Metrological traceability in laboratory medicine

 The establishment of a reference examination system necessary for metrological traceability of the many types of sophisticated examination result in laboratory medicine is a daunting task, which has been made mandatory by the EU Directive on in vitro diagnostic medical devices and the requirements for accreditation. Following a definition of examinand and allowed examination uncertainty, a dedicated calibration hierarchy is established from stated reference through alternating reference examination procedures and calibrators providing a traceability chain from examination result to the reference, often a definition of a measurement unit. The various types of possible calibration hierarchy are outlined in EN ISO Standards. Recent efforts by national and international stakeholders to establish a global reference examination system have led to the creation of a Joint Committee on Traceability in Laboratory Medicine with the International Committee for Weights and Measures, International Bureau of Weights and Measures, International Federation of Clinical Chemistry and Laboratory Medicine, International Laboratory Accreditation Cooperation, and World Health Organization as the principal promoters. This structure will identify reference procedures, reference materials, and reference laboratories, and seek support for further prioritised and coordinated development of the system. Received: 1 August 2002 Accepted: 22 November 2002 Based on a lecture at an IUPAC Seminar, EC JRC Institute for Reference Materials and Measurements, Geel, BE, 2001–12–18 Correspondence to R. Dybkaer     

Metrological traceability for benzo[a]pyrene quantification in airborne particulate matter

Airborne particulate matter (PM) represents one of the most important sources of urban pollution due to its physical and chemical properties. There is a great concern for PM dangerous effects on human health because particles can deeply penetrate into the respiratory system, carrying the contaminants adsorbed onto their surface. Polycyclic aromatic hydrocarbons (PAHs) are a class of organic contaminants that can be adsorbed onto PM and can have harmful effects on health, due to their particular chemical structure. The International Agency for Research on Cancer (IARC) classified PAHs as potential carcinogenic agents and benzo[a]pyrene (BaP) as carcinogenic to humans. In this paper, the development of a metrologically traceable procedure for the quantification of BaP in airborne PM, performed at the Italian National Institute of Metrological Research (Istituto Nazionale di Ricerca Metrologica—I.N.Ri.M.), is presented. The identification and quantification of BaP in PM samples were carried out by gas chromatography coupled with mass spectrometry (GC–MS). Metrological traceability was established in all the procedure steps, after performing the method validation. Suitable certified reference materials (CRMs) were used both to validate the analytical method and to calibrate the GC–MS. The measurement uncertainty was evaluated by identifying and taking into account all the relevant sources deriving from the whole procedure steps.     

Measurement uncertainty and doping control in sport. Part 2: Metrological traceability aspects

The assessment of (non-)compliance in doping control and in particular the appreciation of uncertainty of measurement in such an assessment has become a subject of debate. In a previous paper, the requirements for evaluating measurement uncertainty have been addressed. The debate now focuses on the estimation of the standard uncertainty. The completeness of an uncertainty budget is discussed in view of the (metrological) traceability of the result. It is concluded that despite the fact that the new doping rules dictate that A-tests and B-tests be performed in the same laboratory, the uncertainty budget should encompass all factors, including between-laboratory effects. The assessment of (non-)compliance should be based on a one-sided t-test. There is also consensus about the level of confidence to be applied (99%), despite the fact that the regulations state 95% as the appropriate level.     

Metrological traceability chain for PCBs: I.N.Ri.M. activity

Metrology in chemistry has its own features, which distinguish it from classical metrology: due to the lack of primary methods applicable in routine measurements, metrological traceability of measurement results can be achieved by using in a proper way suitable certified reference materials (CRMs), which can assure a direct relation to a reference. This article deals with the activity of the Italian National Institute of Metrological Research (Istituto Nazionale di Ricerca Metrologica—I.N.Ri.M.) on the analysis of various polychlorinated biphenyls congeners in organic solution by means of gas-chromatography coupled with mass spectrometry. The metrological traceability approach in the quantification step is pursued via calibration solutions prepared by gravimetrically diluting a CRM. The uncertainty for the calibration solutions was evaluated taking into account all the relevant contributions.     

Metrological traceability in gas analysis at I.N.Ri.M: gravimetric primary gas mixtures

Metrologically traceable measurements are needed, in environmental monitoring, to provide meaningful information on the pollution level and the possibility to have suitable reference standards is crucial to this purpose to calibrate instruments. The Italian National Institute of Metrological Research (I.N.Ri.M.), as a primary metrological institute, realizes and maintains primary standards for the basic and derived units of the International System of Units (SI). In this framework and regarding gas analysis, in the last few years I.N.Ri.M. has started a research line on the preparation of primary reference mixtures (PRMs) by the gravimetric method that led to plan and build a facility for evacuating and filling cylinders and a device for high precision weighing. In the present work the developments in such field at I.N.Ri.M. are reported to underline the relevance, in the atmospheric pollutants monitoring, of performing accurate and reliable measurements and having reference standards fit for the calibration of the analytical instrumentation.     

