for controlled targeting of live cells. AngewandteChemie International Edition,2006,45(33):5478-5483
[177] Eun C, Berkowitz M L. Molecular dynamics simulation study of interactionbetween model rough hydrophobic surfaces. The Journal of PhysicalChemistry A,2011,115(23):6059-6067
[178] Eun C, Berkowitz M L. Origin of the hydration force: water-mediatedinteraction between two hydrophilic plates. The Journal of Physical ChemistryB,2009,113(40):13222-13228
[179] Ang P K, Jaiswal M, Lim C H Y X, et al. A bioelectronic platform using agrapheme-lipid bilayer interface. ACS Nano,2010,4(12):7387-7394
[180] Athenstaedt K, Daum G. Phosphatidic acid, a key intermediate in lipidmetabolism. European Journal of Biochemistry,1999,266(1):1-16
[181] Hornberger T A, Chu W K, Mak Y W, et al. The role of phospholipase D andphosphatidic acid in the mechanical activation of mTOR signaling in skeletalmuscle. Proceedings of the National Academy of Sciences of the United Statesof America,2006,103(12):4741-4746
[182] Fezza F, Gasperi V, Mazzei C, et al. Radiochromatographic assay ofN-acyl-phosphatidylethanolamine-specific phospholipase D activity.Analytical Biochemistry,2005,339(1):113-120
[183] Ferguson C G, Bigman C S, Richardson R D, et al. Fluorogenic phospholipidsubstrate to detect lysophospholipase D/autotaxin activity. Organic Letters,2006,8(10):2023-2026
[184] Lee J, Kim Y K, Min D H. Laser desorption/ionization mass spectrometricassay for phospholipase activity based on graphene oxide/carbon nanotubedouble-layer films. Journal of the American Chemical Society,2010,132(42):14714-14717
[185] Majd S, Yusko E C, MacBriar A D, et al. Gramicidin pores report the activityof membrane-active enzymes. Journal of the American Chemical Society,2009,131(44):16119-16126
[186] Ho J A, Hsu H W. Procedures for preparing escherichia coli O157:H7immunoliposome and its application in liposome immunoassay. AnalyticalChemistry,2003,75(16):4330-4334
[187] Hummers Jr W S, Offeman R E. Preparation of graphitic oxide. Journal of theAmerican Chemical Society,1958,80(6):1339-1339
[188] Park S, An J, Jung I, et al. Colloidal suspensions of highly reduced grapheneoxide in a wide variety of organic solvents. Nano Letters,2009,9(4):1593-1597
[189] Wei Z, Wang D, Kim S, et al. Nanoscale tunable reduction of graphene oxidefor graphene electronics. Science,2010,328(5984):1373-1376
[190] Stankovich S, Dikin D A, Dommett G H B, et al. Graphene-based compositematerials. Nature,2006,442(7100):282-286
[191] Dong X, Cheng J, Li J, et al. Graphene as a novel matrix for the analysis ofsmall molecules by MALDI-TOF MS. Analytical Chemistry,2010,82(14):6208-6214
[192] Geng D, Chura J, Roberts M F. Activation of phospholipase D by phosphatidicacid enhanced vesicle binding, phosphatidic acid-Ca2+interaction, or anallosteric effect? Journal of Biological Chemistry,1998,273(20):12195-12202
[193] Estrela-Lopis I, Brezesinski G, M hwald H. Dipalmitoyl-phosphatidylcholine/phospholipase D interactions investigated with polarization-modulatedinfrared reflection absorption spectroscopy. Biophysical Journal,2001,80(2):749-754
[194] Li Z F, Ruckenstein E. Water-soluble poly (acrylic acid) grafted luminescentsilicon nanoparticles and their use as fluorescent biological staining labels.Nano Letters,2004,4(8):1463-1467
[195] Warner J H, Hoshino A, Yamamoto K, et al. Water-soluble photoluminescentsilicon quantum dots. Angewandte Chemie International Edition,2005,44(29):4550-4554
[196] Erogbogbo F, Yong K T, Roy I, et al. Biocompatible luminescent siliconquantum dots for imaging of cancer cells. ACS Nano,2008,2(5):873-878
[197] Erogbogbo F, Yong K T, Roy I, et al. In vivo targeted cancer imaging, sentinellymph node mapping and multi-channel imaging with biocompatible siliconnanocrystals. ACS Nano,2010,5(1):413-423
[198] Shiohara A, Hanada S, Prabakar S, et al. Chemical reactions on surfacemolecules attached to silicon quantum dots. Journal of the American ChemicalSociety,2009,132(1):248-253
[199] Atkins T M, Thibert A, Larsen D S, et al. Femtosecond ligand/core dynamicsof microwave-assisted synthesized silicon quantum dots in aqueous solution.Journal of the American Chemical Society,2011,133(51):20664-20667
