Miniaturised instruments

The war itself also drove the development of improved and miniaturised electronic components for creating oscillators and amplifiers and, ultimately, semiconductors, which made practical the electronic systems needed in portable eddy current test instruments. The refinement of those systems continues to the present day and advances continue to be triggered by performance improvements of components and systems. In the same way that today s pocket calculator outperforms the large, hot room full of intercormected thermionic valves that I first saw in the 50 s, so it is with eddy current instrumentation. Today s handheld eddy current inspection instrument is a powerful tool which has the capability needed in a crack detector, corrosion detector, metal sorter, conductivity meter, coating thickness meter and so on. 

Miniaturisation of electronic components has enabled the construction of a compact, portable, battery-operated recording voltmeter. The principal use of this instrument is to measure pipe/soil potential fluctuations over a period of time. The instrument can be modihed to measure current variations. 

Many of the classical techniques used in the preparation of samples for chromatography are labour-intensive, cumbersome, and prone to sample loss caused by multistep manual manipulations. During the past few years, miniaturisation has become a dominant trend in analytical chemistry. At the same time, work in GC and UPLC has focused on improved injection techniques and on increasing speed, sensitivity and efficiency. Separation times for both techniques are now measured in minutes. Miniaturised sample preparation techniques in combination with state-of-the-art analytical instrumentation result in faster analysis, higher sample throughput, lower solvent consumption, less manpower in sample preparation, while maintaining or even improving limits. 

Miniaturisation of SPE has also been described [504]. Thurman and Mills [508] discussed the history and future of SPE. The technique will continue to replace LLE. More on-line use of both LC and GC are prospected. As instruments such as GC-MS and HPLC-MS become more sensitive, smaller sample sizes may be used. New phases will continue to be introduced to take full advantage of specific interactions. It is expected that at last sample handling and SPE will reach the level of sophistication that its relatives in LC have reached, and perhaps go beyond. 

Implementation of SFC has initially been hampered by instrumental problems, such as back-pressure regulation, need for syringe pumps, consistent flow-rates, pressure and density gradient control, modifier gradient elution, small volume injection (nL), poor reproducibility of injection, and miniaturised detection. These difficulties, which limited sensitivity, precision or reproducibility in industrial applications, were eventually overcome. Because instrumentation for SFC is quite complex and expensive, the technique is still not widely accepted. At the present time few SFC instrument manufacturers are active. Berger and Wilson [239] have described packed SFC instrumentation equipped with FID, UV/VIS and NPD, which can also be employed for open-tubular SFC in a pressure-control mode. Column technology has been largely borrowed from GC (for the open-tubular format) or from HPLC (for the packed format). Open-tubular coated capillaries (50-100 irn i.d.), packed capillaries (100-500 p,m i.d.), and packed columns (1 -4.6 mm i.d.) have been used for SFC (Table 4.27). 

Mass spectrometers must be regularly tuned or calibrated against a known standard, e.g. perfluorotributy-lamine (PFTBA). The trend is towards miniaturisation (10 x 24 x 14 in.). A concept for a micro mass spectrometer, with potential applications in process monitoring, has been presented [167]. Mass-spectrometry instrumentation (1997) has been reviewed [166]. 

Many excellent reviews on the development, instrumentation and applications of LC-MS can be found in the literature [560-563]. Niessen [440] has recently reviewed interface technology and application of mass analysers in LC-MS. Column selection and operating conditions for LC-MS have been reviewed [564]. A guide to LC-MS has recently appeared [565]. Voress [535] has described electrospray instrumentation, Niessen [562] reviewed API, and others [566,567] have reviewed LC-PB-MS. For thermospray ionisation in MS, see refs [568,569]. Nielen and Buytenhuys [570] have discussed the potentials of LC-ESI-ToFMS and LC-MALDI-ToFMS. Miniaturisation (reduction of column i.d.) in LC-MS was recently critically evaluated [571]. LC-MS/MS was also reviewed [572]. Various books on LC-MS have appeared [164,433,434,573-575], some dealing specifically with selected ionisation modes, such as CF-FAB-MS [576] or API-MS [577],... 

Miniaturisation of scientific instruments, following on from size reduction of electronic devices, has recently been hyped up in analytical chemistry (Tables 10.19 and 10.20). Typical examples of miniaturisation in sample preparation techniques are micro liquid-liquid extraction (in-vial extraction), ambient static headspace and disc cartridge SPE, solid-phase microextraction (SPME) and stir bar sorptive extraction (SBSE). A main driving force for miniaturisation is the possibility to use MS detection. Also, standard laboratory instrumentation such as GC, HPLC [88] and MS is being miniaturised. Miniaturisation of the LC system is compulsory, because the pressure to decrease solvent usage continues. Quite obviously, compact detectors, such as ECD, LIF, UV (and preferably also MS), are welcome. 

Minimisation of sample preparation is the main bottleneck in polymer/additive analysis. The importance of sample preparation increases with miniaturisation of the separation techniques. However, there is no point in improving instrumentation when the true sources of errors in measurement are sampling, sample inhomogeneity or sample instability. 

