基于分子开关的微流控芯片构建及其在生物分析中的应用
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摘要
人们一直致力于采用宏观手段对微观世界进行操控,从而通过改变物质微结构来实现对其宏观性质的改变。其中通过对物质微观结构、构成、构象、形态、氧化态等性质的控制来可逆的改变物质性质在近年来引起了越来越多的兴趣。可逆变换类似于“开/关”切换,这类操控使得我们能够随心所欲的对物质的性质进行控制,达到智能操控、反复利用的目的。因此,对具有“开/关”性质的物质、体系的研究一直是人们关注的热点。而要构建这类物质和体系,需要从原子或分子层面上开始建造特殊的微观结构。自下而上的以原子,分子为基本单元,根据人们的意愿进行设计和组装,从而构筑成具有特定开关功能的器件,这些器件就被形象的称为“分子开关”。
所谓分子开关泛指结构上组织化了的具有“开/关”功能的化学体系。它们具有双稳态的量子化体系,外部条件的变化能激励分子开关在这两种稳态间切换。常用于激励分子开关的因素包括光、电、热、磁、化学能(酸碱度、特殊分子和离子)等,这些条件的变化在微观上能引起电子和原子核的重排,使得分子的形状、化学键的生成或断裂、以及旋转等性质会随之变化,这些几何和化学的变化在宏观上表现出亲疏水性、颜色、水溶性等性质的变化,能实现信息传输的功能。随着微电子技术和生物工程这两项高科技的互相渗透,分子开关实际上已为研制分子器件提供了可能。
智能化表面(Smart surface)是一类组织化、集成化、平面化的分子开关,是具有可操控的开关功能的表面。常见的智能表面由聚合物、自组装单分子层(Self-assembled monolayer,SAM)、特殊的纳米金属氧化物等组成,激励它发生性质可逆转化的因素包括温度、光照、电场、pH值、溶剂等等。在这些外界激励下,表面分子可以发生可逆的构象转化、构型转化、氧化态的转化等等,从而在宏观上,使整个表面呈现出亲疏水性、光学性质、带电性等性质的可逆转化,即可呈现出“开/关”的性质。
微流控器件是微型全化学分析系统(Micro total analysis system,μ-TAS)的核心部分,是可用于生物分离分析、环境监测、医疗诊断等的有效手段。由于其操作简便、灵敏、快速、试剂消耗量少,易于实现自动化和在线监测,具有广阔的应用前景,一直是人们关注的热点。微流控芯片是一类被广泛研究和使用的微流控器件,目前对微流控芯片的研究十分广泛和深入,根据不同的用途,人们设计了多种多样的芯片,并将其成功的用在很多研究领域,包括传感器,化学反应器,生物反应器等。
本论文基于超分子包合物、自组装技术、温敏生物复合物等要素构建两类具有开关功能的智能表面,成功将这些智能化的表面用于蛋白质程序吸附释放以及抗原抗体的可逆识别。并基于这些智能表面制作了智能微器件——微流控芯片。一类是对电压敏感的智能表面。这是一种低密度的自组装单分子层(Low densitySAM,LD-SAM),它是电压可操控的亲疏水开关,其亲疏水性可随外加电压变化而切换,并且能实现对抗生物素(Avidin)、链霉抗生物素(Streptavidin)的可控吸附。另一类是和温敏智能表面,利用温敏高分子材料聚-N异丙基丙烯酰胺(Poly(N-isopropylacrylamide),PNIPAAm)与抗BSA抗体合成的生物复合物,构建了具有温度敏感开关功能的可再生免疫表面。该方法实现了免疫表面的再生,使其能够重复使用,同时为研究蛋白质-蛋白质动态相互作用过程提供了一个新平台。
进一步的,我们将这些智能表面引入微流控芯片,构建了有开关功能的电压敏感微流控芯片,并成功将其应用于蛋白质的可控吸附释放及分离中。该芯片制作成本低、能耗少、试剂消耗少,使用方便,易于检测,具有很好的应用前景。也是一个新型的基于自组织单分子层构建智能微器件的成功范例。还尝试了将上述温敏免疫表面修饰到微流控芯片的槽道中,以期构建温度敏感的免疫型微流控芯片,实现在微通道中的可控免疫识别。
本论文共六章内容,主要摘要如下:
第一章综述了分子开关、智能表面和微流控芯片的研究现状及其相关技术在生物传感器领域的应用进展。分子自组装和高分子聚合物是构建分子开关的两条重要途径。自组装单分子层是构膜分子与基底材料间发生物化作用而自发形成的一种热力学稳定、排列规则的单层分子膜。这种构膜方式,可以容易的为表面引入各种各样的功能团,这就为制备具有多种不同功能的智能化表而打下了很好的基础。温敏材料是指对温度有响应并能发生性质变化的一类材料。具有“温度开关”特性的PNIPAAm是被广泛研究的温敏高分子材料。利用它对温度响应的敏感性,使其在可控药物传输、免疫分析、细胞培养等研究领域都有着广泛的潜力。
第二章介绍了基于自组装技术构建对电压敏感的亲疏水开关表面,及其在蛋白质可控吸附方面的应用。该工作基于超分子包合物的概念,利用环糊精分子控制长链巯酸分子的间距,并通过自组装方法在余表面构建了包合物自组装膜,再以乙醇作为高效的洗脱溶剂,得到间距均一、性能稳定的低密度十六巯酸分子LD-SAM,即为对电压敏感的具有可逆亲/疏水性性质的智能化表面。以高密度自组装膜表而的覆盖度为100%计算可知,α,β,γ三种环糊精分子构建的低密度自组装膜表面的覆盖度分别为61.2%,45.3%和29.2%。通过改变外加电压,引发巯酸分子的构型变化,从而实现表面的亲水/疏水性能的转换。利用质谱,核磁,交流阻抗,QCM,荧光等多种检测手段论证的该智能表面的制成,并用接触角实验证明了智能表面对电压的可逆响应。采用荧光标记抗Avidin、Streptavidin蛋白分子作为研究对象,考察十六巯酸LD-SAM智能表面对带不同等电点的蛋白质的可控吸附。结果证明十六巯酸分子LD-SAM对带正电的Avidin蛋白有明显的电压控制的吸附作用。
第三章是进一步的将上述智能表面“移植”到微流控芯片体系,发展了两类利用“分子开关”原理构建的智能微流控芯片,并将其成功用于蛋白质的可控吸附中。本章利用成本低,加工简单的聚甲基丙烯酸甲酯(PMMA)有机玻璃为制作微流控芯片的材料,利用热压法制作“一字槽”的芯片,用电子溅射法在芯片的槽道表面镀金,作为整个芯片功能的核心区域,然后在对金面进行一系列的功能化修饰。在这一章的工作中,我们不仅直接将基于十六巯酸分子LD-SAM制作的智能表面修饰到芯片槽道中,得到智能化的巯酸微流控芯片(COOH-芯片),还进一步扩展思路,设计制作了基于巯胺分子LD-SAM的智能表面,其表面分子的末端带有胺基,不同于十六巯酸分子LD-SAM末端所带的羧基。这种表面与巯酸表面相反,在特定条件下对带负电的被分析物有可控的吸附作用。
COOH-芯片对带正电的蛋白质有可控的吸附作用。基于此巯胺分子LD-SAM制得的巯胺微流控芯片(NH_2-芯片)对带负电的蛋白质有可控的吸附作用。这一工作是利用智能表面制作智能器件的成功尝试。
第四章将上述两类智能微流控芯片进一步应用于蛋白质的程序吸附/释放,以及混合蛋白质的可控分离。以Avidin和Streptavidin为模型蛋白实现蛋白质混合物的分离,采用荧光检测、激光诱导荧光、共聚焦荧光显微镜等手段进行表征,分离效果理想。对COOH-芯片先后施加负、正电压能够先吸附溶液中的Avidin,在转变电压后将其释放,因此该芯片能从Avidin/Streptavidin混合物中将Avidin分离出来,回收率超过80%;对NH_2-芯片先后施加正、负电压能够将混合蛋白中的带负电的Streptavidin吸附,而在转变电压后再释放出来,从而也实现了蛋白分离,回收率也超过了80%。另外还用COOH-芯片成功的从混合的Avidin/Streptavidin蛋白中分离出了低含量的Avidin(Avidin与Streptavidin的摩尔比为1:1000),因此这种基于电压敏感的智能表面的微流控芯片有望成为一种新的分离低丰度蛋白的微器件,这对于蛋白组学微分析系统有重要的意义。
第五章是基于温敏聚合物的表面分子开关构建及抗原抗体可逆识别界面和微流控器件的研究。将温敏高分子材料PNIPAAm与抗BSA抗体合成的生物复合物(Bioconjugate)组装到金表面,得到的温敏免疫表面能对温度做出响应,可逆的与对应抗原BSA进行识别。这种温敏高分子材料的形态随温度发生变化,对抗原结合过程中造成的空间位阻不同,从而影响抗原抗体的结合,能使已结合的抗原抗体分离,由此实现抗体表面的再生。再生率最高可以达到89%以上,与文献报道的有机溶液再生表面法(再生率80%-92%)相当,而且这个方法基本没有破坏生物识别体系的活性和环境,抗原抗体均可重复利用,这种温敏开关免疫传感器可重复使用30次以上,抗疲劳性较好。我们还初步尝试将之应用于微流控芯片体系,有望发展利用温敏“分子开关”原理构建的免疫型微流控芯片。
第六章对整个论文工作进行了全面总结,并对下一步的工作进行了展望和建议,包括多检测对象温敏微流控芯片的的构建和应用、基于咯吡喃等分子构建光敏表面和基于单分散碳纳米管的可控荧光发光体系。
总之,本论文以表面分子开关为基础,研究了不同的智能表面及微流控器件。利用自组装膜技术,温敏聚合物材料,结合不同环境激励,构建了亲疏水开关表面、温度敏感的免疫表面,以及基于这些开关表面的智能化微流控器件。并将其成功应用于可控的蛋白质分离、抗原-抗体可逆识别的考察与研究中。
Lots of work has been focused on controlling the microcosmic world with macrocosmic methods,and subsequently to control the macrocosmic change of the substance property by changing their micro-structures.Among these work,it's becoming more and more attractive to control the properties reversibly through manipulating the structure,compose,conformation and oxidation state and so on.The reversible change is similar to "on/off" switching.With this kind of operation,we can control the properties of substance,to realize intelligent manipulation and reduplicate usage.Therefore,the research of substance and systems with "on/off" property is bewitching.In order to construct these kinds of systems,it's needed to construct special microcosmic structures on the atom or molecule scale.To use atoms and molecules as basic unit to design and assembly with a "bottom-up" style,we can get devices with special "on/off" property,which are called "molecular switches".
"Molecular switches" are chemical systems with organized structures and "on/off" function.They have two stable states,between which they can switch under the external stimulus.The external stimulus could be photo,electrical potential, temperature,chemical energies(pH,specific molecules or ions).When some of these conditions change,the electrons would be rearranged,leading to the change of molecular shape,formation of deformation of chemical bond.And accordingly,these changes will result in the change of wettability,color,solubility,etc.,which could be useful for information convection.Based on the interaction of micro-electronics and bioengineering,it becomes possible to construct molecular devices with molecular switches.
Smart surface is a kind of well organized,compositive,planar molecular switches.It's a surface with controlled "on/off" ability.Usually,smart surfaces are fabricated from polymer,self-assemble monolayer(SAM),special metallic oxide nano materials.The environmental conditions could inspire the property change of smart surface include temperature,light,electric field,pH,solvents and so on.The molecules composing the surface can behave conformational,configurational switching upon the stimuli,and therefore induce reversible changes in wettability, optics,electricity,etc.
Microfluidic devices are the core parts of micro total analysis system(μ-TAS) and effective means for bioseparation,bioassay,environmental inspection,medical diagnosis.Because it's easy to manipulate it,and it's sensitive,fast and low reagent consumption,it's convenient to realize automatization and on-line measurements with the microfluidic devices.Microfluidic chips are well researched and widely used microfluidic devices.Many kinds of microfluidic chips have been designed and fabricated according to different applications,including sensors,reaction containers and so on.
This thesis is about to fabricate two kinds of smart surface based on supermolecules,inclusive complexes,self-assembly technique,and temperature-sensitive polymers.Furthermore,expand these surfaces to protein program adsorption,separation and reproducing of antibody.Thirdly,to make smart microfluidic chips with these surfaces.One of the smart surfaces is electricity-sensitive smart surface.It's a low-density SAM.This layer is a potential controlled hydrophilic/hydrophobic switch.Its wettability could change under the applied electric potential.Subsequently,it can reversibly adsorb and release avidin or streptavidin protein under the potential control.The other is a temperature-sensitive surface,with thermosensitive polymer PNIPAAm,we got bioconjugate between PNIPAAm and anti-BSA antibody,and fabricated a temperature-sensitive and reproducible smart surface.This approach realizes the regeneration of the immune surface,so it can be used again and again.Meanwhile,it supplies a new research platform for protein-protein interaction.
Furthermore,we introduce these smart surfaces into microfluidic chips to prepare smart chips with "on/off" property.And also these chips were successfully applied in controlled protein adsorption/release and separation.This kind of microfluidic chip is cheap,low energy and reagent consumption,easily measured.So it's a successful example of fabricating smart microfluidic devices with SAM.
This paper contains 6 chapters which are outlined below:
In Chapter 1,the research of molecular switches,smart surface and microfluidic chips are reviewed.Molecule self-assembly and polymer are the main two ways to get molecular switches.SAM is a stable,well organized monolayer from the spontaneous interaction between the molecules and the substrate.It's easy to introduce kinds of functional groups to the surface with this method,which supplies a good foundation for smart surface with different functions.Thermosensitive polymers can behave property change upon temperature change.PNIPAAm is a typical and widely studied thermosensitive polymer.They are widely used in drug release,immune assay and cell culture.
In Chapter 2,fabricating potential-sensitive smart surface based on self-assembly technique,and its application in controlled protein adsorption are investigated. Cyclodextrin was used to control the density of the monolayer to get low-density 16-mercaptohexadecanoic acid monolayer(MHA LD-SAM).Referring to high-density MHA SAM,the surface coverage for LD-SAM fromα-,β-,γ-cyclodextrin shows an obvious decrease from 100%to 61.2%,45.3%and 29.2%, respectively.By applying different potentials to this surface,the MHA molecule could behave conformational transformation and accordingly the wettability of the surface could change.The achievement of the smart surface(MHA LD-SAM) was proved with MALDI-TOF-MS,quartz crystal microbalance(QCM),NMR,cyclic voltammetry(CV) and impedance(IMP).Contact angle measurement was used to prove the wettability change of the surface.The prepared smart surface was also used for controlled protein adsorption,which was characterized with QCM and fluorescence measurements.
In Chapter 3,the electric potential-sensitive surface was implemented into microfluidic chip to develpe two kinds of smart chips,which were applied in controlled protein adsorption.With the cheap material,PMMA,we made chips using hot-imprinting method.The prepared microfluidic chips were with a channel in the centre,and on the channel surface a layer of gold was modified,on which the followed fictionalizations were implemented.We fabricated two chips,the one is COOH-chip with terminal carboxyl groups on the channel surface,and the other is NH_2-chip with terminal amino groups on the channel surface.They can adsorb positive and negative potentials under potential control,respectively.
Chapter 4 is about the application of the smart microfluidic chips in protein adsorption/release and separation.Fluorescence,laser induced fluorescence(LIF) and confocal fluorescence microscopy(CFFM) are used to demonstrate the separation. For COOH-chip,it can capture more than 80%avidin from the Avidin/Streptavidin mixture upon external potential;as for NH_2-chip,it can also separate more 80% Streptavidin from the Avidin/Streptavidin mixture.And COOH-chip was used to separate low concentrate Avidin from the Avidin/Streptavidin mixture with a molar ratio of 1:1000 of Avidin:Streptavidin.The results were satisfying.So this electric potential-sensitive smart microfluidic chips is a possible alternative method for concentrating low-abundance proteins,which is very important for proteomics research.
