2009 Elsevier Colloids and Surfaces A Physicochemical and Engineering Aspects
ELSEVIER
elsevier目录[隐藏]【爱思唯尔公司】【爱思唯尔公司部门介绍】【爱思唯尔公司发展里程碑】【Elsev ier数据库】爱思唯尔企业标志[编辑本段]【爱思唯尔公司】Our mission:Elsevi er is an integral p artn er with th e scien tifi c,techni cal and h ealth co mmuni ties,delivering superior inf ormation produ cts and servi ces that foster co mmuni cation,build insigh ts,and enabl e indi vidual and collecti ve advan cemen t in sci enti fic research and health car e.Elsevi er.Building insigh ts.Br eaking bound aries.爱思唯尔致力于为全球三千多万科学家、研究人员、学生、医学以及信息处理的专业人士提供一流的信息产品和革新性的工具。
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Els ev ier公司沿用了Elzev ir 书屋的名字，并将Elzev ir 改为更为现代的书写方式Els ev ier。
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生物材料类影响因子
2010年SCI收录的生物材料类期刊影响因子数据来源：JCR Year and Edition: 2009 Science【资源】生物材料相关期刊和期刊风格、影响因子及投稿经验[size=14px][color=blue][size=4]为了方便大家搜文献、看文献、发文章能够有的放矢，本帖将不断整理出生物材料相关期刊和期刊风格、影响因子及投稿经验！[/size][/color][color=red][size=4]对于提供生物材料相关期刊及其风格介绍、影响因子的跟帖将给予奖励；发表这些生物材料期刊的投稿经验，经历，投稿周期，审稿情况等，将给予重奖！[/size][/color][size=5][font=黑体]相关期刊及其风格、影响因子：[/font][/size]1.Biomaterials（中文名称：生物材料）网址：[url=/]http://www.biomat [/url]07年IF：6.262生物材料最专业的两个期刊之一。
主要展示生物材料的应用以及相关医疗器械的研究成果。
发表关于临床应用材料中最重要问题的研究原著及权威性的综述。
文章涉及生物材料的基础科学和工程学等方面，包括力学、物理学、化学以及生物学特性，相关设计以及用这些材料制造的机械的产品特征和临床性能。
2.Journal of Biomedical Materials Research（中文名称：生物医学材料研究）网址:Part A[url=/journal/117935006/grouphome/home.html]/journal/1179 35006/grouphome/home.html[/url]Part B [url=/journal/117935007/grouphome/home.html]/journal/1179 35007/grouphome/home.html[/url]06年IF：2.497生物材料最专业的两个期刊之一，内容跟Biomaterials非常相似。
硅烷偶联剂对二氧化钛表面改性
abstract
Due to their excellent photo-catalytic activities making TiO2 nanoparticles applicable as self-cleaning and anti-bacterial agents, as well as for UV protection and environmental purification, a great potential for multi-functionalization of fabrics by TiO2 nanoparticles is considered. In order to improve the durability of nanoparticles at a fabric surface, the surface of commercial TiO2 nanoparticles was modified by 3-aminopropyltrimethoxysilane (APTMS) and 3-Isocyanatopropyltrimethoxysilane (IPTMS) by an aqueous process in this study. The grafting efficiency of agents to TiO2 nanoparticles at different reaction conditions was estimated by thermal gravimetric analysis. FTIR spectra confirmed that organic functional groups were successfully grafted onto the TiO2 nanoparticles surface both for APTMS-grafted TiO2 nanoparticles (A-TiO2) and IPTMS-grafted TiO2 nanoparticles (I-TiO2) through Ti O Si chemical bonds. After the surface modification of TiO2 nanoparticles, isoelectric point (IEP) of nanoparticles was shifted approximately from pH 6.4 to pH 9.4 and the zeta potential plateaus increased significantly which was explained by the protonation of NH2 groups in the acidic region. The significant reduction of particle hydrodynamic diameters and polydispersity index (PDI) indicated the particle dispersion stability was positively affected by an increase in particle zeta potential. With increasing the organosilane ratio from 0 wt.% to 200 wt.%, a slight decline of the rate constant of A-TiO2 photocatalytic activity and a rapid decrease for I-TiO2 were revealed, which was significantly dependent on the grafting efficiency.
2009版 材料类期刊影响因子
序号杂志全名中译名ISSN 2009版影响因子1 ADV ANCED MATERIALS 先进材料0935-9648 8.3792 PROGRESS IN SURFACE SCIENCE 表面科学进展0079-6816 7.9133 ANNUAL REVIEW OF MATERIALS RESEARCH 材料研究年度评论1531-7331 7.9114 INTERNA TIONAL MATERIALS REVIEWS 国际材料评论0950-6608 4.8575 CURRENT OPINION IN SOLID STATE & MATERIALS SCIENCE 固态和材料科学的动态1359-0286 4.0006 Langmuir 朗缪尔0743-7463 3.8987 Acta materialia 材料学报1359-6454 3.7608 BIOMETALS 生物金属0966-0844 3.1729 SCRIPTA MA TERIALIA 材料快报1359-6462 2.94910 COMPOSITES SCIENCE AND TECHNOLOGY 复合材料科学与技术0266-3538 2.90111 Nanoscale Research Letters 纳米研究快报1931-7573 2.89412 Science and Technology of Advanced Materials 先进材料科学技术1468-6996 2.59913 JOURNAL OF BIOMATERIALS SCIENCE-POL YMER EDITION 生物材料科学—聚合物版0920-5063 2.50514 COMPOSITES PART A-APPLIED SCIENCE AND MANUFACTURING 复合材料A应用科学与制备1359-835X 2.41015 Journal of Solid State Chemistry 固体化学0022-4596 2.34016 CORROSION SCIENCE 腐蚀科学0010-938X 2.31617 INTERMETALLICS 金属间化合物0966-9795 2.23118 Mechanics of Materials 材料力学0167-6636 2.20619 Solid State Ionics 固体离子0167-2738 2.16220 JOURNAL OF ALLOYS AND COMPOUNDS 合金和化合物杂志0925-8388 2.13521 JOURNAL OF THE EUROPEAN CERAMIC SOCIETY 欧洲陶瓷学会杂志0955-2219 2.09022 MA TERIALS CHEMISTRY AND PHYSICS 材料化学与物理0254-0584 2.01523 COMPOSITE STRUCTURES 复合材料结构0263-8223 2.00624 Materials Letters 材料快报0167-577X 1.94025 SYNTHETIC METALS 合成金属0379-6779 1.90126 MA TERIALS SCIENCE AND ENGINEERING A-STRUCTURAL MATERIALS PROPERTIES MICROST 材料科学和工程A—结构材料的性能、组织与加工0921-5093 1.90127 MA TERIALS RESEARCH BULLETIN 材料研究公告0025-5408 1.87928 SURFACE SCIENCE 表面科学0039-6028 1.79829 SURFACE & COA TINGS TECHNOLOGY 表面与涂层技术0257-8972 1.79330 Wear 磨损0043-1648 1.77131 ADV ANCED ENGINEERING MA TERIALS 先进工程材料1438-1656 1.76132 MA TERIALS SCIENCE AND ENGINEERING B-SOLID STA TE MATERIALS FOR ADV ANCED TECH 材料科学与工程B—先进技术用固体材料0921-5107 1.75633 INTERNA TIONAL JOURNAL OF REFRACTORY METALS & HARD MATERIALS 耐火金属和硬质材料国际杂志0263-4368 1.75034 SMART MATERIALS & STRUCTURES 智能材料与结构0964-1726 1.74935 THIN SOLID FILMS 固体薄膜0040-6090 1.72736 MATERIALS RESEARCH INNOV ATIONS 材料研究创新1432-8917 1.72337 COMPOSITES PART B-ENGINEERING 复合材料B工程1359-8368 1.70438 Solid State Sciences 固体科学1293-2558 1.67539 IEEE Transactions on Nanotechnology IEEE 纳米学报1536-125X 1.67140 JOURNAL OF MATERIALS RESEARCH 材料研究杂志0884-2914 1.66741 APPLIED SURFACE SCIENCE 应用表面科学0169-4332 1.61642 INTERNA TIONAL JOURNAL OF FATIGUE 疲劳国际杂志0142-1123 1.60243 METALLURGICAL AND MA TERIALS TRANSACTIONS A-PHYSICAL METALLURGY AND MATERIAL 冶金与材料会刊A——物理冶金和材料1073-5623 1.56444 Philosophical Magazine Letters 哲学杂志（包括材料）0950-0839 1.53045 COMPUTATIONAL MATERIALS SCIENCE 计算材料科学0927-0256 1.52246 MATERIALS & DESIGN 材料与设计0261-3069 1.51847 Current Nanoscience 当代纳米科学1573-4137 1.47248 JOURNAL OF MATERIALS