Experimental Investigation of Production Behavior of Methane

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中文小论文格式要求

中文小论文格式要求【篇一：中文期刊、小论文格式和要求(工学)】题目三号粗体居中，段前空1行，段后空0.5行学号，姓名（小四粗体居中，段前后各0.5行）日期（五号居中，段前0.5行，段后1行）摘要：这是文献报告写作要求。

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关键词：english title uses the same format as the chinese titleabstract: an english abstract must be included, which shouldbe 400~500 words in length. this will be a part of the basis for the assessment of your technical english proficiency. youmust write it in your own words, rather than just copy from a reference. mind you that anyone who simply copies from materials written by others will not pass the examination.keywords:1. 引言文献报告格式要求：用a4纸，通栏排版。

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原料药生产中的确认与验证欧美GMP培训

在后续跟进过程中对同一家厂家发出的警告信： “… 针对一个API的工艺验证不恰当，因为没有按照书面方案来执行。关键工艺参数没有得到说明，且放大…步骤并没有包括在验证研究中…”
Consequences of Inadequate Qualification and Validation: Warning Letters from the US FDA
储管理与布局 • 详细的、可追溯的所有关于制造与检测作业的记录 • 恰当地设计与维护建筑与设施
设施确认、设备确认与工具确认
• 恰当地设计与操作设备与工具
工艺验证与清洗验证
确认与验证为什么是必要的？
a、简单的回答是药监管理机构要求制药厂承担这些义务
美国食品药品监管署（FDA）：
“…验证是为确保一个专门过程…可以持续地生产满足预设规格与质量特征的一个产品而反复建立的书面依据。”*
*工艺验证总则指南，FDA，1987年5月
b. Regulatory Requirements of Qualification and Validation
Currently, the US FDA and the European Medicines Agency (EMEA) adhere to the International Committee on Harmonization (ICH) Guidance Q7A
United States Food and Drug Administration: “…validation is establishing documented evidence which provides a high degree of assurance that a specific process…will consistently produce a product meeting its predetermined specifications and quality characteristics.”*