Chapter 5 describes establishing the PNIPAAm-antibody surface that could supply the most effective dissociation of the antigen and regeneration of antibody into reuse of the immunosensors.As a model antibody-antigen system,bovine serum albumin(BSA) and the corresponding antibody anti-BSA were chosen.A reversible PNIPAAm-antibody conjugate surface was established by triggered control of external temperature.This took advantage of the thermally tuable conformation changes for the PNIPAAm-conjugated antibody surface,and could be used for switchable antigen association and dissociation.The temperature controlling strategy could realized the regeneration of the immunosensor on which immobilized anti-BSA antibodies retain the activity and specificity necessary to carry out more than 30 reproducible assays for BSA.The dissociation reaches 89%,which can compare with the general recovery methods.The controlled binding and unbinding were monitored by QCM,CFFM,native electrophoresis,laser induced fluorescence,and electrochemical impedance.
Chapter 6 is the summary of this thesis and the future prospects for related research.
This thesis reports the investigation about several smart surface and devices based on molecular switches.With self-assembly technique,thermosensitive polymer, and different environmental stimulus,hydrophilic/hydrophobic surface switches, temperature-responsive immune surface were fabricated successfully,as well as microfluidic chips from these smart surfaces.And they were successfully used in controlled protein separation and reversible immune recognition.
所谓分子开关泛指结构上组织化了的具有“开/关”功能的化学体系。它们具有双稳态的量子化体系,外部条件的变化能激励分子开关在这两种稳态间切换。常用于激励分子开关的因素包括光、电、热、磁、化学能(酸碱度、特殊分子和离子)等,这些条件的变化在微观上能引起电子和原子核的重排,使得分子的形状、化学键的生成或断裂、以及旋转等性质会随之变化,这些几何和化学的变化在宏观上表现出亲疏水性、颜色、水溶性等性质的变化,能实现信息传输的功能。随着微电子技术和生物工程这两项高科技的互相渗透,分子开关实际上已为研制分子器件提供了可能。
智能化表面(Smart surface)是一类组织化、集成化、平面化的分子开关,是具有可操控的开关功能的表面。常见的智能表面由聚合物、自组装单分子层(Self-assembled monolayer,SAM)、特殊的纳米金属氧化物等组成,激励它发生性质可逆转化的因素包括温度、光照、电场、pH值、溶剂等等。在这些外界激励下,表面分子可以发生可逆的构象转化、构型转化、氧化态的转化等等,从而在宏观上,使整个表面呈现出亲疏水性、光学性质、带电性等性质的可逆转化,即可呈现出“开/关”的性质。
微流控器件是微型全化学分析系统(Micro total analysis system,μ-TAS)的核心部分,是可用于生物分离分析、环境监测、医疗诊断等的有效手段。由于其操作简便、灵敏、快速、试剂消耗量少,易于实现自动化和在线监测,具有广阔的应用前景,一直是人们关注的热点。微流控芯片是一类被广泛研究和使用的微流控器件,目前对微流控芯片的研究十分广泛和深入,根据不同的用途,人们设计了多种多样的芯片,并将其成功的用在很多研究领域,包括传感器,化学反应器,生物反应器等。
本论文基于超分子包合物、自组装技术、温敏生物复合物等要素构建两类具有开关功能的智能表面,成功将这些智能化的表面用于蛋白质程序吸附释放以及抗原抗体的可逆识别。并基于这些智能表面制作了智能微器件——微流控芯片。一类是对电压敏感的智能表面。这是一种低密度的自组装单分子层(Low densitySAM,LD-SAM),它是电压可操控的亲疏水开关,其亲疏水性可随外加电压变化而切换,并且能实现对抗生物素(Avidin)、链霉抗生物素(Streptavidin)的可控吸附。另一类是和温敏智能表面,利用温敏高分子材料聚-N异丙基丙烯酰胺(Poly(N-isopropylacrylamide),PNIPAAm)与抗BSA抗体合成的生物复合物,构建了具有温度敏感开关功能的可再生免疫表面。该方法实现了免疫表面的再生,使其能够重复使用,同时为研究蛋白质-蛋白质动态相互作用过程提供了一个新平台。
进一步的,我们将这些智能表面引入微流控芯片,构建了有开关功能的电压敏感微流控芯片,并成功将其应用于蛋白质的可控吸附释放及分离中。该芯片制作成本低、能耗少、试剂消耗少,使用方便,易于检测,具有很好的应用前景。也是一个新型的基于自组织单分子层构建智能微器件的成功范例。还尝试了将上述温敏免疫表面修饰到微流控芯片的槽道中,以期构建温度敏感的免疫型微流控芯片,实现在微通道中的可控免疫识别。
本论文共六章内容,主要摘要如下:
第一章综述了分子开关、智能表面和微流控芯片的研究现状及其相关技术在生物传感器领域的应用进展。分子自组装和高分子聚合物是构建分子开关的两条重要途径。自组装单分子层是构膜分子与基底材料间发生物化作用而自发形成的一种热力学稳定、排列规则的单层分子膜。这种构膜方式,可以容易的为表面引入各种各样的功能团,这就为制备具有多种不同功能的智能化表而打下了很好的基础。温敏材料是指对温度有响应并能发生性质变化的一类材料。具有“温度开关”特性的PNIPAAm是被广泛研究的温敏高分子材料。利用它对温度响应的敏感性,使其在可控药物传输、免疫分析、细胞培养等研究领域都有着广泛的潜力。
第二章介绍了基于自组装技术构建对电压敏感的亲疏水开关表面,及其在蛋白质可控吸附方面的应用。该工作基于超分子包合物的概念,利用环糊精分子控制长链巯酸分子的间距,并通过自组装方法在余表面构建了包合物自组装膜,再以乙醇作为高效的洗脱溶剂,得到间距均一、性能稳定的低密度十六巯酸分子LD-SAM,即为对电压敏感的具有可逆亲/疏水性性质的智能化表面。以高密度自组装膜表而的覆盖度为100%计算可知,α,β,γ三种环糊精分子构建的低密度自组装膜表面的覆盖度分别为61.2%,45.3%和29.2%。通过改变外加电压,引发巯酸分子的构型变化,从而实现表面的亲水/疏水性能的转换。利用质谱,核磁,交流阻抗,QCM,荧光等多种检测手段论证的该智能表面的制成,并用接触角实验证明了智能表面对电压的可逆响应。采用荧光标记抗Avidin、Streptavidin蛋白分子作为研究对象,考察十六巯酸LD-SAM智能表面对带不同等电点的蛋白质的可控吸附。结果证明十六巯酸分子LD-SAM对带正电的Avidin蛋白有明显的电压控制的吸附作用。
第三章是进一步的将上述智能表面“移植”到微流控芯片体系,发展了两类利用“分子开关”原理构建的智能微流控芯片,并将其成功用于蛋白质的可控吸附中。本章利用成本低,加工简单的聚甲基丙烯酸甲酯(PMMA)有机玻璃为制作微流控芯片的材料,利用热压法制作“一字槽”的芯片,用电子溅射法在芯片的槽道表面镀金,作为整个芯片功能的核心区域,然后在对金面进行一系列的功能化修饰。在这一章的工作中,我们不仅直接将基于十六巯酸分子LD-SAM制作的智能表面修饰到芯片槽道中,得到智能化的巯酸微流控芯片(COOH-芯片),还进一步扩展思路,设计制作了基于巯胺分子LD-SAM的智能表面,其表面分子的末端带有胺基,不同于十六巯酸分子LD-SAM末端所带的羧基。这种表面与巯酸表面相反,在特定条件下对带负电的被分析物有可控的吸附作用。
COOH-芯片对带正电的蛋白质有可控的吸附作用。基于此巯胺分子LD-SAM制得的巯胺微流控芯片(NH_2-芯片)对带负电的蛋白质有可控的吸附作用。这一工作是利用智能表面制作智能器件的成功尝试。
第四章将上述两类智能微流控芯片进一步应用于蛋白质的程序吸附/释放,以及混合蛋白质的可控分离。以Avidin和Streptavidin为模型蛋白实现蛋白质混合物的分离,采用荧光检测、激光诱导荧光、共聚焦荧光显微镜等手段进行表征,分离效果理想。对COOH-芯片先后施加负、正电压能够先吸附溶液中的Avidin,在转变电压后将其释放,因此该芯片能从Avidin/Streptavidin混合物中将Avidin分离出来,回收率超过80%;对NH_2-芯片先后施加正、负电压能够将混合蛋白中的带负电的Streptavidin吸附,而在转变电压后再释放出来,从而也实现了蛋白分离,回收率也超过了80%。另外还用COOH-芯片成功的从混合的Avidin/Streptavidin蛋白中分离出了低含量的Avidin(Avidin与Streptavidin的摩尔比为1:1000),因此这种基于电压敏感的智能表面的微流控芯片有望成为一种新的分离低丰度蛋白的微器件,这对于蛋白组学微分析系统有重要的意义。
第五章是基于温敏聚合物的表面分子开关构建及抗原抗体可逆识别界面和微流控器件的研究。将温敏高分子材料PNIPAAm与抗BSA抗体合成的生物复合物(Bioconjugate)组装到金表面,得到的温敏免疫表面能对温度做出响应,可逆的与对应抗原BSA进行识别。这种温敏高分子材料的形态随温度发生变化,对抗原结合过程中造成的空间位阻不同,从而影响抗原抗体的结合,能使已结合的抗原抗体分离,由此实现抗体表面的再生。再生率最高可以达到89%以上,与文献报道的有机溶液再生表面法(再生率80%-92%)相当,而且这个方法基本没有破坏生物识别体系的活性和环境,抗原抗体均可重复利用,这种温敏开关免疫传感器可重复使用30次以上,抗疲劳性较好。我们还初步尝试将之应用于微流控芯片体系,有望发展利用温敏“分子开关”原理构建的免疫型微流控芯片。
第六章对整个论文工作进行了全面总结,并对下一步的工作进行了展望和建议,包括多检测对象温敏微流控芯片的的构建和应用、基于咯吡喃等分子构建光敏表面和基于单分散碳纳米管的可控荧光发光体系。
总之,本论文以表面分子开关为基础,研究了不同的智能表面及微流控器件。利用自组装膜技术,温敏聚合物材料,结合不同环境激励,构建了亲疏水开关表面、温度敏感的免疫表面,以及基于这些开关表面的智能化微流控器件。并将其成功应用于可控的蛋白质分离、抗原-抗体可逆识别的考察与研究中。
Lots of work has been focused on controlling the microcosmic world with macrocosmic methods,and subsequently to control the macrocosmic change of the substance property by changing their micro-structures.Among these work,it's becoming more and more attractive to control the properties reversibly through manipulating the structure,compose,conformation and oxidation state and so on.The reversible change is similar to "on/off" switching.With this kind of operation,we can control the properties of substance,to realize intelligent manipulation and reduplicate usage.Therefore,the research of substance and systems with "on/off" property is bewitching.In order to construct these kinds of systems,it's needed to construct special microcosmic structures on the atom or molecule scale.To use atoms and molecules as basic unit to design and assembly with a "bottom-up" style,we can get devices with special "on/off" property,which are called "molecular switches".
"Molecular switches" are chemical systems with organized structures and "on/off" function.They have two stable states,between which they can switch under the external stimulus.The external stimulus could be photo,electrical potential, temperature,chemical energies(pH,specific molecules or ions).When some of these conditions change,the electrons would be rearranged,leading to the change of molecular shape,formation of deformation of chemical bond.And accordingly,these changes will result in the change of wettability,color,solubility,etc.,which could be useful for information convection.Based on the interaction of micro-electronics and bioengineering,it becomes possible to construct molecular devices with molecular switches.
Smart surface is a kind of well organized,compositive,planar molecular switches.It's a surface with controlled "on/off" ability.Usually,smart surfaces are fabricated from polymer,self-assemble monolayer(SAM),special metallic oxide nano materials.The environmental conditions could inspire the property change of smart surface include temperature,light,electric field,pH,solvents and so on.The molecules composing the surface can behave conformational,configurational switching upon the stimuli,and therefore induce reversible changes in wettability, optics,electricity,etc.
Microfluidic devices are the core parts of micro total analysis system(μ-TAS) and effective means for bioseparation,bioassay,environmental inspection,medical diagnosis.Because it's easy to manipulate it,and it's sensitive,fast and low reagent consumption,it's convenient to realize automatization and on-line measurements with the microfluidic devices.Microfluidic chips are well researched and widely used microfluidic devices.Many kinds of microfluidic chips have been designed and fabricated according to different applications,including sensors,reaction containers and so on.
This thesis is about to fabricate two kinds of smart surface based on supermolecules,inclusive complexes,self-assembly technique,and temperature-sensitive polymers.Furthermore,expand these surfaces to protein program adsorption,separation and reproducing of antibody.Thirdly,to make smart microfluidic chips with these surfaces.One of the smart surfaces is electricity-sensitive smart surface.It's a low-density SAM.This layer is a potential controlled hydrophilic/hydrophobic switch.Its wettability could change under the applied electric potential.Subsequently,it can reversibly adsorb and release avidin or streptavidin protein under the potential control.The other is a temperature-sensitive surface,with thermosensitive polymer PNIPAAm,we got bioconjugate between PNIPAAm and anti-BSA antibody,and fabricated a temperature-sensitive and reproducible smart surface.This approach realizes the regeneration of the immune surface,so it can be used again and again.Meanwhile,it supplies a new research platform for protein-protein interaction.
Furthermore,we introduce these smart surfaces into microfluidic chips to prepare smart chips with "on/off" property.And also these chips were successfully applied in controlled protein adsorption/release and separation.This kind of microfluidic chip is cheap,low energy and reagent consumption,easily measured.So it's a successful example of fabricating smart microfluidic devices with SAM.
This paper contains 6 chapters which are outlined below:
In Chapter 1,the research of molecular switches,smart surface and microfluidic chips are reviewed.Molecule self-assembly and polymer are the main two ways to get molecular switches.SAM is a stable,well organized monolayer from the spontaneous interaction between the molecules and the substrate.It's easy to introduce kinds of functional groups to the surface with this method,which supplies a good foundation for smart surface with different functions.Thermosensitive polymers can behave property change upon temperature change.PNIPAAm is a typical and widely studied thermosensitive polymer.They are widely used in drug release,immune assay and cell culture.
In Chapter 2,fabricating potential-sensitive smart surface based on self-assembly technique,and its application in controlled protein adsorption are investigated. Cyclodextrin was used to control the density of the monolayer to get low-density 16-mercaptohexadecanoic acid monolayer(MHA LD-SAM).Referring to high-density MHA SAM,the surface coverage for LD-SAM fromα-,β-,γ-cyclodextrin shows an obvious decrease from 100%to 61.2%,45.3%and 29.2%, respectively.By applying different potentials to this surface,the MHA molecule could behave conformational transformation and accordingly the wettability of the surface could change.The achievement of the smart surface(MHA LD-SAM) was proved with MALDI-TOF-MS,quartz crystal microbalance(QCM),NMR,cyclic voltammetry(CV) and impedance(IMP).Contact angle measurement was used to prove the wettability change of the surface.The prepared smart surface was also used for controlled protein adsorption,which was characterized with QCM and fluorescence measurements.
In Chapter 3,the electric potential-sensitive surface was implemented into microfluidic chip to develpe two kinds of smart chips,which were applied in controlled protein adsorption.With the cheap material,PMMA,we made chips using hot-imprinting method.The prepared microfluidic chips were with a channel in the centre,and on the channel surface a layer of gold was modified,on which the followed fictionalizations were implemented.We fabricated two chips,the one is COOH-chip with terminal carboxyl groups on the channel surface,and the other is NH_2-chip with terminal amino groups on the channel surface.They can adsorb positive and negative potentials under potential control,respectively.
Chapter 4 is about the application of the smart microfluidic chips in protein adsorption/release and separation.Fluorescence,laser induced fluorescence(LIF) and confocal fluorescence microscopy(CFFM) are used to demonstrate the separation. For COOH-chip,it can capture more than 80%avidin from the Avidin/Streptavidin mixture upon external potential;as for NH_2-chip,it can also separate more 80% Streptavidin from the Avidin/Streptavidin mixture.And COOH-chip was used to separate low concentrate Avidin from the Avidin/Streptavidin mixture with a molar ratio of 1:1000 of Avidin:Streptavidin.The results were satisfying.So this electric potential-sensitive smart microfluidic chips is a possible alternative method for concentrating low-abundance proteins,which is very important for proteomics research.
