Fully automated systems

In principle, on-line SPE-LC can be automated quite easily as well, for instance, by using Such programmable on-line SPE instrumentation as the Prospekt (Spark Holland) or the OSP-2 (Merck) which have the capability to switch to a fresh disposable pre-column for every sample. Several relevant applications in the biomedical field have been described in which these devices have been used. Eor example, a fully automated system comprising an autosampler, a Prospekt and an LC with a UV... 

A complicated analyser system such as that described above can only be maintained if all of the valve-switching events are scheduled in the correct positions in the chromatogram. Mismatch of one of the events will cause (parts of) components to be directed to the wrong columns and thus possible misidentifications. Therefore, accurate determination and maintenance of the cutting windows are essential. This can only be accomplished in a fully automated system with accurate flow and temperature controls. Once these prerequisites are fulfilled, the system will operate unattended and produce results of high quality. The repeatabilities generally achieved are of the order of 1 % rel. 

Fig. 3-1. Block diagram of General Electric X-ray Thickness Gage for steel strip (manually controlled). A similar gage is now part of a fully automated system that controls the rolling of steel strip.6 (Liebhafsky, Anal. Chem., 21, 17.)... 

A programmable device that accurately and precisely delivers predefined quantities of liquid to a MICROPLATE. It may be free-standing incorporated into a WORKSTATION, or part of a fully automated system. 

Most manufacturers of dissolution testing devices offer semi-automated systems that can perform sampling, filtration, and UV reading or data collection. These systems automate only a single test at a time. Fully automated systems typically automate entire processes including media preparation, media dispensing, tablet or capsule drop, sample removal, filtration, sample collection or analysis (via direct connection to spectrophotometers or HPLCs), and wash cycles. A fully automated system allows automatic performance of a series of tests to fully utilize unused night and weekend instrument availability. 

Any decision to establish automated or robotic systems must carefully consider prerequisites such as the annual numbers of samples to be processed to achieve an acceptable cost-to-benefit ratio. Late phase development stability studies may benefit from fully automated systems based on the enormous numbers of samples to be analyzed for each stability time point. The use of automated systems in manufacturing quality control is now required due to the sheer number of samples to be... 

The Gilson Aspec automatic sample preparation system is a fully automated system for solid-phase extraction on disposable columns and online HPLC analysis. The Aspec system offers total automation and total control of the entire sample preparation process including clean-up and concentration. In addition, Aspec can automatically inject prepared samples into on-line HPLC systems. 

This is a fully automated system capable of determining between lpg L 1 and 300pg L 1 total organic carbon. It is equipped with a 36-place autosampler, microprocessor and printer. Total organic carbon measurements down to 40pg L 1 have been achieved at a coefficient of variation of 16.3%. 

Fully automated systems can be purchased off the shelf or fully customized. Customized systems offer exactly what the customer wants and needs, for example a system might be optimized for one high volume product. Off the shelf systems are available that are fully integrated systems with components designed by the provider. As with the semiautomated systems modular approaches are also available primarily through automation companies. Modular approaches allow the use of standard industry apparatus that the user already owns and uses (Fig. 5). 

Early laboratory robots were unreliable, but today, these systems perform quite well. Today s robots simply move plates from one robot-friendly position to another, such as the entrance pad of a plate reader. These simplified movements combined with the low weight of a plate allow engineering to simplify the robot designs. As seen in industrial application of robots, robots that are defined and used for a specific application will work day in and day out quite well. It is always best to keep the automation as simple as possible to get the highest level of performance. This is usually accomplished by minimizing the number of moveable parts associated with the automation. Stackers have also become more reliable. This was due, in part, to the standardization of the microplate by an effort of the Society for Biomolecular Screening (Danbury, CT, U.S.A.) in association with the American National Standards Institute (ANSI, Washington, DC, U.S.A.), but also due to the use of simpler stacker mechanisms. Today, there are many choices for devices, workstations, and fully automated systems. The selection as to which automated devices to purchase for HTS should be driven by a clear set of specifications that define the use of the automation. The choices can be expensive, and therefore, replacement may not be possible, so it is important to choose well. 