SCIENCE 材料科学杂志0022-2461 1.47149 EUROPEAN PHYSICAL JOURNAL B 欧洲物理杂志 B 1434-6028 1.46650 JOURNAL OF V ACUUM SCIENCE & TECHNOLOGY B 真空科学与技术杂志B 1071-1023 1.46051 Journal of Nanoscience and Nanotechnology 纳米科学和纳米技术1533-4880 1.43552 JOURNAL OF MATERIALS PROCESSING TECHNOLOGY 材料加工技术杂志0924-0136 1.42053 MATERIALS CHARACTERIZATION 材料表征1044-5803 1.41654 JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY 溶胶凝胶科学与技术杂志0928-0707 1.39355 JOURNAL OF V ACUUM SCIENCE & TECHNOLOGY A-V ACUUM SURFACES AND FILMS 真空科学与技术A真空表面和薄膜0734-2101 1.29756 Philosophical Magazine 哲学杂志1478-6435 1.27357 JOURNAL OF NON-CRYSTALLINE SOLIDS 非晶固体杂志0022-3093 1.25258 International Journal of Nanotechnology 纳米工程1475-7435 1.23459 PHYSICA STATUS SOLIDI A-APPLIED RESEARCH 固态物理A——应用研究1862-6300 1.22860 JOURNAL OF PHYSICS AND CHEMISTRY OF SOLIDS 固体物理与化学杂志0022-3697 1.18961 JOURNAL OF ADHESION SCIENCE AND TECHNOLOGY 粘着科学与技术杂志0169-4243 1.17562 PHYSICA STATUS SOLIDI B-BASIC RESEARCH 固态物理B—基础研究0370-1972 1.15063 Oxidation of Metals 材料氧化0030-770X 1.10864 METALS AND MATERIALS INTERNATIONAL 国际金属及材料1598-9623 1.09065 MODERN PHYSICS LETTERS A 现代物理快报A 0217-7323 1.07566 PHYSICA B 物理B 0921-4526 1.05667 NANO 纳米1793-2920 1.00868 IEEE TRANSACTIONS ON SEMICONDUCTOR MANUFACTURING IEEE半导体制造会刊0894-6507 1.00769 SURFACE AND INTERFACE ANAL YSIS 表面与界面分析0142-2421 0.99870 Vacuum 真空0042-207X 0.97571 MA TERIALS AND MANUFACTURING PROCESSES 材料与制造工艺1042-6914 0.96872 CORROSION 腐蚀0010-9312 0.95273 IEEE TRANSACTIONS ON COMPONENTS AND PACKAGING TECHNOLOGIES IEEE元件及封装技术会刊1521-3331 0.94474 PHASE TRANSITIONS 相变0141-1594 0.93575 APPLIED COMPOSITE MATERIALS 应用复合材料0929-189X 0.93576 METALLURGICAL AND MA TERIALS TRANSACTIONS B-PROCESSMETALLURGY AND MA TERIALS 冶金和材料会刊B—制备冶金和材料制备科学1073-5615 0.93277 Journal of Computational and Theoretical Nanoscience 计算与理论纳米科学1546-1955 0.89978 JOURNAL OF THE CERAMIC SOCIETY OF JAPAN 日本陶瓷学会杂志1882-0743 0.86279 International Journal of materials research 材料研究杂志1862-5282 0.86280 JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY 材料科学与技术杂志1005-0302 0.82881 JOURNAL OF ENGINEERING MA TERIALS AND TECHNOLOGY-TRANSACTIONS OF THE ASME 工程材料与技术杂志—美国机械工程师学会会刊0094-4289 0.81582 JOURNAL OF COMPOSITE MA TERIALS 复合材料杂志0021-9983 0.80683 International Journal of Fracture 断裂学报0376-9429 0.80484 MATERIALS TRANSACTIONS 材料会刊1345-9678 0.79585 MATERIALS SCIENCE AND TECHNOLOGY 材料科学与技术0267-0836 0.79486 Journal of Porous Materials 多孔材料1380-2224 0.78887 BULLETIN OF MATERIALS SCIENCE 材料科学公告0250-4707 0.78388 RESEARCH IN NONDESTRUCTIVE EVALUATION 无损检测研究0934-9847 0.76089 EUROPEAN PHYSICAL JOURNAL-APPLIED PHYSICS 欧洲物理杂志—应用物理1286-0042 0.75690 MATERIALS AND STRUCTURES 材料与结构1359-5997 0.75391 SYNTHESE 合成0039-7857 0.72992 SCIENCE IN CHINA SERIES E-TECHNOLOGICAL SCIENCES 中国科学E技术科学1006-9321 0.68293 COMPOSITE INTERFACES 复合材料界面0927-6440 0.67094 Mechanics of Advanced Materials and Structures 先进材料结构和力学1537-6494 0.65895 RARE METALS 稀有金属1001-0521 0.60196 MATERIALS TECHNOLOGY 材料技术1066-7857 0.59797 JOURNAL OF MATERIALS ENGINEERING AND PERFORMANCE 材料工程与性能杂志1059-9495 0.59298 Journal of RARE EARTH 稀土学报1002-0721 0.57299 Reviews on Advanced Materials Science 先进材料科学评论1606-5131 0.558100 ADV ANCED COMPOSITE MA TERIALS 先进复合材料0924-3046 0.500101 ACTA METALL SIN 金属学报0412-1961 0.483102 TRANSACTIONS OF NONFERROUS METALS SOCIETY OF CHINA 中国有色金属学会会刊1003-6326 0.445103 Surface Engineering 表面工程0267-0844 0.432104 Journal of Phase Equilibria and Diffusion 相平衡与扩散1547-7037 0.415105 INTERNATIONAL JOURNAL OF MODERN PHYSICS B 现代物理国际杂志B 0217-9792 0.408106 INTERNATIONAL JOURNAL OF MATERIALS & PRODUCT TECHNOLOGY 材料与生产技术国际杂志0268-1900 0.384107 SURFACE REVIEW AND LETTERS 表面评论与快报0218-625X 0.366108 JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION 武汉理工大学学报-材料科学版1000-2413 0.352109 HIGH TEMPERATURE MATERIALS AND PROCESSES 高温材料和加工0334-6455 0.351110 ADV ANCED COMPOSITES LETTERS 先进复合材料快报0963-6935 0.311111 MA TERIALS EV ALUATION 材料评价0025-5327 0.288112 Solid State Technology 固体物理技术0038-111X 0.275113 AMERICAN CERAMIC SOCIETY BULLETIN 美国陶瓷学会公告0002-7812 0.268114 JOURNAL OF ADV ANCED MATERIALS 先进材料杂志1070-9789 0.245115 POWDER METALLURGY AND METAL CERAMICS 粉末冶金及金属陶瓷1068-1302 0.238116 MATERIALS SCIENCE 材料科学1068-820X 0.231 117 ADV ANCED MA TERIALS & PROCESSES 先进材料及工艺0882-7958 0.199118 RARE METAL MATERIALS AND ENGINEERING 稀有金属材料与工程1002-185X 0.161119 SCIENCE AND ENGINEERING OF COMPOSITE MA TERIALS 复合材料科学与工。
荷兰Elsevier公司旗下的英文全文数据库
荷兰Elsevier公司旗下的英⽂全⽂数据库荷兰Elsevier公司旗下的英⽂全⽂数据库-----Science Direct,Wiley数据库――科学研究的必备之选。
现在好了，各⼤出版社均推出了在线投稿系统，这⼏年把⼏个⼤的投稿系统都试过了，总结⼀下谈谈对⼏个投稿系统的感受吧。
1）Nature系列期刊这个系列期刊在线投稿系统⽐较烦，我们当时光研究投稿须知就研究了⼀天，它对稿件要求很具体，也很苛刻，每个图都要独⽴作成单独的⽂件，如果⼀张图由⼏张图构成，还要说明这图是如何由这⼏部分构成的。
不过现在Nature系列期刊都可以先写⼀个⽐较详细的Coverletter过去，介绍⾃已的⼯作，然后主编决定是否让你投稿，这样可以省不少事，因为⼤部分主编看⼀眼就会拒掉，可能你花在投稿上的时间远⽐他看你⽂章的时间长得多。
2）Science系列同为顶级期刊，Science的在线投稿系统简单了许多，你可以将⽂章和Coverletter分别作成⼀个⽂件上传即可，不过基本上也是⼤部分很快被拒，偶们的⽂章在投稿后三天被拒。
3）美国化学会Journal of the American Chemical Society 《美国化学学会会志》ACS Nano 《ACS纳⽶》Analytical Chemistry * 《分析化学》ACS Chemical Biology 《ACS化学⽣物学》Biochemistry 《⽣物化学》Energy & Fuels 《能源和燃料》个⼈⼀直认为美国化学会的期刊是化学类杂志极有代表性的期刊，象JACS，NL都是学界顶尖杂志。
美国化学会在线投稿系统作得也⽐较完善，⼀般要求将⽂章与Coverletter还有Surpporting Information（如果有的话）分别作成单独的⽂件上传，即完成投稿，系统会⾃动为你转成PDF格式，当然你也可以直接上传PDF，但⼀般都还要求同时上传Word⽂件，总体⽽⾔，对美国化学会的在线投稿系统映像是很不错的。
向老外作者要文献的一个常用的模板
向老外作者要文献的一个常用的模板Dear Professor ×××I am in ××× Institute of ×××, Chinese Academy of Sciences.I am writing to request your assistance. I search one of your papers:。
（你的文献题目）but I can not read full-text content, would you mind sending your papers by E-mail? Thank you for your assistance.Best wishes !(or best regards)×××这个暑假中了2篇SCI文章，影响因子都在IF=1.5-2.0之间。
其实，在此之前，本人已经发表了若干SCI，而且已经是两个期刊的Reviewer。
但尽管如此，随着文章积累越多，对SCI写作的认识也有所熟悉和深入。
下面谈谈一些体会，与大家分享。
第一篇：去年12月份投稿，7月份返回意见。
结论是：“I am pl eased to inform you that your paper has been accepted for publication provided that you amend it according to the concerns raised in the review report given below.”实际上，这个结论已经非常好了。
我看了以下审稿意见，然后就逐条的进行了Response。
其中Response letter的格式我是参考了我审稿过的一篇德国学者的回复模式（我认为非常好）。