Chapter 5 describes establishing the PNIPAAm-antibody surface that could supply the most effective dissociation of the antigen and regeneration of antibody into reuse of the immunosensors.As a model antibody-antigen system,bovine serum albumin(BSA) and the corresponding antibody anti-BSA were chosen.A reversible PNIPAAm-antibody conjugate surface was established by triggered control of external temperature.This took advantage of the thermally tuable conformation changes for the PNIPAAm-conjugated antibody surface,and could be used for switchable antigen association and dissociation.The temperature controlling strategy could realized the regeneration of the immunosensor on which immobilized anti-BSA antibodies retain the activity and specificity necessary to carry out more than 30 reproducible assays for BSA.The dissociation reaches 89%,which can compare with the general recovery methods.The controlled binding and unbinding were monitored by QCM,CFFM,native electrophoresis,laser induced fluorescence,and electrochemical impedance.
Chapter 6 is the summary of this thesis and the future prospects for related research.
This thesis reports the investigation about several smart surface and devices based on molecular switches.With self-assembly technique,thermosensitive polymer, and different environmental stimulus,hydrophilic/hydrophobic surface switches, temperature-responsive immune surface were fabricated successfully,as well as microfluidic chips from these smart surfaces.And they were successfully used in controlled protein separation and reversible immune recognition.
引文
[1]刘时铸,汤又文。杯芳烃分子开关的研究进展[J]。化学试剂,2006,28(4):209-213。
[2]李荣金,李洪祥,汤庆鑫,胡文平。分子器件的研究进展[J]。物理,2006,35(12):1003-1009。
[3]Nespurek S,Sworakowski J.Electroactive and Photochromic Molecular Materials for Wires,Switches and Memories[J].IEEE Eng.Med.Biol.,1994,13(1):45-57.
[4]Joachim C,Gimzewski J K,Aviram A.Electronics using hybrid-molecular and mono-molecular devices[J].Nature,2000,408(6812):541-548.
[5]Carroll RL,Gorman CB.The genesis of molecular electronics[J].Angew.Chem.Int.Ed.,2002,41(23):4379-4400.
[6]朱海峰。J.Fraser Stoddart访谈:分子电子开关[J]。科学观察,2006,1(2):51-53。
[7]Nguyen TD,Tseng HR,Celestre PC,Elood AH,Liu Y,Stoddart JF,Zink JI.A reversible molecular valve[J].PNAS(Proceedings of the National Academy of Sciences),2005,102(29):10029-10043.
[8]吴璧耀,张道洪。分子开关研究进展。化工新型材料[J]。2001,29(11):9-13。
[9]Gosztola D,Niemczyk MP,Wasielewski MR.Picosecond molecular switch based on bidirectional inhibition of photoinduced electron transfer using photogenerated electric fields[J].J.Am.Chem.Soc.,1998,120(20):5118-5119.
[10]Raymo FM.Digital processing and communication with molecular switches[J].Adv.Mater.,2002,14(6):401-414.
[11]Brown GJ,de Silva AP,Pagliari S.Molecules that add up[J].Chem.Commun.,2002,(21):2461-2463.
[12]Lavigne JJ,Anslyn EV.Sensing a paradigm shift in the field of molecular recognition:From selective to differential receptors[J].Angew.Chem.Int.Ed.,2001,40(17):3119-3130.
[13]Wasielewski MR.Photoinduced Electron-Transfer in Supermolecular Systems for Artificial Photosynthesis[J].Chem.Rev.,1992,92(3):435-461.
[14]Kavarnos GJ.Fundamentals of Photoinduced Electron Transfer[M].York:VCH Weinheim New,1993.
[15]Park SY,Bae YH.Novel pH-sensitive polymers containing sulfonamide groups[J].Macromol.Rapid.Commun.,1999,20(5):269-273.
[16]Galaev IY,Mattiasson B.Smart polymers and what they could do in biotechnology and medicine[J].Trends Biotechnol,1999,17(8):335-340.
[17]Roy I,Gupta MN.Smart polymeric materials:Emerging biochemical applications[J].Chem.Biol.,2003,10(12):1161-1171.
[18]Gil ES,Hudson M.Stimuli-responsive polymers and their bioconjugates[J].Prog.Polym.Sci.,2004,29(12):1173-1222.
[19]Andersson RM,Carlsson K,Liljeborg A,Brismar H.Characterization of probe binding and comparison of its influence on fluorescence lifetime of two pH-sensitive benzo[c]xanthene dyes using intensity-modulated multiple-wavelength scanning technique[J].Anal Biochem,2000,283(1):104-110.
[20]Grabowski ZR,Rot kiewicz K.Structural changes accompanying intramolecular electron transfer:Focus on twisted intramolecular charge-transfer states and structures[J].Chem.Rev.,2003,103(10):3899-4032.
[21]Kung HF,Lee CW,Zhuang ZP,Kung MP,Hou C,Plossl K.Novel stilbenes as probes for amyloid plaques[J].J.Am.Chem.Soc.,2001,123(50):12740-12741.
[22]黄池宝,任安祥。具有“开-关”特性的pH荧光探针DPVF的合成与表征[J]。化学与生物工程,2007,24(2):44-46。
[23]蒋林玲,丁立平,胡道道,房喻。基于PET过程的分子开关型荧光传感器研究进展[J]。应用化学,2006,23(10):1069-1075。
[24]Tsien RY.Fluorescence imaging creates a windows on the cell[J].Chem.New.,1994,18(7):34-36.
[25]史向阳,孙曹民,吴世康。荧光探针法研究壳聚糖在水溶液中的聚集态行为[J]。感光科学与光化学,1998,16(2):161-166。
[26]Shinkai S.Calixarenes-the third generation of supermolecules[J].Tetrahedron,1993,49(40):8933-8968.
[27]Kroner D,Klaumunzer B.Laser-operated chiral molecular switch:quantum simulations for the controlled transformation between achiral and chiral atropisomers[J].Physical Chemistry Chemical Physics,2007,9(36):5009-5017.
[28]孙亚斌,丁小斌,郑朝晖,成煦,彭宇行。智能表面[J]。化学通报,2006,69(4),252-260。
[29]Nakayama K,Jiang L,Iyoda T,Fujishima A.Photo-induced structural transformation on the surface of azobenzene crystals[J].Jpn J Appl Phys Part 1,1997,36(6B):3898-3902.
[30]Prins MWJ,Welters WJJ,Weekamp JW.Fluid control in multichannel structures by electrocapillary pressure[J].Science,2001,291(5502):277-280.
[31]Abbott NL,Gorman CB,Whitesides GM.Active control of wetting using applied electrical potentials and self-assembled monolayers[J].Langmuir 1995,11(1):16-18.
[32]Byloos M,Al-Maznai H,Morin M.Phase transitions of alkanethiol self-assembled monolayers at an electrified gold surface[J].J Phys Chem B.2001,105(25):5900-5905.
[33]Crevoisier GB,Fabre P,Corpart J,Leibler L.Switchable tackiness and wettability of a liquid crystalline polymer[J].Science,1999,285(5431):1246-1249.
[34]Minko S,Sidorenko A,Goreshnik E.Environment friendly and switchable polymer brushes[J].The American Chemical Society,2000,220:U370-U370.
[35]Chaudhury MK,Whitesides GM.How to make water run uphill[J].Science,1992,256(5063):1539-1541.
[36]Wang ZH,Chen KC,Tian H.Intramolecular fluorescence quenching in ferrocene-naphthalimide dyads[J].Chem.Lett.,1999,(5):423-424.
[37]Raphael E,DeGennes PG.Rubber rubber adhesion with connector molecules[J].J.Phys.Chem.,1992,96(10):4002-4007.
[38]Ruths M,Johannsmann D,Ruhe J,Knoll W.Repulsive forces and relaxation on compression of entangled,polydisperse polystyrene brushes[J].Macromolecules,2000,33(10):3860-3870.
[39]Collier CP,Mattersteig G,Wong EW.A[2]catenane-based solid state electronically reconfigurable switch[J].Science,2000,289(5482):1172-1175.
[40]Klein J,Kumacheva E,Mahalu D,Perahia D,Fetters LJ.Reduction of frictional forces between solid-surfaces bearing polymer brushes[J].Nature,1994,370(6491):634-636.
[41]Galaev IY,Mattiasson B."Smart" polymers and what they could do in biotechnology and medicine[J].Trends In Biotechnology 1999,17(8):335-340.
[42]Aksay IA,Trau MS,Honma I.Biomimetic pathways for assembling inorganic thin films[J].Science,1996,273(5277):892-898.
[43]Russell TP.Surface-responsive materials[J].Science,2002,297(5583):964-967.
[44]姚芳莲,陈炜,王浩,周玉涛,姚康德。智能高分子表面的设计及其在生物医学中的应用[J]。化学通报,2004,67(9):661-666。
[45]Galaev IY,Mattiasson B."Smart" polymers and what they could do inbiotechnology and medicine[J].Trends In Biotechnology 1999,17(8):335-340.
[46]Aksay IA,Trau M,Manne S,Honma I,Yao N,Zhou L,Fenter P,Eisenberger PM,Gruner SM.Biomimetic pathways for assembling inorganic thin films[J].Science,1996,273(5277):892-898.
[47]黄杉生,李苾芬,林辉概,俞汝勤。萘衍生物的聚合膜结构及膜的pH响应[J].湖南大学学报,1996,23(2):36-40。
[48]Ito Y,Ochiai Y,Park YS,Imanishi Y.pH-sensitive gating by conformational change of a polypeptide brush grafted onto a porous polymer membrane[J].J.Am.Chem.Sot.,1997,119(7):1619-1623.
[49]Sun T,Feng L,Gao X,Jiang L.Bioinspired surfaces with special wettability[J].Acc.Chem.Res.,2005,38(8):644-652.
[50]Lahann 5,Mitragotri S,Tran T,Kaido H,Sundaram J,Choi IS,Hoffer S,Somorjai GA,Langer R.A reversibly switching surface[J].Science,2003,299(5605):371-374.
[51]Lim HS,Nan JT,Kwak D,Jin M,Cho K.Photoreversibly switchable superhydrophobic surface with erasable and rewritable pattern[J].J Am.Chem.Soc.,2006,128(45):14458-14459.
[52]刘秀生,唐艳平。微流体芯片及其表面效应[J].医学与社会,2005,18(5):35-36。
[53]Ionov L,Minko S,Stamm M.Reversible chemical patterning on stimuli-responsive polymer film:Environment-responsive lithography[J].J.Am.Chem.Soc.,2003,125(27):8302-8306.
[54]周平,邓延倬,曾云鹗.用温度敏感高分子为载体的激光光声免疫分析及其应用[J].分析化学,1997,25(2):144-148。
[55]Zhu QZ,Liu FH.Mimetic-enzyme fluorescence immunoassay using a thermal phase separating polymer[J].Analyst 1998,123(5):1131-1134.
[56]Chen GH,Hoffman AS.Preparation And Properties Of Thermoreversible,Phase-Separating Enzyme-Oligo(N-Isopropylacrylamide) Conjugates[J].Bioconjugate Chemistry 1993,4(6):509-514.
[57]Chen JP,Hoffman AS.Polymer Protein Conjugates.2.Affinity Precipitation Separation Of Human Immuno-Gamma-Globulin By A Poly(N-Isopropylacrylamide)-Protein-A Conjugate[J].Biomaterials 1990,11(9):631-634.
[58]Ringsdorf H,Venzmer J.Fluorescence Studies Of Hydrophobically Modified Poly(N-Isopropylacrylamides)[J].Macromolecules 1991,24(7):1678-1686.
[59]何庆,盛京。响应性凝胶及其在药物控释上的应用[J].功能高分子学报,1997,10(1):118-127。
[60]Liu F,Tao GL.Synthesis Of Thermal Phase-Separating Reactive Polymers And Their Applications In Immobilized Enzymes[J].Polymer Journal 1993,25(6):561-567.
[61]Kawaguchi H,Fujimoto K.Hydrogel Microspheres.3.Temperature-Dependent Adsorption Of Proteins On Poly-N-Isopropylacrylamide Hydrogel Microspheres[J].Colloid And Polymer Science 1992,270(1):53-57.
[62]张柏林,王敏灿,常文保,慈云祥.高分子控温相变免疫分析法测定苯妥因[J].分析化学,1997,25(9):993-996。
[63]Miyauchi M,Nakajima A,Watanabe T,Hashimoto K.Photocatalysis and photoinduced hydrophilicity of various metal oxide thin films[J].Chem.Mater.,2002,14(2):2812-2816.
[64]Feng X,Feng L,Jin M,Zhai J,Jiang L,Zhu DB.Reversible super-hydrophobicity to super-hydrophilicity transition of aligned ZnO nanorod films[J].J.Am.Chem.Soc.2004,126(1):62-63.
[65]Feng X,Zhai J,Jiang L.The fabrication and switchable superhydrophobicity of Tio2 nanorod films[J].Angew.Chem.,Int.Ed.2005,44(32):5115-5118.
[66]Ho Sun Lim,Donghoon Kwak,Dong Yun Lee,Seung Goo Lee,Kilwon Cho.UV-Driven Reversible Switching of a Roselike Vanadium Oxide Film between Superhydrophobicity and Superhydrophilicity[J].J.Aa.Chem.Soc.2007,129(14):4128-4129.
[67]Feng X,Zhai J,Jiang L.The fabrication and switchable superhydrophobicity of TiO2 nanorod films[J].Angew.Chem.Int.Ed.,2005,44(32):5115-5118.
[68]Shutao Wang,Xinjian Feng,Jiannian Yao,Lei Jiang.Controlling Wettability and Photochromism in a Dual-Responsive Tungsten Oxide Film[J].Angew.Chem.Int.Ed.2006,45(8):1264-1267.
[69]Liping Heng,Yongqiang Dong,Jin Zhai,Benzhong Tang,Lei Jiang.Solvent Fuming Dual-Responsive Switching of Both Wettability and Solid-State Luminescence in Silole Film[J].Langmuir 2008,24(5):2157-2161.
[70]马永正,要旸,冯喜增。智能聚合物在生物化学领域的应用进展[J].化学与生物工程,2007,24(9):1-4。
[71]Ito Y,Ochiai Y,Park YS,Imanishi Y.pH-sensitive gating by conformational change of a polypeptide brushgrafted onto a porous polymer membrane[J].J.Am.Chem.Soc.,1997,119(7):1619-1623.
[72]Ito Y,Park YS,Imanishi YJ.Visualization of critical pH-controlled gating of a porous membrane grafted withpolyelectrolyte brushes[J].Am.Chem.Soc.,1997,119(11):2739-2740.
[73]Ito Y,Nishi S,Park YS.Oxidoreduction-Sensitive control of water permeation through a polymer brushes-grafted porous membrane[J].Macromolecules,1997,30(19):5856-5859.
[74]Ito Y,Park YS,Imanishi Y.Imaging of a pH-sensitive polymer brush on a porous membrane using atomic force microscopy in aqueous solution [J].Macromol.Rapid Commun.,1997,18(3):221-224.
[75]殷以华,孟亚斌,杨亚江。pH-敏感的疏水型凝胶在直流电场中的刺激响应[J].高分子学报,2002,(4):414-417。
[76]李斌,陈文广,王晓工。聚丙烯表面接枝PNIPAAm膜Ⅱ.表面特性和温度响应性研究[J].高分子学报,2003,(1):7-121。
[77]Luo CH,Zuo F,Zheng ZH,Cheng X,Ding XB,Peng YX.Tunable smart surface of gold nanoparticles achieved by light-controlled molecular recognition effection[J].Macromolecular rapid communications,2008,29(2):149-154.
[78]唐黎明,孟晓霞,王慧芬。压敏型胶粘剂的研究进展[J].高分子材料科学与工程,1998,14(5):141-1431。
[79]李治章,李东。基于功能高分子膜的荧光传感器研究--Ⅰ铜离子荧光熄灭型传感器[J].化学传感器,1997,17(3):204-2091。
[80]张建合,杨亚江。亲水/疏水半互穿网络凝胶在直流电场作用下的响应[J].高分子学报,2002,(1):285-291。
[81]Milner ST.Polymer Brushes[J].Science,1991,251(4996):905-914.
