药物稳定性的表征

2019年底在武汉爆发的新冠肺炎(2019 novel coronavirus disease, COVID-19)造成国内外乃至全球的大冲击，无论是医药、经济、贸易及各产业体系均受到巨大考验。藉由全球科学家们日以继夜的努力研究，发现新冠肺炎可能的致病基理；其中较为关键的是新冠病毒感染主要是藉由新冠病毒上的S蛋白(spike protein)，专一性的识别攻击人类细胞受体ACE2 (angiotensin converting enzyme 2)进而引起后续的反应。相较于同是冠状病毒的SARS，COVID-19识别人类细胞受体的专一性更强高出20倍1-3。鉴于新冠肺炎启发，本文将回顾利用等温滴定量热法(isothermal titration calorimetry, ITC)及差式扫描量热法(differential scanning calorimetry, DSC)研究病毒相关的技术文献。期望能对抗病毒药物开发、疫苗、检验试剂及基础研究等领域，提供有用的信息。

Cement is a fnely ground powder of burned limestone. It reacts readily with water (hydrates) to form a solid material, known as hardened cement paste. When cement is mixed together with rock aggregate, sand and filler materials, it forms concrete. Cement is one of the most important base materials in general use in the construction industry. The optimization of concrete with respect to frost resistance, durability, chemical resistance etc. is of great importance.

The fled of biologics, i.e. proteins, particularly monoclonal antibodies (mAbs), as pharmaceutical drugs, is the fastest growing segment in the biopharmaceutical industry. Therapeutic formulations of monoclonal antibodies usually require concentrations on the order of 100 mg/mL or more, a condition that exacerbates protein denaturation and aggregation tendencies. Selecting the monoclonal antibody with the best denaturation/aggregation profile and identifying the solution conditions (formulation) that maximize the long term stability of the antibody are major goals in the development process. To accomplish these goals, researchers routinely measure different aspects of protein denaturation and aggregation using various complementary or orthogonal techniques. Some techniques measure the conformational stability of the protein (e.g., differential scanning calorimetry, differential scanning ?uorometry, isothermal chemical denaturation) and other techniques measure aggregation after lengthy sample incubation (e.g., size exclusion chromatography, light scattering). Since the expected long term stability is longer than one year, incubation times are usually reduced by accelerating denaturation/aggregation process by, for example, increasing the incubation temperature or stressing the sample in different ways. It would be highly desirable for a more efficient development of new therapeutic mAbs, to have access to a technique that provides the rate of denaturation/aggregation fast and accurately. In this technical note, we introduce the Thermal Activity Monitor (TAM) as a way to measure the rates of denaturation and aggregation of monoclonal antibodies and other proteins at constant temperature.

Biofilms are defined as “bacteria growing on a surface as single or multi-layered communities”. Over the past several years the importance of biofilms in research has been increasingly growing as scientists realized that many, if not a large majority, of microorganisms exist naturally as biofilms. Indeed, biofilms studies are common in water science (natural waters or waste waters), environmental studies (biofilm formation on rocks), material science (antifouling surfaces) and finally medical or biomedical studies (infections, implantology). The study of biofilms has evolved with the development of many staining, molecular, or microscopy techniques. However, most of these techniques are destructive and therefore only provide endpoint measurements. Consequently, the metabolism and the dynamic behavior of biofilms remains mostly inaccessible to researchers. In this context, isothermal microcalorimetry is a valuable tool enabling investigation of development and metabolic activities of growing or mature biofilms. Several techniques combined with an isothermal calorimeter can be used to study biofilms and this application note aims at summarizing these techniques and providing some tips and tricks.