A fully automated system for performing detailed studies has been developed to improve the reproducibility and throughput (Fig. 12.2) [8]. It consists of two functional components a sample-deuteration device and a protein processing unit. The preparation operations (shown at the top of Fig. 12.2) are performed by two robotic arms equipped with low volume syringes and two temperature-controlled chambers, one held at 25 °C and the other held at 1 °C. To initiate the exchange experiment, a small amount of protein solution is mixed with a deuter-ated buffer and the mixture is then incubated for a programmed period of time in the temperature-controlled chamber. This on-exchanged sample is immediately transferred to the cold chamber where a quench solution is added to the mixture. 

Fig. 12.2 Diagram of a fully automated system for acquiring H/D exchange MS data starting with a stock solution of the nondeuterated protein. In this system [8], the liquid handler mixes a small amount of concentrated protein solution with a selected deuterated buffer and the mixture is incubated for a programmed period of time. The exchange reaction is conducted in a temperature-controlled chamber held at 25 °C. The mixture is then transferred to an acidic quench solution held at 1 °C. After quenching the exchange reaction, the entire sample is injected onto an LC-MS system...

The majority of commercial developments which relate to the automation of GC and HPLC pay little attention to sample preparation. There are few examples where pretreatment is not required. A fully automated system was developed by Stockwell and Sawyer [23] for the determination of the ethanol content of tinctures and essences to estimate the tax payable on them. An instrument was designed and patented which coupled the sample pre-treatment modules, based on conventional AutoAnalyzer modules, to a GC incorporating data-processing facihties. A unique sample-injection interface is used to transfer samples from the manifold onto the GC column. The pretreated samples are directed to the interface vessel hy a simple hi directional valve. An ahquot (of the order of 1 ml) can then he injected on to the GC column through the capillary tube using a time-over pressure system. 

It is noteworthy to mention that all spheronizers across scales and manufacturers have the same basic design component, i.e., a rotating circular metal plate. A fully automated system, as shown in Figure 18, has two plates rotating in tandem to handle large batch sizes in a continuous operation. There... 

A fully automated system uses either cDNA fragments of known genes or libraries of oligonucleotides, which are then spotted in duplicate onto hybridization filters (nylon membranes or PVDF) with a grid for guidance. When nylon membranes are used, these filters in microarrays can be used several times. There are two possible ways of applying the DNA to the filter (Cahill, 2001) ... 

Buegelsdijk et al. described a fully automated system for preparation of dissolved Pu metal samples using the Zymate II (Zymark Corporation) laboratory robot.67 The sample preparation steps included bar-code label reading, weighing the sample, and transfer to the dissolution vessel. 

By the late 1990s and into the 2000s, a number of additional groups became involved in automated fluidic separations for radiochemical analysis, especially as a front end for ICP-MS. Published journal articles on fluidic separations for radio-metric or mass spectrometric detection are summarized in Tables 9.1 through 9.5. The majority of such studies have used extraction chromatographic separations, and these will be the main focus of the remainder of this chapter. Section 9.4 describes methods that combine separation and detection. Section 9.5 describes a fully automated system that combines sample preparation, separation, and detection. 

The different solid materials are catalytically tested in the liquid phase at 60°C, employing a fully automated system. This enables multiple parallel batch reactions in up to 21 vials under the following conditions ... 

All MSDS documents must be read from a practical as well as scientific viewpoint. The most appropriate grade of safety equipment must be used. The equipment must stop the offending material from reaching the person it is protecting. The useful life of the equipment must not be exceeded. Engineering the problem out is the best solution. An example is the fully automated system for handling MOCA. 

In addition, fully automated systems have to be constructed which combine the synthesis of the molecules to be tested and the subsequent screening of these molecules. Still a few non-automated steps are established in industrial research due to the absence of suitable tools. 

In this report it will be shown how many of these unit operations can be combined into partially- or fully-automated systems. Although several types will be described, the emphasis will be on HPLC-based systems. And that is probably as it should be, because HPLC is still the most popular analytical technique, according to Thomas Mosbacher 0). 

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