Understanding structure does not always explain reactivity: a phosphinoamide anion reacts as an iminophosphide anion

The aminophosphine C(6)H(4)(o-CN)NHPPh(2), 1, containing an electron-withdrawing nitrile group, was prepared from the lithiation of 2-aminobenzonitrile followed by addition of Ph(2)PCl. Lithiation of 1 using (n)BuLi affords the anion [Ph(2)PN(Li)C(6)H(4)(o-CN)(thf)](2), 2. Compound 2 reacts with Ph(2)PCl or MeI to afford C(6)H(4)(o-CN)N=PPh(2)-PPh(2), 3, and [C(6)H(4)(o-CN)N=PPh(2)(CH(3))(LiI)(C(2)H(5)O)](2), 4, respectively. In these products new P-P and P-C bonds have been formed rather than N-P and N-C bonds. The structures of 1-4 have been determined by single-crystal X-ray diffraction analysis, and the synthetic results are discussed in terms of the structural data and NMR spectroscopic studies.     

Electrophoretic mobility does not always reflect the charge on an oil droplet

Electrophoresis is widely used to determine the electrostatic potential of colloidal particles. Oil droplets in pure water show negative or positive electrophoretic mobilities depending on the pH. This is commonly attributed to the adsorption of hydroxyl or hydronium ions, resulting in a negative or positive surface charge, respectively. This explanation, however, is not in agreement with the difference in isoelectric point and point of zero charge observed in experiment. Here we present molecular dynamics simulations of oil droplets in water in the presence of an external electric field but in the absence of any ions. The simulations reproduce the negative sign and the order of magnitude of the oil droplet mobilities at the point of zero charge in experiment. The electrostatic potential in the oil with respect to the water phase, induced by anisotropic dipole orientation in the interface, is positive. Our results suggest that electrophoretic mobility does not always reflect the net charge or electrostatic potential of a suspended liquid droplet and, thus, the interpretation of electrophoresis in terms of purely continuum effects may need to be reevaluated.     

Polycyclic benzenoids: why kinked is more stable than straight

The enhanced stability of bent or kinked polycyclic benzenoids over linear ones is well established, phenanthrene and anthracene being archetypal representatives. The question why kinked is more stable than linear is, however, still a matter of discussion. Recently, it has been proposed that H-H bonding interactions between the two hydrogen atoms in the bay region of phenanthrene are responsible for the larger stability of this molecule as compared to anthracene. This conclusion conflicts with the vast body of evidence for nonbonded steric repulsion between these hydrogen atoms. In this work, we provide new, complementary evidence for the repulsive character of the H-H interactions in phenanthrene's bay region. We have traced the origin of phenanthrene's enhanced stability to the more efficient bonding in the pi-electron system using, among others, a quantitative energy decomposition analysis of the bonding between the two constituting 2-methtriyl-phenyl fragments in both phenanthrene and anthracene (i.e., C14H10 = C6H4*-CH** + C6H4*-CH**). The scope of our study is extended to polycyclic benzenoids by analyzing also hexacene and various bent isomers of the latter. Our results once more falsify one of the core concepts of the theory of atoms-in-molecules (AIM), namely, that the presence of bond paths and the presence of bond critical points (they exist indeed between the two bay H atoms in phenanthrene) are sufficient indicators for a stabilizing interaction. Instead, our results confirm that these AIM parameters merely diagnose the proximity or contact between charge distributions, be this contact stabilizing or destabilizing.     

Aluminum chloride as a solid is not a strong Lewis acid

Aluminum chloride is used extensively as Lewis acid catalyst in a variety of industrial processes, including Friedel-Crafts and Cl/F exchange reactions. There is a common misconception that pure AlCl3 is itself a Lewis acid. In the current study, we use experimental and computational methods to investigate the surface structure and catalytic properties of solid AlCl3. The catalytic activity of AlCl3 for two halide isomerization reactions is studied and compared with different AlF3 phases. It is shown that pure solid AlCl3 does not catalyze these reactions. The (001) surface of crystalline AlCl(3) is the natural cleavage plane and its structure is predicted via first principles calculations. The chlorine ions in the outermost layer of the material mask the Al3+ ions from the external gas phase. Hence, the experimentally found catalytic properties of pure solid AlCl3 are supported by the predicted surface structure of AlCl3.     

Proficiency evaluation as a traceability link in chemical metrology

Traceability implies comparison of the results of measurements, or comparison to national or international measurement standards. One of several approaches that have been used in chemistry to provide for such comparisons is distribution of proficiency evaluation materials which have been measured by a reference laboratory. A newer approach is based on receipt and measurement at a reference laboratory of materials that have been produced and analyzed by other laboratories. Traceability concepts and approaches to realization will be described together with discussion of the relative merits of various approaches. Extension into metrological fields other than chemistry will also be explored. Received: 14 November 2000 Accepted: 11 December 2000     

Treatment of alcohols with tosyl chloride does not always lead to the formation of tosylates

Treatment of substituted benzyl alcohols with tosyl chloride resulted in the formation of the corresponding chlorides, not the usual tosylates. A series of experiments demonstrated that it was possible to predict whether chlorination or tosylation would occur for substituted benzyl alcohols and pyridine methanols. Treatment of electron withdrawing group-substituted benzyl alcohols with tosyl chloride gave the corresponding chlorides in moderate yields under mild conditions, which provided a simple way to directly prepare chlorides from alcohols.