[82]Leduc MR,Hawker CJ,Dao J,Frechet JMJ.Dendritic Initiators for ″Living″ Radical Polymerizations:A Versatile Approach to the Synthesis of Dendritic-Linear Block Copolymers[J].J.Am.Chem.Soc.,1996,118(45):11111-11118.
[83]Inoue K.Functional dendrimers,hyperbranched and star polymers[J].Prog.Polym.Sci.,2000,25(4):453-571.
[84]Schluter AD.Dendrimers with Polymeric Core[A].in:Vogtle F.Top.Curr.Chem.[M].Springer,1998:165-191.
[85]张磊,李文,张阿方。聚合物分子刷的合成与应用[J].化学进展,18(7/8):939-949。
[86]Song SY,Choi HG,Hong JW,Kim BW,Sim SJ,Yoon HC.Selective antigen-antibody recognition on SPR sensor based on the heat-sensitive conformational change of poly(N-isopropylacrylamide)[J].Colloids and surfaces a-physicochemical and engineering aspects,2008,313(Sp.Iss.SI):504-508.
[87]Kim F,Kwan S,Akana J,Yang P.Langmuir-Blodgett Nanorod Assembly[J].J.Am.Chem.Soc.,2001,123(18):4360-4361.
[88]刘欢,翟锦,江雷。纳米材料的自组装研究进展[J]。无机化学学报,2006,22(4):585-597.
[89]Whitesides GM,Mathias JP,Seto C T.Molecular Self-Assembly and Nanochemistry-A Chemical Strategy for the Synthesis of Nanostructures[J].Science,1991,254(5036):1312-1319.
[90]谢永荣,杨瑞卿,付大伟,袁小勇。分子自组装与分子机器[J]。赣南师范学院学报,2005,(6):44-48。
[91]邵建新。分子电子学[J]。现代物理知识,2006,18(5):29-31。
[92]庄小东,陈或,刘莹,蔡良珍,林楹。自组装有机纳米功能材料[J]。化学进展,2007,19(11):1653-1661.
[93]Chia S,Cao J,Stoddart JF,Zink JI.Working Supramolecular Machines Trapped in Glass and Mounted on a Film Surface[J].Angew.Chem.2001,113(13):2513-2517.
[94]Ma X,Wang Q,Qu D,Xu Y,Ji Y,Tian H.A Light-Driven Pseudo[4]rotaxane Encoded by Induced Circular Dichroism in a Hydrogel[J]. Advanced Functional Materials, 2007, 17(5): 829-837.
[95] Balzani V, Credi A, Raymo FM, Stoddart JF. Klinstliche molekulare Maschinen[J]. Angew. Chem., 2000, 112(19): 3484-3530.
[97] Balzani V, Credi A, Raymo FM, Stoddart JF. Artificial Molecular Machines[J]. Angew. Chem. Int. Ed., 2000, 39(19): 3348-3391.
[98] Ballardini R, Balzani V, Credi A, Gandolfi MT, Venturi M. Artificial Molecular-Level Machines: Which Energy To Make Them Work?[J]. Acc. Chem. Res., 2001, 34(6): 445-455.
[99] Ashton PR, Ballardini R, Balzani V, Boyd SE, Williams DJ. Chem. Eur. J., 1997, 3(1): 152.
[100] Kyungpil K, Jeon WS, Kang JK, Lee JW, Jon SY, Kim T, Kim K. A Pseudorotaxane on Gold: Formation of Self-Assembled Monolayers, Reversible Dethreading and Rethreading of the Ring, and Ion-Gating Behavior [J]. Angew. Chem. Int. Ed. 2003, 42(20): 2293-2296.
[101] a) W. L. Mock, Top. Curr. Chem. 1995, 175, 1;
[102] b) P. Cintas, J. I. Phenom, Mol. Recognit. Chem. 1994, 17, 205;
[103] c) W. L. Mock, Compr. Supramol. Chem. 1996, 2, 477.
[104] Whang D, Jeon YM, Heo J, Kim K. Self-Assembly of a Polyrotaxane Containing a Cyclic "Bead" in Every Structural Unit in the Solid State: Cucurbituril Molecules Threaded on a One-Dimensional Coordination Polymer [J]. J. Am. Chem. Soc., 1996, 118(45): 11333- 11334.
[105] Whang D, Kim K. Polycatenated Two-Dimensional Polyrotaxane Net [J]. J. Am. Chem. Soc, 1997, 119(2): 451.
[106] Whang D, Park KM, Heo J, Kim K. Molecular Necklace: Quantitative Self-Assembly of a Cyclic Oligorotaxane from Nine Molecules[J]. J. Am. Chem. Soc, 1998, 120(19): 4899-4900.
[107] Roh SG, Park KM, Park GJ, Sakamoto S, Yamaguchi K, Kim K. Synthesis of a Five-Membered Molecular Necklace: A 2+2 Approach[J]. Angew. Chem. Int. Ed., 1999, 38(5): 637-641.
[108] Lahann J, Mitragotri S, Tran T, Kaido H, Sundaram J, Choi IS, Hoffer S,Somorjai GA,Langer R.A reversibly switching surface[J].Science,2003,299(5605):371-374.
[109]林炳承,秦建华。微流控芯片实验室[J].色谱,2005,23(5):456-463.
[110]Unger MA,Chou HP,Thorsen T,Scherer A,Quake SR.Monolithic microfabricated valves and pumps by multilayer soft lithography[J].Science,2000,288(5463):113-116.
[111]Studer V,Hang G,Pandolfi A,Ortiz M,Anderson WF,Quake SR.Scaling properties of a low-actuation pressure microfluidic valve[J].J.Appl.Phys.,2004,95(1):393-398.
[112]Park SJ,Kim JK,Park J,Chung S,Chung C,Chang JK.Rapid three-dimensional passive rotation micromixer using the breakup process[J].J.Micromech.Microeng.2004,14(1):6- 14.
[113]王辉,戴忠鹏,王利,白吉玲,林炳承。一种玻璃微流控芯片的质量检测方法[P].中国专利:200310119466.5,2005-06-29:
[114]杨友麒。微尺度和纳米尺度过程系统工程的进展和挑战[J].现代化工,2007,27(10):1-9。
[115]Kikutani Y,Ueno M,Hisamoto H,Tokeshi M,Kitamori T.Continuous-flow chemical processing in three-dimensional microchannel network for on-chip integration of multiple reactions in a combinatorial mode[J].QSAR.Comb.Sci.,2005,24(6):742 - 757.
[116]Harrison DJ,Fluri K,Seiler K,Fan ZH,Effenhauser CS,Manz A.Micromachining A Miniaturized Capillary Electrophoresis-Based Chemical-Analysis System on a Chip[J].Science,1993,261(5123):895-897.
[117]Chou HP,Spence C,Scherer A,Quake S.A microfabricated device for sizing and sorting DNA molecules[J].Proc.Natl.Acad.Sci.USA 1999,96(1):11-13.
[118]Chen Y,Pepin A.Nanofabrication:Conventional and nonconventional methods[J].Electrophoresis,2001,22(2):187-207.
[119]Vilkner T,Janasek D,Manz A.Micro total analysis systems.Recent developments[J].Anal.Chem.,2004,76(12):3373-3386.
[120]宋江莉,王秀芬。LCST类水凝胶开关效应的研究进展[J]。化学进展,2004,16(1):56-60。
[121]Ebara M,Hoffman JM,Stayton PS,Hoffman AS.Surface modification of microfluidic channels by UV-mediated graft polymerization of non-fouling and 'smart' polymers[J].Radiation physics and chemistry,2007,76(8-9):1409-1413.
[122]Dong LC,Hoffman AS.A Novel-Approach for Preparation of pH-Sensitive Hydrogels for Enteric Drug Delivery[J].J.Controlled Release,1991,15(2):147-152.
[123]Zhang JT,Huang SW,Cheng SX,Zhuo RX.Preparation and properties of po]y(N-isopropylacrylamide)/poly(N-isopropylacrylamide)interpenetrating polymer networks for drug delivery,J.Polym.Sci.A:Polym.Chem.[J].2004,42(5):1249-1254.
[124]Yin YH,Yang YJ,Xu HB.Swelling behavior of hydrogels for colon-site drug delivery[J].J.Appl.Polym.Sci.,2002,83(13):2835-2842.
[125]Kurisawa M,Yui N.Gelatin/dextran intelligent hydrogels for drug delivery:dual-stimuli-responsive degradation in relation to miscibility in interpenetrating polymer networks[J].Macromol.Chem.Phys.,1998,199(8):1547-1554.
[126]Beebe DJ,Moore JS,Bauer JM,Yu Q,Liu RH,Devadoss C,Jo BH.Functional hydrogel structures for autonomous flow control insidemicro fluidic channels[J].Nature,2000,404(6778):588-590.
[127]Yu C,Mutlu S,Selvaganapathy P,Mastrangelo CH,Svec F,Frechett JMJ.Flow Control Valves for Analytical Microfluidic Chips without Mechanical Parts Based on Thermally Responsive Monolithic Polymers[J].Anal.Chem.,2003,75(8):1958-1961.
[128]Liu YJ,Guo SS,Zhang ZL,Huang WH,Baigl D,Xie M,Chen Y,Pang DW.A micropillar-integrated smart microfluidic device for specific capture and sorting of cells[J].Electrophoresis 2007,28(24):4713 -4722.
[129]Malmstadt N,Yager P,Hoffman AS,Stayton PS.A Smart Microfluidic Affinity Chromatography Matrix Composed of Poly(N-isopropylacrylamide)-Coated Beads[J]. Anal. Chem. , 2003, 75(13): 2943-2949.
[130] Malmstadt N, Hoffman AS, Stayton PS. "Smart" mobile affinity matrix for microfluidic immunoassays[J]. Lab On A Chip, 2004, 4(4): 412-415.
[131] Ding ZL, Fong RB, Long CJ, Stayton PS, Hoffman AS. Size-dependent control of the binding of biotinylated proteins to streptavidin using a polymer shield[J]. Nature, 2001, 411(6833): 59-62.
[132] Kuckling D, Richter A, Arndt KF. Temperature and pH-dependent swelling behavior of poly(N-isopropylacrylamide) copolymer hydrogels and their use in flow control[J]. Macromol. Mater. Eng., 2003, 288(2): 144-151.
[133] Richter A, Kuckling D, Howitz S, GehringT, Arndt KF. Electronically controllable microvalves based on smart hydrogels: Magnitudes and potential applications[J]. J. Microelectromechanical Syst., 2003, 12(5): 748-753.
[134] Ionov L, Houbenov N, Sidorenko A, Stamm M, Minko S, Smart Microfluidic Channels[J]. 2006, Adv. Funct. Mater., 2006, 16(9): 1153-1160.
[1]Russell,TP.Surface-responsive materials[J].Science,2002,297(5583):964-967.
[2]Nath N,Chilkoti A.Creating ″Smart″ surfaces using stimuli responsive polymers[J].Advanced Materials,2002,14(17):1243-1247.
[3]Luzinova I,Minko S,Tsukruk W.Adaptive and responsive surfaces through controlled reorganization of interracial polymer layers[J].Prog.Polym.Sci.,2004,29:635-698.
[4]黄菲。抗精神病类药物电化学传感器研究[D]。复旦大学分析化学专业博士学位论文,2007,7-9。
[5]董绍俊,车广礼,谢远武。化学修饰电极[M]。北京:科学出版社,2003:571-592。
[6]黄菲。吩噻嗪衍生物在硫醇与碳纳米管修饰金电极上的伏安行为及测定[D]。武汉大学分析化学专业硕士学位论文,2004,1-3.
[7]杨生荣,任嗣利,张俊彦,张绪寿。自组装单分子膜的结构及其自组装机理[J]。高等学校化学学报,2001,22(3):470-476.
[8]杨玉霞。吩噻嗪衍生物和肾上腺素在硫醇自组装膜修饰金电极上的电化学行为[D]。武汉大学分析化学专业硕士学位论文,2003,3-4。
[9]Ulman A.An Introduction to Organic Ultra Thin Films[M].Boston:Academic Press,1991:237.
[10]J.Lahann,S.Mitragotri,N.T.Tran,H.Kaido,J.Sundaram,S.I.Choi,S.Holler,A.G.Somorjai and R.Langer.A reversibly switching surface[J].Science,2003,299(5605):371-374.
[11]Auletta T,Van Veggel F.Self-assembled monolayers on gold of ferrocene-terminated Thiols and hydroxyalkanethiols[J].Langmuir 2002,18(4):1288-1293.
[12]ikeda H,Nakamura M,Ise N,Oguma N,Nakamura A,Tkeda T,Toda F,Ueno A.Fluorescent cyclodextrins for molecule sensing:Fluorescent properties,NMR characterization,and inclusion phenomena of N-dansylleucine-modified cyclodextrins[J].Journal of the American Chemical Society,1996,118(45):10980-10988.
[13] Bojinova T, Coppel Y. Complexes between beta-cyclodextrin and aliphatic guests as new noncovalent amphiphiles: Formation and physicochemical studies [J]. Langmuir 2003, 19(13): 5233-5239.
[1]Manz A,Graber N,Widmer H M.Miniaturized Total Chemical-Analysis Systems - A Novel Concept for Chemical Sensing[J].Sensor Actuators B-Chemical,1990,1(1-6):224-248.
[2]Manz A,Verpoorte E,Raymond D E.Micro Total Analysis Systems[M].The Netherlands:1994.Dordrecht.Kluwer Academic Publishers,1995:5.
[3]王立凯,冯喜增.微流控芯片技术在生命科学研究中的应用[J].化学进展,2005,17(3):482-498.
[4]丛辉,王惠民,宋宏伟,鞠少卿,金庆辉,贾春平,庄贵生,刘菁.控制微流控芯片电泳中的蛋白质吸附[J].检验医学,2006,21(5):449-452.
[5]Yu C,Mutlu S,Selvaganapathy P,Mastrangelo CH,Svec F,Frechet J MJ.Flow Control Valves for Analytical Microfluidic Chips without Mechanical Parts Based on Thermally Responsive Monolithic Polymers[y].Analytical Chemistry,2003,75(8):1958-1961.
[6]Beebe DJ,Moore JS,Bauer JM,Yu Q,Liu RH,Devadoss C,Jo BH.Functional hydrogel structures for autonomous flow control insidemicro fluidic channels[J].Nature,2000,404(6778):588-590.
[7]Reyes DR,Iossifidis D,iuroux PA,Manz A.Micro total analysis systems.1.Introduction,theory,and technology[J].Anal.Chem.,2002,74(12):2623-2636.
[8]Buchholz BA,Doherty EAS,Albarghouthi MN,Bogdan FM,Zahn JM,Barron AE.Microchannel DNA Sequencing Matrices with a Thermally Controlled ″Viscosity Switch″[J].Anal.Chem.,2001,73(2):157-164.
[9]almstadt NM,Ager PY,Hoffman AS,Stayton PS.A Smart Microfluidic Affinity Chromatography Matrix Composed of Poly(N-isopropylacrylamide)-Coated Beads[J].Anal.Chem.,2003,75(13):2943-2949.
[10]Yu C,Mutlu S,Selvaganapathy P,Mastrangelo CH,Svec F,Frechett JMJ.Flow Control Valves for Analytical Microfluidic Chips without Mechanical Parts Based on Thermally Responsive Monolithic Polymers [J]. Anal. Chem., 2003, 75(8): 1958-1961.
[11] Kitamura N, Hosoda Y, Iwasaki C, Ueno K , Kim HB. Thermal Phase Transition of an Aqueous Poly(N-isopropylacrylamide) Solution in a Polymer Microchannel-Microheater Chip[J]. Langmuir, 2003, 19(20) : 8484 - 8489.
[12] Bedair MF, Oleschuk RD. Fabrication of porous polymer monoliths in polymeric microfluidic chips as an electrospray emitter for direct coupling to mass spectrometry[J]. Anal. Chem., 2006, 78(4): 1130-1138.
[13] Qu HY, Wang HT, Huang Y, Zhong W, Lu HJ, Kong JL, Yang PY, Liu BH. Stable microstructured network for protein patterning on a plastic microfluidic channel: Strategy and characterization of on-chip enzyme microreactors[J]. Analytical Chemistry, 2004, 76(21): 6426 - 6433.