[200] Sato K, Yokosuka S, Takigami Y, et al. Size-tunable silicon/iron oxide hybridnanoparticles with fluorescence, superparamagnetism, and biocompatibility.Journal of the American Chemical Society,2011,133(46):18626-18633
[201] Mastronardi M L, Maier-Flaig F, Faulkner D, et al. Size-dependent absolutequantum yields for size-separated colloidally-stable silicon nanocrystals. NanoLetters,2011,12(1):337-342
[202] Guan M, Wang W, Henderson E J, et al. Assembling photoluminescent siliconnanocrystals into periodic mesoporous organosilica. Journal of the AmericanChemical Society,2012,134(20):8439-8446
[203] Belomoin G, Therrien J, Smith A, et al. Observation of a magic discrete familyof ultrabright Si nanoparticles. Applied Physics Letters,2002,80(5):841-843
[204] English D S, Pell L E, Yu Z, et al. Size tunable visible luminescence fromindividual organic monolayer stabilized silicon nanocrystal quantum dots.Nano Letters,2002,2(7):681-685
[205] Schuppler S, Friedman S L, Marcus M A, et al. Size, shape, and compositionof luminescent species in oxidized Si nanocrystals and H-passivated porous Si.Physical Review B,1995,52(7):4910-4925
[206] Rogozhina E, Belomoin G, Smith A, et al. Si-N linkage in ultrabright,ultrasmall Si nanoparticles. Applied Physics Letters,2001,78(23):3711-3713
[207] Warner J H, Hoshino A, Yamamoto K, et al. Water-soluble photoluminescentsilicon quantum dots. Angewandte Chemie International Edition,2005,44(29),4450-4454
[208] Zou J, Baldwin R K, Pettigrew K A, et al. Solution synthesis of ultrastableluminescent siloxane-coated silicon nanoparticles. Nano Letters,2004,4(7):1181-1186
[209] Mayne A H, Bayliss S C, Barr P, et al. Biologically interfaced porous silicondevices. Physica Status Solidi A,2000,182(1):505-513
[210] Kirchner C, Liedl T, Kudera S, et al. Cytotoxicity of colloidal CdSe andCdSe/ZnS nanoparticles. Nano Letters,2005,5(2):331-338
[211] Miller D A. Optoelectronics-silicon sees the light. Nature,1995,378(6554):238-238
[212] Nilsson J R. How cytotoxic is zinc? A study on effects of zinc on cellproliferation, endocytosis, and fine structure of the ciliate Tetrahymena. ActaProtozoologica,2003,42(1):19-29
[213] Zhang Y, Chen W, Zhang J, et al. In vitro and in vivo toxicity of CdTenanoparticles. Journal of Nanoscience and Nanotechnology,2007,7(2):497-503
[214] Miller D A. Optoelectronics-silicon sees the light. Nature,1995,378(6554):238-238
[215] Zhang H L, Liu T C, Wang J H, et al. Development of quantum dots inBioimaging. Chinese Journal of Analytical Chemistry,2006,34(10):1491-1495
[216] Zhang Y, Kaji N, Tokeshi M, et al. Nanobiotechnology: quantum dots inbioimaging. Expert Review of Proteomics,2007,4(4):565-572
[217] Kang Z, Liu Y, Tsang C H A, et al. Water-soluble silicon quantum dots withwavelength-tunable photoluminescence. Advanced Materials,2009,21(6):661-664
[218] Hua F, Erogbogbo F, Swihart M T, et al. Organically capped siliconnanoparticles with blue photoluminescence prepared by hydrosilylationfollowed by oxidation. Langmuir,2006,22(9):4363-4370
[219] Hua F, Swihart M T, Ruckenstein E. Efficient surface grafting of luminescentsilicon quantum dots by photoinitiated hydrosilylation. Langmuir,2005,21(13):6054-6062
[220] Li X, He Y, Swihart M T. Surface functionalization of silicon nanoparticlesproduced by laser-driven pyrolysis of silane followed by HF-HNO3etching.Langmuir,2004,20(11):4720-4727
[221] Li X, He Y, Talukdar S S, et al. Process for preparing macroscopic quantitiesof brightly photoluminescent silicon nanoparticles with emission spanning thevisible spectrum. Langmuir,2003,19(20):8490-8496
[222] Holmes J D, Ziegler K J, Doty R C, et al. Highly luminescent siliconnanocrystals with discrete optical transitions. Journal of the AmericanChemical Society,2001,123(16):3743-3748
[223] Pettigrew K A, Liu Q, Power P P, et al. Solution synthesis of alkyl-andalkyl/alkoxy-capped silicon nanoparticles via oxidation of Mg2Si. Chemistryof Materials,2003,15(21):4005-4011
[224] Zhang X, Neiner D, Wang S, et al. A new solution route tohydrogen-terminated silicon nanoparticles: synthesis, functionalization andwater stability. Nanotechnology,2007,18(9):095601-095606
[225] Neiner D, Chiu H W, Kauzlarich S M. Low-temperature solution route tomacroscopic amounts of hydrogen terminated silicon nanoparticles. Journal ofthe American Chemical Society,2006,128(34):11016-11017