Experimental investigation on capillary force of composite wick structure

Experimental investigation on capillary force of composite wick structure by IR thermal imaging cameraYong Tang,Daxiang Deng *,Longsheng Lu,Minqiang Pan,Qinghui WangSchool of Mechanical and Automotive Engineering,South China University of Technology,Wushan Road,Guangzhou 510640,Chinaa r t i c l e i n f o Article history:Received 1January 2009Received in revised form 3October 2009Accepted 19October 2009Keywords:Composite wick Meniscus Heat pipes Capillary forceIR thermal imaginga b s t r a c tA novel sintered–grooved composite wick structures has been developed for two-phase heat transfer devices.With ethanol as the working ﬂuid,risen meniscus test is conducted to study the capillary force of wick structures.Infrared (IR)thermal imaging is used to identify and locate the liquid meniscus.The effects of sintered layer,V-grooves and powder size on capillary force are explored.The results show that the capillary force of composite wick structures is larger than that of grooved and sintered ones.Interac-tion wetting between groove and sintered powder happens during the liquid rise in composite wick,which provides an additional source of capillary force.It exhibits a variation of capillary force of compos-ite wicks with different powder size due to the difference of open pore size and quantity in sintered por-ous matrix.Ó2009Elsevier Inc.All rights reserved.1.IntroductionDevelopment of heat pipes,vapor chambers and capillary pumped loops (CPL)is motivated by the thermal management of electronic components.These heat transfer devices work via two-phase ﬂow.By evaporation and condensation,heat is transported from one end to the other or spread to a large area.Two-phase heat transfer devices consist of a number of components,such as evap-orator,wick and condenser.The wick shows great effects on the heat transfer performances of these devices.Wick structures are generally grooved or sintered.Sintered wicks have large capillary force but low permeability,while grooved wicks have high perme-ability but small capillary force [1].Capillary force and permeabil-ity are somehow contradictory in a single wick.However,composite wicks can balance these two competing factors and im-prove heat transfer performances.Currently,researches have been focused on composite wick structures [2–4].Hwang et al.[2]ob-tained modulated composite wicks by making grooves over a thin uniform porous layer.The modulated composite wick improved heat transfer performance by providing extra cross-sectional area for enhanced axial capillary liquid ﬂow and extra evaporation sur-face area.Wang and Catton [3]investigated a composite structure with a thin porous layer on the triangular groove.It was found that evaporation heat transfer in the composite structure was three to six times higher than that in the groove without a porous layer.Capillary force of wick plays the driving force of the circulation of working liquid in two-phase heat transfer rge capil-lary force makes these devices work well.Capillary force of wick has been determined mainly through two methods.One is the bub-ble point test [5].Pressurized gas is applied to one end of a wick saturated with liquid.With the pressure gradually increasing,the point that bubbles appear on the opposite end of the wick is re-corded for the capillary force.The other method is the risen menis-cus test [6,7].One end of a wick is dipped into the working liquid.Then the liquid level rises in the wick sample until the pressure on both sides of the meniscus equilibrates.Nowadays,the latter method has been widely used due to its convenience.Chen et al.[8]observed the liquid fronts in the inclined wick by optical micro-scope (OM)and CCD camera.Holley and Faghri [9]obtained the closed form solution of effective pore radius and permeability of wicks by sight and weight change.Nevertheless,visualization of the meniscus by sight may be not accurate because most of the working liquid is colorless and transparent.In the case of micro grooved or sintered wick structures,it is difﬁcult to locate the meniscus.This problem may be solved with the technique of infra-red (IR)thermal imaging.IR thermal imaging can provide accurate and non-contact measurement of temperature ﬁeld [10].It has been used for the test of thermal performance and heated ﬂow of liquid ﬁlm of two-phase heat transfer devices [11–15].Due to the infrared emissivity difference between wick samples and working liquid,the meniscus can be accurately located by IR ther-mal imaging.Thus,the rising of the wetted height driven by capil-lary force can be investigated.0894-1777/$-see front matter Ó2009Elsevier Inc.All rights reserved.doi:10.1016/j.expthermﬂusci.2009.10.016*Corresponding author.Tel./fax:+862087114634.E-mail address:dengdaxiang88@ (D.Deng).Experimental Thermal and Fluid Science 34(2010)190–196Contents lists available at ScienceDirectExperimental Thermal and Fluid Sciencejournal homepage:www.else v i e r.c o m /l o c a t e /e t fsThe present study proposes a novel sintered–grooved compos-ite wick structure by covering a layer of sintered copper powderon micro V-grooves.With the risen meniscus test method,the cap-illary force of the wick is investigated by the visualization of IR thermal imaging camera.2.Experimental2.1.Fabrication of composite wick structureSintered–grooved composite wick structure is shown in Fig.1.Micro V-grooves were made in copper base with the thickness of 1.0mm.Then copper powders were sintered on the grooves.Dur-ing sintering,adhesion and mass transfer happened by the driving of surface tension.Different powder particles bonded together.Due to the same material of copper,powder particles and groove ﬁns also partially bonded together,as seen in Fig.2.Thus,sintered–grooved composite wick formed.The copper powders (supplied by ACuPowder International,LLC,USA)are of irregular morphol-ogy,with purity of 99.3%,produced by water atomization method [16].To optimize the sintered powder size,four composite wick samples were made.A grooved sample without powder and a sin-tered sample without grooves were also studied for comparison.For the sintered sample,a 0.5mm thick powder layer was sintered on 1.0mm thick copper base .All the samples had the same dimen-sions,with length 100mm and width 10mm,as shown in Table 1.Copper powder layer was sintered at temperatures 950±10°C in a tube furnace for half an hour under a reduction stream of 10%hydrogen and 90%argon.2.2.Experimental apparatusAn apparatus of the risen meniscus test is set up to determine the capillary force of wick structures,as shown in Fig.3.It consists of vertically adjusting device,sample ﬁxing device,reservoir,IR thermal imaging camera,glass cover with a hole for IR thermal imaging visualization,PLC controller and PC.The classical working liquid,ethanol,is used in the experiment.At ﬁrst,test sample is ﬁxed in vertical in the sample ﬁxing device.Secondly,the sample moves down to dip into ethanol by the vertically adjusting device in a constant speed.The dipped length of samples in the liquid is 2mm.At last,IR camera records the meniscus rising process in 1min from the point that the sample just dips into ethanol.Ambi-ent temperature is 30°C.The glass cover is used to ensure the cir-cumstance airﬂow stable.The volatilization of ethanol is in a constant speed.Therefore,the difference between samples can be observed accurately.2.3.Meniscus locating method in IR thermal imagingA FLIR ThermaCAM SC3000IR camera was used with a thermal sensitivity of 0.02K at 30°C and an accuracy of 1%for tempera-tures below 150°C of the full scale.The back-side of the samples was painted black to provide a uniform emissivity.Due to the infrared emissivity difference between copper and ethanol,differ-ent temperature distributions between samples and ethanol were displayed in IR thermal images.The meniscus could be accurately located as follows.As shown in Fig.4,a measuring line was drawn along the sample from the ﬁxing device to the dipping end.It stoodNomenclature D powder size,l mg gravity acceleration,m/s 2h capillary wetted height,mm h g depth of grooves,mmh t height of total grooves,mm K permeability,mm 2M mass of powder,gr eff effective pore radius,mms spacing interval of grooves,mm T thickness of wick,mm wwidth of grooves,mmGreek symbols4P capcapillary force,Pa 4P cap ,com capillary force of composite wicks,Pa4P cap ,sin capillary force provided by sintered porous zone,Pa 4P cap ,gro capillary force provided by groove bottom zone,Pa 4P cap ,int capillary force provided interaction wetting zone,Pa e porosity,dimensionless l dynamic viscosity,Pa s h liquid–solid contact angle,rad q density,kg/m 3r surface tension,N/mFig.1.Schematic of sintered–grooved composite wickstructure.Fig.2.Sintered bonding of composite wick structure.Y.Tang et al./Experimental Thermal and Fluid Science 34(2010)190–196191for the sample and its length had been measured before the sample dipped into ethanol.A locating point was added in the measuring line.As this point moved vertically along the measuring line,the vertical line moved along the temperature distribution curve until arriving at the inﬂection point.The position of this inﬂection point stood for the meniscus.The height result of the point could be cal-culated.Thus,the wetted height,h ,was obtained.Besides,the wet-ted height over time during the whole visualization process could be accurately obtained.Thus,the rising velocity of wetted height could be also studied.3.Analysis of liquid ﬂow characteristic in composite wick structureDuring the risen meniscus test,working liquid rises in a wick.The following assumptions are given:(i)steady-state laminar ﬂow in the wick,(ii)uniform saturation with liquid along the wetted length and (iii)neglecting inertial effects and evaporation of liquid.In the initial time after the composite wick dips into ethanol,the liquid rises along two channels,micro groove and sintered por-ous layer.In the groove channel,liquid ﬂows along a straight line on the groove surface,whereas in the sintered porous channel,li-quid ﬂows tortuously by the open pores in sintered porous layer.The friction resistance of liquid ﬂow in groove is smaller than that in sintered porous layer.Therefore,the liquid rises faster in the groove channel than in the sintered porous layer.However,there are small voids which interconnect the groove and sintered porous layer (Fig.2).The liquid in the groove channel and sintered porous layer does not ﬂow separately.There is an interaction effect be-tween these two rising channels,that is,the fast liquid in groove channel drags the slow liquid in sintered porous layer.By this interaction effect,the liquid in these two channels converges to-gether and a balanced rising velocity reaches between groove and sintered porous layer.We name this kind of ﬂow in composite wick as interaction wetting.It is somewhat similar to the plate-particle interaction during water saturation in the channels with particles in contact with a plate of the same material,which was analyzed by Lechman [17].Due to the interaction wetting,the composite wick is completely saturated except the closed poresTable 1Samples code and speciﬁcations.Sample code Powder size,D mm Mass ofpowder,M g Thickness of wick,T mm Height of total grooves,h t mm Spacing interval of grooves,s mm Depth of grooves,h g mm Width of grooves,w mm Porosity,e (%)Grooved ––– 1.360.80.650.85–Sintered 80–110 2.00 1.5––––55C40–6040–60 2.00 1.5 1.360.80.650.8554C60–8060–80 2.00 1.5 1.360.80.650.8554C80–11080–110 2.00 1.5 1.360.80.650.8554C110–140110–1402.001.51.360.80.650.8554Fig.3.Schematic of the risen meniscus testapparatus.Fig.4.Meniscus locating method of wick structure in IR images (sample:C110–140).192Y.Tang et al./Experimental Thermal and Fluid Science 34(2010)190–196in sintered porous layer.The interaction wetting repeats as the li-quid rises in wicks until a ﬁnal equilibrium height reaches.As shown in Fig.5,the composite wick can be mainly divided into three parts for liquid ﬂow,sintered porous zone,groove bot-tom zone and interaction wetting zone.Each ﬂow zone provides a source of capillary force.Thus,we can obtain:D P cap ;com ¼D P cap ;sin þD P cap ;gro þD P cap ;int ð1Þwhere D P cap ,com is the capillary force of composite wicks,D P cap ,sin ,D P cap ,gro ,and D P cap ,int is deﬁned to be the capillary force provided by sintered porous zone,groove bottom zone and interaction wet-ting zone,respectively.It should be noted that D P cap ,int is induced by the drag force of the fast liquid in groove,which acts on the slow liquid in sintered porous layer.4.Results and discussionsFor the rise of liquid during the risen meniscus test,capillary force of the wicks,D P cap ,plays the driving force.The total pressure loss,D P total ,plays the ﬂow resistance,which consists of two parts,friction pressure loss and hydrostatic pressure loss,as follows:D P total ¼l e K h d hd tþq ghð2Þwhere l is the viscosity of working liquid,e is the porosity of wick structure,K is the permeability of wick structure,h is the wettedheight,d his the rising velocity of the wetted height,q is the liquid density,g is the gravitational acceleration.Because of the neglect of inertial effects,these are the only source of pressure change dur-ing the liquid rise.Thus,capillary force is equal to the total pressure loss:D P cap ¼l e h d hþq ghð3Þtherefore,the capillary force of different wicks can be compared byh and d hof liquid rise.For different wicks during the same test time,the sample with larger wetted height and rising velocity has larger capillary force.4.1.Effect of sintered layer on capillary forceAs can be seen in Fig.6,the liquid in all samples rose quickly at the early time of the rise process.As the wetted height increased,the rising velocity of the wetted height reduced -pared with the composite samples,the grooved sample had higher rising velocity in the ﬁrst 15s.Without sintered powder in grooves,the friction resistance of liquid ﬂow was small.Ethanol rose very fast in the grooves.The wetted height reached 30mm at 15s and the equilibrium height was obtained at 30s.After that the meniscus did not rise.While in the composite samples,the meniscus rose continuously for a longer time than grooved wick.The equilibrium height had not yet been obtained at the end of one minute.Fig.7shows the meniscus rising process of a compos-ite wick by IR thermal images.At the end of the test time,the wet-ted heights of all the four composite samples were larger than grooved wick.It can be concluded that composite wicks had larger capillary force than grooved one.This can be attributed to the anal-ysis in Wang’s report [3].Capillary force can be also obtained by the Laplace–Young equation as deﬁned below:D P cap ¼2r r effð4Þwhere r is the surface tension of liquid and r eff is the effective cap-illary radius.As the sintered layer covered the grooves,a lot of small menisci formed in the sintered layer.The effective capillary radius decreased from the radius of big meniscus of the groove in grooved wick to the radius of small menisci in the sintered layer in compos-ite wick.Thus,from Eq.(4),the capillary force of composite wicks was larger than that of grooved one.Meanwhile,as analyzed in Sec-tion 3,from Eq.(1),sintered powder layer and interaction wetting provided two additional important portions of capillary force for composite wick.Thus,composite wicks have larger capillary force than grooved one.4.2.Effect of V-grooves on capillary forceA sintered sample,which has the same powder size with com-posite sample (80–110l m),was tested for comparison.The result was shown in Fig.8.During the ﬁrst 10s,the wetted height andtheFig.5.Schematic of three liquid ﬂow zones in a compositewick.Fig.6.Effects of sintered layer and powder size on wetted height of wicks.Y.Tang et al./Experimental Thermal and Fluid Science 34(2010)190–196193rising velocity were almost equal for both sintered and composite sample.It is due to that the capillary force difference between these two samples was small.Sintered porous layer in both wicks provided large capillary force for liquid rise.As the wetted height grew,the rising velocity reduced gradually.During this time,the capillary force difference between these two samples played an important role in liquid rise.Results show that the wetted height and the rising velocity of composite sample were larger than thatof sintered sample after 10s.It resulted from that the groove bot-tom zone and interaction wetting zone provided additional sources of capillary force for composite wick.Besides of the capillary force provided by sintered porous layer,the driving force of groove bot-tom zone and the drag force in interaction wetting zone increased the total capillary force of composite wicks.Thus,the capillary force of composite wick is a little larger than that of sintered wick.4.3.Effect of powder size on capillary force of composite wicks Experimental results in Fig.6shows that the wetted height of sample C80–110is the largest.Following was C110–140and C40–60.The smallest was C60–80.The rising velocity generally fol-lowed a similar order.Thus,the composite sample with the 80–110l m powder had the largest capillary force.It could be found that the capillary force of composite samples with large powder size (C80–110and C110–140)was larger than that with small powder size (C40–60and C60–80).This is mainly due to the porous matrix difference of composite wicks.As shown in Table 1,identi-cal porosity was obtained for these four samples.According to the deﬁnition of porosity [18],the volume sum of open pores and closed pores equaled for the samples,due to the same volume of the sintered layer in these four composite wicks.However,as shown in Fig.9,the open pore size and quantity varied,which strongly affected the liquid ﬂow in wick structures.In porous ma-trix,only open pores could provide channels for liquid ﬂow.Closed pores can not be saturated.Due to the existence of closed pores,li-quid would turn to ﬂow by the adjacent open pores.Thus,theﬂow-Fig.7.IR images of the meniscus rising process of composite wick structure during one minute (sample:C110–140).parison between composite wick and sintered wick with the same powder size (80–110l m),wetted height versus time.194Y.Tang et al./Experimental Thermal and Fluid Science 34(2010)190–196ing channels became longer and the friction resistance of liquid ﬂow increased.For the samples with small powder size (samples C40–60,C60–80),the voids among powder particles were apt to be ﬁlled or covered by other particles during sintering.A lot of closed pores existed.While for the samples with large powder size (samples C80–110,C110–140),there were larger voids among dif-ferent particles than that with small powder size.They could not be ﬁlled or covered by other particles due to their large size.More open pores formed.The open pores were bigger and they were eas-ier to interconnect with each other.Thus,there were more ﬂowing channels for the liquid rise in sintered porous layer.The friction resistance of liquid ﬂow was smaller.The liquid rose higher and faster.As a result,composite samples with large powder size have larger capillary force than that with small powder size.However,it was found in the experiments that capillary force does not increase linearly with powder size.It may be attributed to the difference of the interaction wetting effect.For the sample with large powder size (C80–110,C110–140),the interaction effect in sample C80–110with comparatively smaller powder size may be a little stronger in the liquid rise process,and the liquid in grooves may provide a little larger drag force acting on liquid in sintered porous layer than sample C110–140.Thus,the capillary force of sample C80–110is a little larger than sample C110–140.Similarly for the sample with small powder size,sample C40–60has slightly larger capillary force than sample C60–80.Other stud-ies,such as theoretical veriﬁcation of powder size and other parameters’effects on interaction wetting,are still required in the future work.5.ConclusionsSintered–grooved composite wick has been presented for two-phase heat transfer devices.IR thermal imaging camera was usedin the risen meniscus test of capillary parison of the wetted height and rising velocity among composite,grooved and sintered wicks was conducted.Four composite wicks with different powder size ranged from 40–60l m to 110–140l m were tested.The conclusion can be summarized as follows:(1)For the infrared emissivity difference between liquid andsolid at a given temperature,the liquid meniscus in a wick can be accurately located by IR thermal images,including grooved,sintered and composite wicks.(2)Interaction wetting between groove and sintered powderhappens during the liquid rise,and composite wick can be mainly divided into three parts for liquid ﬂow,sintered por-ous zone,groove bottom zone and interaction wetting zone.Each ﬂow zone provides a source of capillary pos-ite wicks have larger capillary force than grooved and sin-tered ones.(3)Composite wicks with large powder size provide larger cap-illary force than that with small powder size.Friction resis-tance difference of liquid ﬂow exists due to the variation in open pore size and quantity in different porous matrix of composite wicks.But the capillary force varies nonlinearly with the powder size.The optimal powder size of composite wick is suggested to be 80–110l m.Future work is needed for theoretically modeling of the liquid ﬂow in composite wicks.Besides,theoretical analysis of powder size and other parameters’effect on interaction wetting and capil-lary force will be carried out.AcknowledgementsThis work is ﬁnancially supported by the National Natural Sci-ence Foundation of China,Project No.U0834002andNo.Fig.9.SEM photograph of sintered porous matrix of composite samples showing variation in open pore size and quantity:(a–d)correspond to samples C40–60to C110–140,respectively.Y.Tang et al./Experimental Thermal and Fluid Science 34(2010)190–19619550705031,50975092,and Guangdong Natural Science Foundation, Project No.07118064,and No.8151064101000058.References[1]I.Sauciuc,M.Mochizuki,K.Mashiko,Y.Saito,T.Nguyen,The design and testingof the superﬁber heat pipes for electronics cooling applications,in: Proceedings of16th IEEE Semiconductor Thermal Measurement and Management Symposium,San Jose,USA,2000,pp.27–32.[2]G.S.Hwang,M.Kaviany,W.G.Anderson,J.Zuo,Modulated wick heat pipe,Int.J.Heat Mass Transfer50(7–8)(2007)1420–1434.[3]J.L.Wang,I.Catton,Enhanced evaporation heat transfer in triangular groovescovered with a thinﬁne porous layer,Appl.Therm.Eng.21(17)(2001)1721–1737.[4]G.Franchi,X.Huang,Development of composite wicks for heat pipeperformance enhancement,Heat Transfer Eng.29(10)(2008)873–884. [5]D.R.Adkins,R.C.Dykhuizen,Procedures for measuring the properties of heatpipe wick materials,in:Proceedings of the28th Intersociety Energy Conversion Engineering Conference,Washington DC,1993,pp.911–917. [6]A.Das,A.K.Chatterjee,S.P.Basu,A method of measuring capillary rise in a heatpipe,Int.J.Heat Mass Transfer28(10)(1985)1959–1960.[7]A.Faghri,Heat Pipe Science and Technology,Taylor&Francis,Washington,DC,1995.[8]S.W.Chen,J.C.Hsieh,C.T.Chou,H.H.Lin,S.C.Shen,M.J.Tsai,Experimentalinvestigation and visualization on capillary and boiling limits of micro-grooves made by different processes,Sens.Actuat.A:Phys.139(1–2)(2007)78–87.[9]B.Holley, A.Faghri,Permeability and effective pore radius measurementsfor heat pipe and fuel cell applications,Appl.Therm.Eng.26(4)(2006) 448–462.[10]H.Kaplan,Practical applications of infrared thermal sensing and imageequipment,O’Shea Series Editor,Georgia Institute of Technology,USA, 1993.[11]R.Boukhanouf,A.Haddad,M.T.North,C.Buffone,Experimental investigationof aﬂat plate heat pipe performance using IR thermal imaging camera,Appl.Therm.Eng.26(17–18)(2006)2148–2156.[12]C.Buffone,K.Seﬁane,Controlling evaporative thermocapillary convectionusing external heating:an experimental investigation,Exp.Therm.Fluid Sci.32(6)(2008)1287–1300.[13]M.Cerza,B.Boughey,The effects of air inﬁltration on a largeﬂat heat pipe athorizontal and vertical orientations,ASME J.Heat Transfer125(2)(2003)349–355.[14]D.T.Queheillalt,G.Carbajal,G.P.Peterson,H.N.G.Wadley,A multifunctionalheat pipe sandwich panel structure,Int.J.Heat Mass Transfer51(1-2)(2008) 312–326.[15]F.Zhang,J.Peng,J.Geng,Z.X.Wang,Z.B.Zhang,Thermal imaging study on thesurface wave of heated falling liquidﬁlms,Exp.Therm.Fluid Sci.33(3)(2009) 424–430.[16]D.F.Berry, E.Klar,Powder metal technologies and applications.In:ASMHandbook,vol.7.ASM International,Materials Park,USA,1998.p.309. [17]J.Lechman,N.Lu,Capillary force and water retention between two uneven-sized particles,J.Eng.Mech.ASCE134(5)(2008)74–384.[18]J.Banhart,Manufacture,characterisation and application of cellular metalsand metal foams,Prog.Mater.Sci.46(6)(2001)559–632.196Y.Tang et al./Experimental Thermal and Fluid Science34(2010)190–196。