但是，在审稿意见中，有一条意见要我对实验过程做一描述。
Colloids and Surfaces B Biointerfaces
Colloids and Surfaces B:Biointerfaces 65(2008)239–246Contents lists available at ScienceDirectColloids and Surfaces B:Biointerfacesj o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /c o l s u r fbPhysico-chemical properties and cytotoxicity assessment of PEG-modified liposomes containing human hemoglobinVal ´erie Centis a ,Patrick Vermette a ,b ,∗aLaboratoire de Bioing´e nierie et de Biophysique de l’Universit´e de Sherbrooke,Department of Chemical Engineering,Universit´e de Sherbrooke,2500,boul.de l’Universit´e ,Sherbrooke (QC),Canada J1K 2R1bResearch Centre on Aging,Institut universitaire de g´e riatrie de Sherbrooke,1036,rue Belv´e d`e re Sud,Sherbrooke (QC),Canada J1H 4C4a r t i c l e i n f o Article history:Received 5December 2007Received in revised form 14April 2008Accepted 15April 2008Available online 24April 2008Keywords:PEGylated liposomes encapsulating hemoglobin Oxygen carriers Cytotoxicity HUVECCharacterizationTransmission electron microscopy Zeta potentialParticle size distributiona b s t r a c tPEGylated liposomes encapsulating human hemoglobin as oxygen carriers were prepared frompurified carbonylhemoglobin (HbCO)solution and a lipid mixture composed of 1,2-dipalmitoyl-sn -glycero-3-phosphatidylcholine (DPPC),cholesterol,1,2-dimyristoyl-sn -glycero-3-phosphoethanolamine-N -[poly(ethylene glycol)2000](DMPE-PEG 2000)and palmitic acid.Hemoglobin was extracted and purified from human blood samples.SDS-PAGE was used to assess its purity.Diameter of liposomes containing hemoglobin was controlled to approximately 200nm using extrusion as measured by dynamic light scattering and transmission electron microscopy.Liposome size distributions were shown to remain unimodal over 14days,even at different storage temperatures.Zeta potential measurements revealed that liposome containing hemoglobin have a net surface charge of −7.16±0.33mV.Also,hemoglobin encapsulated in liposomes was able to perform several cycles of oxygen loading and unloading using oxygen (O 2)and carbon monoxide (CO).The hemoglobin vesicle dispersion showed some toxicity as revealed by three in vitro assays in which endothelial cell (HUVECs)monolayers were exposed to these dispersions.Cytotoxicity was function of the liposome concentration in the culture medium.©2008Elsevier B.V.All rights reserved.1.IntroductionSince Rabiner et al.in 1967and Savitsky et al.in 1978[1,2]stud-ied stroma-free hemoglobin solution as a possible substitute for human blood,research on the development of universal,safe and effective oxygen carriers has been an ongoing subject.Such a solu-tion,despite its purpose to be used in blood replacement therapy,could also be used to supply oxygen in high-density cell culture sys-tems,where oxygen is often the limiting factor.This is particularly flagrant in tissue engineering applications [3–7].Many perfluorocarbon emulsions and hemoglobin-based prepa-rations have been considered as oxygen carriers,with their loads of advantages and disadvantages.For a complete review on the dif-ferent types of oxygen carriers,their design and characterization,the reader is referred to Riess [8].Liposomes and biodegradable polymer capsules have been examined as confinement vehicles for tetrameric hemoglobin [9–12].Liposomes are double-layered phospholipid vesicles able∗Corresponding author.Tel.:+18198218000x62826;fax:+18198217955.E-mail address:Patrick.Vermette@USherbrooke.ca (P.Vermette).to encapsulate different drugs or molecules [13].They have been thoroughly studied for the past 40years and the reader is directed to the work of Lasic and colleagues for more information [13–15].Surface modification with PEG was reported to improve the cir-culation of liposomes in circulation [8,16].PEG is a biologically inert polymer extensively used in drug delivery to create,once conjugated,a steric barrier and/or a water structure around lipo-somes,with the aim to protect liposomes from plasma proteins in the body [17,18].The steric barrier created by PEG conjugation also prevents liposome fusion and aggregation and thus,stabilizes the dispersions during storage [17,18].It was shown by Sakai et al.[17]that PEGylated liposomes encapsulating hemoglobin stored in a deoxygenated state at 4◦C and 23◦C were stable for 1year,while dispersions stored at 40◦C were stable for 6months before liposome aggregation and hemoglobin leakage were observed [17].To be used in cell cultures,liposome dispersions should have limited cell toxicity and their formulations should be stable throughout the duration of the culture.Also,the liposome prepa-ration should be able to increase the oxygen concentration in the cultures and therefore,have a positive impact on the cell growth.Cytotoxicity of PEGylated liposomes encapsulating hemoglobin was assayed in different studies.For example,hemoglobin vesicles0927-7765/$–see front matter ©2008Elsevier B.V.All rights reserved.doi:10.1016/j.colsurfb.2008.04.009240V.Centis,P.Vermette/Colloids and Surfaces B:Biointerfaces65(2008)239–246were tested on human cord blood hematopoietic progenitor cells [19].Mild toxicity was observed on short-term exposures,while inhibition of proliferation was monitored at longer times[19].Also, the effect of liposome encapsulating hemoglobin(LEH)on human platelet function in plasma was studied.Wakamoto et al.observed neither aggregation,activation,nor adverse effects when human platelets were exposed to liposome dispersions[20].Similarly,the exposure of rat erythrocytes to PEG-LEH did not affect the struc-tural integrity of the blood structures[21].No signs of aggregation and deformation of the erythrocytes were observed,suggesting that liposomes exhibited low,if any toxicity[21].Another study examined the cytokine-induced adhesiveness of monocytic cells to HUVECs[22].The data suggested that,in this specific model,LEH did not induce leukocyte adhesion and could have a beneficial effect in