The New Generation Reaction Calorimeter for iso and non-isothermal Heatflow and Heatbalance Calorimetry

二十多年来，德国安娜泰克有限公司（AnaTec Deutschland GmbH）一直致力于在线及实验室用颗粒图像分析技术的研究与生产，开发出一系列针对不同应用领域的高性能分析仪器。前身为Norsk Hydro集团的研发机构，安娜泰克采用了比常规图像分析方法更为先进的专利技术，为终端客户量身定制，提供颗粒图像分析的全套解决方案，包括硬件配置，软件设计，系统安装，技术支持及反馈。安娜泰克的所有产品结构牢固，操作简单（兼容LIMS系统），在建筑材料，食品工业，矿物加工，制药原料，石油石化等领域有着广泛的应用前景。

Introduction Nucleic acids are common targets for antiviral, anticancer, and antibiotic drugs. DNA-binding drugs are designed to modulate gene activity, and RNA-binding drugs inhibit protein translation. In order to optimize the efficacy of drugs, as well as discover new drugs, it is important to fully characterize the drug-nucleic acid interaction, including sequence recognition, structural details and the thermodynamics of binding. Microcalorimetry is a tool used to determine the thermodynamics of intermolecular binding. Both Isothermal Titration Calorimetry (ITC) and Differential Scanning Calorimetry (DSC) are used to elucidate thermodynamic details of nucleic acid-drug interactions. Thermodynamics, when used in conjunction with structure, sequence, and computational methods, can be used to optimize drugs to bind specific sequences and/or structures of nucleic acid targets. This application note will review the use of calorimetry to study the thermodynamics of drug-nucleic acid binding. For more information, refer to cited references. Several excellent review articles are also available on this topic (References 1-5).

Introduction Sometimes I am being asked: “What is the difference between the Calo 2000 principle and an RC1, an HELSimular, or even our own calorimeters SC1 ... SC4?” The answer is: “The Calo 2000 principle is the first reaction calorimeter commercially available, which allows for the recording of chemical power in absolute Watt and which exhibits practically no time error - except the filter time constant of 60 sec. for the evaluation of the measurement.” To achieve this the baseline has to be set to 0 W exactly. Due to various interferences (temperature ramp, dosing etc.) this is not always possible

Water activity is defined as the current volume and availability of “free” water in a sample and should not be directly compared with the water content (g water/ g substance). The water activity is given as the aw – value and ranges between 0 (absolute dryness) and 1 (condensed humidity). Only this component takes an active part in the exchange with the ambient humidity and can possibly form the ideal medium for microbiological growth on the surface which influences the microbiological stability. The water activity also has an important effect on the chemical reactions in food.

Water activity is defined as the current volume and availability of “free” water in a sample and should not be directly compared with the water content (g water/ g substance). The water activity is given as the aw – value and ranges between 0 (absolute dryness) and 1 (condensed humidity). Only this component takes an active part in the exchange with the ambient humidity and can possibly form the ideal medium for microbiological growth on the surface which influences the microbiological stability. The water activity also has an important effect on the chemical reactions in food.

Aluminum is a known neurotoxic agent and its neurotoxic effects may be due to its binding to DNA. However, the mechanism for the interaction of aluminum ions with DNA is not well understood. Here, we report the application of isothermal titration calorimetry (ITC), fluorescence spectroscopy, and UV spectroscopy to investigate the thermodynamics of the binding of aluminum ions to calf thymus DNA (CT DNA) under various pH and temperature conditions. The binding reaction is driven entirely by a large favorable entropy increase but with an unfavorable enthalpy increase in the pH range of 3.5–5.5 and at all temperatures examined. Aluminum ions show a strong and pH-dependent binding affinity to CT DNA, and a large positive molar heat capacity change for the binding, 1.57 kcal mol
1 K
1, demonstrates the burial of the polar surface of CT DNA upon groove binding. The fluorescence of ethidium bromide bound to CT DNA is quenched by aluminum ions in a dynamic way. Both Stern–Volmer quenching constant and the binding constant increase with the increase of the pH values, reaching a maximum at pH 4.5, and decline with further increasing the pH to 5.5. At pH 6.0 and 7.0, aluminum ions precipitate CT DNA completely and no binding of aluminum ions to CT DNA is observed by ITC. Combining the results from these three methods, we conclude that aluminum ions bind to CT DNA with high affinity through groove binding under aluminum toxicity pH conditions and precipitate CT DNA under physiological conditions.