实验室OOS管理和案例分析

实验室OOS管理和案例分析做药品检验，会没有偏差吗？答案一定是否定的。

药品生产企业的检验偏差，说白了就是与检验相关的一些异常。

通常会涉及到检验的各个环节，比如进厂的物料（包括原料、辅药、包装材料等）、中间产品、待包装产品、成品、稳定性考察样品、市场投诉退货产品、环境监测、工艺用水、公用介质（如：氮气、蒸汽）、辅助生产用品（如：消毒液、手套）、辅助检验用品（如：色谱纯、鲎试剂）等。

一、检验偏差的分类1、OOS(超标）指检验结果超出设定质量标准，包括注册标准以及企业内控标准。

如果对于产品有多个接受标准，结果的评判采用严格的标准执行。

OOS是检验偏差的一种特例，说得是一种检验结果。

2、OOT（超趋势）指随时间的变化，产生的在质量标准限度内，但是超出预期期望的一个结果或一系列结果（比如稳定性降解产物的增加），或未能符合统计学控制标准。

如标准规定为5.5-7.5，测定结果通常是6.0-7.0，检验结果是5.8，则该数据构成OOT数据。

3、OOE（超预期）指实验结果超过历史的，预期的或先前的趋势/限度。

非期望结果有如下两种：一是对于同一制备的样品重复测定结果或重复制备的样品的结果显示不良的精密度，即精密度不符合规定；二是基于对实验物料、实验室样品或实验规程的了解，实验结果不正常(包括该结果虽符合质量标准，但不是正常的值)。

OOT是属于OOE的一种形式。

4、AD(异常数据)指检验数据本身可疑或来自异常测试过程的数据或事件。

结果出人意料，不规则，可疑，不正常。

如仪器设备停机，人为差错，色谱图产生意想不到的峰等产生的数据或事件。

5、检验偏差偏差指与已建立的质量标准、标准操作规程、及其他书面规程不相符合的，并与产品质量直接或间接相关的事项。

检验偏差如仪器校验过期、药品洒掉、样品成分未完全转移、样品存放条件不当、标化室温湿度超标等。

二、OOS调查（包括理化、微生物）1、OOS的由来OOS是指超出药品申请和审批文件、DMF文件 (药物主文件)、药典以及企业标准的所有检验结果，包括所有超出标准的中控过程检验数据。

Investigation, Analysis and Optimization of Exothermic Nitrations in Microreactor Processes

Experimental
Two different types of microreactors were used for the nitration experiments. A commercially available silicon micromixer based on a microfluidic split-andrecombine structure (MiMoCo GmbH, IlmenauiGermany) and a microreactor array made of glass containing 20 reaction channels in parallel with integrated educt mixing zones and cooling structure (development in cooperation with mgt mikroglas technik AG, Mainz/Germany) [2, 3]. Since nitrating agents are highly corrosive media only resistant materials can be applied for such reactions. Silicon, glass and titanium were proved to be suitable for nitration processes. Microstructured devices made of stainless steels did not withstand such corrosion processes. Different nitrating agents were used for the microreaction experiments. Besides concentrated and fuming nitric acid (65% resp. conc. RN0 3), nitrating acid ("mixed acid": RN0 31H2S04 = 1: 1 - 6: 1) and dinitrogen pentoxide (N205) as a less acid nitrating agent were used. N20 5 was either dissolved in CH2Cl 2 or used as a gaseous reactant (in-situ production: N20 4 + 0 3). Nitrating agents were used in up to 6-fold excess. Ureas (dissolved in dichloromethane) and nitrating agents (liquid or dissolved) were supplied by pulsation-free pumps, mixed inside the microreactors (resp. micromixers) and then passed through reaction capillaries (e.g. PTFE tubes) of different lengths representing different retention times (0.6 s - 82 s). Nitrations were carried out in a continuous mode at defined temperatures between O°C and 20°C. The reaction mixture eluting out of the microreaction system was quenched in ice water and/or cold dichloromethane, extracted and passed to NMR, MS, IR, HPLC or GC-MS for analysis. For a more effective investigation and optimization of nitrations analytical devices and sensors for process control (like temperature monitoring, flow control, etc.) were adapted to the microreaction processes. FTIR microscopy was applied for the online monitoring of nitrations in silicon microreactors. Due to a high spatial resolution of this analytical method (~ 10 flm) educts and products of nitrations can be identified and distinguished at different positions inside the microreactor [5]. Both intermediates and final products of nitrations can be IR spectroscopically detected by focusing the IR