preventing leukocyte adhesion to vascular endothelium caused by inflammatory cytokines[22].To our knowledge,in vitro long-term cytotoxicity of LEH formulations towards human cells have not been fully addressed and such testing is afirst and manda-tory step to investigate the applicability of these LEH in tissue engineering.Therefore,this work examines the preparation and characteri-zation of liposomes encapsulating human hemoglobin as potential oxygen carriers for tissue engineering purposes and presents a char-acterization of the LEH dispersions.To assess the feasibility of using LEH as oxygen transporters,size distribution,zeta potential,mor-phology and shape,and cytotoxicity of these LEH dispersions were examined.To our knowledge,no similar study has been reported.2.Materials and methods2.1.Materials1,2-Dipalmitoyl-sn-glycero-3-phosphatidylcholine(DPPC,cat. #PCS-020)and1,2-dimyristoyl-sn-glycero-3-phosphoethanol-amine-N-[poly(ethylene glycol)2000](DMPE-PEG2000,cat.#PPE-010)were purchased from Northern Lipids(Vancouver,BC, Canada).Cholesterol(Chol,cat.#110525)was obtained from Avanti Polar Lipids(Alabaster,AL,USA).Palmitic acid(PA,cat.#P-0500),Medium199(M-199,cat.M-5017),Heparin(cat.#H-1027), Hank’s balances salt solution(HBSS,cat.#H-6648),fetal bovine serum(FBS,cat.#F-1051),endothelial cell growth supplement (ECGS,cat.#E-2759),pyridoxal5 -phosphate(PLP,cat.#P-3657) and dl-homocysteine(Hcy,cat.#H-4628)were purchased from Sigma–Aldrich(Oakville,ON,Canada).Chloroform,sodium dithionite,and dichloromethane used for hemoglobin purification and liposome preparation were of analyt-ical grade and were obtained from Fisher Chemicals.All the water used in these experiments was taken from a Milli-Q Gradient(Milli-pore,Billerca,MA,USA)ultra-pure deionization water system with a resistivity of18.2M cm.CellTiter96®AQueous One Solution Cell Proliferation Assay Kit(cat.#G3580)and CytoTox96®Non-Radioactive Cytotoxicity Assay(Lactate deshydrogenase,cat.#G1780)were obtained from Promega(Madison,WI,USA).CyQuant®NF Cell Proliferation Assay Kit(cat.#C35006)was purchased from Invitrogen(Burlington,ON, Canada).2.2.Hemoglobin purificationHemoglobin was obtained from human whole blood of healthy volunteers.All procedures were approved by the Ethics Committee of the Research Centre on Aging(Sherbrooke,Qc).After the subjects were thoroughly informed about the nature and goal of the study, they provided written consent.The protein was purified accord-ing to an adapted method previously published[23].In summary: (1)hemoglobin was stabilized by CO complexion(HbCO)(60min at room temperature);(2)the removal of membranes and stroma was done by solvent treatment(20%(v/v)CH2Cl2,shaken for3min with subsequent centrifugation at1900×g for15min);(3)traces of dichloromethane were removed by slowly heating the sample with aflow of inert gas(Ar)(heating from40◦C to60◦C,120min);(4)virus inactivation was done by heating the hemoglobin solu-tion(60◦C,overnight,with magnetic stirring agitation);(5)dialysis (MW cutoff of25kDa,against ultra-pure water,for24h,with mag-netic stirring agitation)was used to remove small molecules;(6) ultra-filtration(MW cutoff of30kDa,Millipore,USA)was used to filter out molecules with MW<30kDa.Solutions containing puri-fied HbCO were aliquoted and preserved in liquid nitrogen with PLP(18mM)and Hcy(15mM).SDS-PAGE was used to assess the presence of hemoglobin.2.2.1.SDS-PAGEThe purification of Hb was determined via SDS-PAGE using a FisherBiotech system(Fisher Scientific,cat.#FB200).All the sam-ples were prepared in a Laemmli buffer(Bio-rad,cat.#161–0158) with a4%acrylamide stacking gel and a15%acrylamide resolving gel(Bio-rad,cat.#161–0158).Human hemoglobin is known to have a MW of approximately 64kDa[8,24].The hemoglobin samples were run along with a pre-stained broad-range molecular weight marker(Bio-rad,cat. #161–0318),which consisted of proteins having molecular weights ranging between6.9and210kDa.10L of hemoglobin samples (2g/mL)and7L of the molecular weight marker(dilution ratio of1:75(v/v)i.e.,1part of the marker in75parts of a buffer)were deposited in each well.A purified commercial hemoglobin sam-ple(Sigma,cat.#H7379)was used as a control and was run at a concentration of0.1g/mL.All samples were run at115V until the migration front reached the bottom of the gel(±120min).The gels were then stained using Silver SNAP Stain kit II(Fisher Scientific, cat.#24612)to determine band intensities.2.3.Liposome preparationLiposomes were prepared in a slightly different way than the method previously reported[23].Briefly,the mixture of phos-pholipids DPPC,Chol,PA and DMPE-PEG2000in a molar ratio of 5/5/1/(0.3%[mole/total moles of lipids])was dissolved in chloro-form.The organic solvent was then evaporated using a rotary evaporator(B¨uchi,Switzerland)under reduced pressure to remove all traces of solvent.The resulting thinfilm was then hydrated with a NaOH solution(0.9mM)overnight to allow thefilm to dissolve to yield a lipid concentration of50mg/mL.The solution was then diluted with pure water to obtain a concentration of25mg/mL of lipids.Then,ten cycles of freeze-thawing(−196◦C and40◦C)were performed.The solution was then frozen for10min in liquid nitro-gen and lyophilized for48h.After dispersing the lipid mixture into a hemoglobin solution(4g/mL)for2h,the resulting multilamel-lar vesicles were extruded with the LiposoFast-Basic(Avestin Inc, Ottawa,ON,Canada)using11passes at54◦C through polycarbon-ate membranes with pore sizes of200nm.The resulting solution was then ultra-centrifuged at50,000×g for30min(Optima TLX, Beckman Coulter,Mississauga,On)to recover and eliminate the top layer containing non-encapsulated Hb.2.4.Liposome characterization2.4.1.Particle size distributionThe intensity mean diameter of the liposomes and the polydis-persity index(PI)of the distribution were determined by dynamicV.Centis,P.Vermette/Colloids and Surfaces B:Biointerfaces65(2008)239–246241light