[14] Bi HY, Weng XX, Qu HY, Kong JL, Yang PY, Liu BH. Strategy for allosteric analysis based on protein-patterned stationary phase in microfluidic chip[J]. J. Proteome Res., 2005, 4(6): 2154 -2160.
[15] Baldwin RP, Roussel TJ, Crain MM, Bathlagunda V, Jackson DJ, Gullapalli J, ConklinJA, Pai R, Naber JF, Walsh KM, Keynton RS. Fully integrated on-chip electrochemical detection for capillary electrophoresis in a microfabricated device [J]. Analytical Chemistry, 2002, 74(15): 3690-3697.
[16] Liu Y, Mu L, Liu BH, Zhang S, Yang PY, Kong JL. Controlled protein assembly on a switchable surface[J]. Chem.Commun., 2004, (10): 1194- 1195.
[17] Mu L, Liu Y, Zhang S, Liu BH, Kong J. Selective assembly of specifically charged proteins on an electrochemically switched surface[J]. New J. Chem., 2005, 29(6): 847-852.
[1]Hochstrasser DF,Sanchez JC,Appel RD.Proteomics and its trends facing nature's complexity[J].Proteomics,2002,2(7):807-812.
[2]Zhang Q,Riechers DE.Proteomics:An emerging technology for weed science research[J].Weed science,2008,56(2):306-313.
[3]Auroux PA,Iossifidis D,Reyes DR,Manz A.Micro total analysis systems.2.Analytical standard operations and applications[J].Analytical Chemistry,2002,74(12):2637-2652.
[4]Gorg A,Weiss W,Dunn MJ.Current two - dimensional electrophoresis technology for proteomics[J].Proteomics,2004,4(12):3665-3685.
[5]Zheng XJ,Hong LL,Shi LX,Guo JQ,Sun Z,Zhou JY.Proteomics analysis of host cells infected with infectious bursal disease virus[J].Molecular & Cellular Proteomics,2008,7(3):612-625.
[6]Furusawa T,Rakwal R,Nam HW,Hirano M,Shibato J,Kim YS,Ogawa Y,Yoshida Y,Kramer KJ,Kouzuma Y,Agrawal GK,Yonekura M.Systematic investigation of the hemolymph proteome of Manduca sexta at the fifth instar larvae stage using one- and two-dimensional proteomics platforms[J].Journal of proteome research,2008,7(3):938-959.
[7]Blankley RT,Robinson NJ,Crocker IP,Baker PN,Myers JE.Unlocking the potential of proteomics:Achieving relative quantification of proteins recovered from placental explant-conditioned culture media using an optimised mass spectrometry-based workflow[J].Reproductive sciences,2008,15(2):140A-140A.
[8]Lim D,Kamotani Y,Cho B,Mazumder J,Takayama S.Fabrication of microfluidic mixers and artificial vasculatures using a high-brightness diode-pumped Nd:YAG laser direct write method[J].Lab on a Chip,2003,3(4):318-323.
[9]Sun XF,Sun XF,Zhen ZJ,Zhang X,Zhang Y,Xia Y.Serum protein profiling of lymphoblastic lymphoma by protein Chip SELDI-TOF technology[J].Pediatric blood & cancer,2007,49(4):447-447.
[10]王立凯,冯喜增.微流控芯片技术在生命科学研究中的应用[J].化学进展,2005,17(3):482-498.
[11] Hardouin J, Joubert-Caron R, Caron M. HPLC-chip-mass spectrometry for protein signature identifications[J]. Journal of separation science, 2007, 30(10): 1482-1487. Blazer LL, Boyle MDP. Use of protein chip mass spectrometry to monitor biotinylation reactions [J]. Applied microbiology and biotechnology, 2007, 74(3): 717-722.
[12] Bi HY, Meng S, Li Y, Guo K, Chen YP, Kong JL, Yang PY, Zhong W, Liu BH. Deposition of PEG onto PMMA microchannel surface to minimize nonspecific adsorption. Lab on a Chip, 2006, 6(6): 769-775.
[13] Huber DL, Manginell RP. Programmed adsorption and release of proteins in a microfluidic device [J]. Science 2003, 301(5631): 352-354.
[14] Sikes HD , Smalley JF. Rapid electron tunneling through oligophenylenevinylene bridges [J]. Science 2001 , 291(5508): 1519-1523.
[15] Nitzan A, Ratner MA. Electron transport in molecular wire junctions [J]. Science 2003, 300(5624): 1384-1389.
[1] Hoffman AS. Hoffman AS, Stayton PS, Bulmus V, Chen GH, Chen JP, Cheung C, Chilkoti A, Ding ZL, Dong LC, Fong R, Lackey CA, Long CJ, Miura M, Morris JE, Murthy N, Nabeshima Y, Park TG, Press OW, Shimoboji T, Shoemaker S, Yang HJ, Monji N, Nowinski RC, Cole CA, Priest JH, Harris JM, Nakamae K, Nishino T, Miyata T. Really smart bioconjugates of smart polymers and receptor proteins [J]. Journal of Biomedical Materials Research 2000, 52(4): 577-586.
[2] Malmstadt N, Yager P, Hoffman AS, Stayton PS. A smart microfluidic affinity chromatography matrix composed of poly(N-isopropylacrylamide)-coated beads[J]. Analytical Chemistry, 2003, 75(13): 2943-2949.
[3] Fuertges F, Abuchowski A. The clinical efficacy of poly(ethylene glycol)-modified proteins [J]. Journal of Controlled Release, 1990, 11(1-3): 139-148.
[4] Maeda H. SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy [J]. Advanced drug delivery reviews, 1991, 6(2): 181-202.
[5] Maeda H, Seymour LW, Miyamoto Y. Conjugates of anticancer agents and polymers - advantages of macromolecular therapeutics invivo[J]. Bioconjugate Chem., 1992, 3(5): 351-362.
[6] Duncan R, Kopecek J. Soluble synthetic polymers as potential drug carriers. Adv Polym Sci 1984,57:53-101.
[7] Hoffman AS. A commentary on the advantages and limitations of synthetic polymer-biomolecule conjugates [A]. In: Okano T. Biorelated Functional Polymers: Controlled Release and Applications in Biomedical Engineering[M]. New York: Academic Press, 1998: 231 -248.
[8] Stayton PS, Hoffman AS. Immobilization of smart polymerprotein conjugates[A]. In: Cass T, Ligler FS, editors. Immobilized Biomolecules in Analysis[M]. Oxford, United Kingdom: Oxford Univ Press, 1998: 135-147.
[9] Monji N, Hoffman AS. A novel immunoassay system and bioseparation process based on thermal phase separating polymers[J]. Appl. Biochem. Biotechnol., 1987, 14(2): 107-120.
[10] Cole CA, Schreiner SM, Priest JH, Monji N, Hoffman AS. Nisopropylamide and N-acryloxysuccinimide copolymer: a thermally reversible water-soluble, activated polymer for protein conjugation[A]. In: Russo P, editor. Reversible Polymeric Gels and Related Systems, ACS Symposium Series 350[M]. Washington, DC: American Chemical Society, 1987: 245-254.
[11] Nowinski RC, Hoffman AS. Polymerization-induced separation immunoassays[P]. US Patent: 4,711,840, 1987:
[12] Monji N, Hoffman AS, Priest JH, Houghton RL. Thermallyinduced phase separation immunoassay[P]. US Patent: 4,780,409, 1988:
[13] Kinney TE, Nowinski RC, Schwartz D, Priest JH, Hoffman AS. Polymerization-induced separation assay using recognition pairs. US Patent: 4,749,647, 1988:
[14] Chen JP, Hoffman AS. Polymer protein conjugates .2. affinity precipitation separation of human immuno-gamma-globulin by a poly(n-isopropylacrylamide)-protein-a conjugate [J]. Biomaterials, 1990, 11(9): 631-634.
[15] Chen G, Hoffman AS. Preparation and properties of thermoreversible, phase-separating enzyme-oligo(N-isopropylacrylamide) conjugates [J]. Bioconjugate Chem 1993,4:509-514.
[16] Chen GH, Hoffman AS. Synthesis of carboxylated poly-(NIPAAm) oligomers and their application to form thermoreversible polymer-enzyme conjugates [J]. J Biomater Sci Polyme Ed., 1994, 5(4) : 371 -382.
[17] Ding Z, Chen GH, Hoffman AS. Unusual properties of thermally sensitive oligomer-enzyme conjugates of poly(N-isopropylacrylaraide)-trypsin[J]. J. Biomed. Mater. Res., 1998, 39(3): 498-505.
[18] Lackey CA, Murthy N, Press OW, Tirrell DA, Hoffman AS, Stayton PS. Hemolytic activity of pH-responsive polymerstreptavidin bioconjugates[J]. Bioconjugate Chera., 1999, 10(3): 401-405.
[19] Monji N, Cole CA, Hoffman AS. Dual analyte affinityprecipitation irnmunoassay for human IgG and IgM using two different thermally-sensitive polymer-antibody conjugates[J]. Bioconjugate Chem., To appear.
[20] Chilkoti A, Chen G, Stayton PS, Hoffman AS. Site-specific conjugation of a temperature-sensitive polymer to a geneticallyengineered protein [J]. Bioconjugate Chem., 1994, 5(6): 504-507.
[21] Stayton, PS, Shimoboji T, Long C, Chilkoti A, Chen G, Harris JM, Hoffman AS. Control of protein-ligand recognition using a stimuli-responsive polymer [J]. Nature 1995, 378(6556): 472-474.
[22] Stayton PS, Hoffman AS. Interactive molecular conjugates. US Patent, 5,998,588, 1999. 24. Ding Z, Long CJ, Hayashi Y, Bulmus EV, Hoffman AS, Stayton PS. Temperature control of biotin binding and release with a streptavidin-poly(N-isopropylacrylamide) site-specific conjugate [J]. Bioconjugate Chem., 1999, 10(3): 395-400.
[23] Bulmus V, Ding Z, Long CJ, Stayton PS, Hoffman AS. Site-Specific Polymer-Streptavidin Bioconjugate for pH-Controlled Binding and Triggered Release of Biotin [J]. Bioconjugate Chem., 2000, 11(1): 78 - 83.
[24] Fong RB, Ding Z, Long CJ, Hoffman AS, Stayton PS. Thermoprecipitation of Streptavidin via Oligonucleotide-Mediated Self-Assembly with Poly(N-isopropylacrylamide)[J]. Bioconjugate Chem., 1999, 10(5): 720 - 725.
[25] Larsson PO, Mosbach K. Affinity precipitation of enzymes[J]. FEBS Lett., 1979, 98(2): 333-338.
[26] Schneider M, GuillotC, Lamy B. The affinity precipitation technique: Application to the isolation and purification of trypsin from bovine pancreas [J]. Ann. NY. Acad. Sci., 1981, 369(11): 257-263.
[27] Pecs M, Eggert M, Schugerl K. Affinity precipitation of extacellular microbial enzymes [J]. J. Biotechnol., 1991, 21(1-2): 137-142.
[28] Galaev IY, Mattiasson B. Affinity thermoprecipitation: Contribution of the efficiency and access of the ligand[J]. Biotechnol. Bioeng., 1993, 41(11): 1101 -1106.
[29] Morris JE, Hoffman AS, Fisher RR. Affinity precipitation of proteins by polyligands[J]. Biotechnol. Bioeng., 1993, 41(10): 991-997.
[30] Karr LJ, Donnelly DL, Kozlowski A, Harris JM. Use of poly-(ethylene glycol)-raodified antibody in cell extraction[J]. Methods Enzymol., 1994, 228: 377-390.
[31] Okamura K, IkuraK, YoshikawaM, Sakaki R, ChibaH. Soluble-insoluble interconvertible enzymes[J]. Agric. Biol. Chem., 1984, 48(10): 2435 - 2440.
[32] Nguyen AL, Luong JHT. Syntheses and application of water-soluble reactive polymers for purification and immobilization of biomolecules[J]. Biotechnol. Bioeng., 1989, 34(9): 1186-1190.
[33] Taniguchi M, Kobayashi M, Fujii M. Properties of a reversible soluble-insoluble cellulase and its application to repeated hydrolysis of crystalline cellulose[J]. Biotechnol. Bioeng., 1989, 34(8): 1092-1097.
[34] Taniguchi M, Hoshino K, Watanabe K, Sugai K, Fujii M. Production of soluble sugar from cellulosic materials by repeated use of a reversibly soluble-autoprecipitating cellulase[J]. Biotechnol. Bioeng., 1992, 39(3): 287-292.
[35] Takei YG, Aoki T, Sanui K, Ogata N, Okano T, Sakurai Y. Temperature-responsive bioconjugates. 1. Synthesis of temperature-responsive oligomers with reactive end groups and their coupling to biomolecules[J]. Bioconjugate Chem., 1993, 4(1): 42-46.
[36] Takei YG, Aoki T, Sanui K, Ogata N, Okano T, Sakurai Y. Temperature-responsive bioconjugates. 2. Molecular design for temperature-modulated bioseparations[J]. Bioconjugate Chem., 1993, 4(5): 341 -346.
[37] Takei YG, Aoki T, Sanui K, Ogata N, Okano T, Sakurai Y. Temperature-responsive bioconjugates. 3. Antibody-poly(N-isopropylacrylamide) conjugates for temperature-modulated precipitations and affinity bioseparations[J].Biocon jugates Chem.,1994,5(6):577-582.
[38]高志贤,张超,陶桂全.压电免疫传感器抗体固定方法研究[J].中华微生物学和免疫学杂志,1996,16(3):191-195.
[39]陆斌,韦钰.基于全内反射荧光原理的免疫传感器[J].中国生物医学工程学报,1993,12(2):142-147.
[40]高志贤,陶桂全,李新如.压电免疫传感器用于C2型葡萄球菌肠毒素的测定[J].分析化学,1997,25(9):1061-1063.
[41]李凡超,徐京宁,何兵.免疫电化学方法测定C干扰素[J].分析化学,1994,2(1):55-57.
[42]楚霞,林朝晖,沈国励.甲胎蛋白压电免疫传感器的研究[J].高等学校化学学报,1996,17(6):870-873.
[43]裴仁军,胡继明,胡毅.蛋白A定向固定抗体的纤维蛋白压电免疫传感器的研究[J].高等学校化学学报,1998,19(3):363-366.
[44]袁若,唐点平,柴雅琴,张凌燕,刘颜,钟霞,戴建远.高灵敏电位型免疫传感器对乙型肝炎表面抗原的诊断技术研究[J].中国科学B辑-化学2004,34(4):279-286.
[45]Takei YG,Matsukata M.Temperature-Responsive Bioconjugates.3.Antibody Poly(N-Isopropylacrylamide) Conjugates For Temperature-Modulated Precipitations And Affinity Bioseparations [J].Bioconjugate Chemistry,1994,5(6):577-582.
[46]Bi HY,Weng XX,Qu HY,Kong JL,Yang PY,Liu BH.Strategy for allosteric analysis based on protein-patterned stationary phase in microfluidic chip[J].J.Proteome Res.,2005,4(6):2154 -2160.
[47]Baldwin RP,Roussel TJ,Crain MM,Bathlagunda V,Jackson DJ,Gullapalli J,Conklin JA,Pal R,Naber JF,Walsh KM,Keynton RS.Fully integrated on-chip electrochemical detection for capillary electrophoresis in a microfabricated device[J].Analytical Chemistry,2002,74(15):3690-3697.
[48]Huber DL,Manginell RP.Programmed adsorption and release of proteins in a microfluidic device [J]. Science, 2003, 301(5631): 352-354.
[49] Rehberg CE, Fisher CH. Preparation and Properties of the n-Alkyl Acrylates [J]. J. Am. Chem. Soc., 1944, 66: 1203-1207.
[50] Zhang Y, Telyatnikov V, Sathe M. Studying the Interaction of r-Gal Carbohydrate Antigen and Proteins by Quartz-Crystal Microbalance [J]. Journal of the American Chemical Society, 2003, 125(31): 9292-9293.
[51] Ebara Y, Itakura K, Okahata Y. Kinetic Studies of Molecular Recognition Based on Hydrogen Bonding at the Air-Water Interface by Using a Highly Sensitive Quartz-Crystal Microbalance [J]. Langmuir, 1996, 12(21): 5165-5170.