Experimental investigation of air–water, two-phase flow regimes in

Scientia Iranica B(2011)18(4),923–929Sharif University of TechnologyScientia IranicaTransactions B:Mechanical EngineeringExperimental investigation of air–water,two-phase flow regimes in vertical mini pipeP.Hanafizadeh,M.H.Saidi∗,A.Nouri Gheimasi,S.GhanbarzadehSchool of Mechanical Engineering,Sharif University of Technology,Tehran,P.O.Box11155-9567,IranReceived8November2010;revised28April2011;accepted12June2011KEYWORDSMini pipes;Two-phase flow; Flow pattern; Visualization; Flow pattern map.Abstract In this study,the flow patterns of air–water,two-phase flows have been investigated experimentally in a vertical mini pipe.The flow regimes were observed by a high speed video recorder in pipes with diameters of2,3and4mm and length27,31and25cm,respectively.The comprehensive visualization of air–water,two-phase flow in a vertical mini pipe has been performed to realize the physics of such a two-phase flow.Different flow patterns of air–water flow were observed simultaneously in the mini pipe at different values of air and water flow rates.Consequently,the flow pattern map was proposed for flow in the mini-pipe,in terms of superficial velocities of liquid and gas phases.The flow pattern maps are compared with those of other researchers in the existing literature,showing reasonable agreement.©2011Sharif University of Technology.Production and hosting by Elsevier B.V.All rights reserved.1.IntroductionGas–liquid,two-phase flow in micro structures has played an important role in several industrial and medical applications, such as micro heat exchangers,lab-on-chips,bio-MEMS and micro cooling electronics.Physical perception of micro flows is critical in order to optimize and develop the design of such devices.Two-phase flows at mini and micro scale have recently attracted the attention of scientists as a result of its wide usage in advanced science and technology,namely Micro-Electro-Mechanical Systems(MEMS),chemical engineering, bioengineering,medical devises,micro cooling systems,micro structures in computers,etc.The literature survey on this issue has been categorized into adiabatic and phase change work, which has been summarized in this paper.∗Corresponding author.E-mail address:saman@(M.H.Saidi).1.1.Adiabatic worksThe works of Suo and Griffith[1]were among the first studies concentrating on flow patterns in microchannels.They detected three different flow patterns,namely,bubbly/slug, slug and annular flow,in their studies,using channels with widths in the range of0.514–0.795mm.Sadatomi et al.[2] proposed flow regime maps in vertical rectangular channels and indicated that channel geometries have little influence in noncircular channels with large hydraulic diameters greater than10mm.Xu et al.[3]investigated concurrent vertical two-phase flow in a vertical rectangular channel with a narrow gap, experimentally.They reported that with a decrease in channel gap,the transition from one flow regime to another occurs at smaller gas flow rates.They developed a new criterion to predict transition from annular flow,as well.Hestroni et al.[4] performed experiments for air–water and steam–water flow in parallel triangular micro-channels,developed a practical modeling approach for two-phase micro-channel heat sinks and considered the discrepancy between flow patterns of air–water and steam–water flow in parallel micro-channels. Fukagata et al.[5]simulated an air–water two-phase flow in a20µm ID tube,numerically,with focus upon flow and heat transfer characteristics in the bubble train flows.He and Kasagi[6]simulated numerically adiabatic air water slug flow in a micro tube.They focused on pressure drop characteristics and their modeling.They found that the total pressure drop of a slug flow can be decomposed into a frictional pressure drop and a pressure drop over the bubble itself.Carlson et al.[7]1026-3098©2011Sharif University of Technology.Production and hosting by Elsevier B.V.All rights reserved.Peer review under responsibility of Sharif University of Technology.doi:10.1016/j.scient.2011.07.003924P.Hanafizadeh et al./Scientia Iranica,Transactions B:Mechanical Engineering18(2011)923–929investigated characteristics of multiphase dynamics,especially two-phase gas–liquid flow,by means of advanced numerical simulations.They compared two Computational Multi-Fluid Dynamic(CMFD)codes,Fluent and TransAT,and reported a prediction of recirculating flow in the bubbly flow case using TransAT,while significant recirculation was not observed in the solution using Fluent.Saison and Wongwises[8]performed a series of experiments in a horizontal circular micro channel with an inner diameter of0.15mm.They presented a flow pattern map in terms of the phase superficial velocities, and proposed a new pressure drop correlation for practical application.1.2.Phase change worksThe pool boiling heat transfer,in a vertical narrow annular with closed bottoms,was observed through a transparent quartz shroud by Yao and Chang[9],and stages of evolving boiling phenomena with an increase in heat flux were reported. Several researchers observed three basic flow patterns,namely, bubbly,slug and annular flow,in the mini pipe and channel. Damianides and Westwater[10]performed experiments with a1mm tube,and Mertz et al.[11]and Kasza et al.[12] studied the flow visualization of water nucleation in a single rectangular channel of2.5mm by6mm.Lin et al.[13]used a single round tube with2.1mm inside diameter for their experiments,and compared the flow transitions with those predicted by Bernea et al.[14].Sheng and Palm[15]performed their experiments with1–4mm diameter tubes.Cornwell and Kew[16]found three different flow patterns for R-113, namely,isolated bubbles confined bubbles and slug/annular flow,in rectangular channels with cross sectional areas of 1.2–0.9mm and3.5–1.1mm.Ory et al.[17]considered the effects of capillary,inertia,friction and gravity forces on the velocity distribution and temperature field along a single capillary two-phase flow in a heated micro-channel.Research dealing with gas–liquid,two-phase flow in micro-channels,in situations where fluid inertia was significant in comparison with surface tension,was reviewed by Ghiaasiaan and Abdel-Khalik[18].Jiang et al.[19]studied the boiling of water in triangular micro-channels,having widths of50and100µm. They observed individual bubbles at low heat fluxes,and an abrupt change in flow pattern to an unstable slug flow with increasing heat flux.Chedester and Ghiaasiaan[20]addressed the hydro-dynamically controlled Onset of a Significant Void (OSV)in heated micro tubes.They derived a simple semi-empirical correlation for the radius of departing bubbles at the OSV point to show the accuracy of their hypothesis.Some experimental studies have been reported on gas liquid two-phase flow in mini and micro conduits by Kandlikar[21],Lee and Mudawar[22]and Serizawa et al.[23].The three zone boiling heat transfer model was developed by Thome et al.[24]. Revellin and Thome[25]used an optical measurement method for two-phase characteristics of R-134a and R-245fa,in0.5mm and0.8mm diameter channels,to determine the frequency of bubbles existing in the microevaporator.They detected four flow patterns,namely,bubbly,slug,semi-annular and annular flow,whose transitions were not well compatible with neither the macroscale map of refrigerants nor the microscale map of air–water flow.Sobierska et al.[26] experimentally investigated the water boiling phenomena in a vertical rectangular microchannel,with a hydraulic diameter of0.48mm.They observed three main flow patterns,namely, bubbly,slug and annularflow.Figure1:Schematic of test apparatus.Due to the effects of surface tension,two-phase flows at mini and micro scale have different behavior in comparison with the macro scale.The aim of the present work is to visualize flow regimes in air–water two-phase flows and propose a flow regime map for such flows in vertical mini pipes.The neural network technique is implemented to recognize and predict a gas–liquid,two-phase flow pattern in mini tubes,having diameters of2,3and4mm.2.Experimental setupThis study is carried out by experimental apparatus schematically shown in Figure1.Air and water are used as gas and liquid phases in the experiments.The water flow rates are regulated by the needle valves and are measured by the cali-brated rotameter.Air and water are mixed together in a mixer made of acrylic glass and placed at the bottom of the riser pipe. The compressed air is fed by the compressor via an air injec-tor,which is schematically depicted in Figure2.The water flows from the center hole of a mixer,with a diameter of2mm,while air is injected into the holes around the center hole,each having 1mm diameter.The air flow rates are set by the regulator valve and are continuously measured by the calibrated gas rotameter. The overall height and inside diameter of the riser pipe are sum-marized in Table1.In order to have the opportunity to visually observe the two-phase flow patterns,the riser pipe was made of transparent glass.The air water mixture was directed upward through the riser,separated in the separation tank at the top of the riser and the air was discharged into the atmosphere.Differ-ent flow regime images were captured by a digital high speed camera,with a frame rate of1200fps,from the test section of the upriser.The test section is placed after the entrance section to diminish the effect of the entrance region.The length of the entrance section is about500mm.The superficial air and water velocities are0.5–10m/s and0.05–1m/s,respectively.P.Hanafizadeh et al./Scientia Iranica,Transactions B:Mechanical Engineering 18(2011)923–929925Figure 2:Schematic of air and watermixer.Figure 3:(a)RGB picture;(b)gray picture;and (c)subtracting and median process of flow in the pipe (3mm diameter).3.Experimental results 3.1.Image processingImage processing techniques must be performed in order to extract features from the images of the two-phase flow.Each picture has 8bit RGB (red,green and blue)color format,being converted from RGB to a grey scale mode.The output image has 256grey levels from 0(black)to 255(white).It is difficult to extract the bubbles directly from an original digital image and therefore preprocessing procedures must be undertaken to reduce noise and improve the quality of the images.An image-subtracted algorithm was used to reduce background noise by subtracting the background image from each dynamic image.In order to smooth the image border,a median filter was also used.A sliding window (3×3)was used in this process,and the median gray level of the pixels in the window was ter,the gray level of the pixels located at the center of the window was replaced by the median.The result of these processes is shown in Figure 3.3.1.1.Inverting binary imageThe images were converted from grayscale to binary mode by threshold segmentation,and an iterative procedure was used to calculate the optimizing threshold as follows [27]:Figure 4:Binary image of two-phase flow in the mini pipe.(a)The minimum and maximum of the gray level,namely Z land Z k ,are found in the image,and the initial value of the threshold is derived from their arithmetic average as:T 0=(Z k +Z l )/2.(1)(b)According to the initial value of threshold T K ,the imageis divided into two parts,namely,object and background,and the average value of the gray level in each part is calculated as:Z O =−Z (i ,j )<T kZ (i ,j )N O,(2)Z B =−Z (i ,j )>T kZ (i ,j )N B,(3)where Z (i ,j )is the gray level of the pixel (i ,j )in the image,N O is the number of the pixels in which Z (i ,j )is less than T K ,and N B is the number of pixels in which Z (i ,j )is more than T K .(c)The new threshold is calculated based on the arithmeticaverage of the object and background segments of the image as:T k +1=(Z O +Z B )/2.