scattering(DLS)using a Zetasizer Nanoseries(Malvern Instru-ments,UK).Samples of liposomes stored at4◦C,22◦C and37◦C were analyzed.The refractive index and viscosity of pure water were used as calculation parameters and each sample was mea-sured3times for25runs using the unimodal model for size distribution.All samples were diluted to an appropriate counting rate prior to analysis.2.4.2.Zeta potentialThe zeta potential was measured by electrophoresis at25◦C (Zetasizer Nanoseries,Malvern Instruments,UK).The surface charge of the particles was obtained by measuring the velocity of the dispersion in an electricalfield.Samples were diluted and placed in an electrophoretic cell where a potential of±60mV was established.Actual values were calculated from the mean elec-trophoretic mobility using Smoluchowski’s equation.The viscosity and dielectric constant of pure water were used as calculation parameters and each sample was measured in quadruplicate.All samples were diluted to an appropriate counting rate prior to anal-ysis.2.4.3.Influence of pH and osmolaritySlight changes in pH and osmolarity can have deleterious effects on cells in culture.To ensure that seeded cells would not respond to a change in pH and osmolarity due to the addition of liposomes in culture media,these parameters were moni-tored over24h(6,12,and24h).HUVECs were seeded onto 24-well plates(6000cells/well)(Corning,cat.#3527)and let to adhere in normal incubator conditions.The next day,HUVECs were either exposed to:(1)LEH(2mg/mL),(2)“Empty”lipo-somes i.e.,liposomes with no hemoglobin(2mg/mL),or(3)M-199 media.After6,12and24h,250L were pipetted and used for osmolarity analyses using a pre-calibrated osmometer(Advanced Instruments,model3250,Norwood,MS,USA).The rest of the solution was used for pH monitoring(Orion Research,model 710A,Lausanne,Switzerland).Measurements were done in triplicate.2.5.Functionality of the LEH as oxygen carriersHemoglobin possesses characteristic bands throughout the vis-ible spectra.Q-band(around500–600nm)and Soret band(in the blue region,around400nm)are typical regions that provide infor-mation about the hemoglobin state.Therefore,functionality of hemoglobin entrapped in liposomes and its ability to shift from its oxygen-loaded position to unloaded position was assayed by spectrometry.LEH dispersions(2mg/mL,using HBSS buffer)were exposed to pure oxygen and halogen light(90min,400W)[25]and sub-sequently compared to carbon monoxide(CO)exposure(15min, in the dark).To obtain deoxygenated spectra of hemoglobin,solu-tions were equilibrated with inert gas(Ar)to remove most of the oxygen before treatment with dithionite[26].Wavelengths shifts of the Q-band and Soret band under these conditions were mea-sured using a micro-plate reader(Bio-Tek Instruments,Winooski, VT,USA).2.6.Transmission electron microscopy(TEM)analysesThe samples were diluted appropriately and were negatively stained with uranyl acetate and allowed to air-dry directly on TEM grids.Observations were made using an H-7500transmission elec-tron microscope(HITASHI,Pleasanton,CA,USA)at a voltage of 60kV.2.7.HUVEC cultureHuman Umbilical Vein Endothelial Cells(HUVEC,PromoCell, Heidelberg,Germany)were cultured in M-199supplemented with10%(v/v)de-complemented FBS.ECGS(20g/mL),heparin (90mg/L),and antibiotics(100U/mL penicillin G and100g/mL streptomycin)were also added.Culture media was replenished three times a week.All cells were maintained at37◦C in an incu-bator with a humidified atmosphere containing5%CO2.Cells of passages4and5were used throughout this study.2.8.Cytotoxicity of LEHFollowing cell exposure to LEH,cell proliferation assays were performed to evaluate the cytotoxicity of the LEH formulations.For this purpose,HUVECs were incubated with three concentrations of LEH dispersions(5,2and1mg/mL)for6,12,and24h.The M-199culture medium concentration was adjusted to compensate for the dilution caused by the addition of liposomes.Empty liposomes (5mg/mL)were used as controls.Three assays were performed to evaluate the cytotoxicity of the LEH dispersions.Different assays were used since it was reported that cellular metabolic processes vary greatly over time and that methodologies that rely only on measurements of ATP content can cause some problems in further cytotoxicity interpretation[27].LEH cytotoxicity wasfirst examined using the MTS assay,a colorimetric method optimized for adherent cells.Viable cells enzymatically reduce the colorless tetrazolium salt MTS to inten-sively colored MTS-formazan.Briefly,4000cells/well were seeded inflat bottom96-well plates(Corning Incorporated,Corning,NY, USA)and incubated for24h.After removing the culture medium, 100L of LEH dispersions were applied,and the plates were incu-bated at37◦C for a period of4h.The absorbance was read at490nm on a micro-plate reader(Bio-Tek Instruments,Winooski,VT,USA). Values were corrected for background absorbance.Secondly,cell number was assessed using the CyQuant®Cell Proliferation Assay Kit,a highly sensitive,fluorescence-based micro-plate assay[27].The CyQuant®assay measures the ability of CyQuant®dye to bind to the cellular nucleic acids of viable cells. Measurements of cellular proliferation provide a general measure of toxicity.Cell cultures were seeded at103cells/well in duplicate inflat bottom96-well plates.After exposure of the liposomes to adherent cells,cells were rinsed with HBSS buffer to remove dead cells no longer adhering to the plate,lysed,and the DNA was stained using the CyQuant®fluorescent dye solution as recommended by the manufacturer.Plates were incubated at37◦C for60min.Flu-orescence was measured using afluorescence micro-plate reader (Bio-Tek Instruments,Winooski,VT,USA).The excitation maximum was480nm and the emission maximum was530nm.Values were corrected for background absorbance.Finally,quantification of the release of the cytoplasmic enzyme, lactate deshydrogenase(LDH)in culture media was evaluated.LDH liberation is correlated