面向半导体湿法制程的超洁净流控技术综述

湿法工艺作为半导体工艺的重要组成部分,通过化学品(酸、碱、溶剂等)与超纯水等液体介质,对晶圆表面进行刻蚀、清洗等处理,其制程需避免颗粒、金属、离子、细菌等污染物带来的工艺缺陷。为此,湿法工艺相关的化学品系统、超纯水系统与制程装备均需采用超洁净流控部件,但相关产品被国外垄断,我国对该技术领域的研究仍处起步阶段。该研究首先阐述了半导体湿法制程对超洁净流控部件的需求,剖析了该类部件的主要技术特征。进而,重点介绍了磁悬浮泵、波纹管泵、隔膜阀以及超声波流量传感器等超洁净流控部件的工作原理与发展历程,并分析了其关键技术与研究现状。最后,对超洁净流控技术的发展做出了展望。     

Methods for data readout,acquisition, and transfer in experimental nuclear physics setups (<Emphasis Type="Italic">A review,part 2</Emphasis>)

The aim of this review is to provide, whenever possible, a complete picture of the evolution of methods and systems for data readout, acquisition, and transfer at experimental nuclear physics setups over recent years for specialists who use electronics in experiments or measurements in applied research. In view of the large body of information, this review is divided into two parts; medium (according to the contemporary measures) and large systems for nuclear physics setups and accelerator experiments are considered in this, the second, part. Both parts have a common classification table and common numbering of cited papers and figures.     

飞行时间质谱和高性能电子学控制技术

飞行时间质量分离器是飞行时间质谱仪的主要组成部分。飞行时间质谱（TOF MS）具有分析质量范围宽、分析速度快、仪器结构简单等优点,但离子初始动能和初始位置容易分散是影响其分辨率的核心因素。本综述根据本课题组多年的研制经验,着重介绍离子束垂直引入方式的反射式有栅网飞行时间质谱的离子光学以及相关电子学控制的核心技术原理。离子光学核心技术涉及到离子加速场和离子反射场的机械加工控制和精密装配控制等,电子学控制核心技术主要包括高压电源和高压脉冲电源的精密制作。     

NEGATIVE ION MASS SPECTROMETRY FOR THE ANALYSIS OF N-LINKED GLYCANS

N-glycans from glycoproteins are complex, branched structures whose structural determination presents many analytical problems. Mass spectrometry, usually conducted in positive ion mode, often requires extensive sample manipulation, usually by derivatization such as permethylation, to provide the necessary structure-revealing fragment ions. The newer but, so far, lesser used negative ion techniques, on the contrary, provide a wealth of structural information not present in positive ion spectra that greatly simplify the analysis of these compounds and can usually be conducted without the need for derivatization. This review describes the use of negative ion mass spectrometry for the structural analysis of N-linked glycans and emphasises the many advantages that can be gained by this mode of operation. Biosynthesis and structures of the compounds are described followed by methods for release of the glycans from the protein. Methods for ionization are discussed with emphasis on matrix-assisted laser desorption/ionization (MALDI) and methods for producing negative ions from neutral compounds. Acidic glycans naturally give deprotonated species under most ionization conditions. Fragmentation of negative ions is discussed next with particular reference to those ions that are diagnostic for specific features such as the branching topology of the glycans and substitution positions of moieties such as fucose and sulfate, features that are often difficult to identify easily by conventional techniques such as positive ion fragmentation and exoglycosidase digestions. The advantages of negative over positive ions for this structural work are emphasised with an example of a series of glycans where all other methods failed to produce a structure. Fragmentation of derivatized glycans is discussed next, both with respect to derivatives at the reducing terminus of the molecules, and to methods for neutralization of the acidic groups on sialic acids to both stabilize them for MALDI analysis and to produce the diagnostic fragments seen with the neutral glycans. The use of ion mobility, combined with conventional mass spectrometry is described with emphasis on its use to extract clean glycan spectra both before and after fragmentation, to separate isomers and its use to extract additional information from separated fragment ions. A section on applications follows with examples of the identification of novel structures from lower organisms and tables listing the use of negative ions for structural identification of specific glycoproteins, glycans from viruses and uses in the biopharmaceutical industry and in medicine. The review concludes with a summary of the advantages and disadvantages of the technique. © 2020 John Wiley & Sons Ltd. Mass Spec Rev     

靶向抗肿瘤药物的ESI-MS/MS解析和代谢物鉴定

靶向抗肿瘤药物是新药研发的热点,也是我国近年来批准上市的新药中数目最多的一类药物.电喷雾质谱(ESI-MS)在当前新药研发中发挥着重要作用,质谱碎裂信息是建立药动学生物样品分析方法的基础,也是鉴定药物代谢产物结构的主要依据.本文总结了我国研发的靶向抗癌药物埃克替尼、阿帕替尼、吡咯替尼、氟马替尼、伏美替尼、法米替尼等及其...     