(4)If T K =T K +1,then the algorithm is finished,else K ≪=K +1,and turn to step (b).The binary image of the bubbles in the vertical pipe,which is the result of the above procedure,is shown in Figure 4.3.1.2.Image morphology processingSome morphological functions,such as dilation,erosion,opening and closing operations,were applied to modify the shapes of bubbles.Dilation adds pixels to the boundaries of the objects in an image,while erosion removes pixels on the object boundaries.The definition of a morphological opening of an image is erosion followed by dilation,using the same structuring element for both operations.The related operation,morphological closing of an image,is the reverse.It consists of dilation followed by erosion,with the same structuring element.Both of them do not significantly alter the area or shape of objects.The opening operation removes small objects and smoothes boundaries.Borders removed by erosion are restored by dilation,but small objects that were absorbed during erosion do not reappear after dilation.The closing operation was used to fill tiny holes and smooth boundaries.Objects were expanded by dilation and then reduced by erosion,so borders were smoothed and holes were filled [28,29].After926P.Hanafizadeh et al./Scientia Iranica,Transactions B:Mechanical Engineering 18(2011)923–929Figure 5:Final image of two-phase flow in the mini pipe.these operations,the result of image processing is shown in Figure 5.Bubble images of two-phase flow were clear using the above image processing,and it prepared bubbles for quantitative analysis,such as measuring area,perimeter and diameter.3.2.Flow pattern mapIn the experimental procedure while varying gas or liquid mass flow rate,a 10s film was recorded from the flow regime at a speed of 1200fps.The recorded film was replayed in slow motion for recognition of flow regimes.Each film converted to separate frames in a picture format using Adobe Premiere software.The achieved pictures were used as inputs of image processing techniques.The final binary pictures were used for the mentioned post processing procedure,such as flow regimedetection,void fraction and bubble velocity calculation,etc.Figure 6shows those typical flow regimes observed in the vertical,co-current,air–water,two-phase flows,in the 3mm mini pipe.Four basic flow patterns,namely,bubbly,slug,churn and annular,accompanied by their transitions,are illustrated in these figures.The visualization shows that air–water two-phase flows in mini pipes do not have three dimensional behaviors,especially in bubbly and slug flows.The final processed images of different flow regimes in air–water,two-phase flow in mini pipes have been presented in Figure 7.Figures 8–10show the flow pattern map for a vertical round tube with inner diameters of 2,3and 4mm,respectively.The proposed maps are in terms of superficial velocities of phases,and the four main flow patterns are depicted in these maps.In Figure 11,the achieved flow pattern for the pipe with 2mm ID was compared to the work of Ide et al.[30],shown by a solid line.They divided the flow pattern map into the four main regions,namely,dispersed bubbly flow,intermittent flow,churn flow and annular flow.The comparison shows that the bubbly and annular flows in the present work are not well in accordance with those of Ide et al.In the present work,the dispersed bubbles were not seen,because the air bubble injector did not have very thin holes.As a result,the created bubbles mostly have diameters in the range of the pipe diameter.Even the existence of air injectors with thin holes cannot guarantee the creation of bubbly flow.In the case of small bubbles occurring,as a result of thin holes in the air injector and the developed two-phase flow,they would collapse,resulting in large bubbles know as intermittent flow.Bubbly flows are mainly promoted by bubble breaking mechanisms,due to turbulence effects.It seems that in small diameter pipes,the formation of a specific flowpatterns(a)Bubbly.(b)Bubbly-slug.(c)Slug.(d)Messy-slug.(e)Churn.(f)Wispy-annular.(g)Ring.(h)Wavy-annular.(i)Annular.Figure 6:Different flow patterns in a vertical pipe with 2mm diameter.P.Hanafizadeh et al./Scientia Iranica,Transactions B:Mechanical Engineering18(2011)923–929927(a)Bubbly.(b)Slug.(c)Messy-slug.(d)Churn.(e)Ring.(f)Wavy-annular.Figure7:Final processed image of different two-phase flow regimes in the minipipe.Figure8:Flow patterns for2mm innerdiameter.Figure9:Flow patterns for3mm inner diameter.mainly depends on mixer configuration.The radial air supplierused in this study makes intermittent flow patterns,such asslug and churn flows,while the air supply in the tube centerfavors annular flow.This can be the reason for an absence ofannular flow in the proposed flow patterns.The comparison offlow patterns also reveals that the slug,messy slug andsemi-Figure10:Flow patterns for4mm inner diameter.annular flows in the proposed map are in accordance with theintermittent flow of Ide et al.[30].In the present study,a noticeable difference between flowpattern maps for vertical pipes with various diameters of2,3and4mm is not seen.This can be justified in regard tothe fact that the dominant forces acting on the air–watermixture in the small diameter pipes,namely,gravitation,inertia,surface tension and buoyancy forces,are in the sameorder of magnitude.This concept clearly indicates that thesethree flow patterns can be combined to form a new flow patternfor the gas–liquid,two-phase flow in small diameter pipes.A combination of these three flow patterns results in a newflow pattern map,which is illustrated in Figure12.A FuzzyC-Means clustering technique(FCM)was used to classify theflow patterns.The solid lines in the figure show the transitionregion of the flow patterns.This figure shows the achieved flowmap for mini pipes with diameters in the range of2–4mm.4.ConclusionIn this paper,air–water,two-phase flow patterns wereinvestigated experimentally for mini pipes with diameters of2,3and4mm.An image processing technique was used fordetection of flow patterns from pictures derived from filmsrecorded with a high speed camcorder.The obtained flowpatterns reveal that there is no noticeable difference between928P.Hanafizadeh et al./Scientia Iranica,Transactions B:Mechanical Engineering 18(2011)923–929Figure 11:Comparison between the achieved flow patterns with the work of Ide et al.[30]for a pipe with diameter of 2mm.Figure 12:Proposed two-phase vertical upward flow pattern map.two-phase,upward flow patterns in this range of diameters.A new flow pattern map was achieved for vertical mini pipes,due to a comparison of the flow patterns of these three diameters of pipe.The proposed map was compared with existing research.A comparison of the present work and previous research shows that the flow patterns of slug,messy slug and semi-annular in the present work are compatible with the intermittent flow pattern of Ide et al.[30].However,in the present study,the annular flow is seen at a lower superficial air velocity than that in the work of Ide et al.[30].AcknowledgmentsThis research was funded by Iran Supplying Petrochemical Industries,Parts,Equipment and Chemical Design Corporation (SPEC),as a joint research project with Sharif University of Technology (project No.KPR-8628077).References[1]Suo,M.and Griffith,P.‘‘Two-phase flow in capillary tubes’’,Int.J.Basic Eng.,86,pp.576–582(1964).[2]Sadatomi,Y.,Sato,Y.and Saruwatari,S.‘‘Two-phase flow in verticalnoncircular channels’’,Int.J.Multiphase Flow ,8,pp.641–655(1982).[3]Xu,J.L.,Cheng,P.and Zhao,T.S.‘‘Gas–liquid two-phase flow regimes inrectangular channels with mini/micro gaps’’,Int.J.Multiphase Flow ,25,pp.411–432(1999).[4]Hetsroni,G.,Mosyak, A.,Segal,Z.and Pogrebnyak, E.‘‘Two-phaseflow patterns in parallel micro-channels’’,Int.J.Multiphase Flow ,29,pp.341–360(2003).[5]Fugakata,K.,Kasagi,N.,Ua-arayaporn,P.and Himeno,T.‘‘Numericalsimulation of gas liquid two-phase flow and convective heat transfer in a micro tube’’,Int.J.Heat and Fluid Flow ,28,pp.72–82(2007).[6]He,Q.and Kasagi,N.‘‘Numerical investigation on flow pattern andpressure drop characteristics of slug flow in a micro tube’’,6th Int.ASME Conf.on Nanochannels,Microchannels and Minichannels ,Darmstadt,Germany,pp.24–35(2008).[7]Carlson,A.,Kudinov,P.and Narayanan,C.‘‘Prediction of two-phase flowin small tubes:a systematic comparison of state-of-the-art CMFD codes’’,5th Europe Thermal-Sci.Conf.,The Netherlands,pp.138–150(2008).[8]Saisorn,S.and Wongwises,S.‘‘An experimental investigation of two-phaseair–water flow through a horizontal circular micro-channel’’,Exp.Thermal Fluid Sci.,33,pp.306–315(2009).[9]Yao,S.C.and Chang,Y.‘‘Pool boiling heat transfer in a confined space’’,Int.J.Heat Mass Transf.,26,pp.841–848(1983).[10]Damianides,D.A.and Westwater,J.W.‘‘Two-phase flow patterns in acompact heat exchanger and in small tubes’’,2nd UK National Conf.on Heat Transf.,11,United Kingdom,London,pp.1257–1268(1988).[11]Mertz,R.,Wein,A.and Groll,C.‘‘Experimental investigation of flow boilingheat transfer in narrow channels’’,Calore e Technologia ,14(2),pp.47–54(1996).[12]Kasza,K.E.,Didascalou,T.and Wambsganss,M.W.‘‘Microscale flow visu-alization of nucleate boiling in small channels:mechanisms influencing heat transfer’’,Int.Conf.on Compact Heat Exchanges for the Process Indus-tries ,New York,USA,pp.343–352(1997).[13]Lin,S.,Kew,P.A.and Cornwell,K.‘‘Two-phase flow regimes and heattransfer in small tubes and channels’’,11th Int.Heat Transf.Conf.,Kyongju,Korea,2,pp.45–50(1998).[14]Barnea,D.,Luninsky,Y.and Taitel,Y.‘‘Flow pattern in horizontal andvertical two-phase flow in small diameter pipes’’,Canadian J.Chem.Eng.,61,pp.617–620(1983).[15]Sheng, C.H.and Palm, B.‘‘The visualization of boiling in small-diameter tubes’’,Int.Conf.on Heat Transport and Transport Phenomena in Microsystems ,Banff,Canada,pp.44–53(2001).[16]Cornwell,K.and Kew,P.A.‘‘Boiling in small parallel channels’’,CEC Conf.on Energy Eff.in Process Tech.,Athens,Greece,pp.624–638(1992).[17]Ory, E.,Yuan,H.,Prosperetti, A.,Popinet,S.and Zaleski,S.‘‘Growthand collapse of a vapor bubble in a narrow tube’’,Phys.Fluids ,12,pp.1268–1277(2000).[18]Ghiaasiaan,S.M.and Abdel-Khalik,S.I.‘‘Two-phase flow in micro-channels’’,Adv.Heat Transf.,34,pp.145–253(2001).[19]Jiang,L.,Wong,M.and Zohar,Y.‘‘Forced convection boiling in a micro-channel heat sink’’,Int.J.Micro-Electro-Mech.Sys.,10,pp.80–87(2000).[20]Chedester,R.C.and Ghiaasiaan,S.M.‘‘A proposed mechanism for hydrodynamically-controlled onset of significant void in microtubes’’,Int.J.Heat Fluid Flow ,23,pp.769–775(2002).[21]Kandlikar,S.G.‘‘Fundamental issues related to flow boiling in minichan-nels and microchannels’’,Exp.Therm.Fluid Sci.,26,pp.389–407(2002).[22]Lee,J.and Mudawar,I.‘‘Two phase flow in high heat flux micro channelheat sink for refrigeration cooling applications’’,Int.J.Heat Mass Transf.,48,pp.928–955(2005).[23]Serizawa,A.‘‘Gas liquid two-phase flow in microchannels’’,In MultiphaseFlow Handbook ,C.T.Crowe,Ed.,2nd ed.,pp.830–887,CRC Press (2006).[24]Thome,J.R.,Dupont,V.and Jacobi, A.M.‘‘Heat transfer model forevaporation in micro channels’’,Int.J.Heat Mass Transf.,47,pp.3375–3385(2004).P.Hanafizadeh et al./Scientia Iranica,Transactions B:Mechanical Engineering18(2011)923–929929[25]Revellin,R.and Thome,J.R.‘‘Experimental investigation of R-134a andR-245fa two-phase flow in microchannels for different flow conditions’’, Int.J.Heat Fluid Flow,28,pp.63–71(2007).[26]Sobierska, E.,Kulenovic,R.and Mertz,R.‘‘Heat transfer mechanismand flow pattern during flow boiling of water in a vertical narrow channel experimental results’’,Int.J.Thermal Sci.,46,pp.1172–1181 (2007).[27]Shi,L.‘‘Fuzzy recognition for gas–liquid two-phase flow pattern based onimage processing’’,Proc.of13rd IEEE Int.Conf.on Control and Automation, pp.1424–1427(2007).[28]Heijmans,H.J.A.M.,Morphological Image Operators,Academic Press,NewYork(1994).[29]/help/toolbox/images/index.html.[30]Ide,H.,Kariyasaki,A.and Fukano,T.‘‘Fundamental data on the gas–liquidtwo-phase flow in minichannels’’,Int.J.Thermal Sci.,46,pp.519–530 (2007).Pedram Hanafizadeh received his M.S.and Ph.D.Degrees in Mechanical Engineering from the Centre of Excellence in Energy Conversion at Sharif University of Technology,Tehran,Iran,in2005and2010,respectively.His work is mainly concentrated on the field of Multiphase Flow,Experimentally, Numerically and Analytically.His research interests include Characteristics of Multiphase Flow,Heat Transfer,Boiling and Condensation,Instrumentation in Fluid Flow,Image Processing for Flow Field Analysis,and Industrial and Applicable Usage of Multiphase Flow.Mohammad Hassan Saidi is Professor and Chairman of the School of Mechanical Engineering at Sharif University of Technology,Tehran,Iran. His current research interests include Multiphase Flows,Heat Transfer Enhancement in Boiling and Condensation,Modelling of Pulse Refrigeration, Vortex Tube Refrigerator,Indoor Air Quality and Clean Room Technology, Energy Efficiency in Home Appliances and Desiccant Cooling Systems.Arash Nouri Gheimasi obtained his B.S.Degree in Mechanical Engineering in2010,and is currently an M.S.student at the Centre of Excellence in Energy Conversion at the School of Mechanical Engineering,Sharif University of Technology,Tehran,Iran,under the supervision of Professor Saidi.His B.S. thesis involved work on the Characteristics of Gas-Liquid Two-Phase Flow in Mini Pipes and he is now working on Application of Visual Techniques in Two-Phase Flow.His research interests include the area of Two Phase Flow and Its Industrial Applications.Soheil Ghanbarzade received his B.S.and M.S.Degrees in Mechanical Engineering from the Centre of Excellence in Energy Conversion at Sharif University of Technology in2008and2010,respectively.Since then he has worked under the supervision of Professor M.H.Saidi as research staff in the Multiphase Group.His research interests include:Analytical,Numerical and Experimental Methods to Study Characteristics of Large Scale and Mini Scale Air-Water,Two-Phase Flows.He holds a Gold medal from the13th National Olympiad of Mechanical Engineering in Iran,and is currently a Ph.D.student of Petroleum Engineering at the University of Texas,Austin,USA.。