with the number of lysed cells.Briefly,4000 cells/well were seeded inflat bottom96-well plates(Corning Incor-porated,Corning,NY,USA)and incubated for24h.After HUVEC exposure to the different concentrations of LEH,cells were lysed using a lysis buffer,as described by the manufacturer.LDH activ-ities in the culture media and in the corresponding cell lysates were measured at490nm on a micro-plate reader(Bio-Tek Instru-ments,Winooski,VT,USA).Values were corrected for background absorbance.2.8.1.Assessment of potential residual CH2Cl2cytotoxicityTo ensure that the dichloromethane used in the hemoglobin purification process was not responsible for any cell death,a sample242V.Centis,P.Vermette/Colloids and Surfaces B:Biointerfaces65(2008)239–246 of M-199culture media was treated in the same way.In a con-trol experiment,M-199was exposed to CH2Cl2with subsequentcentrifugation and evaporation procedures(steps2–3,Section2.2).Then,10%(v/v)of de-complemented FBS was added to the media.This“CH2Cl2treated”M-199sample was then added inflat bot-tom96-well plates seeded with4000cells/well.Cells were thenincubated for24h with this M-199and a standard MTS assay wasperformed after the exposure.Normal M-199media was used ascomparison.The absorbance was read at490nm on a micro-platereader(Bio-Tek Instruments,Winooski,VT,USA).Values were onceagain corrected for background absorbance.Results were done intriplicate.2.9.Statistical analysisAll the data collected throughout the study were expressed asmeans±standard deviations(S.D.s).Analysis of variance(ANOVA)was used to determine if data were significantly different usingp≤0.05.3.Results and discussion3.1.Hemoglobin purification3.1.1.SDS-PAGEFig.1shows SDS-PAGE results for the Hb purification proceduredescribed above.In this study,the SDS-PAGE technique was usedas a qualitative method to show the presence of hemoglobin in thesample.Proteins of interest were well defined on the ne Bshows the molecular weight marker containing proteins rangingfrom6.9to210kDa while lanes A and C show purified samples ofhuman Hb and a commercial hemoglobin standard,respectively.It is possible to observe the tetramer,dimer and monomer com-posing hemoglobin at values of,respectively,64,32and16kDa(black arrows on left side,respectively noted1,2and3).The sub-units are visible since the sample was heated prior to its run,thusdenaturing the protein.When purified Hb was compared with thecommercial sample,it was possible to observe the same bandsexcept for one(under the last arrow),which was present only ontheFig.1.SDS-PAGE nes A and C show a purified human hemoglobin sample and a commercial hemoglobin ne B presents broad-range molecular weight markers.Black arrows on left side(1,2,and3)show,respectively,the64,32 and16kDa subunits of the protein.purified sample.It was published by Pearson et al.that this band is not apparent on freshly prepared specimens[28],as opposed to outdated blood,as in our case.Also,the observed streaking in the obtained SDS-PAGE analyses can be caused by the presence of other proteins.Therefore,the effect of the presence of these other proteins on the functionality of Hb has been tested(see below).3.2.Hemoglobin functionalitySpectra of hemoglobin encapsulated in liposomes are presented in Fig.2.Fig.2A clearly shows the difference between oxygen-loaded and unloaded states of the hemoglobin.This difference is even more evident in Fig.2B,showing the characteristic Q-bands and the shift from538and569nm to540and577nm.Panel C of Fig.2summarizes the shifts of hemoglobin from oxygen-loaded states to unloaded ones.Also,Fig.2C shows that hemoglobin can be oxygen-loaded and unloaded several times.The ability of the pro-tein to shift back and forth from one position to another(in thiscase,Fig.2.(A)Complete visible spectra of oxygen-loaded and unloaded purified human hemoglobin,(B)zoom on Q-bands showing the shift between oxygen-loaded and unloaded positions of purified human hemoglobin,and(C)variation of Q-band wavelengths after exposure to carbon monoxide and oxygen.V.Centis,P.Vermette /Colloids and Surfaces B:Biointerfaces 65(2008)239–246243Table 1Mean particle diameter of empty liposomes and liposomes encapsulating hemoglobin stored at 4◦C,22◦C and 37◦C over 2weeks4◦C22◦C37◦CEmpty liposomesLiposomes encapsulating hemoglobin Empty liposomes Liposomes encapsulating hemoglobin Empty liposomes Liposomes encapsulating hemoglobin Day 1220(39.6)226(48.5)240(45.6)269(47.2)229(48.1)239(53.3)Day 7229(41.8)237(47.7)245(46.2)252(45.1)249(44.2)255(42.7)Day 14240(40.7)239(57.6)249(45.9)247(47.8)248(45.6)254(50.1)Data in parentheses indicate the %Polydispersity (%Pd).from oxygen to carbon monoxide)demonstrates the functionality of hemoglobin even after its encapsulation into liposomes.3.3.Liposome characterization3.3.1.Particle size distributionResults of size distribution of liposomes encapsulating hemoglobin are presented in Table 1.It is evident from the data that the size distributions were unimodal and relatively narrow for all samples.%Polydispersity (%Pd)values of all LEH disper-sions were higher than 40%(Table 1).Therefore,LEH dispersions can be considered to as polydispersed.The term polydispersity is derived from the polydispersity index (PdI).PdI is a number cal-culated from a simple two-parameter fit to the correlation data called a cumulants analysis.PdI is known as the relative variance,while %Pd is the coefficient of variation or relative polydisper-sity and can be expressed as (PdI)1/2×100(Malvern Instruments,UK).As a rule of thumb,samples with %Pd ≤20%are considered monodisperse.The size of a particle is an important factor in determining its use as an oxygen carrier.Size is of great importance when one wishes to use these particle-systems in a body to supply increased (or opti-mized)oxygen concentration.Rapid extravasion from the body by the reticulo-endothelial system (RES)and immunogenic effects are only a few of the problems foreign particles