Severe acute respiratory syndrome (SARS) coronavirus is a novel human coronavirus and is responsible for SARS infection. SARS coronavirus 3C-like proteinase (SARS 3CLpro) plays key roles in viral replication and transcription and is an attractive target for anti-SARS drug discovery. In this report, we quantitatively characterized the dimerization features of the full-length and N-terminal residues 1–7 deleted SARS 3CLpros by using glutaraldehyde cross-linking SDS-PAGE, size-exclusion chromatography, and isothermal titration calorimeter techniques. Glutaraldehyde cross-linking SDSPAGE and size-exclusion chromatography results show that, similar to the full-length SARS 3CLpro, the N-terminal deleted SARS 3CLpro still remains a dimer/monomer mixture within a wide range of protein concentrations. Isothermal titration calorimeter determinations indicate that the equilibrium dissociation constant (Kd) of the N-terminal deleted proteinase dimer (262
M) is very similar to that of the full-length proteinase dimer (227
M). Enzymatic activity assay using the fluorescence resonance energy transfer method reveals that N-terminal deletion results in almost complete loss of enzymatic activity for SARS 3CLpro. Molecular dynamics and docking simulations demonstrate the N-terminal deleted proteinase dimer adopts a state different from that of the full-length proteinase dimer, which increases the angle between the two protomers and reduces the binding pocket that is not beneficial to the substrate binding. This conclusion is verified by the surface plasmon resonance biosensor determination, indicating that the model substrate cannot bind to the N-terminal deleted proteinase. These results suggest the N terminus is not indispensable for the proteinase dimerization but may fix the dimer at the active state and is therefore vital to enzymatic activity.

摘要：用测定游离水量的方法表征水泥浆稳定性不能反映水泥浆悬浮体系的稳定性随时间的变化。本文介绍了一种用TURBISCAN MA2000悬浮/乳化液稳定性分析仪测试水泥浆动态稳定性的新方法。该方法把静置水泥浆分成上层清液区、中间特征区和底部沉淀区，发现中部特征区的水泥颗粒浓度的分布随着外加剂改变。

稳定性是研究添加颜料后的喷墨打印机墨水配方的一个关键因素。颜料颗粒由于和连 续相的密度不同，很容易在体系中有沉降现象发生。由于喷墨管的结构特征，墨水沉 降这个现象并不容易通过增加黏度来克服。同时也会有聚合现象发生。所有这些过程 都能被Turbiscan稳定性分析仪定量的监控。分析过程可以在真实体系中进行，无须 稀释。也可以通过温度控制（AGEING STATION），来加速分析过程。

改变水/非离子表面活性剂/油体系中的浓度，研究不同配比对形成乳液颗粒大小的影 响。我们选择的表面活性剂研究对象为Span20，Span80,Tween20,Tween80。实验证明 ，复合表面活性剂溶液与单一表面活性剂相比，性能更高。实验研究了复合表面活性 剂的最佳配比，通过专用仪器TURBISCAN动态光散射手段，分析微米乳液，纳米乳液 的形成规律及其稳定性。测得平均乳液粒径30~120纳米，得出规律水浓度越高，粒径 越大。另一方面，纳米乳液的稳定性也可以通过动态光散射方法进行分析，得出乳液 平均粒径与稳定性的相关规律。对于水相浓度较低的体系，纳米乳液破乳主要由于奥 斯特瓦尔德熟化，对于水相浓度较高的体系，纳米乳液破乳主要由于液滴聚合长大。

Water is an important basic element in foods. For a long time, the industry has known how important it is to check free water. The water activity (aw) measurement forms the basis of this and provides important information about the quality of a product. Finally it provides information regarding the possibility of microbiological growth on the surface. Only with this conclusions can be made about the stability and durability of a sample