[226] Zou J, Sanelle P, Pettigrew K A, et al. Size and spectroscopy of siliconnanoparticles prepared via reduction of SiCl4. Journal of Cluster Science,2006,17(4):565-578
[227] Wilcoxon J P, Samara G A. Tailorable, visible light emission from siliconnanocrystals. Applied Physics Letters,1999,74(21):3164-3166
[228] Wilcoxon J P, Samara G A, Provencio P N. Optical and electronic propertiesof Si nanoclusters synthesized in inverse micelles. Physical Review B,1999,60(4):2704-2714
[229] Tilley R D, Warner J H, Yamamoto K, et al. Micro-emulsion synthesis ofmonodisperse surface stabilized silicon nanocrystals. ChemicalCommunications,2005(14):1833-1835
[230] Mayeri D, Phillips B L, Augustine M P, et al. NMR study of the synthesis ofalkyl-terminated silicon nanoparticles from the reaction of SiCl4with the zintlsalt, NaSi. Chemistry of Materials,2001,13(3):765-770
[231] Rogozhina E V, Eckhoff D A, Gratton E, et al. Carboxyl functionalization ofultrasmall luminescent silicon nanoparticles through thermal hydrosilylation.Journal of Materials Chemistry,2006,16(15):1421-1430
[232] Sato S, Swihart M T. Propionic-acid-terminated silicon nanoparticles:synthesis and optical characterization. Chemistry of Materials,2006,18(17):4083-4088
[233] Sa'Ar A, Reichman Y, Dovrat M, et al. Resonant coupling between surfacevibrations and electronic states in silicon nanocrystals at the strongconfinement regime. Nano Letters,2005,5(12):2443-2447
[234] Veinot J G C. Synthesis, surface functionalization, and properties offreestanding silicon nanocrystals. Chemical Communications,2006(40):4160-4168
[235] Sun Q Y, De Smet L C P M, van Lagen B, et al. Covalently attachedmonolayers on crystalline hydrogen-terminated silicon: extremely mildattachment by visible light. Journal of the American Chemical Society,2005,127(8):2514-2523
[236] Buriak J M, Stewart M P, Geders T W, et al. Lewis acid mediatedhydrosilylation on porous silicon surfaces. Journal of the American ChemicalSociety,1999,121(49):11491-11502
[237] Rosso-asic M, Spruijt E, van Lagen B, et al. Alkyl-unctionalized oxide-freesilicon nanoparticles: synthesis and optical properties. Small,2008,4(10):1835-1841
[238] Nelles J, Sendor D, Ebbers A, et al. Functionalization of silicon nanoparticlesvia hydrosilylation with1-alkenes. Colloid and Polymer Science,2007,285(7):729-736
[239] Canham L T. Silicon quantum wire array fabrication by electrochemical andchemical dissolution of wafers. Applied Physics Letters,1990,57:1046-1048
[240] Godefroo S, Hayne M, Jivanescu M, et al. Classification and control of theorigin of photoluminescence from Si nanocrystals. Nature Nanotechnology,2008,3(3):174-178
[241] Landes C, Burda C, Braun M, et al. Photoluminescence of CdSe nanoparticlesin the presence of a hole acceptor: n-butylamine. The Journal of PhysicalChemistry B,2001,105(15):2981-2986
[242] Landes C F, Braun M, El-Sayed M A. On the nanoparticle to molecular sizetransition: fluorescence quenching studies. The Journal of Physical ChemistryB,2001,105(43):10554-10558
[243] Bruchez M, Moronne M, Gin P, et al. Semiconductor nanocrystals asfluorescent biological labels. Science,1998,281(5385):2013-2016
[244] Michalet X, Pinaud F F, Bentolila L A, et al. Quantum dots for live cells, invivo imaging, and diagnostics. Science,2005,307(5709):538-544
[245] Alivisatos P. The use of nanocrystals in biological detection. NatureBiotechnology,2003,22(1):47-52
[246] Michalet X, Pinaud F, Lacoste T D, et al. Properties of fluorescentsemiconductor nanocrystals and their application to biological labeling. SingleMolecules,2001,2(4):261-276
[247] Gerion D, Pinaud F, Williams S C, et al. Synthesis and properties ofbiocompatible water-soluble silica-coated CdSe/ZnS semiconductor quantumdots. The Journal of Physical Chemistry B,2001,105(37):8861-8871
[248] Dabbousi B O, Rodriguez-Viejo J, Mikulec F V, et al.(CdSe) ZnS core-shellquantum dots: synthesis and characterization of a size series of highlyluminescent nanocrystallites. The Journal of Physical Chemistry B,1997,101(46):9463-9475
[249] He Y, Su Y, Yang X, et al. Photo and pH stable, highly-luminescent siliconnanospheres and their bioconjugates for immunofluorescent cell imaging.Journal of the American Chemical Society,2009,131(12):4434-4438