encounter in the body [8,19,20,29–34].For tissue engineering purposes,particle size is also an important issue to consider.Liposomes added to a culture medium should be able,for example,to circulate through porous scaffolds often used in tissue engineering.Also,as for LEH,their small size (±200nm)should enable to increase the surface area between the liposomes and the dispersing medium phase allowing a better oxygen transfer.The results in Table 1show that LEH sizes are within the expected range of the 200-nm pores of the extrusion membrane used.These results are comparable and consistent with the findings of Arifin and Palmer [35,36].Using asymmetric field flow fraction-ation coupled to a multi-angle static light scattering photometer,they found that liposomes extruded through membranes having 200-nm pore diameter exhibited a mean diameter that was close to that of the membrane.The dispersion observed was unimodal with distribution widths of 10–20nm.Mean LEH diameter does not vary significantly with storage tem-perature (p ≤0.01).Still,LEH samples should be kept at 4◦C prior to their use in order to limit possible particle size enlargement.Stor-age time of 14days affected to some extent particle size growth in the samples (p ≥0.05).On the other hand,all the preparations exhibited a unimodal distribution,allowing to conclude,that over a short period of time (≤7days),the particles should not aggregate or fuse (p ≤0.05).PEG grafted onto the surface of the vesicles cer-tainly help to stabilize LEH by creating a steric hindrance around liposomes [18].The molar ratio of PEG used in our study is fairly small compared to those of other studies in which PEG was used.But this PEG concentration was sufficient to stabilize the liposomes over 14days,a time corresponding to a culture period required to grow a network of vascular micro-vessels,for instance.The data presented in Table 1reveal that the encapsulation of hemoglobin molecules does not seem to affect the size distribution of the liposomes.Liposomes encapsulating hemoglobin exhibit the same size distribution behaviour as “empty”ones [37].3.3.2.Zeta potentialMeasurements of zeta potential can yield information about the colloidal stability of particle dispersions [36–39].On one hand,in a solution containing no proteins,no amino acids,and little to no multi-valent electrolytes,the larger the magnitude of the zeta potential the more stable the dispersion should be.Limited floccu-lation occurs between |5|and |15|mV [37].For “naked”liposomes (prepared in the same manner as LEH,but hydrated with M-199culture media instead of hemoglobin),it was shown that the zeta potential at the surface of liposomes was approximately −45mV [12,40].When PEG 2000was added to the liposome preparation,the zeta potential increased to reach a plateau around −5mV [12].ThisFig.3.TEM images revealing shape,structure,and sizes of liposomes encapsulating hemoglobin molecules.244V.Centis,P.Vermette/Colloids and Surfaces B:Biointerfaces65(2008)239–246increase of the surface charge was thought in part to be because of the drag caused by the presence of PEG chains on the liposome sur-face,decreasing the mobility of the liposomes,hence affecting the zeta potential[12,41].On the other hand,the presence of surface charge should be counter-balanced with a good steric hindrance in solutions containing proteins and amino acids(e.g.,culture media), as these often charged molecules can adsorb on the surface of the particles and enhance particle aggregation.For the PEGylated liposomes encapsulating Hb studied here,the mean zeta potential on the particle surface was−7.16±0.33mV. This indicates that limited aggregation of the particles should be observed and that stability over time can be,to some extent,con-trolled,as observed in Table1.In fact,over14days,the particle size did not vary for a given temperature and confirmed the stability of the distribution.The values obtained can also be compared with results obtained by Sakai et al.[37].They reported LEH,without PEG and PA,with a surface charge of−21mV.PA was reported to decrease surface charge proportionally to its increase in concentra-tion in the lipid bilayer[37,42].3.3.3.pH and osmolarity of culture media with LEHpH and osmolarity of culture media containing either“empty”liposomes or LEH were monitored over24h.All the solutions had a constant pH of7.4.As for osmolarity measurements,for both“empty”liposomes and M-199controls,the values remained constant at approximately330±3mOsm.The osmolarity of LEH dispersions was319±2mOsm.From these data,it can be concluded that the addition of dispersions of“empty”liposomes and LEH does not affect the osmolarity of the culture medium used in this study.3.4.Transmission electron microscopy(TEM)analysesTEM images of LEH are presented in Fig.3.In the TEM images, the characteristic aspects of large unilamellar vesicles(LUV)can be observed[14].Large unilamellar vesicles are liposomal structures exhibiting a rather empty core that can be used to encapsulate different molecules,such as drugs or proteins[15].LUV’s can be prepared from large“onion-like”structures of multilamellar vesi-cles(MLV)by different methods such as extrusion.The TEM images clearly show that the extrusion method was convenient to produce LEHs.The distinctively recognizable double-layered membrane and the empty core are good indications of a LUV structure[13,14].TEM images revealed that LEH(over62individual liposomes)have a mean diameter of170±50nm.These results are in good agreement with the ones obtained from dynamic light scattering analyses. 