Examples of aw-measurements around the world, classified by the approximative aw-range: aw: 0.95 fresh fish, fresh meat, fresh and canned vegetables and fruits, butter, sausages, milk, mayonnaise, bread 0.90 cheese (Swiss, Cheddar, Muenster), cured ham, fruit concentrates 0.85 fermented sausages (salami), processed cheese, fruit cakes, dry sausages, orange juice concentrates, margarine 0.80 fruit juice concentrates, syrups, flours, bakery goods 0.75 jams, condensed milk, marmelade, marzipan 0.70 molasses, dried figs, salted fish 0.65 nuts, raw cane sugar, jelly 0.60 cereals, dried fruits, caramel, ground coffee, liquorice, parmesan / sprinz type cheese 0.50 honey, pasta (noodles, ravioli), chocolate, confectionaries, chewing gum, herbs, spices 0.40 cocoa, egg powder 0.30 dried potatoes, crackers, biscuits, cookies, corn flakes, soup powder, stock cubes 0.20 dried milk powder, dried vegetables 0.10 freeze dried products, Nescafé, pharmaceutical powders (down to 0.03aw)

Christensen T., Gooden D. M., Kung J. E., and Toone E. J. (2003) Additivity and the physical basis of multivalency effects: a thermodynamic investigation of the calcium EDTA interaction. J Am Chem Soc 125, 7357-7366. Abstract: To better understand the origin of multivalency effects in ligand binding, the binding of a series of mono-, bi-, tri- and tetravalent carboxylate ligands to Ca(II) was examined by isothermal titration calorimetry (ITC). The data are inconsistent with an entropic origin of enhanced affinity, but rather show that at least in this instance the multivalency effect is enthalpic in origin. Analysis of binding data using the Jencks model shows the addition of incremental carboxylate "ligands" produces an unfavorable interaction entropy that is more than offset by a strongly favorable interaction enthalpy. The most likely source of this interaction enthalpy is the relief of repulsive Coulombic interactions in the unbound state. The conformational entropy penalty arising from the restriction of flexible dihedrals is negligible, within experimental error. On the other hand, an enthalpic contribution from linker restriction contributes strongly to the overall thermodynamics of ligand binding. Together, these data suggest that enthalpic effects dominate ligand binding, and design strategies should seek to optimize these interactions. The incorporation of unfavorable interactions in the unbound ligand that are relieved during binding provides an important mechanism by which to enhance ligand affinities.

RNA helical junctions are common in RNA structures, including ribozymes, mRNA untranslated regions, rRNAs, and regulatory RNAs.?RNA junctions are also in complex with proteins.?However, little was known about the thermodynamic forces that drive the folding of RNA junctions, and it is difficult to dissect these forces for several reasons, including non-two-state folding, secondary and tertiary folding components are superimposable, and opposing enthalpic and entropic contributions to RNA folding.?The authors used Isothermal Titration Calorimetry (ITC) to study the folding of hammerhead ribozyme, a three-way RNA helical junction.?In their work, they had RNA in both the ITC cell and syringe, and during titration, both RNA stands annealed to form complete folded bimolecular ribozyme. This approach was different than other published ITC research on hammerhead ribozymes, which titrated concentrated MgCl2 into unimolecular hammerhead ribozyme, and measured Mg2+ binding (Hammann, C., Cooper, A., Lilley, D.M., Biochemistry 40, 1423-1429, 2001).

Background This paper was chosen for it’s technical novelty and the application area. Review. · Some classic protein biophysics used to address a very important and highly ‘fundable’ process, namely amyloidosis, which can be the cause of very common diseases. · ITC used to study a polymerisation process by titrating protein nucleation ‘seeds’ with monomeric protein · The protein understudy is immunologically important and can be found in monomeric form in the blood. It is only a problem once it starts to form fibrils. · DSC was employed for classical reasons i.e. protein unfolding. Amyloidosis is an areas where many classical protein unfolding people have found a good source of funding and applicability of protein biophysics. · CD was also used but in addition it is nice to see a calorimetric paper with Electron microscopy and classic ‘wet’ biochemistry. · ITC was used to obtain equilibrium thermodynamic data but also to measure the rates of polymerisation i.e. as a kinetic tool. The event was slow and accessible by ITC. · The DCp and DH of fibril formation were compared to that of the native, monomeric protein. The DCps were similar but the DHs were very different suggesting that the fibrils are more loosely packed and have a larger number of cavities than the native protein.

Applications of Differential Scanning Calorimetry (DSC) in the Development of Liquid Formulations for Protein Biopharmaceuticals

刚使用该扫描仪时人们似乎对数据图形感到有点儿复杂,本文的目的就是帮助你解释及理解分析仪得的数据及图形.它细分几个步骤介绍,这样比较容易阐明也更有效果.

