Micro safety

At the micro-safety level, system safety is a trade-off between safety cost and risk for eliminating or controlling known hazards. However, at the macrosafety level, system safety is more than just cost versus risk it is also a matter of safety culture, integrity, and ethics. Should an organization decide how much risk they are willing to pay for and then pass that risk to the user, or are they obligated to provide risk acceptable to the user ... 

We have seen that only certain micro-organisms that conform to nutritional and safety requirements are suitable for food or feed, and that food has more strict requirements than feed. In addition, for use as food, SCP should have a reduced nudeic add content and should be palatable. Most often this means that its use is limited to processed foods, in which food technologists can produce acceptable tastes, smells and textures. 

One of the most far reaching analyzes along these lines of thought was given by Commenge [114] in the context of gas-phase reactions in continuous-flow processes. Specifically, he analyzed four different aspects of micro reaction devices, namely the expenditure in mechanical energy, the residence-time distribution, safety in operation, and the potential for size reduction when the efficiency is kept fixed. 

In order to exemplify the potential of micro-channel reactors for thermal control, consider the oxidation of citraconic anhydride, which, for a specific catalyst material, has a pseudo-homogeneous reaction rate of 1.62 s at a temperature of 300 °C, corresponding to a reaction time-scale of 0.61 s. In a micro channel of 300 pm diameter filled with a mixture composed of N2/02/anhydride (79.9 20 0.1), the characteristic time-scale for heat exchange is 1.4 lO" s. In spite of an adiabatic temperature rise of 60 K related to such a reaction, the temperature increases by less than 0.5 K in the micro channel. Examples such as this show that micro reactors allow one to define temperature conditions very precisely due to fast removal and, in the case of endothermic reactions, addition of heat. On the one hand, this results in an increase in process safety, as discussed above. On the other hand, it allows a better definition of reaction conditions than with macroscopic equipment, thus allowing for a higher selectivity in chemical processes. 

Many pubhcahons refer to the use of micro reactors for process intensificahon, with all the imphcahons related to this definition - safety, cost reduchon, high productivity rate, environmental friendliness, energy efficiency and so on [5, 25, 104]. A particular feature of interest is the reduction of the equipment size (see also Section 1.4.3.5 for a systematic top-down description of this topic). 

Rinard dedicated his research to a detailed analysis of methodological aspects of a micro-reactor plant concept which he also termed mini-plant production [85] (see also [4, 9, 10] for a commented, short description). Important criteria in this concept are JIT (Just-in-time) production, zero holdup, inherent safety, modularity and the KISS (keep it simple, stupid) principle. Based on this conceptual definition, Rinard describes different phases in plant development. Essential for his entire work is the pragmatic way of finding process solutions, truly of hybrid character ]149] (miniaturization only where really needed). Recent investigations are concerned with the scalability of hybrid micro-reactor plants and the limits thereof ]149], Expliddy he recommends jointly using micro- and meso-scale components. 

Tausend Kandlejur eine Reaktion, Chemische Rundschau, February 2003 Industrial and institutional expert opinions general advantages of micro flow safety work of institutes particle precipitation pilot-scale operation challenges process control plugging miniature sensing and controlling emulsification market situation [204]. 

Gezdhmte Chemie im Mikroreaktor, VDI Nachrichten, June 2000 Micro-reactor enterprises shape and material variety of micro reactors selectivity gains and new project regimes direct fluorination faster process development BASF investigations safety increase speed-up of catalyst development production for fine chemistry and pharmacy numbering-up first industrial examples for micro-reactor production [215]. 

Smallness of micro-flow components safety gains tool for kinetics evaluation process development for large-scale processes polymerization combinatorial catalyst screening hydrogen via reforming [218],... 

Process Miniaturization Second International Conference, CATTECH, December 1998 Steep progress in microelectronics in the past key players topics of IMRET 2 general advantages of micro flow energy, safety, process development, combinatorial catalyst testing, lab-on-a-chip biological applications anodically oxidized catalyst supports as alternatives to non-porous supports [220]. 