3.5.Cytotoxicity of liposomes encapsulating hemoglobin(LEH)Fig.4shows the behaviour of HUVECs in contact with disper-sions made of different concentrations of LEH.Similar cytotoxicity trends were observed when the same experiments were conducted using humanfibroblasts from foreskin(data not shown).Fig.4A and B illustrate the percentage of live cells when HUVECs were exposed to LEH dispersions,while Fig.4C shows the percent-age of cell death after similar exposure.Statistical analyses of the results of these three cytotoxicity assays reveal that exposure time had a significant effect on cell viability(p=0.05).The analyses also show that LEH concentration had an effect on the cell death rate.For example,a significant difference(p≤0.05)was observed between 5and1mg/mL for all tested exposure times.From Fig.4,it can be seen that approximately50%cell loss occurred following24-h cell exposure to the LEH dispersions.The results obtained from the three assays are consistent with one another(p≤0.05).Unfor-tunately,these results cannot be directly correlated with thoseof Fig.4.Cytotoxicity assays of HUVECs exposed to PEGylated liposomes containing hemoglobin for different exposure times.(A)AQueous One assay,(B)CyQuant®assay,and(C)lactate deshydrogenase assay.All data are significantly different with p≤0.05.other studies since very few long-term in vitro tests have been car-ried out.A recent study by Yamaguchi et al.[19]investigated the short and long-term effects of hemoglobin vesicles(HbVs)on the clono-genic and proliferative activity of human hematopoietic progenitor cells derived from umbilical cord blood.They found that,at a concentration of3%(v/v),continuous exposure of HbV signif-icantly decreased the number and size of mature-committed colonies[19].Moreover,HbVs also notably reduced the number of high-proliferative potential colony-forming cells and lead to the suppression of cellular proliferation and differentiation in liquid culture[19].On the other hand,the same study presents the effect of HbV exposure to cord blood for20h or3days.Yamaguchi et。
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Contents lists available at ScienceDirect
Colloids and Surfaces A: Physicochemical and Engineering Aspects
using hydroxy-terminated poly(ethylene oxide) of various molecular weights. The process for aggrega-
tion in organic solvents is proposed to occur in two stages: aggregation caused by polymer adsorption on
size and size distribution of the aggregates formed, and the optimal
polymer concentration and molecular weight.
此体系具有
One of the challenges of this system is the sensitivity o挑f 战性的一
water, and reproducible aggregation can be understood in terms 化学吸附
journal homepage: /locate/colsurfa
Covalent assembly of silica nanoparticle aggregates for oligonucleotide synthesis
Weian Zhao a, Elodie Pacard a,b, Carole Chaix-Bauvais b,1, Christian Pichot b, Michael A. Brook a,∗
等离子体激元 based on nanoparticle-ampilified surface plasmon enhanced signals [8,9], and conjugated polymer-based biosensors [10,11]. All of these techniques possess certain attributes and shortcomings. For instance, quantum dots, although with higher sensitivity and photostability, are still controversial for the routine applications due to their toxicity and relative water-insolubility, etc. [2]. In contrast, particularly from practical application point of view, DNA microarrays (i.e., DNA chips) are by far the most commonly used DNA detection tools, especially for large-scale DNA analysis [2–5]. DNA芯片是最常见的DNA检测工具尤其是进行大规模DNA
RdC, 43, Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France.
寡聚核苷酸
Previously, we described the use of oligonucleotide (ODN)-
modified silica aggregates as sensitive detectors for DNA via
ticles of comparable size (Fig. 1b) because of higher surface area
and, thus, concentrations of ODN:DNA [1]. However, the synthe-
sis of the materials was not always reproducible with respect to the
gate formation using the reaction of isocyanate terminated poly(ethylene oxide) with amino-modified
silica particles was not always reproducible with respect to size of aggregates formed and their stability
检测
∗ Corresponding author. E-mail addresses: carole.chaix-bauvais@univ-lyon1.fr (C. Chaix-Bauvais),
mabrook@mcmaster.ca (M.A. Brook). 1 Current address: UMR des Sciences Analytiques 5180, University Lyon 1, Bât. CPE,
article info
Article history: Received 9 July 2008 Received in revised form 8 January 2009 Accepted 15 January 2009 Available online 23 January 2009
Keywords: Controlled aggregation Silica particles Poly(ethylene oxide) Oligonucleotide Solid-phase synthesis
oligonucleotide synthesis in conventional DNA synthesis machines, and that high sensitivity is observed in
subsequent DNA capture and detection in DNA microarray-based assays. However, the process for aggre-
to water. To address reproducibility and to better understand the colloidal assembly processes occur-
ring, isocyanate-modified silica particles were prepared. The particles can be reproducibly aggregated
the particle – if appropriate concentration and molecular weight conditions are met – and subsequent
irreversible interparticle linkage of the aggregated assembly via covalent bond formation. These aggre-
surface areas, that were amenable for use in conventional oligonu-
cleotide synthesizers [1]. The aggregates had far higher signal
intensities upon capturing DNA via hybridization than solid par-
hybridization (Fig. 1a) [1]. The reaction in organic solvents
of amine-modified silica nanoparticles (∼300 nm) with an
isocyanate-terminated poly(ethylene oxide) (NCO–PEO–NCO) led to functional ag聚gre合g体ates, of >5 m in diameter with very high
1. Introduction
The sensitive and specific detection and quantification of nucleic acids has becoming increasingly important in applications ranging from basic research to diagnostics and genomics [1]. A variety of 生物传感 策略 DNA biosensing strategies have therefore been developed, including DNA 微m阵ic列roarray techniques [2–5], the use of semicondu半ct导or体 晶体 crystals or quantum dots as fluorescent pr探ob针es [6,7], detection
abstract
Bioassays need to be explicit, reproducible and therefore reliable, and have the highest sensitivity possi-
ble. It has previously been demonstrated that high surface area silica aggregates can serve as substrates for