酸奶（或酸奶酪）是用带菌牛奶的移植，温度在42度C到44度C之间不断生长且丢弃一些乳酸而制得。这个乳酸是负责使酪蛋白束胶凝结成一体从而使牛奶凝胶成酸奶。这个凝结过程的研究常常是用一个PH测量来完成。然而，PH值的变化是十分小的（从4.5-6.5）而且在实际过程中只给了很少的信息。

背景描述 粉体涂料– 它是具有保护性的及装饰性的物质，或两者特性都具有的物质– 这种物质是应用涂料粉体加到底层上形成, 然后利用热能或辐射能熔化涂料到一种连续的薄膜. 涂料粉体被精细分成有机聚合物粒子, 有机聚合物一般包含颜料,填料及添加剂, 它们在适当地条件下储存并且存储时要精细地分开. 它和水性涂料相反, 水性涂料可能含有挥发性的有机溶剂, 而它能达到和水性涂料相同或更好的特性, 比如质量好, 经久耐用, 及抗腐蚀等等特性. 生产成本比液体涂料要低, 因为粉体涂料的生产是一个高效率的过程且需要的能源及劳动力少. 因为粉体涂料没有挥发性有机溶剂, 它的更吸引人的好处是消除了有机溶剂的散发及降低了废物处理的成本. 一种粉体涂料的性能是受各种因素影响的. 粉体粒子的尺寸大小可以对生产过程许多阶段中的性能有一个主要的影响, 包括处理, 装料, 递送, 及涂料特征化等过程. 涂料的配方是不同的, 它取决于应用时的各种情况的要求, 比如涂层的厚度, 被涂物体的形状, 及周围环境条件.

背景描述 聚合物科学包含有几种科学性的学科– 有机化学, 胶体科学, 和生物化学. 聚合物分子, 包括塑料, 树脂, 蛋白质, 晶格(lattices), 及核酸, 全归为高分子重量的种类中, 它们是由较小的分子单位重复地构成的. 这些物质通常有天然的, 或是人工的有机物源.

水可以分散和溶解许多种化合物. 有一种可溶解于水中的离子种是氯化钠, 由于水的电解性质的特点氯化钠可以容易地将它分成单个带电的原子（离子）, 它就成为水合物(溶剂化物). 电解常数(D)是反比于离子之间的距离此时离子之间的吸引力是正比于离子电荷的. 因而水(电解常数D=80)就容易溶解氯化钠而盐是不溶解在苯中的(苯的电解常数D=2.3).

· This paper discusses the identification of a peptide substrate for molecular chaperone Hsp40 Ydj1 using combination of phage display library screening and ITC · Molecular chaperone heat shock protein 40s (Hsp40s) play roles with Hsp70s to promote protein folding, assembly, translocation, degradation, and prion propagation. Hsp40 proteins interact with hydrophobic side chains of non-native polypeptides to prevent the non-native polypeptides from aggregating. Mechanism for binding is not understood

TOC made easy Concept The concept of the high temperature TOC analyzer liquiTOC includes a separation of matrix compounds like salts or non combustible particles which is important to protect the catalyst from being poisoned or blocked. On the other hand a dynamic heating process allows high sample volumes up to 4ml thus giving a high sensitivity for low level TOC measurements. The basic concept of the instrument is shown in fig. 1. Summary The concept of matrix separation offers new applications for routine TOC analysis. The dynamic sample heating enables not only an effective matrix separation, it is as well possible to run high sample volumes up to 4 ml which was beyond the possibilities for high temperature TOC analyzer up to now. References [1] Verordnung über die Qualität von Wasser für den menschlichen Gebrauch –TrinkwV 2001, Bundesministerium für Gesundheit [2] Guidelines for the determination of total organic carbon (TOC) and dissolved organic carbon (DOC) in water, EN 1484, European Committee for Standardization, 1997

Nanotechnology and Biotechnology Particel Size. Measurement Solutions, High Speed and High Efficiency Dynamic Light Scattering.

不可溶解于水的性能允许类脂物进入特殊的化学键, 这种特殊化学键产生像血脂蛋白, 细胞膜, 胶束(胶态分子团)和脂质体.本论文着重描写脂肪蛋白质和胶束在或是稀释或是浓缩液体环境中的脂质体粒子的测量.

