Automatic Rapid Chemistry

The experiments within the frame of the REHE project were performed in the aqueous phase in a discontinuous, batch-wise manner. It was necessary, in order to get a statistically significant result, to repeat the same experiment several hundred or even several thousand times with a cycle time of typically 45 s. These studies were performed with the Automatic Rapid Chemistry Apparatus (ARCA) II (SchSdel et al, 1989), a computer-controlled apparatus for fast, repetitive high-performance liquid chromatography (HPLC) separations. A schematic of the ARCA II components is shown in Figure 6.2. 

One area of analytical chemistry which is currently developing rapidly is the automation of methods. Some degree of automation has been used for a number of years in instruments such as automatic burettes coupled to absorptiometric or electrometric end-point detectors, and in data output devices which provide continuous pen recording or signal integration facilities. The major features of recent developments include the scope for instrumental improvements provided by solid-state electronic circuits and the increasing application of digital computers (Chapter 13). 

Special or routine chemistry runs can be interrupted at any time to perform rapid STATs with simultaneous multi-analyte analysis. The Cobas Fara II provides STAT test results in as httle as 60 seconds with true Sample-Prioritized capabihty. Routine testing resumes automatically from the point of STAT interruption. 

In 1991, we first introduced the one-bead one-compound (OBOC ) combinatorial library method.1 Since then, it has been successfully applied to the identification of ligands for a large number of biological targets.2,3 Using well-established on-bead binding or functional assays, the OBOC method is highly efficient and practical. A random library of millions of beads can be rapidly screened in parallel for a specific acceptor molecule (receptor, antibody, enzyme, virus, etc.). The amount of acceptor needed is minute compared to solution phase assay in microtiter plates. The positive beads with active compounds are easily isolated and subjected to structural determination. For peptides that contain natural amino acids and have a free N-terminus, we routinely use an automatic protein sequencer with Edman chemistry, which converts each a-amino acid sequentially to its phenylthiohydantoin (PTH) derivatives, to determine the structure of peptide on the positive beads. 

One area of analytical chemistry which is currently developing rapidly is the automation of methods. Some degree of automation has been used for a. number of years in instruments such as automatic burettes coupled to... 

Probably no technique in analytical chemistry has been more quickly and widely adopted than gas chromatography. It is ideally suited to the separation and analysis of nonpolar volatile materials such as hydrocarbons. Factors that have contributed to this rapid development are (/) the success of the method in performing quantitative separations of closely related substances, (2) the ease with which the operation can be made automatic, (5) the speed, predsion, and accuracy with which quantitative determinations can be made, (4) the small quantities of simple required, and (5) the rapid development of sensitive detection devices. The prindpal limitation is that the method is restricted to materials that exert vapor pressures of at least 10 mm Hg at the temperature of the column (ranging up to 300°C or somewhat higher). 

What follows is intended as a review of our own work, which is a small part of a rapidly growing area of chemistry. Note, for example, reference 1. Our emphasis has been on redox events at chemically fabricated metal and semiconductor interfaces. Given the chemical sites used and the configuration of the resulting structures, the presence of the electrode automatically provides a method of analysis and a means for monitoring interfacial events. The electrode also serves as a controlled potential source of oxidizing or reducing equivalents for the interface. 

The simplex methods, as the very name implies, are based on very simple algorithms that can be very easily implemented on analjrtic instruments, transforming the optimization of their performance into an automatic procedure. On the other hand, simplex optimization is always sequential since we can only go to the next step after we know the result of the immediately preceding step. Whereas when we are determining a response siuface we can perform several experiments at the same time to complete a factorial design, the simplex methods only permit us to do one experiment at a time (that is why they are called sequential). This characteristic makes simplex use most convenient for rapid response instruments that are ofl en encountered in anal3d ical chemistry laboratories. 

---