[250] He Y, Kang Z H, Li Q S, et al. Ultrastable, highly fluorescent, andwater-dispersed silicon-based nanospheres as cellular probes. AngewandteChemie International Edition,2009,48(1),128-132
[251] He Y, Zhong Y, Peng F, et al. Highly luminescent water-dispersible siliconnanowires for long-term immunofluorescent cellular imaging. AngewandteChemie International Edition,2011,50(13),30803083
[252] He Y, Zhong Y, Peng F, et al. One-pot microwave synthesis ofwater-dispersible, ultraphoto-and pH-stable, and highly fluorescent siliconquantum dots. Journal of the American Chemical Society,2011,133(36):14192-14195
[253] Zhong Y, Peng F, Wei X, et al. Microwave-assisted synthesis of biofunctionaland fluorescent silicon nanoparticles using proteins as hydrophilic ligands.Angewandte Chemie International Edition,2012,51(34):8485-8489
[254] Sreenivasan V K A, Zvyagin A V, Goldys E M. Luminescent nanoparticles andtheir applications in the life sciences. Journal of Physics: Condensed Matter,2013,25(19):194101
[255] Choi Y, Cho Y, Kim M, et al. Fluorogenic quantum dot-gold nanoparticleassembly for beta secretase inhibitor screening in live cell. AnalyticalChemistry,2012,84(20):8595-8601
[256] Baker S N, Baker G A. Luminescent carbon nanodots: emergent nanolights.Angewandte Chemie International Edition,2010,49(38):6726-6744
[257] Korzeniowska B, Nooney R, Wencel D, et al. Silica nanoparticles for cellimaging and intracellular sensing. Nanotechnology,2013,24(44):442002
[258] Yang S T, Wang X, Wang H, et al. Carbon dots as nontoxic andhigh-performance fluorescence imaging agents. The Journal of PhysicalChemistry C,2009,113(42):18110-18114
[259] Mulder W J M, Koole R, Brandwijk R J, et al. Quantum dots with aparamagnetic coating as a bimodal molecular imaging probe. Nano Letters,2006,6(1):1-6
[260] Yu H, Xiao Y, Jin L. A Lysosome-targetable and two-photon fluorescentprobe for monitoring endogenous and exogenous nitric oxide in living cells.Journal of the American Chemical Society,2012,134(42):17486-17489
[261] Dickinson B C, Chang C J. A targetable fluorescent probe for imaginghydrogen peroxide in the mitochondria of living cells. Journal of the AmericanChemical Society,2008,130(30):9638-9639
[262] Karunakaran S C, Babu P S S, Madhuri B, et al. In vitro demonstration ofapoptosis mediated photodynamic activity and NIR nucleus imaging through anovel porphyrin. ACS Chemical Biology,2012,8(1):127-132
[263] Kuo C W, Chueh D Y, Singh N, et al. Targeted nuclear delivery usingpeptide-coated quantum dots. Bioconjugate Chemistry,2011,22(6):1073-1080
[264] Tan S J, Jana N R, Gao S, et al. Surface-ligand-dependent cellular interaction,subcellular localization, and cytotoxicity of polymer-coated quantum dots.Chemistry of Materials,2010,22(7):2239-2247
[265] Huang D, Su L, Peng X, et al. Quantum dot-based quantification revealeddifferences in subcellular localization of EGFR and E-cadherin betweenEGFR-TKI sensitive and insensitive cancer cells. Nanotechnology,2009,20(22):225102
[266] Du F, Min Y, Zeng F, et al. A targeted and FRET-based ratiometricfluorescent nanoprobe for imaging mitochondrial hydrogen peroxide in livingcells. Small,2013
[267] Nan X, Sims P A, Chen P, et al. Observation of individual microtubule motorsteps in living cells with endocytosed quantum dots. Journal of PhysicalChemistry B,2005,109(51):24220-24224
[268] Courty S, Luccardini C, Bellaiche Y, et al. Tracking individual kinesin motorsin living cells using single quantum-dot imaging. Nano Letters,2006,6(7):1491-1495
[269] Cao L, Wang X, Meziani M J, et al. Carbon dots for multiphoton bioimaging.Journal of the American Chemical Society,2007,129(37):11318-11319
[270] Yang S T, Cao L, Luo P G, et al. Carbon dots for optical imaging in vivo.Journal of the American Chemical Society,2009,131(32):11308-11309
[271] Sun Y P, Zhou B, Lin Y, et al. Quantum-sized carbon dots for bright andcolorful photoluminescence. Journal of the American Chemical Society,2006,128(24):7756-7757
[272] Yang S T, Wang X, Wang H, et al. Carbon dots as nontoxic andhigh-performance fluorescence imaging agents. The Journal of PhysicalChemistry C,2009,113(42):18110-18114
