Sample processing, miniaturization

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). 

Cell harvesters were developed to capture multiple samples of cells on membrane filters, wash away unincorporated isotopes, and prepare samples for liquid scintillation counting on special equipment developed to process and count multiple samples. Despite miniaturization and improvements in efficiency of this technique, the disadvantages of multiple liquid handling steps and increasing costs for disposal of radioactive waste materials severely limit its usefulness. Although specific applications require measuring DNA synthesis as a marker for cell proliferation, much better choices are available for detecting viable cell number for HTS. 

Microfluidics and miniaturization include the development of small and microscale devices to permit chemical measurements, with the objective of field portability or bedside use. Examples include Raman spectroscopy and mass spectrometry. The category also includes devices that employ small-scale fluidics to provide automated sample processing, chemical reactions, separation, and measurement in devices popularly called lab-on-a-chip. 

Agilent s Bioanalyzer is another breakthrough system which enables real-time analysis of different bioagents. It combines a variety of approaches, including DNA microarrays, bioinformatics, and Lab-on-Chip. This device integrates fluid handling, sample processing, separation, and detection in miniature chip. 

These miniature size samples have been developed and correlated to standard ASTM size samples for tensile and flexural methods which use fairly large samples. These miniature samples were first developed so that test samples could be cut from main propellant valve lip seals. The whole lip seal would have to be cut up and remolded in order to have enough material for one standard ASTM-size sample. Since many properties of the material are dependent on the processing techniques used in its fabrication, this remolding could result in a material very different from the original lip seal. These samples and their accompanying scaled-down test fixtures have also made it possible to accurately determine the low-temperature mechanical properties of materials with a minimum quantity of coolant. Because of the small sample and small jaw size and the attendant quick cooling, additional economies are effected by the ability to test samples in a comparatively short time. 

Y. Yu, Y. Jiang, M. Chen, J. Wang, Lan-on-valve in the miniaturization of analytical systems and sample processing for metal analysis. Trends Anal. Chem. 30 (2011) 1649—1658. 

Figure 2, Top view of the miniature centrifugal analyzer. The sample disc, not shown, fits on the rotor holder and can process 16 samples and 1 reference simultaneously, (Courtesy of Dr, Carl A, Burtis),...

---