Today s use of microtechnical products microfabrication techniques general advantages of micro flow parallelization for screening steep transport gradients plant safety numbering-up industrial response outlook on market [222]. 

Mikroreaktoren sind so klein wie ein Fingerhut, Handdsblatt, May 1998 Steep progress in microelectronics, sensor and analytical techniques in the past transport intensification for catalysis first catalytic micro reactors available partial oxidation to acrolein partial hydrogenation to cyclododecene anodically oxidized catalyst supports as alternatives to non-porous supports study group on micro reactors at Dechema safety, selectivity, high pressure exclusion of using particle solutions limited experience with lifetime of micro reactors [236],... 

Chemiefabrik in der Grojie eines Chips, Handdsblatt, May 1996 Vision of shoe box-sized micro reactors plant cells as model for micro-reactor development cost, performance, and safety advantages LIGA process numbering-up safety processing of hazardous substances [237]. 

Special attention was also paid to the search for operation in the explosive regime as micro reactors are said to have much greater safety here. In this way, improvements in terms of space-time yield were expected. 

GP 11] [R 19] Based on an analysis of the thermal and kinetic explosion limits, inherent safety is ascribed to hydrogen/oxygen mixtures in the explosive regime when guided through channels of sub-millimeter dimensions under ambient-pressure conditions [9], This was confirmed by experiments in a quartz micro reactor [9],... 

The Sudan series of azo dyes, which have also been synthesized in micro reactors, are commonly used as microbial stains. The thermally unstable nature of the diazonium precursors and reported explosions often demand extensive safety procedures when going to an industrial scale, which limits the commercial applicability of the azo reaction. 

The small reaction volumes in micro reactors and the large specific surface areas created are seen as beneficial to cope with the problems caused by the release of the large amounts of heat, as mentioned above [37, 38]. Delicate temperature control is expected for micro-reactor operation isothermal processing is said to be achievable even when high reaction heats are released [94]. Small size should increase process safety and suppress unwanted secondary reactions [37, 38]. 

Concerning safety issues, micro reactors are beneficial as they efficiently remove the reaction heat and also may intrinsically prevent explosions by terminating the radical chains. This has been impressively shown for the reaction between hydrogen and oxygen, widely known as being very dangerous [75, 76]. 

Low-intensity light sources should give efficient irradiation of thin liquid layers [21]. Sample heating is reduced and so is radical recombination. In addition, oxygen enrichment of solutions before and after micro reactor passage can be handled differently and is no longer a major safety problem [21]. 

The worst hazard scenarios (excessive temperature and pressure rise accompanied by emission of toxic substances) must be worked out based upon calorimetric measurements (e.g. means to reduce hazards by using the inherent safety concept or Differential Scanning Calorimetry, DSC) and protection measures must be considered. If handling hazardous materials is considered too risky, procedures for generation of the hazardous reactants in situ in the reactor might be developed. Micro-reactor technology could also be an option. Completeness of the data on flammability, explosivity, (auto)ignition, static electricity, safe levels of exposure, environmental protection, transportation, etc. must be checked. Incompatibility of materials to be treated in a plant must be determined. 

The Food and Drug Administration (FDA) published a safety alert in 1994 in response to two deaths associated with calcium-phosphate precipitation in PN.16 Autopsy reports from these patients revealed diffuse micro vascular pulmonary emboli containing calcium-phosphate precipitates. Because calcium and phosphate can bind and precipitate in solution, caution must be exercised when mixing these two electrolytes in PN admixtures. Several factors can affect calcium-phosphate solubility, including... 

Although the initial reason for the development of solvent-free conditions for micro-wave irradiation was safety, it soon became apparent that use of these conditions had many other benefits - simplicity, efficiency, easy work-up, very often higher yields, and enhanced reaction rates. The absence of solvent is, furthermore, time- and moneysaving and often enables elimination of waste treatment. 

The lack of temperature and pressure control in these systems could lead to safety problems, because of overpressure resulting from the heating rate caused by micro-waves. These problems can be reduced by using solvent-free methodology, which also enables the use of larger quantities of reagents. Yields have been greatly improved, and reaction times reduced, in comparison with conventional procedures in solvents under reflux. 

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