[273] Ray S C, Saha A, Jana N R, et al. Fluorescent carbon nanoparticles: synthesis,characterization, and bioimaging application. The Journal of PhysicalChemistry C,2009,113(43):18546-18551
[274] Zhao Q L, Zhang Z L, Huang B H, et al. Facile preparation of low cytotoxicityfluorescent carbon nanocrystals by electrooxidation of graphite. ChemicalCommunications,2008,41:5116-5118
[275] Sun Y P, Wang X, Lu F, et al. Doped carbon nanoparticles as a new platformfor highly photoluminescent dots. The Journal of Physical Chemistry C,2008,112(47):18295-18298
[276] Xu X, Ray R, Gu Y, et al. Electrophoretic analysis and purification offluorescent single-walled carbon nanotube fragments. Journal of the AmericanChemical Society,2004,126(40):12736-12737
[277] Wang X, Cao L, Lu F, et al. Photoinduced electron transfers with carbon dots.Chemical Communications,2009,25:3774-3776
[278] Peng H, Travas-Sejdic J. Simple aqueous solution route to luminescentcarbogenic dots from carbohydrates. Chemistry of Materials,2009,21(23):5563-5565
[279] Baker S N, Baker G A. Luminescent carbon nanodots: emergent nanolights.Angewandte Chemie International Edition,2010,49(38):6726-6744
[280] Wang X, Qu K, Xu B, et al. Multicolor luminescent carbon nanoparticles:synthesis, supramolecular assembly with porphyrin, intrinsic peroxidase-likecatalytic activity and applications. Nano Research,2011,4(9):908-920
[281] Ravindran S, Chaudhary S, Colburn B, et al. Covalent coupling of quantumdots to multiwalled carbon nanotubes for electronic device applications.Nano Letters,2003,3(4):447-453
[282] Dong Y, Zhou N, Lin X, et al. Extraction of electrochemiluminescent oxidizedcarbon quantum dots from activated carbon. Chemistry of Materials,2010,22(21):5895-5899
[283] Tian L, Ghosh D, Chen W, et al. Nanosized carbon particles from natural gassoot. Chemistry of Materials,2009,21(13):2803-2809
[284] Qiao Z A, Wang Y, Gao Y, et al. Commercially activated carbon as the sourcefor producing multicolor photoluminescent carbon dots by chemical oxidation.Chemical Communications,2010,46:8812-8814
[285] Zhou J, Booker C, Li R, et al. An electrochemical avenue to blue luminescentnanocrystals from multiwalled carbon nanotubes (MWCNTs). Journal of theAmerican Chemical Society,2007,129(4):744-745
[286] Lu J, Yang J, Wang J, et al. One-pot synthesis of fluorescent carbonnanoribbons, nanoparticles, and graphene by the exfoliation of graphite inionic liquids. ACS Nano,2009,3(8):2367-2375
[287] Hu S L, Niu K Y, Sun J, et al. One-step synthesis of fluorescent carbonnanoparticles by laser irradiation. Journal of Materials Chemistry,2009,19(4):484-488
[288] Li H, He X, Kang Z, et al. Water-soluble fluorescent carbon quantum dots andphotocatalyst design. Angewandte Chemie International Edition,2010,49(26):4430-4434
[289] Bourlinos A B, Stassinopoulos A, Anglos D, et al. Surface functionalizedcarbogenic quantum dots. Small,2008,4(4):455-458
[290] Zhu H, Wang X, Li Y, et al. Microwave synthesis of fluorescent carbonnanoparticles with electrochemiluminescence properties. ChemicalCommunications,2009,34:5118-5120
[291] Bourlinos A B, Stassinopoulos A, Anglos D, et al. Photoluminescentcarbogenic dots. Chemistry of Materials,2008,20(14):4539-4541
[292] Chandra S, Das P, Bag S, et al. Synthesis, functionalization and bioimagingapplications of highly fluorescent carbon nanoparticles. Nanoscale,2011,3(4):1533-1540
[293] Mitra S, Chandra S, Patra P, et al. Novel fluorescent matrix embedded carbonquantum dots for the production of stable gold and silver hydrosols. Journal ofMaterials Chemistry,2011,21(44):17638-17641
[294] Liu H, Ye T, Mao C. Fluorescent carbon nanoparticles derived from candlesoot. Angewandte Chemie International Edition,2007,46(34):6473-6475
[295] Zhang H, Huang H, Ming H, et al. Carbon quantum dots/Ag3PO4complexphotocatalysts with enhanced photocatalytic activity and stability undervisible light. Journal of Materials Chemistry,2012,22(21):10501-10506
[296] Chandra S, Mitra S, Laha D, et al. Fabrication of multi-structure nanocarbonsfrom carbon xerogel: a unique scaffold towards bioimaging. ChemicalCommunications,2011,47(30):8587-8589
[297] Yu S J, Kang M W, Chang H C, et al. Bright fluorescent nanodiamonds: nophotobleaching and low cytotoxicity. Journal of the American ChemicalSociety,2005,127(50):17604-17605
