Synthesis robot, automated

If small or medium libraries for lead optimization are demanded and all synthetic products are to be screened individually, most often parallel synthesis is the method of choice. Parallel syntheses can be conducted in solution, on solid phase, with polymer-assisted solution phase syntheses or with a combination of several of these methods. Preferably, parallel syntheses are automated, either employing integrated synthesis robots or by automation of single steps such as washing, isolation, or identification. The latter concept often allows a more flexible and less expensive automation of parallel synthesis. 

The temperature optimization for the RAFT polymerization of EAA revealed an optimum reaction temperature of 70 °C. Block copolymers with a poly(methyl acrylate) (PMA), a poly(n-butyl acrylate) (PnBA), a PMMA, or a poly(A,A-dimethyl aminoethyl methacrylate) (PDMAEMA) first block and a poly(l-ethoxyethyl acrylate) (PEEA) second block were successfully synthesized in an automated synthesizer. The synthesis robot was employed for the preparation of 16 block copolymers consisting of 25 units of the first block composed of PMA (exp. 1 ), PnBA (exp. 5-8), PMMA (exp. 9-13), and PDMAEMA (exp. 13-16) and a second block of PEEA consisting of 25, 50, 75, or 100 units, respectively. The first blocks were polymerized for 3 h and a sample from each reaction was withdrawn for SEC analysis. Subsequently, EAA was added and the reactions were continued for 12 h. The molar masses and PDI values of the obtained block copolymers are shown in Fig. 15. 

An important feature is that, with the exception of the catalyst synthesis, this is a fully automated process. Indeed, we envisage that in industry the entire process, including the synthesis and testing, can be automated using commercially available synthesis robots. If robotic synthesis and screening is available, the size of the test sets can be increased. Moreover, it is precisely the automated modelling and analysis aspect that is lacking in the robotic laboratory workflow. 

Key Words Cell-free protein synthesis wheat embryo extract 5 and 3 ORF design pEU construction bilayer reaction method robotic automation. 

The Bilayer Reaction and the Robotic Automation of Protein Synthesis... 

Integration of automated amide synthesis with automated purification has been implemented by workers at Bristol-Myers Squibb [89] using a Zymark robotic system. 

The preparation according to the recipes involved both automated and manual operations. Impregnation and drying steps were carried out on a Sophas synthesis robot described elsewhere [8], Samples were then transferred manually to ceramic crucibles and calcined in air in programmable ovens. 

Automated high-throughput screening Combinatorial synthesis Robotic search for marketable materials Systematic discovery of new drugs Testing substances for synergetic effects... 

For catalyst preparation all techniques are available that are used in standard lab preparation of inorganic materials. Most of the preparation steps can be automated and can be done in parallel using synthesis robots. In the next sections, the most frequently used preparation routes are discussed. Postsynthesis treatment steps common to many different preparation routes are discussed separately at the end of the section. 

To understand the effect of molecular structure on the thermoresponsive OEGMA (co) polymers, polymer libraries were evaluated. By systematically varying the structure, for example, length or composition, of the copolymers followed by evaluation of the thermoresponsive properties, structure-property relationships are revealed. However, the preparation of such libraries of polymers can be very time consuming and is prone to human errors due to less-challenging repetition of similar experiments. Therefore, we have adapted the use of automated parallel synthesis robots for both the optimization of polymerization conditions as well as the preparation of polymer libraries (Hoogenboom et al, 2003 Meier et al, 2004). These synthesis robots will be discussed in this section as well as their use for the optimization of the RAFT polymerization process to demonstrate the added value of such equipment. 

At first, the RAFT polymerization with CBDB and AIBN was optimized in the automated parallel synthesis robot for the polymerization of MMA (Fijten et aL, 2004). The RAFT agent AIBN ratio was varied from I I to 1 0.05 for polymerizations in toluene at 70°C revealing uncontrolled polymerizations at a 1 1 ratio and very slow controlled polymerizations with a... 

Will this allow syntheses to be automated It depends how difficult syntheses are (and will provide a way of quantifying this). It may be that the best possible synthesis is not required, provided that a good route is available, as assessed by total cost (including waste disposal and safety precautions), by time required, by certainty of success, by ease of using robots to follow the procedure, and so on. 

As already mentioned above, a different strategy to achieve high throughput in microwave-assisted reactions can be realized by performing automated sequential microwave synthesis in monomode microwave reactors. Since it is currently not feasible to have more than one reaction vessel in a monomode microwave cavity, a robotic system has been integrated into a platform that moves individual reaction... 

We use the term programmable to describe the rational (and ideally, computer-aided and automated) approach to polysaccharide synthesis.20 To reduce the synthesis of complex carbohydrates to routine, we envision a four-step protocol (1) the sequence of interest is keyed into a computer, (2) the computer selects appropriate reagent combinations, (3) a laboratory worker (human or robotic) prepares the reagent... 

The PNA chain was linked to the peptide spacer glutamic acid-(y-tert-butyl ester)-(fi-aminohexanoic acid)-(fi-aminohexanoic acid) (Glu [OtBuj-fiAhx-fiAhx) via an enzymatically cleavable Glu-Lys handle. The Glu [OtBuj-fiAhx-fiAhx spacer was coupled to the amino-functionalized membrane by standard Fmoc-Chemistry. Then the membranes were mounted in an ASP 222 Automated SPOT Robot and a grid of the desired format was dispensed at each position. The free amino groups outside the spotted areas were capped and further chain elongation was performed with Fmoc-protected PNA monomers to synthesize the desired PNA oligomers (18). After completion of the synthesis, the PNA oligomers were cleaved from the solid support by incubation with bovine trypsin solution in ammonium bicarbonate at 37 °C for 3 h. 

Enrichment of high affinity candidates is usually achieved in 8 to 15 rounds of SELEX. Each rotmd takes approximately 2 days to perform. The process has been automated using robotic liquid handlers both for DNA (SomaLogic) and RNA aptamers (Cox, 2002). Next, the sequenced aptamer is prepared in bulk by conventional DNA synthesis chemistry and purified, then the aptamer arrayed onto a solid support. Thus, an aptamer is ready for application within 2 to 3 mo. Because the sequence is known, preparation of additional aptamer is easily accomplished using conventional oligonucleotide chemical synthesis. 

Rojas R, Harris NK, Piotrowska K, Kohn J (2009) Evaluation of automated synthesis for chain and step-growth polymerizations can robots replace the chemists J Poly Sd Part A Polym Chem 47 48-58... 

The next step in the process involves the implementation of the automated synthesis and generation of the library. Significant lead time is anticipated before a library can be produced because even the most reliable chemical reactions require optimization if they are to be carried out by a robot, particularly if... 

---