[1]Byrne RJ,Stitzel SE,Diamond D.Photo-regenerable surface with potential for optical sensing[J].J.Mater.Chem.,2006,16(14):1332-1337.
[2]Ipe BI,Mahima S,Thomas KG.Light-Induced Modulation of Self-Assembly on Spiropyran-Capped Gold Nanoparticles:A Potential System for the Controlled Release of Amino Acid Derivatives[J].J.Am.Chem.Soc.,2003,125(24):7174-7175.
[3]Barone PW,Baik S,Heller DA,Strano MS.Near-infrared optical sensors based on single-walled carbon nanotubes[J].Nature,2005,4(1):86-92.
[2]李荣金,李洪祥,汤庆鑫,胡文平。分子器件的研究进展[J]。物理,2006,35(12):1003-1009。
[3]Nespurek S,Sworakowski J.Electroactive and Photochromic Molecular Materials for Wires,Switches and Memories[J].IEEE Eng.Med.Biol.,1994,13(1):45-57.
[4]Joachim C,Gimzewski J K,Aviram A.Electronics using hybrid-molecular and mono-molecular devices[J].Nature,2000,408(6812):541-548.
[5]Carroll RL,Gorman CB.The genesis of molecular electronics[J].Angew.Chem.Int.Ed.,2002,41(23):4379-4400.
[6]朱海峰。J.Fraser Stoddart访谈:分子电子开关[J]。科学观察,2006,1(2):51-53。
[7]Nguyen TD,Tseng HR,Celestre PC,Elood AH,Liu Y,Stoddart JF,Zink JI.A reversible molecular valve[J].PNAS(Proceedings of the National Academy of Sciences),2005,102(29):10029-10043.
[8]吴璧耀,张道洪。分子开关研究进展。化工新型材料[J]。2001,29(11):9-13。
[9]Gosztola D,Niemczyk MP,Wasielewski MR.Picosecond molecular switch based on bidirectional inhibition of photoinduced electron transfer using photogenerated electric fields[J].J.Am.Chem.Soc.,1998,120(20):5118-5119.
[10]Raymo FM.Digital processing and communication with molecular switches[J].Adv.Mater.,2002,14(6):401-414.
[11]Brown GJ,de Silva AP,Pagliari S.Molecules that add up[J].Chem.Commun.,2002,(21):2461-2463.
[12]Lavigne JJ,Anslyn EV.Sensing a paradigm shift in the field of molecular recognition:From selective to differential receptors[J].Angew.Chem.Int.Ed.,2001,40(17):3119-3130.
[13]Wasielewski MR.Photoinduced Electron-Transfer in Supermolecular Systems for Artificial Photosynthesis[J].Chem.Rev.,1992,92(3):435-461.
[14]Kavarnos GJ.Fundamentals of Photoinduced Electron Transfer[M].York:VCH Weinheim New,1993.
[15]Park SY,Bae YH.Novel pH-sensitive polymers containing sulfonamide groups[J].Macromol.Rapid.Commun.,1999,20(5):269-273.
[16]Galaev IY,Mattiasson B.Smart polymers and what they could do in biotechnology and medicine[J].Trends Biotechnol,1999,17(8):335-340.
[17]Roy I,Gupta MN.Smart polymeric materials:Emerging biochemical applications[J].Chem.Biol.,2003,10(12):1161-1171.
[18]Gil ES,Hudson M.Stimuli-responsive polymers and their bioconjugates[J].Prog.Polym.Sci.,2004,29(12):1173-1222.
[19]Andersson RM,Carlsson K,Liljeborg A,Brismar H.Characterization of probe binding and comparison of its influence on fluorescence lifetime of two pH-sensitive benzo[c]xanthene dyes using intensity-modulated multiple-wavelength scanning technique[J].Anal Biochem,2000,283(1):104-110.
[20]Grabowski ZR,Rot kiewicz K.Structural changes accompanying intramolecular electron transfer:Focus on twisted intramolecular charge-transfer states and structures[J].Chem.Rev.,2003,103(10):3899-4032.
[21]Kung HF,Lee CW,Zhuang ZP,Kung MP,Hou C,Plossl K.Novel stilbenes as probes for amyloid plaques[J].J.Am.Chem.Soc.,2001,123(50):12740-12741.
[22]黄池宝,任安祥。具有“开-关”特性的pH荧光探针DPVF的合成与表征[J]。化学与生物工程,2007,24(2):44-46。
[23]蒋林玲,丁立平,胡道道,房喻。基于PET过程的分子开关型荧光传感器研究进展[J]。应用化学,2006,23(10):1069-1075。
[24]Tsien RY.Fluorescence imaging creates a windows on the cell[J].Chem.New.,1994,18(7):34-36.
[25]史向阳,孙曹民,吴世康。荧光探针法研究壳聚糖在水溶液中的聚集态行为[J]。感光科学与光化学,1998,16(2):161-166。
[26]Shinkai S.Calixarenes-the third generation of supermolecules[J].Tetrahedron,1993,49(40):8933-8968.
[27]Kroner D,Klaumunzer B.Laser-operated chiral molecular switch:quantum simulations for the controlled transformation between achiral and chiral atropisomers[J].Physical Chemistry Chemical Physics,2007,9(36):5009-5017.
[28]孙亚斌,丁小斌,郑朝晖,成煦,彭宇行。智能表面[J]。化学通报,2006,69(4),252-260。
[29]Nakayama K,Jiang L,Iyoda T,Fujishima A.Photo-induced structural transformation on the surface of azobenzene crystals[J].Jpn J Appl Phys Part 1,1997,36(6B):3898-3902.
[30]Prins MWJ,Welters WJJ,Weekamp JW.Fluid control in multichannel structures by electrocapillary pressure[J].Science,2001,291(5502):277-280.
[31]Abbott NL,Gorman CB,Whitesides GM.Active control of wetting using applied electrical potentials and self-assembled monolayers[J].Langmuir 1995,11(1):16-18.
[32]Byloos M,Al-Maznai H,Morin M.Phase transitions of alkanethiol self-assembled monolayers at an electrified gold surface[J].J Phys Chem B.2001,105(25):5900-5905.
[33]Crevoisier GB,Fabre P,Corpart J,Leibler L.Switchable tackiness and wettability of a liquid crystalline polymer[J].Science,1999,285(5431):1246-1249.
[34]Minko S,Sidorenko A,Goreshnik E.Environment friendly and switchable polymer brushes[J].The American Chemical Society,2000,220:U370-U370.
[35]Chaudhury MK,Whitesides GM.How to make water run uphill[J].Science,1992,256(5063):1539-1541.
[36]Wang ZH,Chen KC,Tian H.Intramolecular fluorescence quenching in ferrocene-naphthalimide dyads[J].Chem.Lett.,1999,(5):423-424.
[37]Raphael E,DeGennes PG.Rubber rubber adhesion with connector molecules[J].J.Phys.Chem.,1992,96(10):4002-4007.
[38]Ruths M,Johannsmann D,Ruhe J,Knoll W.Repulsive forces and relaxation on compression of entangled,polydisperse polystyrene brushes[J].Macromolecules,2000,33(10):3860-3870.
[39]Collier CP,Mattersteig G,Wong EW.A[2]catenane-based solid state electronically reconfigurable switch[J].Science,2000,289(5482):1172-1175.
[40]Klein J,Kumacheva E,Mahalu D,Perahia D,Fetters LJ.Reduction of frictional forces between solid-surfaces bearing polymer brushes[J].Nature,1994,370(6491):634-636.
[41]Galaev IY,Mattiasson B."Smart" polymers and what they could do in biotechnology and medicine[J].Trends In Biotechnology 1999,17(8):335-340.
[42]Aksay IA,Trau MS,Honma I.Biomimetic pathways for assembling inorganic thin films[J].Science,1996,273(5277):892-898.
[43]Russell TP.Surface-responsive materials[J].Science,2002,297(5583):964-967.
[44]姚芳莲,陈炜,王浩,周玉涛,姚康德。智能高分子表面的设计及其在生物医学中的应用[J]。化学通报,2004,67(9):661-666。
[45]Galaev IY,Mattiasson B."Smart" polymers and what they could do inbiotechnology and medicine[J].Trends In Biotechnology 1999,17(8):335-340.
[46]Aksay IA,Trau M,Manne S,Honma I,Yao N,Zhou L,Fenter P,Eisenberger PM,Gruner SM.Biomimetic pathways for assembling inorganic thin films[J].Science,1996,273(5277):892-898.
[47]黄杉生,李苾芬,林辉概,俞汝勤。萘衍生物的聚合膜结构及膜的pH响应[J].湖南大学学报,1996,23(2):36-40。
[48]Ito Y,Ochiai Y,Park YS,Imanishi Y.pH-sensitive gating by conformational change of a polypeptide brush grafted onto a porous polymer membrane[J].J.Am.Chem.Sot.,1997,119(7):1619-1623.
[49]Sun T,Feng L,Gao X,Jiang L.Bioinspired surfaces with special wettability[J].Acc.Chem.Res.,2005,38(8):644-652.
[50]Lahann 5,Mitragotri S,Tran T,Kaido H,Sundaram J,Choi IS,Hoffer S,Somorjai GA,Langer R.A reversibly switching surface[J].Science,2003,299(5605):371-374.
[51]Lim HS,Nan JT,Kwak D,Jin M,Cho K.Photoreversibly switchable superhydrophobic surface with erasable and rewritable pattern[J].J Am.Chem.Soc.,2006,128(45):14458-14459.
[52]刘秀生,唐艳平。微流体芯片及其表面效应[J].医学与社会,2005,18(5):35-36。
[53]Ionov L,Minko S,Stamm M.Reversible chemical patterning on stimuli-responsive polymer film:Environment-responsive lithography[J].J.Am.Chem.Soc.,2003,125(27):8302-8306.
[54]周平,邓延倬,曾云鹗.用温度敏感高分子为载体的激光光声免疫分析及其应用[J].分析化学,1997,25(2):144-148。
[55]Zhu QZ,Liu FH.Mimetic-enzyme fluorescence immunoassay using a thermal phase separating polymer[J].Analyst 1998,123(5):1131-1134.
[56]Chen GH,Hoffman AS.Preparation And Properties Of Thermoreversible,Phase-Separating Enzyme-Oligo(N-Isopropylacrylamide) Conjugates[J].Bioconjugate Chemistry 1993,4(6):509-514.
[57]Chen JP,Hoffman AS.Polymer Protein Conjugates.2.Affinity Precipitation Separation Of Human Immuno-Gamma-Globulin By A Poly(N-Isopropylacrylamide)-Protein-A Conjugate[J].Biomaterials 1990,11(9):631-634.
[58]Ringsdorf H,Venzmer J.Fluorescence Studies Of Hydrophobically Modified Poly(N-Isopropylacrylamides)[J].Macromolecules 1991,24(7):1678-1686.
[59]何庆,盛京。响应性凝胶及其在药物控释上的应用[J].功能高分子学报,1997,10(1):118-127。
[60]Liu F,Tao GL.Synthesis Of Thermal Phase-Separating Reactive Polymers And Their Applications In Immobilized Enzymes[J].Polymer Journal 1993,25(6):561-567.
[61]Kawaguchi H,Fujimoto K.Hydrogel Microspheres.3.Temperature-Dependent Adsorption Of Proteins On Poly-N-Isopropylacrylamide Hydrogel Microspheres[J].Colloid And Polymer Science 1992,270(1):53-57.
[62]张柏林,王敏灿,常文保,慈云祥.高分子控温相变免疫分析法测定苯妥因[J].分析化学,1997,25(9):993-996。
[63]Miyauchi M,Nakajima A,Watanabe T,Hashimoto K.Photocatalysis and photoinduced hydrophilicity of various metal oxide thin films[J].Chem.Mater.,2002,14(2):2812-2816.
[64]Feng X,Feng L,Jin M,Zhai J,Jiang L,Zhu DB.Reversible super-hydrophobicity to super-hydrophilicity transition of aligned ZnO nanorod films[J].J.Am.Chem.Soc.2004,126(1):62-63.
[65]Feng X,Zhai J,Jiang L.The fabrication and switchable superhydrophobicity of Tio2 nanorod films[J].Angew.Chem.,Int.Ed.2005,44(32):5115-5118.
[66]Ho Sun Lim,Donghoon Kwak,Dong Yun Lee,Seung Goo Lee,Kilwon Cho.UV-Driven Reversible Switching of a Roselike Vanadium Oxide Film between Superhydrophobicity and Superhydrophilicity[J].J.Aa.Chem.Soc.2007,129(14):4128-4129.
[67]Feng X,Zhai J,Jiang L.The fabrication and switchable superhydrophobicity of TiO2 nanorod films[J].Angew.Chem.Int.Ed.,2005,44(32):5115-5118.
[68]Shutao Wang,Xinjian Feng,Jiannian Yao,Lei Jiang.Controlling Wettability and Photochromism in a Dual-Responsive Tungsten Oxide Film[J].Angew.Chem.Int.Ed.2006,45(8):1264-1267.
[69]Liping Heng,Yongqiang Dong,Jin Zhai,Benzhong Tang,Lei Jiang.Solvent Fuming Dual-Responsive Switching of Both Wettability and Solid-State Luminescence in Silole Film[J].Langmuir 2008,24(5):2157-2161.
[70]马永正,要旸,冯喜增。智能聚合物在生物化学领域的应用进展[J].化学与生物工程,2007,24(9):1-4。
[71]Ito Y,Ochiai Y,Park YS,Imanishi Y.pH-sensitive gating by conformational change of a polypeptide brushgrafted onto a porous polymer membrane[J].J.Am.Chem.Soc.,1997,119(7):1619-1623.
[72]Ito Y,Park YS,Imanishi YJ.Visualization of critical pH-controlled gating of a porous membrane grafted withpolyelectrolyte brushes[J].Am.Chem.Soc.,1997,119(11):2739-2740.
[73]Ito Y,Nishi S,Park YS.Oxidoreduction-Sensitive control of water permeation through a polymer brushes-grafted porous membrane[J].Macromolecules,1997,30(19):5856-5859.
[74]Ito Y,Park YS,Imanishi Y.Imaging of a pH-sensitive polymer brush on a porous membrane using atomic force microscopy in aqueous solution [J].Macromol.Rapid Commun.,1997,18(3):221-224.
[75]殷以华,孟亚斌,杨亚江。pH-敏感的疏水型凝胶在直流电场中的刺激响应[J].高分子学报,2002,(4):414-417。
[76]李斌,陈文广,王晓工。聚丙烯表面接枝PNIPAAm膜Ⅱ.表面特性和温度响应性研究[J].高分子学报,2003,(1):7-121。
[77]Luo CH,Zuo F,Zheng ZH,Cheng X,Ding XB,Peng YX.Tunable smart surface of gold nanoparticles achieved by light-controlled molecular recognition effection[J].Macromolecular rapid communications,2008,29(2):149-154.
[78]唐黎明,孟晓霞,王慧芬。压敏型胶粘剂的研究进展[J].高分子材料科学与工程,1998,14(5):141-1431。
[79]李治章,李东。基于功能高分子膜的荧光传感器研究--Ⅰ铜离子荧光熄灭型传感器[J].化学传感器,1997,17(3):204-2091。
[80]张建合,杨亚江。亲水/疏水半互穿网络凝胶在直流电场作用下的响应[J].高分子学报,2002,(1):285-291。
[81]Milner ST.Polymer Brushes[J].Science,1991,251(4996):905-914.
[82]Leduc MR,Hawker CJ,Dao J,Frechet JMJ.Dendritic Initiators for ″Living″ Radical Polymerizations:A Versatile Approach to the Synthesis of Dendritic-Linear Block Copolymers[J].J.Am.Chem.Soc.,1996,118(45):11111-11118.
[83]Inoue K.Functional dendrimers,hyperbranched and star polymers[J].Prog.Polym.Sci.,2000,25(4):453-571.
[84]Schluter AD.Dendrimers with Polymeric Core[A].in:Vogtle F.Top.Curr.Chem.[M].Springer,1998:165-191.