[298] Bharali D J, Lucey D W, Jayakumar H, et al. Folate-receptor-mediateddelivery of InP quantum dots for bioimaging using confocal and two-photonmicroscopy. Journal of the American Chemical Society,2005,127(32):11364-11371
[299] Zhu S, Zhang J, Qiao C, et al. Strongly green-photoluminescent graphenequantum dots for bioimaging applications. Chemical Communications,2011,47:6858-6860
[300] Zhao Q L, Zhang Z L, Huang B H, et al. Facile preparation of low cytotoxicityfluorescent carbon nanocrystals by electrooxidation of graphite. ChemicalCommunications,2008,41:5116-5118
[301] Yang Y, Cui J, Zheng M, et al. One-step synthesis of amino-functionalizedfluorescent carbon nanoparticles by hydrothermal carbonization of chitosan.Chemical Communications,2012,48(3):380-382
[302] Yang Z C, Wang M, Yong A M, et al. Intrinsically fluorescent carbon dotswith tunable emission derived from hydrothermal treatment of glucose in thepresence of monopotassium phosphate. Chemical Communications,2011,47:11615-11617
[303] Sun Y P, Zhou B, Lin Y, et al. Quantum-sized carbon dots for bright andcolorful photoluminescence. Journal of the American Chemical Society,2006,128(24):7756-7757
[304] Wang F, Xie Z, Zhang H, et al. Highly luminescentorganosilane-functionalized carbon dots. Advanced Functional Materials,2011,21(6):1027-1031
[305] Li Q, Ohulchanskyy T Y, Liu R, et al. Photoluminescent carbon dots asbiocompatible nanoprobes for targeting cancer cells in vitro. The Journal ofPhysical Chemistry C,2010,114(28):12062-12068
[306] Esteves da Silva J C G, Gon alves H M R. Analytical and bioanalyticalapplications of carbon dots. TrAC Trends in Analytical Chemistry,2011,30(8):1327-1336
[307] Mao X J, Zheng H Z, Long Y J, et al. Study on the fluorescence characteristicsof carbon dots. Spectrochimica Acta Part A: Molecular and BiomolecularSpectroscopy,2010,75(2):553-557
[308] Bolger P M, Schwetz B A. Mercury and health. The New England Journal ofMedicine,2002,347(22):1735
[309] Stern A H. A review of the studies of the cardiovascular health effects ofmethylmercury with consideration of their suitability for risk assessment.Environmental Research,2005,98(1):133-142
[310] Morel F M M, Kraepiel A M L, Amyot M. The chemical cycle andbioaccumulation of mercury. Annual Review of Ecology and Systematics,1998:543-566
[311] Onyido I, Norris A R, Buncel E. Biomolecule-mercury interactions: modalitiesof DNA base-mercury binding mechanisms. Remediation strategies. ChemicalReviews,2004,104(12):5911-5930
[312] Prodi L, Bargossi C, Montalti M, et al. An effective fluorescent chemosensorfor mercury ions. Journal of the American Chemical Society,2000,122(28):6769-6770
[313] Nolan E M, Lippard S J. A “turn-on” fluorescent sensor for the selectivedetection of mercuric ion in aqueous media. Journal of the American ChemicalSociety,2003,125(47):14270-14271
[314] Zhu X J, Fu S T, Wong W K, et al. A near-infrared-fluorescentchemodosimeter for mercuric ion based on an expanded porphyrin.Angewandte Chemie International Edition,2006,45(19):3150-3154
[315] Yang Y K, Yook K J, Tae J. A rhodamine-based fluorescent and colorimetricchemodosimeter for the rapid detection of Hg2+ions in aqueous media. Journalof the American Chemical Society,2005,127(48):16760-16761
[316] Nolan E M, Lippard S J. Turn-on and ratiometric mercury sensing in waterwith a red-emitting probe. Journal of the American Chemical Society,2007,129(18):5910-5918
[317] Zhu C, Li L, Fang F, et al. Functional InP nanocrystals as novel near-infraredfluorescent sensors for mercury ions. Chemistry Letters,2005,34(7):898-899
[318] Huang C C, Chang H T. Selective gold-nanoparticle-based “turn-on”fluorescent sensors for detection of mercury (II) in aqueous solution.Analytical Chemistry,2006,78(24):8332-8338
[319] Kim I B, Bunz U H F. Modulating the sensory response of a conjugatedpolymer by proteins: an agglutination assay for mercury ions in water. Journalof the American Chemical Society,2006,128(9):2818-2819
[320] Liu X, Tang Y, Wang L, et al. Optical detection of mercury (II) in aqueoussolutions by using conjugated polymers and label-free oligonucleotides.Advanced Materials,2007,19(11):1471-1474