Accuracy and precision have distinct meanings. Generally, accuracy refers to the ability of an analytical device to provide a measurement that is within a defined error from an established, true, and verifiable value. Precision is a measure of the recurrence of a value whether it is accurate or not. Two types of precision can be described: repeatability and reproducibility. In terms of particle size measurement, repeatability refers to the ability of an instrument to repeat its own measurement while the same sample resides in the circulating system. Reproducibility, on the other hand, is related to the comparison of two or more instruments in which representative samples are introduced to each of the instruments. Repeatability is statistically more variation-free than reproducibility because a single instrument measures the same recirculating sample when fluid suspended particles are measured. 准确度和精密度是两种不同的概念。通常地，准确度是指分析仪器提供在一定误差测量范围内的准确性，而精密度是对数值的准确性的重复测量。精密度的两种类型可描述为：重复性和重现性。 对于粒度测量，重复性是指在分析仪器的循环系统内的样品不断地重复同一种测量方法，另一方面，重现性是指两种或多种分析方法对样品的测量结果的比较。从统计学来说，对于一种分析方法测量悬浮液颗粒样品时，重复性比重现性更可变。

Light has properties that can be used for determining particle size and particle size distributions. In the case of diffraction instruments, such as the Microtrac S3500, the angle at which the light is diffracted depends upon the wavelength of the light and the particle size. The angle of diffraction is measured to determine size. For a particular particle size, should the wavelength change, the angle will change. There is another feature of light that can be used for determining the particle size – it is the frequency. Frequency is a measure of how many waves pass through a given point during one second. The more waves that cross the point or the closer the distance between the waves, the higher the frequency. Frequency change or shift information is used in Dynamic Light Scattering.

Microtrac has played a leading role in the development of light scattering particle size measurement. Commencing 25 years ago, diffraction measurements have been central to the Microtrac product line. A description of the basic diffraction concepts and the technology used in the S3500 is presented below.

美国康塔仪器公司及NOVA系列自动比表面和孔隙度分析仪 康塔(Quantachrome)是著名的当代颗粒技术开创者。三十年来，康塔(Quantachrome)的科学家革新了测量技术并设计了相应的仪器，使得粉体及多孔物质的测量更加精确、精密，更加可靠。这包括比表面测量、孔径分布、化学吸附研究、真实粉体密度、压汞法孔隙度测量等。 美国康塔公司产品自1998年正式在中国推广以来，以其鲜明的特点和性能价格比及其出色的服务占据了同类产品中国市场的50%。 康塔(Quantachrome)被公认为是对样品权威分析的优秀供应商，它可为实验室提供全套装备及完美的粉末技术，及最佳的性能价格比。康塔公司不仅通过了ISO9001及欧洲CE认证，也取得了美国FDA IQ/OQ认证。 康塔公司的专利产品NOVA系列是全方位的高质量、高性能的比表面和孔隙度分析仪，可满足任何研究或质控实验室的需要。结合专利投气程序，可节约分析时间约30%，并大大节约了占地空间，是世界上唯一既能进行比表面和孔隙度分析，也能实现真密度测量的分析仪。 NOVA系列独一无二的特征包括： l 专利技术，无需氦气，降低了分析费用 l 真空和流动两种标准脱气方式 l 分析站数可达4个，各站独立运行 l 唯一机械泵条件下进行微孔分析，实际碳样品微孔分析至0.3nm (x200系列，CO2/DFT法) l 唯一可进行真密度分析 l 可进行统计厚度比表面（STSA）, 微孔面积, 微孔体积, 平均吸附能,统计厚度, 超临界吸附分析 l 唯一可计算分形维数，判断孔型 l NOVA x200型可使用绝大多数非腐蚀性吸附气，如Ar、 CO、 CO2、 CH4、 C2H6 等。 l 仪器操作可脱离计算机控制，进行问答式菜单操作 l ACC II 码存储数据文件，可用其他软件处理 l 符合美国FDA 21 CFR Part 11 最新标准 （ NOVA4200P） 2002年最新NOVA-Win 软件（选件）： l 仪器控制及实时等温曲线观察 l 吸附及脱附等温曲线 l BET , Langmuir, DR, DA, BJH, DH, MP l NLDFT, GCMC l 分形维数: NK, FHH l 开放软件，无软件狗 文章介绍了在燃料电池开发中的最新应用成果