【中文】Q2(R2)：分析方法验证(草案)

国际人用药品技术协调会ICH协调指导原则分析方法验证Q2草案2022年3月24日签署目前公开征求意见在ICH进程的第2阶段， ICH大会将由ICH专家工作组认可的共识草案文本或指导原则按照国家或地区程序交给ICH区域的监管机构进行内部和外部征求意见。

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ICH协调指导原则分析方法验证Q2ICH共识指导原则目录1引言 (1)2范围 (2)3分析方法验证研究 (2)3.1分析方法生命周期中的验证 (4)3.2可报告范围 (5)3.3稳定性指示特性的证明 (6)3.4多变量分析方法的考虑 (6)3.4.1参比分析方法 (6)4验证试验、方法学和评价 (7)4.1专属性/选择性 (7)4.1.1无干扰 (7)4.1.2正交方法比较 (7)4.1.3技术固有合理性 (7)4.1.4数据要求 (8)4.1.4.1鉴别 (8)4.1.4.2含量测定、纯度和杂质检查 (8)4.2工作范围 (9)4.2.1响应 (9)4.2.1.1线性响应 (9)4.2.1.2非线性响应 (10)4.2.1.3多变量校正 (10)4.2.2范围下限验证 (10)4.2.2.1根据信噪比 (10)4.2.2.2根据线性响应值的标准偏差和标准曲线斜率 (11)4.2.2.3根据范围下限的准确度和精密度 (12)i4.2.2.4数据要求 (12)4.3准确度和精密度 (12)4.3.1准确度 (12)4.3.1.1参比物比较 (13)4.3.1.2加标研究 (13)4.3.1.3正交方法比较 (13)4.3.1.4数据要求 (13)4.3.2精密度 (14)4.3.2.1重复性 (14)4.3.2.2中间精密度 (14)4.3.2.3重现性 (14)4.3.2.4数据要求 (14)4.3.3准确度和精密度的合并评价方式 (15)4.3.3.1数据要求 (15)4.4耐用性 (15)5术语 (16)6参考文献 (24)7附件1验证试验选择 (24)8附件2分析技术例证 (25)ii1引言12本指导原则是讨论药物在ICH成员监管机构注册申请时，递交的分析方法验证所3需考虑的要素。