[321] Nolan M A, Kounaves S P. Microfabricated array of iridium microdisks as asubstrate for direct determination of Cu2+or Hg2+using square-wave anodicstripping voltammetry. Analytical Chemistry,1999,71(16):3567-3573
[322] Wang S, Forzani E S, Tao N. Detection of heavy metal ions in water byhigh-resolution surface plasmon resonance spectroscopy combined with anodicstripping voltammetry. Analytical Chemistry,2007,79(12):4427-4432
[323] Hollenstein M, Hipolito C, Lam C, et al. A highly selective DNAzyme sensorfor mercuric ions. Angewandte Chemie International Edition,2008,47(23):4346-4350
[324] Chen P, He C. A general strategy to convert the merR family proteins intohighly sensitive and selective fluorescent biosensors for metal ions. Journal ofthe American Chemical Society,2004,126(3):728-729
[325] Miyake Y, Togashi H, Tashiro M, et al. Mercury(II)-mediated formation ofthymine-Hg(II)-thymine base pairs in DNA duplexes. Journal of the AmericanChemical Society,2006,128(7):2172-2173
[326] Tanaka Y, Oda S, Yamaguchi H, et al.15N-15N J-coupling across Hg(II): directobservation of Hg(II)-mediated TT base pairs in a DNA duplex. Journal of theAmerican Chemical Society,2007,129(2):244-245
[327] Lee J S, Han M S, Mirkin C A. Colorimetric detection of mercuric ion (Hg2+)in aqueous media using DNA-functionalized gold nanoparticles. AngewandteChemie International Edition,2007,46(22):4093-4096
[328] Xue X, Wang F, Liu X. One-step, room temperature, colorimetric detection ofmercury (Hg2+) using DNA/nanoparticle conjugates. Journal of the AmericanChemical Society,2008,130(11):3244-3245
[329] Liu C W, Hsieh Y T, Huang C C, et al. Detection of mercury (II) based onHg2+-DNA complexes inducing the aggregation of gold nanoparticles.Chemical Communications,2008(19):2242-2244
[330] Li D, Wieckowska A, Willner I. Optical analysis of Hg2+ions byoligonucleotide-gold-nanoparticle hybrids and DNA-based machines.Angewandte Chemie International Edition,2008,47(21):3927-3931
[331] Ono A, Togashi H. Highly selective oligonucleotide-based sensor for mercury(II) in aqueous solutions. Angewandte Chemie International Edition,2004,43(33):4300-4302
[332] Liu J, Lu Y. Rational design of “Turn-On” allosteric DNAzyme catalyticbeacons for aqueous mercury ions with ultrahigh sensitivity and selectivity.Angewandte Chemie International Edition,2007,46(40):7587-7590
[333] Chiang C K, Huang C C, Liu C W, et al. Oligonucleotide-based fluorescenceprobe for sensitive and selective detection of mercury (II) in aqueous solution.Analytical Chemistry,2008,80(10):3716-3721
[334] Wang J, Liu B. Highly sensitive and selective detection of Hg2+in aqueoussolution with mercury-specific DNA and sybr green I. ChemicalCommunications,2008(39):4759-4761
[335] Fan C, Plaxco K W, Heeger A J. Electrochemical interrogation ofconformational changes as a reagentless method for the sequence-specificdetection of DNA. Proceedings of the National Academy of Sciences,2003,100(16):9134-9137
[336] Xiao Y, Lubin A A, Heeger A J, et al. Label-free electronic detection ofthrombin in blood serum by using an aptamer-based sensor. AngewandteChemie International Edition,2005,44(34):5456-5459
[337] Radi A E, Acero Sánchez J L, Baldrich E, et al. Reagentless, reusable,ultrasensitive electrochemical molecular beacon aptasensor. Journal of theAmerican Chemical Society,2006,128(1):117-124
[338] Xiao Y, Rowe A A, Plaxco K W. Electrochemical detection of parts-per-billionlead via an electrode-bound DNAzyme assembly. Journal of the AmericanChemical Society,2007,129(2):262-263
[339] Willner I, Zayats M. Electronic aptamer-based sensors. Angewandte ChemieInternational Edition,2007,46(34):6408-6418
[340] Wu Z S, Guo M M, Zhang S B, et al. Reusable electrochemical sensingplatform for highly sensitive detection of small molecules based onstructure-switching signaling aptamers. Analytical Chemistry,2007,79(7):2933-2939
[341] Zhang Y L, Huang Y, Jiang J H, et al. Electrochemical aptasensor based onproximity-dependent surface hybridization assay for single-step, reusable,sensitive protein detection. Journal of the American Chemical Society,2007,129(50):15448-15449
[342] Huang Y, Zhang Y L, Xu X, et al. Highly specific and sensitiveelectrochemical genotyping via gap ligation reaction and surface hybridizationdetection. Journal of the American Chemical Society,2009,131(7):2478-2480