5,6,7,4′-四羟基黄酮和5,6,7,4′-四甲氧基黄酮高分辨电喷雾串联质谱裂解规律对比研究

以5,6,7,4′-四羟基黄酮和5,6,7,4′-四甲氧基黄酮为例,运用高分辨电喷雾串联质谱在正离子模式下(HR-ESI-MS/MS)获得的碎片离子,根据一、二级质谱离子的精确质荷比,分别推导出两种黄酮可能的裂解途径,并比较多甲氧基、多羟基黄酮质谱裂解规律的异同。结果表明:在正离子模式下,5,6,7,4′-四羟基黄酮和5,6,7,4′-四甲氧基黄酮的一级质谱均可获得稳定的准分子离子。5,6,7,4′-四羟基黄酮的二级质谱碎片离子由准分子离子[M+H]+经RDA裂解及进一步脱水和(或)脱一氧化碳中性分子产生,直接由准分子离子脱水及一氧化碳中性分子获得的碎片离子丰度比较低;5,6,7,4′-四甲氧基黄酮二级质谱碎片即可由准分子离子[M+H]+直接经RDA裂解,还可先脱去乙烷或甲烷中性分子再经RDA裂解(1,3断裂)获得。此外,该化合物还有大量的碎片离子是由准分子离子[M+H]+分别经脱水、甲烷、乙烷或进一步脱甲基、一氧化碳而获得。两个化合物质谱碎片的比较结果表明,多甲氧基黄酮的二级质谱碎片裂解机制更复杂,碎片信息更丰富。该方法可为黄酮类化合物成分的快速定性分析提供支持,也可为黄酮类化合物体内代谢产物的LC-MS/MS鉴定提供依据。     

Mass spectrometric glycan rearrangements

Mass spectrometric rearrangement reactions have been reported for a large variety of compounds such as peptides, lipids, and carbohydrates. In the case of carbohydrates this phenomenon has been described as internal residue loss. Resulting fragment ions may be misinterpreted as fragments arising from conventional glycosidic bond cleavages, which may result in incorrect structural assignment. Therefore, awareness of the occurrence of glycan rearrangements is important for avoiding misinterpretation of tandem mass spectra. In this review mass spectrometric rearrangements of both derivatized and underivatized (native) oligosaccharide structures are discussed. Similar phenomena have been reported for glycopeptides, labeled glycan structures and other biomolecules containing a carbohydrate part. Rearrangements in oligosaccharides and glycoconjugates have been observed with different types of mass spectrometers. Most of the observed carbohydrate rearrangement reactions appear to be linked to the presence of a proton. Hence, tandem mass spectrometric analysis of alkali adducts or deprotonated ions often prevents rearrangement reactions, while they may happen with high efficacy with protonated glycoconjugates.     

毛细管电泳-质谱联用技术及其在药物和生物分析中的应用

毛细管电泳-质谱（CE-MS）联用技术是在液相色谱-质谱联用技术基础上发展起来的一项新型分析技术,它结合了毛细管电泳具有的分离效率高、分离速度快、样品消耗量少以及质谱检测具有的高灵敏度和强结构解析能力等优点,现已成为倍受分析化学工作者关注的新型微量分析技术。目前,CE-MS联用技术是中药有效成分分析,体内药物分析以及生物样品,如氨基酸、多肽、蛋白质和多糖等分析的重要手段。本文对CE-MS联用技术中同轴鞘流及无鞘流纳流电喷雾等几种接口装置的研究进展,CE-MS技术在中药活性成分分析及多级质谱结构解析以及氨基酸、多肽及蛋白质等生物样品分析中的应用研究进行了综述,并对该技术的发展进行了展望。     

