**4.2 Microorganisms**

Although there are some useful microorganisms as essentially required in important biological processes such as fermentation, many microorganisms have been life-threatening enemies in long history. Especially, food-born infectious microorganisms are very near to our everyday life to often cause epidemics. The recent *E coli* O157-outbreak in Europe carried by fresh vegetables killed more than 50 people and infected about 4400 people. This incidence reminds that we are not well prepared against such outbreaks. Especially the insufficient technical levels in analysis of microorganisms for surveillance and investigation in a global network is of a great concern. While constructing or improving the global infrastructure against such outbreaks, adopting metrological principles as possible will reduce controversy or legal suits associated with the interpretation on the analytical data. In this regard, CCQM of BIPM moves in a swift manner to organize an international symposium and ad hoc Steering Group on Microbial Measurements to ensure food quality and safety. What to do for establishment metrology in microbial measurements are yet to be rummaged among experts in the field and metrologists. Measurements are for detection, identification, and characterization, and enumeration of target microorganisms. Microorganisms are proliferating dependent upon environmental conditions and frequently mutated. Due to these properties, none of quantification, identification, or characterization of a microorganism is straightforward. Characteristic properties and their relevance on infection should be carefully thought and selected for effective measurement. In addition, such measurements had better be in the domain of metrology, which will guarantee the comparability in a global network (Verhoef et al., 2011). Such a grand task is being organized among relevant experts groups and metrological institutes.

#### **4.3 Glycans**

Glycan is a polysaccharide, which is a linear or branched polymer of monosaccharide units linked by glycosidic bonds. Glycans exist in nature as free or glycoconjugates (e.g.

4. **Stability** — confirms the integrity of nuclear genomes using cytogenetics and SNP

5. **Pluripotency** — confirms the ability of hESCs to generate various differentiated cell types using teratoma formation and characterization, as well as embryoid bodies formation. Appropriateness of such tests is to be determined by experts in the field, and the quantities here are more likely method-dependent. As discussed in the later section, metrology for such quantities needs to be established to support 'metrological execution' of the given measurement protocols, where those protocols is not fully established yet. In this regard, the advancement of cell testing protocols should be closely tracked for prompt implementation

Counting of well specified cells is rather straight forward in terms of quantification. CCQM BAWG has executed or is preparing for two international comparisons: 1) flow cytometric determination (CCQM-P102) and 2) microscopic determination (CCQM-P123). It is noteworthy that physical parameters such as motility and morphology could be important in characterization of cells. Among NMIs, NIST scientists are in particular active in such

Although there are some useful microorganisms as essentially required in important biological processes such as fermentation, many microorganisms have been life-threatening enemies in long history. Especially, food-born infectious microorganisms are very near to our everyday life to often cause epidemics. The recent *E coli* O157-outbreak in Europe carried by fresh vegetables killed more than 50 people and infected about 4400 people. This incidence reminds that we are not well prepared against such outbreaks. Especially the insufficient technical levels in analysis of microorganisms for surveillance and investigation in a global network is of a great concern. While constructing or improving the global infrastructure against such outbreaks, adopting metrological principles as possible will reduce controversy or legal suits associated with the interpretation on the analytical data. In this regard, CCQM of BIPM moves in a swift manner to organize an international symposium and ad hoc Steering Group on Microbial Measurements to ensure food quality and safety. What to do for establishment metrology in microbial measurements are yet to be rummaged among experts in the field and metrologists. Measurements are for detection, identification, and characterization, and enumeration of target microorganisms. Microorganisms are proliferating dependent upon environmental conditions and frequently mutated. Due to these properties, none of quantification, identification, or characterization of a microorganism is straightforward. Characteristic properties and their relevance on infection should be carefully thought and selected for effective measurement. In addition, such measurements had better be in the domain of metrology, which will guarantee the comparability in a global network (Verhoef et al., 2011). Such a grand task is being

organized among relevant experts groups and metrological institutes.

Glycan is a polysaccharide, which is a linear or branched polymer of monosaccharide units linked by glycosidic bonds. Glycans exist in nature as free or glycoconjugates (e.g.

profile

of metrology in such testing protocols.

investigations (Ni and Chiang, 2007).

**4.2 Microorganisms** 

**4.3 Glycans** 

glycoproteins, proteoglycans, and glycolipids) with cell or tissue. Their function in living organisms is important. Especially the conjugated glycans in proteins and lipids affect physicochemical properties, such as solubility, stability as well as biological properties. Particularly, glycosylated biopharmaceuticals contain various glycoforms, and the heterogeneity of carbohydrate moiety is altered according to the manufacturing process. For this reason, glycan analysis is an essential part of protein characterization in development and quality control of biopharmaceuticals as well (Harazono et al., 2011). Therefore, the study of protein with post-translational modifications has increased explosively in recent proteomic research, and this phenomenon represents importance of glycans in this area (Wei and Li, 2009). Though the advanced mass spectrometry plays a versatile role in current glycan analysis, due to the complexity of structure and the difficulty of isolation of glycans, there is no single method which can clearly and efficiently analyze all of them (Zaia, 2010). The glycan analysis is processed by a combination of several methods, such as monosaccharide composition analysis after the hydrolysis (Harazono et al., 2011), profiling of liberated glycans (Pabst and Altmann, 2011), and structural assignment (Zaia, 2010). A number of methods have been developed for glycomics using either chromatographic, electromigratory or mass spectrometric method as qualitative and quantitative methods. Glycomics has been recognized as an emerging technology in this post-genome generation in worldwide. The term 'glycomics' includes the systematic study of all glycan structures as well as the comprehensive study in genetic, physiologic and pathologic areas. The dynamic complexity and variety, and the essential roles in physiology, drive the need of generally accepted methodology for glycoconjugates. However, the challenging task to implement metrological rigorousness in such complex analysis is yet to be launched. As new glycomics and glycoproteomics problems will require unique solutions, a wide range of methodological and instrumental techniques will be needed to address them.