[343] Zhang Y, Wang Y, Wang H, et al. Electrochemical DNA biosensor based onthe proximity-dependent surface hybridization assay. Analytical Chemistry,2009,81(5):1982-1987
[344] Fahlman R P, Sen D. DNA conformational switches as sensitive electronicsensors of analytes. Journal of the American Chemical Society,2002,124(17):4610-4616
[345] Salaün P, van den Berg C M G. Voltammetric detection of mercury and copperin seawater using a gold microwire electrode. Analytical Chemistry,2006,78(14):5052-5060
[346] Steel A B, Levicky R L, Herne T M, et al. Immobilization of nucleic acids atsolid surfaces: effect of oligonucleotide length on layer assembly. BiophysicalJournal,2000,79(2):975-981
[347] Demers L M, Mirkin C A, Mucic R C, et al. A fluorescence-based method fordetermining the surface coverage and hybridization efficiency of thiol-cappedoligonucleotides bound to gold thin films and nanoparticles. AnalyticalChemistry,2000,72(22):5535-5541
[348] Hirst J, Duff J L C, Jameson G N L, et al. Kinetics and mechanism ofredox-coupled, long-range proton transfer in an iron-sulfur protein.Investigation by fast-scan protein-film voltammetry. Journal of the AmericanChemical Society,1998,120(28):7085-7094
[349] Anne A, Bouchardon A, Moiroux J.3'-ferrocene-labeled oligonucleotidechains end-tethered to gold electrode surfaces: novel model systems forexploring flexibility of short DNA using cyclic voltammetry. Journal of theAmerican Chemical Society,2003,125(5):1112-1113
[350] Patolsky F, Lichtenstein A, Willner I. Electronic transduction of DNA sensingprocesses on surfaces: amplification of DNA detection and analysis ofsingle-base mismatches by tagged liposomes. Journal of the AmericanChemical Society,2001,123(22):5194-5205
[351] Bonfil Y, Brand M, Kirowa-Eisner E. Trace determination of mercury byanodic stripping voltammetry at the rotating gold electrode. Analytica ChimicaActa,2000,424(1):65-76
[352] Xiao L, Dietze W, Nyasulu F, et al. Ultramicroband array electrode.1. analysisof mercury in contaminated soils and flue gas exposed samples using agold-plated iridium portable system by anodic stripping voltammetry.Analytical Chemistry,2006,78(14):5172-5178
[353] Griffiths-Jones S, Saini H K, van Dongen S, et al. MiRBase: tools formicroRNA genomics. Nucleic Acids Research,2008,36(suppl1): D154-D158
[354] Johnson S M, Grosshans H, Shingara J, et al. RAS is regulated by the let-7microRNA fimily. Cell,2005,120:635-647
[355] Stahlhut E C E, Slack F J. The role of microRNAs in cancer. The Yale Journalof Biology and Medicine,2006,79(3-4),131-140
[356] Reinhart B J, Slack F J, Basson M, et al. The21-nucleotide let-7RNAregulates developmental timing in caenorhabditis elegans. Nature,2000,403(6772):901-906
[357] Lee R C, Ambros V. An extensive class of small RNAs in caenorhabditiselegans. Science,2001,294(5543):862-864
[358] Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identification of novelgenes coding for small expressed RNAs. Science,2001,294(5543):853-858
[359] Calin G A, Dumitru C D, Shimizu M, et al. Frequent deletions and down-regulation of microRNA genes miR15and miR16at13q14in chroniclymphocyticleukemia. Proceedings of the National Academy of Sciences,2002,99(24):15524-15529
[360] Yan J, Li Z, Liu C, et al. Simple and sensitive detection of microRNAs withligase chain reaction. Chemical Communications,2010,46(14):2432-2434
[361] Zhang Y, Li Z, Cheng Y, et al. Colorimetric detection of microRNA andRNase H activity in homogeneous solution with cationic polythiophenederivative. Chemical Communications,2009,22:3172-3174
[362] Allawi H T, Dahlberg J E, Olson S, et al. Quantitation of microRNAs using amodified invader assay. RNA,2004,10(7):1153-1161
[363] Hartig J S, Grüne I, Najafi-Shoushtari S H, et al. Sequence-specific detectionof microRNAs by signal-amplifying ribozymes. Journal of the AmericanChemical Society,2004,126(3):722-723
[364] Maroney P A, Chamnongpol S, Souret F, et al. A rapid, quantitative assay fordirect detection of microRNAs and other small RNAs using splinted ligation.RNA,2007,13(6):930-936
[365] Matthew M L, Samuel J L, Bennett E, et al. Characterization of the5' to3'exonuclease associated with Therrmus aquaticus DNA polymerase. NucleicAcids Research,1990,18(24):7317-7322