Effect of Alkali-NaOH Solution on the Nature of Sy

J. Chem. Chem. Eng. 5 (2011) 246-249Effect of Alkali-NaOH Solution on the Nature of Synthesized Zeolite from 2:1 Tunisian Clays: XRD and MAS-NMR InvestigationMahdi Meftah1, Walid Oueslati1, 2 and Abdesslem Ben Haj Amara11. Laboratoire de Physique des Matériaux Lamellaires et Nanomatériaux Hybrides, UR05/13-01 (PMLNMH) Faculté des Sciences de Bizerte, 7021 Zarzouna, Tunisia2. Faculté des Sciences de Gafsa, Département de Physique, Campus Universiatire Sidi Ahmed Zarrouk, 2112 Gafsa, Tunisia Received: October 12, 2010 / Accepted: November 17, 2010 / Published: March 30, 2011.Abstract: This work focuses the effect of alkali-NaOH solution on the nature of synthesized zeolite from 2:1 Tunisian clays. This study was achieved using correlation between results obtained from X-ray diffraction (XRD) and MAS-NMR analysis. Preliminary treatment was adopted to prepare the starting sample that is placed in contact with NaOH solution at variable concentration. A specific hydrothermal reactor, allowing the control of pH > 9, temperature and a continuous stirring of the sample in the NaOH solution, was used to achieve these syntheses. The obtained results showed that, for concentration value ≈1N, the final complex presented characteristic XRD and MAS-NMR line of zeolite P. For 3N solution concentration we obtained zeolite HS. All synthesize process are controlled by XRD and MAS-NMR investigation.Key words: Alkali-NaOH solution, hydrothermal reactor, zeolite P, HS.1. IntroductionZeolites are crystalline aluminosilicates with a 3-dimensional and open anion framework consisting of oxygen-sharing TO4 tetrahedral, where T is Si or Al. Their framework contains interconnected voids which can be occupied with adsorbed molecules or cations. The general empirical formula is M x/n Al x Si(2-x)O4·mH2O where n is the valence of the exchangeable cation M, m water content and 0 ≤ x ≤ 1. The flexibility of the zeolite Si-O-Si bond explains the fact that more than 200 structures have been determined. The synthesized process of zeolite from natural clay minerals (i.e. 1:1 and 2:1 clay) was studied by several authors [1, 2]. In 1948, the first confirmation of zeolite synthesis had been traced by Barrer who reported the synthesis of the modernite [3].Corresponding author:Mahdi Meftah, Ph.D., research fields: materiel sciences, zeolite synthesize, spectroscopic methods, condensed matter. E-mail:********************.At the same time Milton and Back succeeded in synthesizing other zeolite, using lower temperature (≈100 ℃) and higher alkalinity [4]. Later, great successful progress is recorded by discovering one of the most commercially zeolite type Linde A (LTA) [5]. After that, the applied zeolite field was integrated in all industry aspect with the use of zeolite A: (1) to substitute the phosphate in detergent. Later zeolite P and X, AX (80% A, 20% X) were also introduced into the marked for detergent [6, 7], (2) in catalysis, ion exchange, molecular sieves, photochemistry and solar energy conversion [8]. In other way, zeolite type HS was synthesized using well and poorly ordered kaolinites and metakaolinites [9]. Indeed, the experimental protocol adopted on zeolite synthesis process does not be considered like novelty but some experimental parameters as the starting material, the particle size and the preparation mode influence the resulting material andcrystallisation rate. The main objective of this workAll Rights Reserved.Effect of Alkali-NaOH Solution on the Nature of Synthesized Zeolite from 2:1 Tunisian Clays: XRD andMAS-NMR Investigation247consists of characterizing zeolite synthesis process from 2:1 Tunisian clay and demonstrating the effect of alkali-NaOH concentration on the final obtained product.2. Materials and Methods2.1 Starting MaterialsThe starting materials are originated from the region Bir El Hfay (southern Tunisia). It is an irregular interstratified illite-smectite. The < 2 µm fraction was prepared according to the classic protocol of extraction which was developed by Tessier et al. [10]. The obtained structural formula per half unit cell is: (Si 4.00)(Al 1.10, Fe 0.50, Mg 0.40)O10(OH)2(M+ 0.4) with M+ is a monovalent cation. Preliminary treatment consisted of preparing an amorphous phase by heating the host mineral. This process is assured by heating ~50 g of solid at T > 800 ℃ [11].2.2 Experimental ProtocolA total of 100 mL of a given NaOH solution was heated to 100 ℃ in 250 mL reactor provided with a refrigerant system. A total of 10 g of clay was introduced. Reaction was maintained with magnetic stirring for periods of time ranging from 2 to 24 h. The final mixture was centrifuged to 10,000 rpm. The solid phase was washed several times with distilled water until pH 9.5-10, dialyzed with distilled water and dried at 80 ℃.2.3 Characterizing Method2.3.1 XRD AnalysisPowder X-ray diffraction patterns were obtained by a BRUKER D8 Advance diffractometer using Cu-Kαradiation and the 2θ range between 5-50° and operating at 40 KV and 30 mA. The determination of the lattice parameters from the XRD patterns requires identification of the peak positions, which can normally be achieved using a peak-search process, provided that all systematic errors have been eliminated by careful measurements of the zero-point detector position. The pattern indexing was performed using the indexing software TOPAS.2.3.2 MAS-NMR AnalysisThe Magic Angle Spinning Nuclear Magnetic Resonance (MAS-NMR) spectra were recorded on a BRUKER-300 MHz Ulrashield spectrometer. Experiments were performed using a 7.1 T magnetic field intensity corresponding to resonance frequencies 78.22 MHz and 59.62 MHz respectively for the core 27Al and 29Si. Impulse period has been optimized for each signal and does not exceed some μs. The numberof accumulation is higher than 500 in the case of the core 29Si (4.6% of abundance) and about 200 for the core 27Al (100% of abundance) for the two cores (27Al and 29Si).3. Results and Discussion3.1 XRD InvestigationWe reported in Fig. 1 that the XRD spectra of the solids obtained after reaction of clay with 1N NaOH solutions during different periods of time (i.e. 2 h, 4 h and 24 h). We noted that little change is observed for reaction times (Fig. 1) of 2 and 4 h. After 24 h, new peaks appeared, the most intense ones were situated at 12.44, 17.67, 21.62, 27.97 and 33.30° 2θ (Cu-Kα). They correspond to the P-zeolite as it was described by Ref. [2]. After a reaction time of 24 h the diffraction peaks of clay became very weak.Fig. 1 Experimental XRD patterns of heated illite-smectite and 1N NaOH treated at T = 100 ℃ during (a) 2 h; (b) 4 h; (c) 24 h, phases of zeolite P.All Rights Reserved.Effect of Alkali-NaOH Solution on the Nature of Synthesized Zeolite from 2:1 Tunisian Clays: XRD andMAS-NMR Investigation248When 3N NaOH solutions were used, changesappeared after a reaction time of 4 hours (Fig. 2). A newphase appeared having the following XRD peaks, 14,24.3, 27.99, 33.28 and 34.65° 2θ (Cu-Kα), according toRefs. [12, 13], this corresponds to the HS zeolite. Fromthe comparison of the patterns reported in Fig. 2, wenoted that after 24 h of reaction, it is clear that the peaksintensity related to the HS phase increase. This is in linewith the increasing amount of the zeolite phase.3.2 MAS-NMR AnalysisAccording to the NMR study of zeolite [14], the 29Sisignal of the sample obtained from treated startingmateriel with 1N NaOH solution. Fig. 3a presents achemical shifts observed at 79.82, 86.52, 91.36, and102.97 ppm with a low intensity corresponding tozeolite P. After 24 h of alkaline treatment, the 27AlMAS-RMN spectrum in Fig. 3b shows a line ofresonance at 58.21 ppm which can be attributed totetrahedral aluminium.The 29Si MAS-NMR and 27Al MAS-NMR spectra ofHS zeolite obtained by 3N NaOH solution treatmentare reported respectively in Figs. 4a and 4b. After 24 htreatment, we obtained five lines of chemical shiftlocated at -107.35, -106.92, -97.28, -91.87, -87.25 ppmfor 29Si and -58.32 ppm for 27Al. These shifts arerelated to zeolite HS [14, 15].Fig. 2 Experimental XRD patterns of heated illite-smectite and 1.5N NaOH treated at T = 100 ℃ during (a) 2 h; (b) 4 h;(c) 24 h, phases of zeolite HS. Fig. 3 (a) 29Si MAS-NMR spectrum of zeolite P obtained from heated illite-smectites. (b) 27Al MAS-NMR spectrum of zeolite P obtained from heated illite-smectites.These results demonstrate that the concentration of alkaline NaOH solution affect the final product nature (i.e synthesized zeolite). Indeed, zeolite can be synthesized using respectively low and high concentration value of NaOH solution.The characteristics and structural parameters for all synthesized phases are summarised in Table 1.4. ConclusionsIn this work we demonstrate that zeolite P is the main crystalline products obtained when heated interstratified illite-smectite is used as a starting materials with a low value of NaOH concentration.(a)(b)All Rights Reserved.Effect of Alkali-NaOH Solution on the Nature of Synthesized Zeolite from 2:1 Tunisian Clays: XRD andMAS-NMR Investigation249Fig. 4 (a) 29Si MAS-NMR spectrum of zeolite HS obtainedfrom heated illite-smectites. (b) 27Al MAS-NMR spectrumof zeolite HS obtained from heated illite-smectites.Table 1 Characteristics and structural parameters for allsynthesized phases.Sample heated illite-smectite T > 800 ℃NaOH solution 1.5N 3NTemp (℃) 100 100Time reaction (h) 24 24XRD analysis zeolite P zeolite HSComposition of material Na6(H2O)12[Si10Al6O32]Na6(H2O)8|[Si6Al6O24]Cell parameters a = b = c = 10.043 Åα = β = γ = 90°a =b =c = 8.848 Åα = β = γ = 90°NMR spectroscopy Si/Al ratio ≈1= 1Whereas zeolite HS is obtained by increasing the amount of NaOH solution.AcknowledgmentsThe manuscript was much improved by the constructive reviews of two anonymous reviewers. The editorial assistance of the editorial staff of the Journal of Chemistry and Chemical Engineering is acknowledged.References[1]M. Murat, A. Amokrane, J.P. Bastide, L. Montanaro,Synthesis of zeolites from thermally activated kaolinite,Some observations on nucleation and growth, Clay Miner.27 (1992) 119-130.[2] D.W. Breck, Zeolite Molecular Sieves: Structure,Chemistry and Uses, Wiley, New York, 1974.[3]R.M. Barrer, Syntheses and reactions of mordenite, J.Chem. Soc. 23(1948) 2158- 2163.[4]R.M. Milton, U.S. Patent 2 882 244, 1959.[5] A. Carlos, R. Ríos, D.W. Craig, M.C. Oscar, Synthesis ofzeolite LTA from thermally treated kaolinite, Rev. Fac. Ing.Univ. Antioquia 53 (2010) 30-41.[6]R.C. Adams, L. Xu, K. Moller, T. Bein, W.N. Delgass,Zeolite encapsulated vanadium oxo species for the catalyticreduction of NO by NH3, Catalysis and Photocatalysis onMetal Oxides 33 (1-3) (1997) 263-278.[7]H.G. Hautal, Laundry, Detergent Zeolites in anEcobalance Spotligt-Sepawa, Tagung Bad Diirkheim, 1996.[8] A. Corma, C. Corell, J. Perez-Pariente, Synthesis andcharacterization of the MCM-22 zeolite, Zeolites 15 (1995)2-8.[9] D.S. Coombs, T. Whetten, Geological society of americacomposition of 4-analcime from sedimentary and burialmetamorphic rocks, GSA Bulletin 78 (2) (1967) 269-282.[10]H.B. Rhaim, D. Tessier, A.B.H. Amara, Mineralogy of the< 2 µm fraction of three mixed-layer clays from southernand central Tunisia, Clay Mineral 35 (2) (2000) 375-381.[11]M. Meftah, W. Oueslati, A.B.H. Amara, Synthesis processof zeolite P using a poorly crystallized kaolinite, PhysicsProcedia (2009) 1081-1086.[12]R.M. Barrer, E.A.D. White, The hydrothermal chemistryof silicates, part I: Synthesis lithium aluminosilicates, J.Chem. Soc. (1951) 1267.[13]I. Hassan, H.D. Grundy, The crystal structures ofsodalite-group minerals, Acta Cryst. B 40 (1984) 6-13. [14] A. Madani, A. Aznar, J. Sanz, J.M. Serratosa, 29Si and27Al NMR study of zeolite formation from alkali-leachedkaolinites: Influence of thermal preactivation, J. Phys.Chem. 94 (1990) 760-765.[15]N. Benharrats, M. Belbachir, A.P. Legrand, J.B.D’Espinose de la Caillerie, 29Si and 27Al MAS NMR studyof the zeolitization of kaolin by alkali leaching, ClayMiner. 38 (2003) 49-61.(a)(b) All Rights Reserved.。

