Miniaturization strategies

Fig. 14.2 Merging of electrochemistry with the concepts of combinatorial chemistry and high-through-put screening employing miniaturization strategies...

Jourdier E, Poughon L, Larroche C, Monot F, Chaabane FB. A new stoichiometric miniaturization strategy for screening of industrial microbial strains application to cellulase hyper-producing... 

Pantoliano MW, Petrella EC, Kwasnoski JD, Lobanov VS, Myslik J, GrafE, Carver T, Asel E, Springer BA, Lane P, Salemme FR High-Density miniaturized thermal shift assays as a general strategy for drug discovery. / Biomol Screen 2001, 6, 429-440. 

Each method has both strengths and weaknesses the best strategy will usually involve a combination of the two. Many miniature tape recorders require wind screens for use out of doors. 

Despite successful proof of principle that NO-releasing materials can be employed to fabricate a functional glucose sensor, the toxicity of the particles that leached from the polymer membrane remained a concern. Additionally, the amount and the duration of NO release were limited by the mass of the particles in the polymer film. Upon device miniaturization, the NO release may not prove sufficient to sustain biocompatibility. Two alternative strategies were explored to address these... 

Nine strategies consistently appear in LC/MS-based methods for accelerated development (Table 5.1). The nine strategies are standard methods, template structure identification, databases, screening, integration, miniaturization, parallel processing, visualization, and... 

One example of a miniaturized LC/MS strategy is the use of 96-well sample plates (Kaye et al., 1996) for extraction. This sample extraction procedure combines batch sample processing within a miniaturized format. Increased sensitivity and decreased volume advances have fostered a new wave of scale-down models. Experiments that were formerly performed at the bench are, instead, performed at the microliter scale in the batch mode. For example, synthetic process research was traditionally performed manually with apparatus at the milliliter level. This approach involves the testing of a range of synthetic conditions for optimum yield and minimum impurity production. Now, process research conditions are tested in microliter levels to produce information on purity and structure (Rourick et al., 1996). This strategy requires fewer reagents and accelerates the evaluation of a wider range of conditions in a shorter time. Another example includes the direct analysis of samples from cell culture experiments (Kerns et al., 1997). 

Even the lawn format still does not represent the final limit of miniaturization. The one well/one catalyst or one bead/one catalyst strategy, where catalyst identity is spatially coded, can be replaced by in situ synthesis combined with mass spectrometry [48]. The advantage of this strategy is the use of a mass spectrometer for the synthesis, reaction and analysis. The described electrospray ionization procedure helps to avoid the cleavage of chemical bonds, which would falsify the results. The synthesis step does not have to deliver clean and isolated products. Instead, after synthesis, the reactants are first separated by a quadrupole. In a second step, they are further reacted in an octapole and the reaction products are finally isolated in a second quadrupole and analyzed. Figure 3.15 describes the screening process in detail [49],... 

Wiessmeier, G., Honicke, D., Strategy for the development of micro channel reactors for heterogeneously catalyzed reactions, in Ehrfeld, W., Rinard, I. H., Wegeng, R. S. (Eds.), Process Miniaturization 2nd International Conference on Microreaction Technology, IMRET 2,... 

Another alternative technique, solid-phase microextraction (SPME), was used for the determination of fluoxetine [79] and several TCAs [80], SPME is a miniaturized and solvent-free technique, where analytes are extracted from the sample by adsorption on a thin polymer coating fixed to the solid surface of a fiber, located inside an injection needle or a capillary. Its main disadvantage is that special strategies are needed to couple SPME to the LC-MS analysis. 

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