Sensitivity improvement techniques

There has for some years been a considerable backlog in the development of practicable prechromatographic methods [5]. It is becoming more and more recognized that the future direction to be taken by trace analysts is to make improvements in the extraction, enrichment and clean-up of the sample and in the optimization of derivatization. It is only in this way that it is possible to employ the sensitive chromatographic techniques optimally for the solution of practically relevant problems. 

Practical constraints prevent this technique from living up to its potential, even in this, the era of the superconducting probe. Until sensitivity improves by at least another order of magnitude, the INADEQUATE experiment will remain just that - inadequate by name and by nature. 

NMR offers many unique advantages that other methods cannot provide in spite of some limitations. Biopharmaceutical product development will certainly benefit from including NMR as an option for solving analytical problems. NMR instrumentation and methodology are constantly being improved. As better and more sensitive NMR techniques become available, the use of NMR as a standard analytical tool in biopharmaceutical process development and validation is expected to increase. 

Standard heat capacities of transfer can be derived from the temperature dependence of standard enthalpies of solution (8). While this technique can give general trends in the transfer functions from water to mixed solvents (9), it is not always sufficiently precise to detect the differences between similar cosolvents, and the technique is rather laborious. Direct measurements of the difference between heat capacities per unit volume of a solution and of the solvent a — gq can be obtained with a flow microcalorimeter (10) to 7 X 10 5 JK 1 cm-3 on samples of the order of 10 cm3. A commercial version of this instrument (Picker dynamic flow calorimeter, Techneurop Inc.) has a sensitivity improved by a factor oi about two. 

Extracts from —3 X 107 cells and a mixture of GM, and GMg were compared by TLC after staining with resorcinol. To improve sensitivity of technique, the spray was applied heavily, giving rise to some nonspecific staining. Only those bands that reproducibly stained the characteristic blue of gangliosides are bracketed. 

The fluorescence technique combines the advantages of the large dynamic range of emission techniques with the simplicity and high selectivity of absorption techniques. Flame sources have been extensively used, however, for elements with refractory oxides, the ICP source has been found to be more satisfactory for AFS. A system for hollow cathode lamp excited ICP-AFS, as proposed by Demers and Allemand (1981), is commercially available as a modular simultaneous multielement ICP system. Although fluorescence techniques often offer two orders of magnitude sensitivity improvement over absorption, the multielement approach for AFS has not yet been commercially successful. Also promising for the future is the laser-excited furnace AFS where the detection limits for most elements are comparable to those of ICP-AES and for some elements, for eg, As, Cd, Pb, Tl, Lu, even lower (Omenetto and Human, 1984). The future for AFS techniques has been discussed by Stockwell and Corns (1992). 

The versatility of the SPR technique has been shown by a vast amount of publications in the past decades the method has matured into a well-accepted analytical tool for the characterization of interfaces and thin films as well as for the sensitive detection of interfacial biomolecular interaction. With a significant input from engineering, SPR has reached a decent signal-to-noise level with a lower limit for a reliable signal detection corresponding to an effective layer of about 0.3 A [6], which is sufficient for most thin film studies. However, the intrinsic label-free characteristic of SPR detection technique still imposes limitation on further sensitivity improvement, especially if the analysis involves small molecules. 

Other methods of reducing the crosslink density have also led to sensitivity improvements, of which the most promising is the uneven copolymer mixtures with a potential 60-70% reduction in operating dose. However, the solutions must be aged after mixing in order to obtain reproducible performance. This technique also requires work on a developer system. Flood exposure yields a 50% improvement in sensitivity but creates additional processing difficulties due to double exposure effects. 

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