Infrared consequence spectroscopy of gaseous protonated and metal ion cationized complexes

In this article, the new and exciting techniques of infrared consequence spectroscopy (sometimes called action spectroscopy) of gaseous ions are reviewed. These techniques include vibrational predissociation spectroscopy and infrared multiple photon dissociation spectroscopy and they typically complement one another in the systems studied and the information gained. In recent years infrared consequence spectroscopy has provided long‐awaited direct evidence into the structures of gaseous ions from organometallic species to strong ionic hydrogen bonded structures to large biomolecules. Much is being learned with respect to the structures of ions without their stabilizing solvent which can be used to better understand the effect of solvent on their structures. This review mainly covers the topics with which the author has been directly involved in research: structures of proton‐bound dimers, protonated amino acids and DNA bases, amino acid and DNA bases bound to metal ions and, more recently, solvated ionic complexes. It is hoped that this review reveals the impact that infrared consequence spectroscopy has had on the field of gaseous ion chemistry. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:586–607, 2009     

Hydrated metal ions in the gas phase

Studying metal ion solvation, especially hydration, in the gas phase has developed into a field that is dominated by a tight interaction between experiment and theory. Since the studied species carry charge, mass spectrometry is an indispensable tool in all experiments. Whereas gas-phase coordination chemistry and reactions of bare metal ions are reasonably well understood, systems containing a larger number of solvent molecules are still difficult to understand. This review focuses on the rich chemistry of hydrated metal ions in the gas phase, covering coordination chemistry, charge separation in multiply charged systems, as well as intracluster and ion-molecule reactions. Key ideas of metal ion solvation in the gas phase are illustrated with rare-gas solvated metal ions.     

Evaluation of major historical ICR cell designs using electric field simulations

In Fourier-transform ion cyclotron resonance mass spectrometry, ions are detected by measuring image current induced in the detecting electrodes by trapped ions rotating in a magnetic field at their cyclotron frequencies. The ion trap used for this purpose is called the Penning trap. It can have various configurations of electrodes that are used to create a trapping electric field, to excite cyclotron motion, and to detect the induced signal. The evolution of this type of mass spectrometry is mainly driven by progress in the technology of superconducting magnets and in the constantly improved design of the ion cyclotron resonance (ICR) measuring cell. In this review, we focus on ICR cell designs. We consider that the driving forces of this evolution are the desire to increase resolution, mass accuracy and dynamic range, as well as to adapt new methods for creating and trapping ions.     

Activation of large ions in FT-ICR mass spectrometry

The advent of soft ionization techniques, notably electrospray and laser desorption ionization methods, has enabled the extension of mass spectrometric methods to large molecules and molecular complexes. This both greatly extends the applications of mass spectrometry and makes the activation and dissociation of complex ions an integral part of these applications. This review emphasizes the most promising methods for activation and dissociation of complex ions and presents this discussion in the context of general knowledge of reaction kinetics and dynamics largely established for small ions. We then introduce the characteristic differences associated with the higher number of internal degrees of freedom and high density of states associated with molecular complexity. This is reflected primarily in the kinetics of unimolecular dissociation of complex ions, particularly their slow decay and the higher energy content required to induce decomposition--the kinetic shift (KS). The longer trapping time of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) significantly reduces the KS, which presents several advantages over other methods for the investigation of dissociation of complex molecules. After discussing general principles of reaction dynamics related to collisional activation of ions, we describe conventional ways to achieve single- and multiple-collision activation in FT-ICR MS. Sustained off-resonance irradiation (SORI)--the simplest and most robust means of introducing the multiple collision activation process--is discussed in greatest detail. Details of implementation of this technique, required control of experimental parameters, limitations, and examples of very successful application of SORI-CID are described. The advantages of high mass resolving power and the ability to carry out several stages of mass selection and activation intrinsic to FT-ICR MS are demonstrated in several examples. Photodissociation of ions from small molecules can be effected using IR or UV/vis lasers and generally requires tuning lasers to specific wavelengths and/or utilizing high flux, multiphoton excitation to match energy levels in the ion. Photodissociation of complex ions is much easier to accomplish from the basic physics perspective. The quasi-continuum of vibrational states at room temperature makes it very easy to pump relatively large amounts of energy into complex ions and infrared multiphoton dissociation (IRMPD) is a powerful technique for characterizing large ions, particularly biologically relevant molecules. Since both SORI-CID and IRMPD are slow activation methods they have many common characteristics. They are also distinctly different because SORI-CID is intrinsically selective (only ions that have a cyclotron frequency close to the frequency of the excitation field are excited), whereas IRMPD is not (all ions that reside on the optical path of the laser are excited). There are advantages and disadvantages to each technique and in many applications they complement each other. In contrast with these slow activation methods, the less widely appreciated activation method of surface induced dissociation (SID) appears to offer unique advantages because excitation in SID occurs on a sub-picosecond time scale, instantaneously relative to the observation time of any mass spectrometer. Internal energy deposition is quite efficient and readily adjusted by altering the kinetic energy of the impacting ion. The shattering transition--instantaneous decomposition of the ion on the surface--observed at high collision energies enables access to dissociation channels that are not accessible using SORI-CID or IRMPD. Finally, we discuss some approaches for tailoring the surface to achieve particular aims in SID.     