[85]张磊,李文,张阿方。聚合物分子刷的合成与应用[J].化学进展,18(7/8):939-949。
[86]Song SY,Choi HG,Hong JW,Kim BW,Sim SJ,Yoon HC.Selective antigen-antibody recognition on SPR sensor based on the heat-sensitive conformational change of poly(N-isopropylacrylamide)[J].Colloids and surfaces a-physicochemical and engineering aspects,2008,313(Sp.Iss.SI):504-508.
[87]Kim F,Kwan S,Akana J,Yang P.Langmuir-Blodgett Nanorod Assembly[J].J.Am.Chem.Soc.,2001,123(18):4360-4361.
[88]刘欢,翟锦,江雷。纳米材料的自组装研究进展[J]。无机化学学报,2006,22(4):585-597.
[89]Whitesides GM,Mathias JP,Seto C T.Molecular Self-Assembly and Nanochemistry-A Chemical Strategy for the Synthesis of Nanostructures[J].Science,1991,254(5036):1312-1319.
[90]谢永荣,杨瑞卿,付大伟,袁小勇。分子自组装与分子机器[J]。赣南师范学院学报,2005,(6):44-48。
[91]邵建新。分子电子学[J]。现代物理知识,2006,18(5):29-31。
[92]庄小东,陈或,刘莹,蔡良珍,林楹。自组装有机纳米功能材料[J]。化学进展,2007,19(11):1653-1661.
[93]Chia S,Cao J,Stoddart JF,Zink JI.Working Supramolecular Machines Trapped in Glass and Mounted on a Film Surface[J].Angew.Chem.2001,113(13):2513-2517.
[94]Ma X,Wang Q,Qu D,Xu Y,Ji Y,Tian H.A Light-Driven Pseudo[4]rotaxane Encoded by Induced Circular Dichroism in a Hydrogel[J]. Advanced Functional Materials, 2007, 17(5): 829-837.
[95] Balzani V, Credi A, Raymo FM, Stoddart JF. Klinstliche molekulare Maschinen[J]. Angew. Chem., 2000, 112(19): 3484-3530.
[97] Balzani V, Credi A, Raymo FM, Stoddart JF. Artificial Molecular Machines[J]. Angew. Chem. Int. Ed., 2000, 39(19): 3348-3391.
[98] Ballardini R, Balzani V, Credi A, Gandolfi MT, Venturi M. Artificial Molecular-Level Machines: Which Energy To Make Them Work?[J]. Acc. Chem. Res., 2001, 34(6): 445-455.
[99] Ashton PR, Ballardini R, Balzani V, Boyd SE, Williams DJ. Chem. Eur. J., 1997, 3(1): 152.
[100] Kyungpil K, Jeon WS, Kang JK, Lee JW, Jon SY, Kim T, Kim K. A Pseudorotaxane on Gold: Formation of Self-Assembled Monolayers, Reversible Dethreading and Rethreading of the Ring, and Ion-Gating Behavior [J]. Angew. Chem. Int. Ed. 2003, 42(20): 2293-2296.
[101] a) W. L. Mock, Top. Curr. Chem. 1995, 175, 1;
[102] b) P. Cintas, J. I. Phenom, Mol. Recognit. Chem. 1994, 17, 205;
[103] c) W. L. Mock, Compr. Supramol. Chem. 1996, 2, 477.
[104] Whang D, Jeon YM, Heo J, Kim K. Self-Assembly of a Polyrotaxane Containing a Cyclic "Bead" in Every Structural Unit in the Solid State: Cucurbituril Molecules Threaded on a One-Dimensional Coordination Polymer [J]. J. Am. Chem. Soc., 1996, 118(45): 11333- 11334.
[105] Whang D, Kim K. Polycatenated Two-Dimensional Polyrotaxane Net [J]. J. Am. Chem. Soc, 1997, 119(2): 451.
[106] Whang D, Park KM, Heo J, Kim K. Molecular Necklace: Quantitative Self-Assembly of a Cyclic Oligorotaxane from Nine Molecules[J]. J. Am. Chem. Soc, 1998, 120(19): 4899-4900.
[107] Roh SG, Park KM, Park GJ, Sakamoto S, Yamaguchi K, Kim K. Synthesis of a Five-Membered Molecular Necklace: A 2+2 Approach[J]. Angew. Chem. Int. Ed., 1999, 38(5): 637-641.
[108] Lahann J, Mitragotri S, Tran T, Kaido H, Sundaram J, Choi IS, Hoffer S,Somorjai GA,Langer R.A reversibly switching surface[J].Science,2003,299(5605):371-374.
[109]林炳承,秦建华。微流控芯片实验室[J].色谱,2005,23(5):456-463.
[110]Unger MA,Chou HP,Thorsen T,Scherer A,Quake SR.Monolithic microfabricated valves and pumps by multilayer soft lithography[J].Science,2000,288(5463):113-116.
[111]Studer V,Hang G,Pandolfi A,Ortiz M,Anderson WF,Quake SR.Scaling properties of a low-actuation pressure microfluidic valve[J].J.Appl.Phys.,2004,95(1):393-398.
[112]Park SJ,Kim JK,Park J,Chung S,Chung C,Chang JK.Rapid three-dimensional passive rotation micromixer using the breakup process[J].J.Micromech.Microeng.2004,14(1):6- 14.
[113]王辉,戴忠鹏,王利,白吉玲,林炳承。一种玻璃微流控芯片的质量检测方法[P].中国专利:200310119466.5,2005-06-29:
[114]杨友麒。微尺度和纳米尺度过程系统工程的进展和挑战[J].现代化工,2007,27(10):1-9。
[115]Kikutani Y,Ueno M,Hisamoto H,Tokeshi M,Kitamori T.Continuous-flow chemical processing in three-dimensional microchannel network for on-chip integration of multiple reactions in a combinatorial mode[J].QSAR.Comb.Sci.,2005,24(6):742 - 757.
[116]Harrison DJ,Fluri K,Seiler K,Fan ZH,Effenhauser CS,Manz A.Micromachining A Miniaturized Capillary Electrophoresis-Based Chemical-Analysis System on a Chip[J].Science,1993,261(5123):895-897.
[117]Chou HP,Spence C,Scherer A,Quake S.A microfabricated device for sizing and sorting DNA molecules[J].Proc.Natl.Acad.Sci.USA 1999,96(1):11-13.
[118]Chen Y,Pepin A.Nanofabrication:Conventional and nonconventional methods[J].Electrophoresis,2001,22(2):187-207.
[119]Vilkner T,Janasek D,Manz A.Micro total analysis systems.Recent developments[J].Anal.Chem.,2004,76(12):3373-3386.
[120]宋江莉,王秀芬。LCST类水凝胶开关效应的研究进展[J]。化学进展,2004,16(1):56-60。
[121]Ebara M,Hoffman JM,Stayton PS,Hoffman AS.Surface modification of microfluidic channels by UV-mediated graft polymerization of non-fouling and 'smart' polymers[J].Radiation physics and chemistry,2007,76(8-9):1409-1413.
[122]Dong LC,Hoffman AS.A Novel-Approach for Preparation of pH-Sensitive Hydrogels for Enteric Drug Delivery[J].J.Controlled Release,1991,15(2):147-152.
[123]Zhang JT,Huang SW,Cheng SX,Zhuo RX.Preparation and properties of po]y(N-isopropylacrylamide)/poly(N-isopropylacrylamide)interpenetrating polymer networks for drug delivery,J.Polym.Sci.A:Polym.Chem.[J].2004,42(5):1249-1254.
[124]Yin YH,Yang YJ,Xu HB.Swelling behavior of hydrogels for colon-site drug delivery[J].J.Appl.Polym.Sci.,2002,83(13):2835-2842.
[125]Kurisawa M,Yui N.Gelatin/dextran intelligent hydrogels for drug delivery:dual-stimuli-responsive degradation in relation to miscibility in interpenetrating polymer networks[J].Macromol.Chem.Phys.,1998,199(8):1547-1554.
[126]Beebe DJ,Moore JS,Bauer JM,Yu Q,Liu RH,Devadoss C,Jo BH.Functional hydrogel structures for autonomous flow control insidemicro fluidic channels[J].Nature,2000,404(6778):588-590.
[127]Yu C,Mutlu S,Selvaganapathy P,Mastrangelo CH,Svec F,Frechett JMJ.Flow Control Valves for Analytical Microfluidic Chips without Mechanical Parts Based on Thermally Responsive Monolithic Polymers[J].Anal.Chem.,2003,75(8):1958-1961.
[128]Liu YJ,Guo SS,Zhang ZL,Huang WH,Baigl D,Xie M,Chen Y,Pang DW.A micropillar-integrated smart microfluidic device for specific capture and sorting of cells[J].Electrophoresis 2007,28(24):4713 -4722.
[129]Malmstadt N,Yager P,Hoffman AS,Stayton PS.A Smart Microfluidic Affinity Chromatography Matrix Composed of Poly(N-isopropylacrylamide)-Coated Beads[J]. Anal. Chem. , 2003, 75(13): 2943-2949.
[130] Malmstadt N, Hoffman AS, Stayton PS. "Smart" mobile affinity matrix for microfluidic immunoassays[J]. Lab On A Chip, 2004, 4(4): 412-415.
[131] Ding ZL, Fong RB, Long CJ, Stayton PS, Hoffman AS. Size-dependent control of the binding of biotinylated proteins to streptavidin using a polymer shield[J]. Nature, 2001, 411(6833): 59-62.
[132] Kuckling D, Richter A, Arndt KF. Temperature and pH-dependent swelling behavior of poly(N-isopropylacrylamide) copolymer hydrogels and their use in flow control[J]. Macromol. Mater. Eng., 2003, 288(2): 144-151.
[133] Richter A, Kuckling D, Howitz S, GehringT, Arndt KF. Electronically controllable microvalves based on smart hydrogels: Magnitudes and potential applications[J]. J. Microelectromechanical Syst., 2003, 12(5): 748-753.
[134] Ionov L, Houbenov N, Sidorenko A, Stamm M, Minko S, Smart Microfluidic Channels[J]. 2006, Adv. Funct. Mater., 2006, 16(9): 1153-1160.
[1]Russell,TP.Surface-responsive materials[J].Science,2002,297(5583):964-967.
[2]Nath N,Chilkoti A.Creating ″Smart″ surfaces using stimuli responsive polymers[J].Advanced Materials,2002,14(17):1243-1247.
[3]Luzinova I,Minko S,Tsukruk W.Adaptive and responsive surfaces through controlled reorganization of interracial polymer layers[J].Prog.Polym.Sci.,2004,29:635-698.
[4]黄菲。抗精神病类药物电化学传感器研究[D]。复旦大学分析化学专业博士学位论文,2007,7-9。
[5]董绍俊,车广礼,谢远武。化学修饰电极[M]。北京:科学出版社,2003:571-592。
[6]黄菲。吩噻嗪衍生物在硫醇与碳纳米管修饰金电极上的伏安行为及测定[D]。武汉大学分析化学专业硕士学位论文,2004,1-3.
[7]杨生荣,任嗣利,张俊彦,张绪寿。自组装单分子膜的结构及其自组装机理[J]。高等学校化学学报,2001,22(3):470-476.
[8]杨玉霞。吩噻嗪衍生物和肾上腺素在硫醇自组装膜修饰金电极上的电化学行为[D]。武汉大学分析化学专业硕士学位论文,2003,3-4。
[9]Ulman A.An Introduction to Organic Ultra Thin Films[M].Boston:Academic Press,1991:237.
[10]J.Lahann,S.Mitragotri,N.T.Tran,H.Kaido,J.Sundaram,S.I.Choi,S.Holler,A.G.Somorjai and R.Langer.A reversibly switching surface[J].Science,2003,299(5605):371-374.
[11]Auletta T,Van Veggel F.Self-assembled monolayers on gold of ferrocene-terminated Thiols and hydroxyalkanethiols[J].Langmuir 2002,18(4):1288-1293.
[12]ikeda H,Nakamura M,Ise N,Oguma N,Nakamura A,Tkeda T,Toda F,Ueno A.Fluorescent cyclodextrins for molecule sensing:Fluorescent properties,NMR characterization,and inclusion phenomena of N-dansylleucine-modified cyclodextrins[J].Journal of the American Chemical Society,1996,118(45):10980-10988.
[13] Bojinova T, Coppel Y. Complexes between beta-cyclodextrin and aliphatic guests as new noncovalent amphiphiles: Formation and physicochemical studies [J]. Langmuir 2003, 19(13): 5233-5239.
[1]Manz A,Graber N,Widmer H M.Miniaturized Total Chemical-Analysis Systems - A Novel Concept for Chemical Sensing[J].Sensor Actuators B-Chemical,1990,1(1-6):224-248.
[2]Manz A,Verpoorte E,Raymond D E.Micro Total Analysis Systems[M].The Netherlands:1994.Dordrecht.Kluwer Academic Publishers,1995:5.
[3]王立凯,冯喜增.微流控芯片技术在生命科学研究中的应用[J].化学进展,2005,17(3):482-498.
[4]丛辉,王惠民,宋宏伟,鞠少卿,金庆辉,贾春平,庄贵生,刘菁.控制微流控芯片电泳中的蛋白质吸附[J].检验医学,2006,21(5):449-452.
[5]Yu C,Mutlu S,Selvaganapathy P,Mastrangelo CH,Svec F,Frechet J MJ.Flow Control Valves for Analytical Microfluidic Chips without Mechanical Parts Based on Thermally Responsive Monolithic Polymers[y].Analytical Chemistry,2003,75(8):1958-1961.
[6]Beebe DJ,Moore JS,Bauer JM,Yu Q,Liu RH,Devadoss C,Jo BH.Functional hydrogel structures for autonomous flow control insidemicro fluidic channels[J].Nature,2000,404(6778):588-590.
[7]Reyes DR,Iossifidis D,iuroux PA,Manz A.Micro total analysis systems.1.Introduction,theory,and technology[J].Anal.Chem.,2002,74(12):2623-2636.
[8]Buchholz BA,Doherty EAS,Albarghouthi MN,Bogdan FM,Zahn JM,Barron AE.Microchannel DNA Sequencing Matrices with a Thermally Controlled ″Viscosity Switch″[J].Anal.Chem.,2001,73(2):157-164.
[9]almstadt NM,Ager PY,Hoffman AS,Stayton PS.A Smart Microfluidic Affinity Chromatography Matrix Composed of Poly(N-isopropylacrylamide)-Coated Beads[J].Anal.Chem.,2003,75(13):2943-2949.
[10]Yu C,Mutlu S,Selvaganapathy P,Mastrangelo CH,Svec F,Frechett JMJ.Flow Control Valves for Analytical Microfluidic Chips without Mechanical Parts Based on Thermally Responsive Monolithic Polymers [J]. Anal. Chem., 2003, 75(8): 1958-1961.
[11] Kitamura N, Hosoda Y, Iwasaki C, Ueno K , Kim HB. Thermal Phase Transition of an Aqueous Poly(N-isopropylacrylamide) Solution in a Polymer Microchannel-Microheater Chip[J]. Langmuir, 2003, 19(20) : 8484 - 8489.
[12] Bedair MF, Oleschuk RD. Fabrication of porous polymer monoliths in polymeric microfluidic chips as an electrospray emitter for direct coupling to mass spectrometry[J]. Anal. Chem., 2006, 78(4): 1130-1138.
[13] Qu HY, Wang HT, Huang Y, Zhong W, Lu HJ, Kong JL, Yang PY, Liu BH. Stable microstructured network for protein patterning on a plastic microfluidic channel: Strategy and characterization of on-chip enzyme microreactors[J]. Analytical Chemistry, 2004, 76(21): 6426 - 6433.
[14] Bi HY, Weng XX, Qu HY, Kong JL, Yang PY, Liu BH. Strategy for allosteric analysis based on protein-patterned stationary phase in microfluidic chip[J]. J. Proteome Res., 2005, 4(6): 2154 -2160.
[15] Baldwin RP, Roussel TJ, Crain MM, Bathlagunda V, Jackson DJ, Gullapalli J, ConklinJA, Pai R, Naber JF, Walsh KM, Keynton RS. Fully integrated on-chip electrochemical detection for capillary electrophoresis in a microfabricated device [J]. Analytical Chemistry, 2002, 74(15): 3690-3697.