Liquid crystals, commonly referred to as the fourth state of matter, are materials which are intermediate in character between the solid and liquid states. Unlike normal isotropic liquids, they show some time-averaged positional orientation of the molecules, but they retain many of the properties of liquids, such as the ability to flow. In recent decades, liquid crystals have played an increasingly important part in our lives. Probably their most familiar application is in the information displays which provide the visual interface with microprocessor-controlled instrumentation. Liquid crystal displays have superseded more traditional display technology, such as light-emitting diodes and cathode ray tubes, for many appliances principally because of the advantages of visual appeal, low power consumption, and their ability to facilitate the miniaturisation of devices into which they are incorporated. They are encoun-... 

Despite these caveats, IR is an excellent tool for API process monitoring because of its chemical information content. This is particularly valuable in early-stage development when it can yield crucial information about unexpected reaction intermediates and side reactions and therefore lead directly to a more robust process. Commercial instrumentation is widely available for this purpose [78] and development of cheaper, smaller and more rugged instrumentation continues apace [79]. For example, a miniaturised mid-infrared spectrometer and... 

The identification of a compound using only its retention time is vulnerable to error. It is essential that a standard compound is injected in order to verify the retention time. As is the case in gas chromatography, more sophisticated detectors can be used. These detectors provide complementary information and can be installed at the end of the column. These can be other types of spectrophotometers or a mass spectrometer and they are used simultaneously as classical detectors (to obtain the chromatogram) or for identification purposes of the analytes (cf. Chapter 16). For example, the coupling of HPLC to NMR, which has long been considered impossible, has now been realised through the miniaturisation of the probes and the increased sensitivity of the NMR instruments (cf. Chapter 9). 

This type of instrument resembles a spectrograph because it allows the simultaneous measurement of all wavelengths. It uses an array of up to 2 000 miniaturised photodiodes (Fig. 11.13). A full spectrum can be recorded in milliseconds with this type of simultaneous acquisition detector, each diode measuring the light intensity over a small interval of wavelength. The resolution power of these diode-array spectrometers is limited (usually 1 to 2nm) by the size of the diodes. 

Mass spectrometry (MS) is an analytical method based on the determination of atomic or molecular masses of individual species in a sample. Information acquired allows determination of the nature, composition, and even structure of the analyte. Mass spectrometers can be classified into categories based on the mass separation technique used. Some of the instruments date back to the beginning of the twentieth century and were used for the study of charged particles or ionised atoms using magnetic fields, while others of modest performance, such as bench-top models often used in conjunction with chromatography, rely on different principles for mass analysis. Continuous improvements to the instruments, miniaturisation and advances in new ionisation techniques have made MS one of the methods with the widest application range because of its flexibility and extreme sensitivity. 

The technical development is still very rapid and addresses the growing need within process monitoring. The current trend includes further improvement of instrument design for smaller and more rugged equipment, integration into automated analytical systems and miniaturisation for multiple installations and portability. 

Further advances in miniaturisation and reduction of power consumption are envisaged that could lead to more effective handheld instruments that outperform the existing ones and approach the performance of current larger instruments. The wider applications and lower cost of the new devices will be expected to further drive the emergence of new application areas across many disciplines including those covered in this book. 

EC detection is a promising alternative for capillary electrophoresis microchips due to its inherent characteristics, allowing a proper miniaturisation of the devices and compatibility with the fabrication processes, in case of an integrated detection. Moreover, the low cost associated permit the employment of disposable elements. As the EC event occurs on the surface of electrodes and the decrease in size usually results in new advantages (see Chapter 32), the possibilities of incorporating EC detectors are broad. The simplicity of the required instrumentation, portable in many cases, suit well with the scaling-down trend. Moreover, as the sample volume in conventional micro-channel devices is less than 1 nL, a very highly sensitive detector should be constructed to analyse even modest concentrations of sample solutions. Since sensitivity is one of the accepted characteristics of EC detection EC-CE microchips approach to the ideal analytical devices. 

The miniaturisation of analytical devices has obvious uses in high throughput screening in drag discovery and the developments are being driven along by collaboration between instrument manufacturers and the large pharmaceutical companies. The term miniaturised total analysis system or pTAS is also used in the analytical field. 

However, as is the case with all techniques, there are some disadvantages in the miniaturisation of LC columns. These are mainly due to technical and instrumental problems. Table 4.1 compares how reducing the column diameter affects the size of the injection and detection volumes, for the equivalent conditions, with different diameter columns. 

The evolution of flow analysis has caused a paradigm shift in Analytical Chemistry. Modern innovations are more associated with the duality of chemical equilibria and kinetics than simply with chemical equilibria. Instrumentation has experienced continuous downsizing, and the availability of miniaturised systems generating lower volumes of... 

Major trends in the future growth of flow analysis are likely to include the evolution of instrument design (including miniaturisation and expert flow systems), the recognition of more flow-based standard methods, hyphenation with other detection systems and an impact on chemical measurements in new and emerging areas of science. 

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