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Bioanalysis assays that reliably quantify biotherapeutics and biomarkers in biological samples play pivotal roles in drug discovery and development. Liquid chromatography coupled with mass spectrometry (LC–MS), owing to its superior specificity, faster method development and multiplex capability, has evolved as one of the most important platforms for bioanalysis of biotherapeutics, particularly new scaffolds such as half-life extension platforms for proteins and peptides, as well as antibody drug conjugates. Intact LC–MS analysis is orthogonal to bottom-up surrogate peptide approach by providing whole molecule quantitation and high-level sequence and structure information. Here we review the latest development in LC–MS bioanalysis of intact proteins and peptides by summarizing recent publications and discussing the important topics such as the comparison between top-down intact analysis and bottom-up surrogate peptide approach, as well as simultaneous quantitation and catabolite identification. Key bioanalytical issues around intact protein bioanalysis such as sensitivity, data processing strategies, specificity, sample preparation and LC condition are elaborated. For peptides, topics including quantitation of intact peptide vs. digested surrogate peptide, metabolites, sensitivity, LC condition, assay performance, internal standard and sample preparation are discussed. 相似文献
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以介质填充的平行板放电结构为例,本文主要研究了介质填充后微波低气压放电和微放电的物理过程.为了探究介质材料特性对微波低气压放电和微放电阈值的影响,本文采用自主研发的二次电子发射特性测量装置,测量了7种常见介质材料的二次电子发射系数和二次电子能谱.依据二次电子发射过程中介质表面正带电的稳定条件,计算了介质材料稳态表面电位与二次电子发射系数以及能谱参数的关系.在放电结构中引入与表面电位相应的等效直流电场后,依据电子扩散模型和微放电中电子谐振条件,分别探讨了介质表面稳态表面电位的大小对微波低气压放电和微放电阈值的影响.结果表明,介质材料的二次电子发射系数以及能谱参数越大,介质材料的稳态表面电位也越大,对应的微波低气压放电和微放电阈值也越大.所得结论对于填充介质的选择有一定的理论指导价值. 相似文献
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在激光驱动的惯性约束聚变装置中,常采用多种束匀滑手段对焦斑的时空特性进行调控.光传输链路中涉及的光学元件众多、传输变换复杂,往往导致光传输模型复杂,且在运用衍射光学方法分析焦斑形态和特征时面临大量的数据处理和计算,致使出现计算量大、计算效率低等问题,亟需寻求快速而简便的新方法来描述焦斑的统计特征.本文利用光场特性的统计表征方法对靶面光场进行表征,采用圆型复数高斯随机变量直接描述靶面光场的统计特征,并基于典型焦斑评价参数对衍射光学方法和统计表征方法得到的远场焦斑进行了对比和分析.结果表明,采用衍射光学方法和统计表征方法获得的焦斑的瞬时特征基本一致,其时间积分的远场焦斑有所不同,但仍可进一步采用相关系数来表征其远场焦斑的时间变化特征. 相似文献
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Modifying the position and numbers of lateral fluorine substituent is a common method to design and adjust the mesophase of liquid crystal compounds. Here, a series of 2-(2,2?-difluoro-4?-alkoxy-1,1?-biphenyl-4-yl)-5-substituted benzoxazole with both non-polar (H, CH3) and polar (NO2) groups (coded as nPF(2)PF(2)Bx) is synthesised and characterised. All of the compounds show a conspicuous inter-ring twist angle of 38° compared with corresponding reference compounds I and II which are calculated by density functional theory method, and it is interesting to note that the final compounds nPF(2)PF(2)Bx show only nematic mesophase during heating or cooling. Meanwhile, the UV-vis absorption bands and photoluminescence emission peaks both display remarkable blue-shifted. The aforementioned results reveal that lateral difluoro substituents play a key role to stable the nematic mesophase by increasing the dihedral angle of biphenyl. 相似文献
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Dr. Wenyan Hao Yuchen Sha Dr. Yi Deng Yi Luo Li Zeng Shan Tang Dr. Yue Weng Prof. Dr. Chien-Wei Chiang Prof. Dr. Aiwen Lei 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(19):4931-4934
An in situ generated oxidation species of nickel quinolinylpropioamide intermediate was produced. Characterization by X-ray absorption near edge structure (XANES) and EPR provides complementary insights into this oxidized nickel species. With aliphatic amides and isocyanides as substrates, a nickel-catalyzed facile synthesis of structurally diverse five-membered lactams could be achieved. 相似文献
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Lirong Ma Xuanlin Yang Xiuzhong Yao Weiyu Weng 《Photochemistry and photobiology》2020,96(5):1088-1095
Hexyl aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinic acid (5-ALA) and can induce more protoporphyrin IX (PpIX) formation and stronger fluorescence intensity (FI) than 5-ALA, which will greatly facilitate photodynamic diagnosis and therapy. The main drawback of HAL is its low solubility in neutral aqueous media. In this study, surfactants were used to increase HAL solubility in the cell culture medium and serum, followed by in vitro fluorescence formation measurement in human pancreatic cancer cells (SW1990) and in vivo fluorescence detection in tumor-bearing mice. The results showed that Tween 80 (TW80) and Kolliphor® HS 15 (HS15) increased the solubility of HAL in the selected media. Although TW80 and HS15 exhibited in vitro cytotoxicity at high concentrations (5 mg mL−1), they facilitated fluorescent signal formation at the early stage of cell incubation. When surfactants were used, the FI should be determined without the routine washing process because surfactant-containing culture medium caused the loss of synthesized PpIX during the washing process. When HAL dissolved in TW80 solution was injected intraperitoneally into pancreatic cancer-bearing mice at a dose of 50 mg kg−1, the tumors exhibited red fluorescence, which indicated that systemic administration of surfactant-solubilized HAL might be applicable for tumor fluorescence detection in vivo. 相似文献
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Conjugated polymer nanoparticles with aggregation induced emission characteristics for intracellular Fe3+ sensing 下载免费PDF全文
Dongliang Yang Fei Li Zhimin Luo Biqing Bao Yanling Hu Lixing Weng Yixiang Cheng Lianhui Wang 《Journal of polymer science. Part A, Polymer chemistry》2016,54(12):1686-1693
In this article, a novel zwitterionic conjugated polyelectrolyte containing tetraphenylethene unit was synthesized via Pd‐catalyzed Sonogashira reaction. The resulting polymer (P2), which exhibited typical aggregation‐induced emission (AIE) properties, was weakly fluorescent in dilute DMSO solution and showed bright fluorescence emissions when aggregated in DMSO/water mixtures or fabricated into conjugated polymer nanoparticles (CPNs). The nanoparticles from P2 could be prepared by reprecipitation method with an average diameter around 23 nm. Notably, the cell‐staining efficiencies of lipid‐P2 nanoparticles could be enhanced with lipid encapsulation and these nanoparticles were endocytosed via caveolae‐mediated and clathrin‐mediated endocytosis pathways. Furthermore, the lipid‐P2 nanoparticles with low cytotoxicity, high photostability and efficient cell staining ability could be employed for in vitro detection of Fe3+ ions in A549 cells. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1686–1693 相似文献