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Experimental Investigation of Production Behavior of MethaneHydrate under Ethylene Glycol Injection in UnconsolidatedSedimentGang Li,Xiao-Sen Li,*Liang-Guang Tang,and Yu ZhangGuangzhou Center of Gas Hydrate Research,Key Laboratory of Renewable Energy and Gas Hydrate, Guangzhou Institute of Energy Con V ersion,The Chinese Academy of Sciences,Guangzhou,P.R.China510640Recei V ed December18,2006.Re V ised Manuscript Recei V ed July23,2007This article investigates the gas production behavior from methane hydrate(MH)in porous sediment by injecting ethylene glycol(EG)solution with the different concentrations and the different injection rates in an one-dimensional experimental apparatus.The results suggest that the gas production process can be divided into the four stages:(1)the initial injection,(2)the EG diluteness,(3)the hydrate dissociation,and(4)the remained gas output.Nevertheless,the water production rate keeps nearly constant during the whole production process.The production efﬁciency is affected by both the EG concentration and the EG injection rate,and it reaches a maximum with the EG concentration of60wt%.IntroductionNatural gas hydrates are solid,nonstoichiometric compounds of small gas molecules and water.1The recent seismic explora-tions and geological researches show that natural gas hydrate existing in the sediment constitutes a large natural gas reservoir2 and was considered to be a potential strategic energy resource.3,4 The formation of gas hydrate requires favorable thermodynamic conditions,such as low temperatures and high pressures,along with physical contact of natural gas and water.Techniques for gas production from hydrate reservoir are based on three major dissociation principles,i.e.,(1)depressurization,to decrease the reservoir pressure below the hydrate dissociation pressure at a speciﬁed temperature;(2)thermal stimulation,to heat the reservoir above hydrate dissociation temperature with hot water, steam,or hot brine injection;(3)chemical inhibitor stimulation, to inject chemicals,such as methanol or EG,to shift the hydrate pressure–temperature equilibrium conditions.It is essential for safely and efﬁciently producing natural gas to characterize the hydrate dissociation mechanism and multiphaseﬂowing mech-anism of dissociated gas and water in hydrate-existing sediment. Experimental investigations of hydrate dissociation behaviors under depressurization or thermal stimulation in sediment have been reported.Yousif et al.5–7developed a one-dimensional model to study depressurization-induced hydrate dissociation in berea sandstone cores and suggested that a moving boundary model provides a satisfactoryﬁt to hydrate dissociation mea-surements.Kono et al.8measured the dissociation rate of methane gas hydrate by the depressurizing method and derived the kinetic dissociation rate equation and the order of reaction. Tang et al.9experimentally investigated the temperature distri-bution,gas and water production rate,and the thermal efﬁciency during the hydrate dissociation process after the hot water injection using a one-dimensional physical model.The chemical injection is considered to be an effective gas hydrate dissociation method.However,there are only limited studies in addressing the dissociation kinetics by chemicals injection.Sira et al.10reported the characteristics of hydrate dissociation process during methanol and EG injection.They concluded that the rate of hydrate dissociation is a function of chemical concentration,injection rate,pressure,temperature of chemical solution,and hydrate–chemical interfacial area.Sung et al.11examined theﬂowing characteristics of the dissociated gas and water from hydrate in porous rock by the depressuriza-tion and methanol injection schemes,using electric resistance to distinguish the hydrate formation and dissociation.Kawamura et al.12analyzed the dissociation behavior of an artiﬁcial hydrate*To whom correspondence should be addressed:Tel8620-87057037; Fax8620-87057037;e-mail lixs@.(1)Sloan,E.D.Clathrate Hydrates of Natural Gas,2nd ed.;Marcel Dekker:New York,1998.(2)Makogon,Y.F.Hydrates of Natural Gas;Penn Well Publishing Co.:Tulsa,OK,1997.(3)Lee,S.Y.;Holder,G.D.Methane hydrates potential as a future energy source.Fuel Process.Technol.2001,71,181–186.(4)Collett,T.S.Gas hydrates as a future energy resource.Geotimes 2004,49,24–27.(5)Yousif,M.H.;Li,P.M.;Selim,M.S.;Sloan,E.D.Depressurization of natural gas hydrates in Berea sandstone cores.J.Inclusion Phenom.Mol. Recognit.Chem.1990,8,71–88.(6)Yousif,M.H.;Abass,H.H.;Selim,M.S.;Sloan,E.D.Experimental and theoretical investigation of methane-gas-hydrate dissociation in porous media.SPE Reser V oir Eng.1991,69–76.(7)Yousif,M.H.;Sloan,E.D.Experimental Investigation of Hydrate Formation and Dissociation in Consolidated Porous Media.SPE Reser V oir Eng.1991,452–458.(8)Kono,H.O.;Narasimhan,S.;Song,F.;Smith,D.H.Synthesis of methane gas hydrate in porous sediments and its dissociation by depres-surizing.Powder Technol.2002,122(2–3),239–246.(9)Tang,L.G.;Xiao,R.;Huang,C.;Feng,Z.P.;Fan,S.S.Experimental investigation of production behavior of gas hydrate under thermal stimulation in unconsolidated sediment.Energy Fuels2005,19,2402–2407.(10)Sira,J.H.;Patil,S.L.;Kamath,V.A.Study of hydrate dissociation by methanol and glycol injection.SPE Annu.Tech.Conf.Exhibit.1990, 977–984.(11)Sung,W.;Lee,H.;Kim,S.;Kang,H.Experimental investigation of production behaviors of methane hydrate saturated in porous rock.Energy Source2003,25(8),845–856.(12)Kawamura,T.;Yamamoto,Y.;Ohtake,M.;Sakamoto,Y.;Komai, T.;Haneda,H.Experimental study on dissociation of hydrate core sample accelerated by thermodynamic inhibitors for gas recovery from natural gas hydrate.In The5th International Conference on Gas Hydrate,Trondheim, Norway,2005.Energy&Fuels2007,21,3388–3393338810.1021/ef060644d CCC:$37.00 2007American Chemical SocietyPublished on Web09/19/2007core sample in methanol aqueous solution,and the experiment was carried out by varying the temperature and concentration of chemical inhibitors.The dissociation kinetics of mixed gas hydrates that contain propane as a guest molecule has been investigated as well.12Although EG is widely known as a thermodynamic inhibitor of gas hydrate,studies of natural gas dissociation in the presence of EG are limited;especially the impacts of the EG concentration and injection rate on hydrate dissociation are not well understood yet.In this work,the production behavior of MH in unconsoli-dated sediment under EG injection was studied.The experiment was carried out by varying the concentration and injection rate of the EG solution.The relationship between these two parameters and the production behavior was obtained.In addition,the efﬁciency of the gas production process during MH dissociation was determined.Experimental Section1.Experimental Apparatus.The schematic diagram for the experimental apparatus used in this work is shown in Figure 1.The hydrate vessel was immersed in an air bath to maintain a constant temperature.The vessel is made of stainless steel (1Cr18Ni9Ti)and has an internal diameter of 30mm and a length of 534mm,and it can be operated up to 20MPa.Four resistance thermometers and two pressure sensors with three differential pressure transducers were uniformly spaced,shown in Figure 1,to measure the temperature and pressure proﬁle along the vessel.The thermometers are Pt100with the range of -20to 200°C,(0.1°C.The pressure transducers are KELLER PA-21S 80400,0–20MPa,(0.25%.Two gas ﬂow meters,which were used to measure the gas injection or production rate and the cumulative gas produced from the vessel,are both of D07-11A/ZM,0–1000mL/min,(1%,from Seven Star Co.The pressure transducers,thermometers,and gas ﬂow meters were calibrated using a pressure test gauge with the error of (00.05%,a mercury thermometer with the tolerance of (001°C,and a wet gas meter with the accuracy of (10mL/min,respectively.The two balances,which were are used to measure the rates of liquid input and output,respectively,are Sartorius BS 2202S,0–2200g,(0.01g.In order to protect the metering pump from corrosion by the hot brine or chemicalinhibitors,the middle containers have been used for the solution injection.The data acquisition system records pressure,differential pressure,temperature,gas/water injection rate,and production rate.In this work,the EG used was analytically pure,and the methane gas with its purity of 99.99%was used.2.Experiments.During the experiment,quartz sand with the size range between 300and 450µm was pushed tightly into the vessel,and then the vessel was evacuated twice to remove air in it with the vacuum pump.The quartz sand in the vessel was wetted to saturation with distilled water using a metering pump.The sand sediment was saturated when the amount of water produced from the vessel was equal to the amount of water injected.It was assumed that the volume of water injected in the vessel was the total volume available in the vessel.Then the methane gas was injected into the vessel until the pressure in the vessel reaches much higher than the equilibrium hydrate formation pressure at the working temper-ature.After that,the vessel was closed as an isochoric system.The temperature was gradually decreased to form the hydrate by changing the air bath temperature.The hydrate formation was considered to be completed until there was no pressure decrease in the system.The hydrate formation process in general lasts for 2–5days.The hydrate dissociation by EG injection was carried out in the following procedures.First,the EG solution with the desired concentration was prepared in the middle containers.The back-pressure regulator was set to 3.8MPa,which is the system pressure during the hydrate dissociation process under EG injection.Then the dissociation run was started by injecting the EG solution from the middle containers into the vessel.The EG solution was cooled to the temperature in the air bath before being injected into the vessel.After injecting the EG solution for approximately 5min,hydrate began to dissociate and gas and water solution were observed to release from the vessel through the outlet valve.The gas production process lasted for 30–100min,depending on the EG concentrations and injection rates.When there was no signiﬁcant gas released,the EG injection was ﬁnished and the system pressure was released to 1atm gradually.During the entire dissociation run,the temperature and pressure in the vessel,the gas production,the amount of EG solution injected,and the water production were recorded at 2s intervals.Results and Discussion1.Hydrate Formation.Table 1provides the hydrate forma-tion conditions.The volume of the water and gas before hydrateFigure 1.Schematic plot of the experimental facility.Production Beha V ior of Methane Hydrate Energy &Fuels,Vol.21,No.6,20073389formation is equal to the total volume of water,gas,and hydrate after hydrate formation:V w1+V g1)V w2+V g2+V h2(1)It was assumed that there is 5.75mol of water in 1mol of methane hydrate,and the density of methane hydrate is 0.94g/cm 3and water in the vessel is incompressible.The volume of the gas in the vessel after hydrate formation was calculated by the pressure and temperature conditions in the vessel using the Peng–Robinson equation.The inlet and outlet pressures of the vessel change simulta-neously due to the high porosity and permeability of the sediment,so the pressure in the vessel in this work takes the average of the inlet and outlet pressures.Figure 2shows a typical experimental result of the pressure and temperature proﬁles with time during MH formation in the sediment.It can be seen from Figure 2that the pressure proﬁle during MH formation could be divided into four sections.In section I (0–175min),the temperature decreased from 17.0to 2.0°C in isochoric condition,and the pressure decreases from 5.4to 5.1MPa due to the gas adsorption on porous the quartz sand and the gas contraction in the vessel.After section I,the closed system was maintained at a constant temperature (2.0°C)until the end of the experiment.In section II (175–280min),the pressure of the closed system was above 5.0MPa,which was much higher than the pure hydrate equilibrium pressure of 3.5MPa at 2.0°C.1This section was considered to be the hydrate nucleation process,and in this period of time there was no hydrate formed in the vessel.13Section III is the hydrate formation process.In this section,the pressure gradually decreased due to the gas consumption during the hydrate formation,and this section takes much longer time than sections I and II.In the last section (section IV),no further pressure decrease was observed,and the system was maintained at a constant temperature.Hence,the system reached the thermo-dynamic stable state.A total of seven experimental runs of hydrate dissociation by EG injection have been carried out.Run 0as the blank experiment,which injected the distilled water instead of EG solution,was used to eliminate the inﬂuence of the gas production by the liquid injection.Table 2provides the experimental conditions during hydrate dissociation by EG injection,including the EG injection rate,the EG concentration,and the average pressure and temperature during MH dissocia-tion.The hydrate dissociation runs in Table 2were related to the formation runs in Table 1.2.Temperature Distribution in the Vessel during EG Solution Injection.Before injected into the vessel,the EG solution was cooled by the coil in the air bath.In an unstirred system,such as the vessel used in the experiment,it is difﬁcultfor the methane gas and water to form methane hydrate completely.Hence,only a little hydrate was formed,and most of the water or gas remained in the vessel.Besides,the existing quartz sand disperses the formed hydrate.Thus,the temperature neither sharply increases in the process of methane hydrate formation shown in Figure 2nor sharply decreases in the process of methane hydrate dissociation.So the temperature in the vessel remained constant during EG solution injection.The inlet (port 1)and outlet (port 4)temperature in the vessel during the EG injection for run 3is shown in Figure 3,and the temperature proﬁles for all other runs show a similar trend with run 3.3.Gas and Liquid Production Rate during EG Solution Injection.The gas production rate for whole produc-tion process for run 5,which is a typical one,is shown in Figure4.The gas production rates for other runs show the similar characteristics.As shown in Figure 4,the process of the hydrate dissociation with the EG injection in one-dimensional vessel can be divided into four main sections.In section I,the free methane gas in the vessel was released.This caused the sudden increase of instantaneous gas release rate,up to 800mL/min.After the free gas released,the gas production rate decreased and remained at about 30mL/min.This section is considered to be section II.In sections I and II,the EG was diluted by the remaining water in the vessel after hydrate formation,and there were little hydrate dissociated due to the low concentration of EG solutions.With further injection of the EG,the concentration of the EG solution in the vessel increased gradually.The EG is a hydrophilic chemical that lowers the activity of water and destroys the structure of the hydrate.When the EG concentration increased high enough to make the hydrate dissociate,the gas production rate suddenly increased to about 100mL/min,which indicated that the hydrate in the vessel began to dissociate.This is the hydrate dissociation section (section III).The dissociation section lasted approximately 25min,which is the longest time among(13)Fan,S.S.;Zhang,Y.Z.;Tian,G.L.;Liang,D.Q.;Li,D.L.Natural gas hydrate dissociation by presence of ethyleneglycol.Energy Fuels 2006,20,324–326.Table 1.Formation Conditions of Hydrate Related to the Study of Hydrate Dissociation by EG Injectionexperimental runs1234567initial pressure (MPa) 5.403 5.519 5.488 5.476 5.306 5.311 5.416 5.409initial temperature (°C)17.8317.8918.0117.7117.8317.4617.7717.95ﬁnal pressure (MPa) 3.556 3.502 3.467 3.480 3.557 3.566 3.516 3.486ﬁnal temperature (°C)1.97 1.92 1.81 1.922.00 2.07 1.81 1.73ﬁnal amount of water (mL)43.7347.5346.2245.5342.1841.9542.9243.26conversion of gas to hydrate (%)33.0336.7736.8236.2231.4431.4933.8334.52hydrate content (vol %)7.338.168.178.046.986.997.517.66Figure 2.Pressure and temperature proﬁles during hydrate formation in isochoric experiment.3390Energy &Fuels,Vol.21,No.6,2007Li et al.the four sections,as shown in Figure 4.Section IV was the last section of the experiment,with remaining gas released.Table 3provides the run time and gas produced from hydrate dissociation by EG injection for all runs.The EG injection time is from the beginning of EG injection to the end of hydrate dissociation.Onset time for hydrate dissociation is the starting point of section III,and the duration of hydrate dissociation is the length of time of section III.For example,in run 5in Figure 4,the onset time for the hydrate dissociation section is 8min and the end of this section is 32min,resulting in the duration of hydrate dissociation of approximately 24min.The gas production ratio is deﬁned as the ratio of the amount of gas generated from hydrate in the hydrate dissociation section and the initial amount of gas contained in all hydrate excluding the free gas in the vessel.Total gas produced after EG injection is also given in Table 3.The rate of hydrate dissociation by EG injection is a function of EG concentration,injection rate of EG solution,pressure,temperature of the system,and hydrate–EG interfacial area.10In this work,the pressure,temperature,and the EG injection rate remained constant after the EG injection.The instantaneous gas production rates during the whole process were unsteady,as shown in Figure 4,while the hydrate dissociation rate decreased continuously with time,as illustrated by a typical run (run 5)in Figure 5.The hydrate dissociation rate was calculated by the gas production rate of section III in Figure 4,in which the gas production was caused by the hydrate dissociation at the certain pressure and temperature.Figure 6shows the effect of the EG injection rate on the cumulative gas produced from hydrate dissociation as a function of time for runs 1–3.The cumulative gas produced from the vessel was measured by the gas ﬂow meter in Figure 1.In runs 1–3,the EG concentration was kept the same at 30wt %,and the injection rate was varied from 4.9to 8.8mL/min.As shown in Figure 6,in general,with the increase of the EG injection rate,the cumulative gas produced increased.As the EG injection rate increase,there were more EG injected into the vessel at the same time,which increased the hydrate–EG interfacial area and stimulated more hydrate dissociate at the same time.Thegeneral trend for gas production rate proﬁle is similar in runs 1–3,but the onset time and duration of hydrate dissociation section are all different with different EG injection rate.As shown in Table 3,from run 1to run 3,the duration of hydrate dissociation section decrease from 73to 35min,while the gas production ratio increased from 38.9%to 50.6%.Figure 7shows the effect of the EG concentration on the cumulative gas produced from hydrate dissociation as a function of time for ﬁxed injection rate (runs 3–7).From runs 3to 7,the EG injection rate was maintained the same at 8.8mL/min and the EG concentration was varied from 30to 70wt %.Run 0was the blank experiment,which injected the distilled water instead of EG solution,with the same injection rate as runs 3–7.Although the general trend for gas production rate proﬁle is similar in runs 3–7with the same EG injection rate,the duration of hydrate dissociation decrease as the EG concentration increased from 30to 70wt %.As shown in Table 3,from runs 3to 7,the gas production ratio increased from 50.6%to 96.2%.The gas production ratio is larger than 90%while the EG concentration is over 60wt %during hydrate dissociation.On the other hand,the EG injection time for all runs are different,which decreases with the increase of injection rate and concentration of the injected EG solution in general.The EG injection and the solution production rate proﬁles are much simpler than that of the gas production,and Figure 8gives a typical proﬁle (run 5).The solution produced from the outlet of the vessel was composed of the EG solution,water in the vessel before EG injection,and water produced from the hydrate dissociation.From Figure 8,the EG injection rate kept nearly constant for the whole production process,while there was ﬂuctuation for the solution production rate due to the unsteady state during the hydrate dissociation process under the chemical stimulation.4.Production Efﬁciency Analysis.The efﬁciency of pro-ducing gas from hydrate by EG injection is investigated here.In order to compare the efﬁciency of different runs,the production efﬁciency has been deﬁned as the ratio of the volume of produced gas to the mass of EG injected in unit time.Under the EG stimulation,the hydrate dissociated only on the hydrate dissociation section (section III shown in FigureTable 2.Experimental Conditions during Hydrate Dissociation by EG Injectionexperimental runs1234567EG injection rate (mL/min)8.8 4.9 6.88.88.88.88.88.8EG concentration (wt %)030303040506070pressure (MPa) 3.889 3.862 3.926 3.862 3.864 3.85 3.901 3.825temperature (°C)2.0431.6452.0151.9852.0611.9012.0101.846Figure 3.Inlet and outlet temperature during the EG injection for run 3.Figure 4.Gas production rate for run 5.Production Beha V ior of Methane Hydrate Energy &Fuels,Vol.21,No.6,200733914).Table4shows three production efﬁciencies:(1)production efﬁciency for hydrate dissociation section(section III)(mL g-1 min-1);(2)production efﬁciency at50%hydrate dissociation (section III)(mL g-1min-1);(3)production efﬁciency for whole injection process(sections I–III)(mL g-1min-1).Theﬁrst one was calculated with the volume of gas,the mass of EG injected,and the duration time of the hydrate dissociation section(section III in Figure4).It can be used to measure the gas production efﬁciency of hydrate dissociation process by the effect of EG in section III.The second one was calculated the same way with theﬁrst one,while it used the values of50%hydrate dissociation point. In this work,the hydrate dissociation runs were divided into four sections,and the hydrate dissociation only happened in section III.The amount of dissociated hydrate was measured by the gas volume released from the vessel in section III.So 100%hydrate dissociation point was the end of section III,when the gas produced from hydrate dissociation all released from the vessel.In the same way,50%hydrate dissociation point was some time in section III,when50%gas produced from hydrate dissociation.Both theﬁrst and second production efﬁciencies were calculated on the basis of the experimental result of section III (the hydrate dissociation section).The third one was used to measure the whole experimental runs,from the beginning of EG injection to the end of the hydrate dissociation process,which includes sections I–III. The formation conditions of hydrate used in the work was same for all runs,including pressure,temperature,amount of water,and the hydrate content in the vessel.For all EG injection runs,the impact of the hydrate content,the amount of water and free gas in the vessel,and the difference of the operating conditions(including the pressure and temperature) during EG injection were all eliminated,while the impact of the EG concentration and injection rate on the production efﬁciency is reﬂected in Table4.As shown in Table4,the production efﬁciency for the whole EG injection process was between0.20and0.88mL g-1min-1,while the efﬁciency for hydrate dissociation section was between0.12and0.80 mL g-1min-1.But the production efﬁciency at50%hydrate dissociation was much higher,with the maximum of2.03 mL g-1min-1.Table3.Run Time and Gas Produced from Hydrate Dissociation by EG Injectionexperimental runs01234567 EG injection time(min)107714333322924 onset time for hydrate dissociation(min)342186874 duration of hydrate dissociation(min)73503527242220 gas produced from hydrate(mL)977108812521547180021942268 gas production ratio(%)38.943.350.672.183.795.096.2 gas produced after EG injection(mL)3496333440253210393341803368Figure5.Hydrate dissociation rate for run5.Figure6.Cumulative gas produced during the hydrate dissociation for runs1–3.Figure7.Cumulative gas produced during the hydrate dissociation for runs3–7.Figure8.Solution injection and production rate proﬁle for run5.3392Energy&Fuels,Vol.21,No.6,2007Li etal.From the efﬁciency analysis,the following conclusions can be drawn:(1)the production efﬁciency of the hydrate dissocia-tion section,50%hydrate dissociation,and the whole injection process varied with the EG concentration and injection rate, and the variation presented the same trend.(2)The hydrate dissociation rate decreased as the experiments go on,as shown in Figure5.This can explain why the efﬁciencies at50%hydrate dissociation were all higher than that of the whole injection process.(3)With the increase of the EG injection rate,the production efﬁciency increases,as runs1–3.The production efﬁciencies for hydrate dissociation section of runs1–3increase from0.12to0.50when the injection rate increase from4.9to 8.8mL/min.(4)The EG concentration also inﬂuences the production efﬁciency,as runs3–7.From the result shown in Table4,there was a maximum point for the EG concentration on the production efﬁciency with the same injection rate(9mL/ min),as run6with60wt%EG solution.With the increase of the EG concentration,the gas production rate increases,as the result shown in Figure7.While the mass of EG injected into the vessel increases with the increase of the concentration,the production efﬁciency reaches a maximum of0.80in run6.The same result was also concluded on the production efﬁciency at 50%hydrate dissociation and the whole production process including the free gas release section.ConclusionsIn this study,the experimental apparatus was set up to investigate the production behavior of MH dissociated from unconsolidated porous sands by EG injection.From the experimental results,the following conclusions were drawn:(1)During hydrate formation,a typical pressure–time curve can be divided into four sections,which correspond to temper-ature decrease,hydrate nucleation,crystal growth,and stable state of MH in the vessel.(2)After the EG injection,the hydrate dissociation in the vessel can be divided into four sections,that is,the free gas producing section,EG diluting section,the hydrate dissociating section,and the remnant gas producing section.(3)The gas and water production rate were both unsteady during hydrate dissociation rate decreasing continuously with time under the EG stimulation,while the EG injection rate kept nearly constant for the whole production process.(4)Under the experimental conditions,with the EG injection rate increasing,the gas production ratio increased,the duration of hydrate dissociation shortened,and the production efﬁciency increased.(5)Under the experimental conditions,with the EG concen-tration increasing,the gas production ratio increased and the duration of the hydrate dissociation process shortened.The EG concentration also affects the production efﬁciency.The produc-tion efﬁciency for the whole EG injection process increased with the EG concentration increasing from0to60wt%,and after that the production efﬁciency began to decrease. Acknowledgment.This work is supported by the National High Technology Research and Development Program of China(No. 2006AA09A209,No.2006AA05Z319),the National Natural Sci-ence Foundation of China(No.20676133),and the Natural Science Foundation of Guangdong(No.06020461),which are gratefully acknowledged.EF060644DTable4.Production Efﬁciency Analysis for the Hydrate Dissociation by EG Injectionexperimental runs01234567 production efﬁciency for hydrate dissociation section(section III)(mL g-1min-1)0.120.280.500.570.600.800.76 production efﬁciency at50%hydrate dissociation(section III)(mL g-1min-1)0.44 1.32 1.60 1.61 1.75 2.03 1.53production efﬁciency for whole injection process (sections I–III)(mL g-1min-1)0.200.310.790.790.810.880.86Production Beha V ior of Methane Hydrate Energy&Fuels,Vol.21,No.6,20073393。