浅议施工项目成本分析

施工项目成本分析是根据会计核算、业务核算、统计核算的资料,按照成本分析的基本方法（比较法、因素分析法、差额计算法、比率法等）对施工项目成本的形成过程和影响成本升降的因素进行分析,以寻求进一步降低成本的途径。单位工程竣工成本分析主要包括竣工成本分析、主要资源节超分析、主要技术节约措施分析及经济效果分析。从时间和空间上对综合成本、分部分项工程成本、特殊问题进行具体分析,可以全面了解单位工程的成本构成,并可为降低成本提供因素来源,从而可以增强成本的明晰性,使施工项目成本得到有效控制,为实现成本目标创造条件。     

Recent developments in the ion/ion chemistry of high-mass multiply charged ions

The ability to form multiply charged high-mass ions in the gas-phase, most notably via electrospray ionization (ESI), has allowed the study of many different combinations of positively and negatively charged ions. The charged products are directly amenable to study with mass spectrometry. Ion/ion reactions have proved to be "universal" in the sense that the high exothermicities and large rate constants associated with essentially any combination of oppositely charged ions lead to reaction regardless of the chemical functionalities associated with the ions. These characteristics make ion/ion reactions potentially analytically useful provided reagent ion densities and spatial overlap of the oppositely charged ions are high. These conditions can be readily met by several instrumental configurations. The focus of this review is to highlight developments in this field since 1998. Novel instrumentation has been developed to study ion/ion reactions, such as atmospheric pressure ion/ion reactors followed by mass analysis, or electrodynamic ion trap mass spectrometers, which are used as reaction vessels at sub-atmospheric pressures. A wide variety of reaction phenomenologies have been observed in various ion/ion reactions, with proton transfer being the most common. New phenomenologies have been observed in the reactions of multiply charged positive ions with singly charged negative ions, including cation transfer and cation exchange. A new series of reactions between multiply charged positive ions and multiply charged negative ions have been made possible by recent instrumentation developments. These reactions have led to the observation of proton transfer and complex formation. These observations have provided new insights into ion/ion reaction dynamics and a bound orbit model appears to best account for experimental results. New applications are also discussed for a several ion/ion reaction.     

蛋白质立体化学修饰的离子淌度质谱研究进展

蛋白质立体化学修饰是一类低丰度、与人类多种疾病相关的翻译后修饰,由于其并未改变蛋白质的分子质量,难以通过传统的蛋白组学鉴定方法进行发现与鉴定。离子淌度质谱(IM-MS)技术依据不同离子在漂移管中与缓冲气体碰撞后迁移速率的不同而快速分离离子,提供了一种基于构象、电荷数、尺寸和分子质量的分离手段,已在蛋白质立体化学修饰的鉴定与分离分析中取得了阶段性进展。本文从非变性离子淌度质谱实验的角度出发,介绍了漂移管离子淌度仪、行波离子淌度仪、微分迁移率分析仪、高场不对称离子淌度仪以及捕获离子淌度仪等5种商业化离子淌度仪的性能。在此基础上,总结了立体化学修饰高分辨离子淌度质谱分离分析与鉴定方法的最新研究进展,同时介绍了立体化学修饰调控的配体-受体相互作用的结构质谱表征策略,尤其对碰撞诱导去折叠技术在复合物手性构象差异中的研究进行阐述。最后,展望了基于IM-MS的立体化学修饰鉴定与定量等研究方向,以期为立体化学修饰的下一发展阶段提供参考。     

Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions

In principle mass spectral imaging has enormous potential for discovery applications in biology. The chemical specificity of mass spectrometry combined with spatial analysis capabilities of liquid metal cluster beams and the high yields of polyatomic ion beams should present unprecedented ability to spatially locate molecular chemistry in the 100 nm range. However, although metal cluster ion beams have greatly increased yields in the m/z range up to 1000, they still have to be operated under the static limit and even in most favorable cases maximum yields for molecular species from 1 µm pixels are frequently below 20 counts. However, some very impressive molecular imaging analysis has been accomplished under these conditions. Nevertheless although molecular ions of lipids have been detected and correlation with biology is obtained, signal levels are such that lateral resolution must be sacrificed to provide a sufficient signal to image. To obtain useful spatial resolution detection below 1 µm is almost impossible. Too few ions are generated! The review shows that the application of polyatomic primary ions with their low damage cross‐sections offers hope of a new approach to molecular SIMS imaging by accessing voxels rather than pixels to thereby increase the dynamic signal range in 2D imaging and to extend the analysis to depth profiling and 3D imaging. Recent data on cells and tissue analysis suggest that there is, in consequence, the prospect that a wider chemistry might be accessible within a sub‐micron area and as a function of depth. However, these advances are compromised by the pulsed nature of current ToF‐SIMS instruments. The duty cycle is very low and results in excessive analysis times, and maximum mass resolution is incompatible with maximum spatial resolution. New instrumental directions are described that enable a dc primary beam to be used that promises to be able to take full advantage of all the capabilities of the polyatomic ion beam. Some new data are presented that suggest that the aspirations for these new instruments will be realized. However, although prospects are good, the review highlights the continuing challenges presented by the low ionization efficiency and the complications that arise from matrix effects. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:142–174, 2011     

Bi_(0.5)Na_(0.5)TiO_3基无铅压电陶瓷的研究进展

Bi_(0.5)Na_(0.5)TiO_3基无铅压电陶瓷是目前应用前景最广阔的一类无铅压电陶瓷,本文综述了无铅压电陶瓷的发展概况,系统地概括了国内外从离子掺杂、添加第二组元形成固溶体和晶粒定向生长形成织构陶瓷3个方面对改善Bi_(0.5)Na_(0.5)TiO_3基无铅压电陶瓷性能的研究现状,对无铅压电陶瓷的发展进行了展望。     

Charge-State distributions of heavy ions and nuclear reaction products at the exit from solid targets

Using a stepped-pole broad-range magnetic analyzer, the charge-state distributions of heavy ions have been measured upon their passing through thin carbon and gold foils. A review is presented of works on the charge distribution of heavy ions passing through solid targets and reaction products at the exits from these targets. The measured charge distributions of accelerated ions and ion-induced reaction products at the exit from the targets are compared to the theoretical values. It is shown that the calculated mean charges of heavy ions and reaction products can be used only as estimates.     

Flow behavior control in immersion lithography

Over the past decade, immersion lithography has been the primary technology for exposure process in semiconductor manufacturing. Compared with traditional dry lithography method, this technology improves the exposure resolution greatly by inserting a high index liquid into the gap between lens and wafer surface. Keeping the immersion liquid pure and uniform as well as avoiding residual droplets during high speed scanning motion are two challenges faced by the development of immersion lithography. Contaminations, particles, bubbles, heating and stress in the liquid will destroy the continuity of the refractive index. High speed motion of the wafer during scanning may break the meniscus stability on the interface between the liquid and the gas surrounding it, and then generate residual droplets on the wafer. All above phenomena will affect the exposure performance of immersion lithography and corresponding flow behavior control methods are required to solve the problems. This paper gives a review of the studies on flow behavior control in immersion lithography, which contains two parts: studies for liquid purity and uniformity and studies for meniscus stability. In each part, the mechanism and character of the flow behaviors as well as their effects to exposure performance are presented firstly. Then, control approaches adopted by now, including material and surface modifications as well as immersion head utilization, are introduced. In addition, the challenges faced in future studies are also pointed out. The purpose of this review paper is to help the researchers to understand the flow control problems in immersion lithography and to provide better control approaches for exposure performance improvement.