[16] Liu Y, Mu L, Liu BH, Zhang S, Yang PY, Kong JL. Controlled protein assembly on a switchable surface[J]. Chem.Commun., 2004, (10): 1194- 1195.
[17] Mu L, Liu Y, Zhang S, Liu BH, Kong J. Selective assembly of specifically charged proteins on an electrochemically switched surface[J]. New J. Chem., 2005, 29(6): 847-852.
[1]Hochstrasser DF,Sanchez JC,Appel RD.Proteomics and its trends facing nature's complexity[J].Proteomics,2002,2(7):807-812.
[2]Zhang Q,Riechers DE.Proteomics:An emerging technology for weed science research[J].Weed science,2008,56(2):306-313.
[3]Auroux PA,Iossifidis D,Reyes DR,Manz A.Micro total analysis systems.2.Analytical standard operations and applications[J].Analytical Chemistry,2002,74(12):2637-2652.
[4]Gorg A,Weiss W,Dunn MJ.Current two - dimensional electrophoresis technology for proteomics[J].Proteomics,2004,4(12):3665-3685.
[5]Zheng XJ,Hong LL,Shi LX,Guo JQ,Sun Z,Zhou JY.Proteomics analysis of host cells infected with infectious bursal disease virus[J].Molecular & Cellular Proteomics,2008,7(3):612-625.
[6]Furusawa T,Rakwal R,Nam HW,Hirano M,Shibato J,Kim YS,Ogawa Y,Yoshida Y,Kramer KJ,Kouzuma Y,Agrawal GK,Yonekura M.Systematic investigation of the hemolymph proteome of Manduca sexta at the fifth instar larvae stage using one- and two-dimensional proteomics platforms[J].Journal of proteome research,2008,7(3):938-959.
[7]Blankley RT,Robinson NJ,Crocker IP,Baker PN,Myers JE.Unlocking the potential of proteomics:Achieving relative quantification of proteins recovered from placental explant-conditioned culture media using an optimised mass spectrometry-based workflow[J].Reproductive sciences,2008,15(2):140A-140A.
[8]Lim D,Kamotani Y,Cho B,Mazumder J,Takayama S.Fabrication of microfluidic mixers and artificial vasculatures using a high-brightness diode-pumped Nd:YAG laser direct write method[J].Lab on a Chip,2003,3(4):318-323.
[9]Sun XF,Sun XF,Zhen ZJ,Zhang X,Zhang Y,Xia Y.Serum protein profiling of lymphoblastic lymphoma by protein Chip SELDI-TOF technology[J].Pediatric blood & cancer,2007,49(4):447-447.
[10]王立凯,冯喜增.微流控芯片技术在生命科学研究中的应用[J].化学进展,2005,17(3):482-498.
[11] Hardouin J, Joubert-Caron R, Caron M. HPLC-chip-mass spectrometry for protein signature identifications[J]. Journal of separation science, 2007, 30(10): 1482-1487. Blazer LL, Boyle MDP. Use of protein chip mass spectrometry to monitor biotinylation reactions [J]. Applied microbiology and biotechnology, 2007, 74(3): 717-722.
[12] Bi HY, Meng S, Li Y, Guo K, Chen YP, Kong JL, Yang PY, Zhong W, Liu BH. Deposition of PEG onto PMMA microchannel surface to minimize nonspecific adsorption. Lab on a Chip, 2006, 6(6): 769-775.
[13] Huber DL, Manginell RP. Programmed adsorption and release of proteins in a microfluidic device [J]. Science 2003, 301(5631): 352-354.
[14] Sikes HD , Smalley JF. Rapid electron tunneling through oligophenylenevinylene bridges [J]. Science 2001 , 291(5508): 1519-1523.
[15] Nitzan A, Ratner MA. Electron transport in molecular wire junctions [J]. Science 2003, 300(5624): 1384-1389.
[1] Hoffman AS. Hoffman AS, Stayton PS, Bulmus V, Chen GH, Chen JP, Cheung C, Chilkoti A, Ding ZL, Dong LC, Fong R, Lackey CA, Long CJ, Miura M, Morris JE, Murthy N, Nabeshima Y, Park TG, Press OW, Shimoboji T, Shoemaker S, Yang HJ, Monji N, Nowinski RC, Cole CA, Priest JH, Harris JM, Nakamae K, Nishino T, Miyata T. Really smart bioconjugates of smart polymers and receptor proteins [J]. Journal of Biomedical Materials Research 2000, 52(4): 577-586.
[2] Malmstadt N, Yager P, Hoffman AS, Stayton PS. A smart microfluidic affinity chromatography matrix composed of poly(N-isopropylacrylamide)-coated beads[J]. Analytical Chemistry, 2003, 75(13): 2943-2949.
[3] Fuertges F, Abuchowski A. The clinical efficacy of poly(ethylene glycol)-modified proteins [J]. Journal of Controlled Release, 1990, 11(1-3): 139-148.
[4] Maeda H. SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy [J]. Advanced drug delivery reviews, 1991, 6(2): 181-202.
[5] Maeda H, Seymour LW, Miyamoto Y. Conjugates of anticancer agents and polymers - advantages of macromolecular therapeutics invivo[J]. Bioconjugate Chem., 1992, 3(5): 351-362.
[6] Duncan R, Kopecek J. Soluble synthetic polymers as potential drug carriers. Adv Polym Sci 1984,57:53-101.
[7] Hoffman AS. A commentary on the advantages and limitations of synthetic polymer-biomolecule conjugates [A]. In: Okano T. Biorelated Functional Polymers: Controlled Release and Applications in Biomedical Engineering[M]. New York: Academic Press, 1998: 231 -248.
[8] Stayton PS, Hoffman AS. Immobilization of smart polymerprotein conjugates[A]. In: Cass T, Ligler FS, editors. Immobilized Biomolecules in Analysis[M]. Oxford, United Kingdom: Oxford Univ Press, 1998: 135-147.
[9] Monji N, Hoffman AS. A novel immunoassay system and bioseparation process based on thermal phase separating polymers[J]. Appl. Biochem. Biotechnol., 1987, 14(2): 107-120.
[10] Cole CA, Schreiner SM, Priest JH, Monji N, Hoffman AS. Nisopropylamide and N-acryloxysuccinimide copolymer: a thermally reversible water-soluble, activated polymer for protein conjugation[A]. In: Russo P, editor. Reversible Polymeric Gels and Related Systems, ACS Symposium Series 350[M]. Washington, DC: American Chemical Society, 1987: 245-254.
[11] Nowinski RC, Hoffman AS. Polymerization-induced separation immunoassays[P]. US Patent: 4,711,840, 1987:
[12] Monji N, Hoffman AS, Priest JH, Houghton RL. Thermallyinduced phase separation immunoassay[P]. US Patent: 4,780,409, 1988:
[13] Kinney TE, Nowinski RC, Schwartz D, Priest JH, Hoffman AS. Polymerization-induced separation assay using recognition pairs. US Patent: 4,749,647, 1988:
[14] Chen JP, Hoffman AS. Polymer protein conjugates .2. affinity precipitation separation of human immuno-gamma-globulin by a poly(n-isopropylacrylamide)-protein-a conjugate [J]. Biomaterials, 1990, 11(9): 631-634.
[15] Chen G, Hoffman AS. Preparation and properties of thermoreversible, phase-separating enzyme-oligo(N-isopropylacrylamide) conjugates [J]. Bioconjugate Chem 1993,4:509-514.
[16] Chen GH, Hoffman AS. Synthesis of carboxylated poly-(NIPAAm) oligomers and their application to form thermoreversible polymer-enzyme conjugates [J]. J Biomater Sci Polyme Ed., 1994, 5(4) : 371 -382.
[17] Ding Z, Chen GH, Hoffman AS. Unusual properties of thermally sensitive oligomer-enzyme conjugates of poly(N-isopropylacrylaraide)-trypsin[J]. J. Biomed. Mater. Res., 1998, 39(3): 498-505.
[18] Lackey CA, Murthy N, Press OW, Tirrell DA, Hoffman AS, Stayton PS. Hemolytic activity of pH-responsive polymerstreptavidin bioconjugates[J]. Bioconjugate Chera., 1999, 10(3): 401-405.
[19] Monji N, Cole CA, Hoffman AS. Dual analyte affinityprecipitation irnmunoassay for human IgG and IgM using two different thermally-sensitive polymer-antibody conjugates[J]. Bioconjugate Chem., To appear.
[20] Chilkoti A, Chen G, Stayton PS, Hoffman AS. Site-specific conjugation of a temperature-sensitive polymer to a geneticallyengineered protein [J]. Bioconjugate Chem., 1994, 5(6): 504-507.
[21] Stayton, PS, Shimoboji T, Long C, Chilkoti A, Chen G, Harris JM, Hoffman AS. Control of protein-ligand recognition using a stimuli-responsive polymer [J]. Nature 1995, 378(6556): 472-474.
[22] Stayton PS, Hoffman AS. Interactive molecular conjugates. US Patent, 5,998,588, 1999. 24. Ding Z, Long CJ, Hayashi Y, Bulmus EV, Hoffman AS, Stayton PS. Temperature control of biotin binding and release with a streptavidin-poly(N-isopropylacrylamide) site-specific conjugate [J]. Bioconjugate Chem., 1999, 10(3): 395-400.
[23] Bulmus V, Ding Z, Long CJ, Stayton PS, Hoffman AS. Site-Specific Polymer-Streptavidin Bioconjugate for pH-Controlled Binding and Triggered Release of Biotin [J]. Bioconjugate Chem., 2000, 11(1): 78 - 83.
[24] Fong RB, Ding Z, Long CJ, Hoffman AS, Stayton PS. Thermoprecipitation of Streptavidin via Oligonucleotide-Mediated Self-Assembly with Poly(N-isopropylacrylamide)[J]. Bioconjugate Chem., 1999, 10(5): 720 - 725.
[25] Larsson PO, Mosbach K. Affinity precipitation of enzymes[J]. FEBS Lett., 1979, 98(2): 333-338.
[26] Schneider M, GuillotC, Lamy B. The affinity precipitation technique: Application to the isolation and purification of trypsin from bovine pancreas [J]. Ann. NY. Acad. Sci., 1981, 369(11): 257-263.
[27] Pecs M, Eggert M, Schugerl K. Affinity precipitation of extacellular microbial enzymes [J]. J. Biotechnol., 1991, 21(1-2): 137-142.
[28] Galaev IY, Mattiasson B. Affinity thermoprecipitation: Contribution of the efficiency and access of the ligand[J]. Biotechnol. Bioeng., 1993, 41(11): 1101 -1106.
[29] Morris JE, Hoffman AS, Fisher RR. Affinity precipitation of proteins by polyligands[J]. Biotechnol. Bioeng., 1993, 41(10): 991-997.
[30] Karr LJ, Donnelly DL, Kozlowski A, Harris JM. Use of poly-(ethylene glycol)-raodified antibody in cell extraction[J]. Methods Enzymol., 1994, 228: 377-390.
[31] Okamura K, IkuraK, YoshikawaM, Sakaki R, ChibaH. Soluble-insoluble interconvertible enzymes[J]. Agric. Biol. Chem., 1984, 48(10): 2435 - 2440.
[32] Nguyen AL, Luong JHT. Syntheses and application of water-soluble reactive polymers for purification and immobilization of biomolecules[J]. Biotechnol. Bioeng., 1989, 34(9): 1186-1190.
[33] Taniguchi M, Kobayashi M, Fujii M. Properties of a reversible soluble-insoluble cellulase and its application to repeated hydrolysis of crystalline cellulose[J]. Biotechnol. Bioeng., 1989, 34(8): 1092-1097.
[34] Taniguchi M, Hoshino K, Watanabe K, Sugai K, Fujii M. Production of soluble sugar from cellulosic materials by repeated use of a reversibly soluble-autoprecipitating cellulase[J]. Biotechnol. Bioeng., 1992, 39(3): 287-292.
[35] Takei YG, Aoki T, Sanui K, Ogata N, Okano T, Sakurai Y. Temperature-responsive bioconjugates. 1. Synthesis of temperature-responsive oligomers with reactive end groups and their coupling to biomolecules[J]. Bioconjugate Chem., 1993, 4(1): 42-46.
[36] Takei YG, Aoki T, Sanui K, Ogata N, Okano T, Sakurai Y. Temperature-responsive bioconjugates. 2. Molecular design for temperature-modulated bioseparations[J]. Bioconjugate Chem., 1993, 4(5): 341 -346.
[37] Takei YG, Aoki T, Sanui K, Ogata N, Okano T, Sakurai Y. Temperature-responsive bioconjugates. 3. Antibody-poly(N-isopropylacrylamide) conjugates for temperature-modulated precipitations and affinity bioseparations[J].Biocon jugates Chem.,1994,5(6):577-582.
[38]高志贤,张超,陶桂全.压电免疫传感器抗体固定方法研究[J].中华微生物学和免疫学杂志,1996,16(3):191-195.
[39]陆斌,韦钰.基于全内反射荧光原理的免疫传感器[J].中国生物医学工程学报,1993,12(2):142-147.
[40]高志贤,陶桂全,李新如.压电免疫传感器用于C2型葡萄球菌肠毒素的测定[J].分析化学,1997,25(9):1061-1063.
[41]李凡超,徐京宁,何兵.免疫电化学方法测定C干扰素[J].分析化学,1994,2(1):55-57.
[42]楚霞,林朝晖,沈国励.甲胎蛋白压电免疫传感器的研究[J].高等学校化学学报,1996,17(6):870-873.
[43]裴仁军,胡继明,胡毅.蛋白A定向固定抗体的纤维蛋白压电免疫传感器的研究[J].高等学校化学学报,1998,19(3):363-366.
[44]袁若,唐点平,柴雅琴,张凌燕,刘颜,钟霞,戴建远.高灵敏电位型免疫传感器对乙型肝炎表面抗原的诊断技术研究[J].中国科学B辑-化学2004,34(4):279-286.
[45]Takei YG,Matsukata M.Temperature-Responsive Bioconjugates.3.Antibody Poly(N-Isopropylacrylamide) Conjugates For Temperature-Modulated Precipitations And Affinity Bioseparations [J].Bioconjugate Chemistry,1994,5(6):577-582.
[46]Bi HY,Weng XX,Qu HY,Kong JL,Yang PY,Liu BH.Strategy for allosteric analysis based on protein-patterned stationary phase in microfluidic chip[J].J.Proteome Res.,2005,4(6):2154 -2160.
[47]Baldwin RP,Roussel TJ,Crain MM,Bathlagunda V,Jackson DJ,Gullapalli J,Conklin JA,Pal R,Naber JF,Walsh KM,Keynton RS.Fully integrated on-chip electrochemical detection for capillary electrophoresis in a microfabricated device[J].Analytical Chemistry,2002,74(15):3690-3697.
[48]Huber DL,Manginell RP.Programmed adsorption and release of proteins in a microfluidic device [J]. Science, 2003, 301(5631): 352-354.
[49] Rehberg CE, Fisher CH. Preparation and Properties of the n-Alkyl Acrylates [J]. J. Am. Chem. Soc., 1944, 66: 1203-1207.
[50] Zhang Y, Telyatnikov V, Sathe M. Studying the Interaction of r-Gal Carbohydrate Antigen and Proteins by Quartz-Crystal Microbalance [J]. Journal of the American Chemical Society, 2003, 125(31): 9292-9293.
[51] Ebara Y, Itakura K, Okahata Y. Kinetic Studies of Molecular Recognition Based on Hydrogen Bonding at the Air-Water Interface by Using a Highly Sensitive Quartz-Crystal Microbalance [J]. Langmuir, 1996, 12(21): 5165-5170.
[1]Byrne RJ,Stitzel SE,Diamond D.Photo-regenerable surface with potential for optical sensing[J].J.Mater.Chem.,2006,16(14):1332-1337.
[2]Ipe BI,Mahima S,Thomas KG.Light-Induced Modulation of Self-Assembly on Spiropyran-Capped Gold Nanoparticles:A Potential System for the Controlled Release of Amino Acid Derivatives[J].J.Am.Chem.Soc.,2003,125(24):7174-7175.
[3]Barone PW,Baik S,Heller DA,Strano MS.Near-infrared optical sensors based on single-walled carbon nanotubes[J].Nature,2005,4(1):86-92.