1 Gilson 222
5 arm with needle
7 reactionzone with glassware
8 variable reagents/TLC/SPE
9 central reagents
11 bar (Waste/HPLC/transfer ports) Fig. 6.6. ASW2000 layout.
Their main objective was to develop an unattended automated system that allowed parallel preparation of compounds in glassware reactors with online purification and analysis in a compact workstation approach (Fig. 6.6).
Chemspeed delivers the system on a trolley (footprint 1.4 m x 0.8 m) covered with a hood. Because of this compact design, the very flexible system can be used in nearly every laboratory. Within one run, 80 parallel reactions (with an option of 112) can be performed that have the following features:
• liquid capability of 13, 27, 75 or 100 ml per vial;
• fully inert environment inside and outside the reactors;
• reagent additions while shaking or stirring and while heating or cooling;
• classical laboratory procedures:
- mixing, vortexing, filtration,
- liquid-liquid extraction,
- drying, evaporation, cold finger refluxing;
• temperature range from —70 to +150 °C, measured and controlled in the reaction mixture;
• online analysis of purity and yield by thin layer chromatography (TLC) or analytical HPLC (optional);
• rheodyne valves for preparative HPLC.
The whole system can be upgraded into the ASW2000P workstation, which allows pressurized reactions that integrate work-up and analysis procedures during the synthesis. The pressure capabilities of the system are:
• up to five reactor blocks (80 parallel reactions at maximum);
• pressure sensor;
• autosecurity system to provide optimum seal performance.
Advanced ChemTech Since 1985, Advanced ChemTech (ACT)  has supplied systems for organic synthesis, which in the beginning were especially for peptide synthesis. Today ACT offers a broad "family" of manual, semiautomated, and automated synthesizers for solution- and solid-phase synthesis (Table 6.1).
The Venture 576 (launched in May 1999) is designed to be a platform for fully automated high-throughput synthesis (Fig. 6.7).
The heart of the Venture 576 is a special reaction block combined with two multiprobe XYZ arms. The microplate reactor block contains 96 wells and is constructed of glass-impregnated polytetrafluoroethylene (PTFE) constructions. The usable reaction well volume is approximately 3 ml compared with a total volume of 6 ml and allows parallel reactions in milligram scale even under a reactive gas atmosphere because reaction vessels can be pressurized up to 150 psi. The system is capable of up to 10,000 simultaneous reactions that are determined by the customer. The following description summarizes the main features of the system:
• inert atmosphere for reactor, reactants, and the whole platform;
• classical laboratory procedures:
- vortexing, filtration, liquid-liquid extraction;
• reactor block with integrated condenser module;
• temperature range from —70 to +150 °C, electric resistive heating, cooling by nitrogen gas generated from liquid nitrogen.
The floor-standing cabinet is equipped with connections for a ventilation system. Because the system is capable of performing up to 10,000 reactions per run, it is recommended for combinatorial laboratories producing large numbers libraries.
MultiSyn Tech Syro II MultiSyn Tech  offers manual, semiautomated, and fully automated systems for combinatorial chemistry. The fully automated Syro system
(Fig. 6.8) consists of two independent XYZ robot arms and a specially designed reaction block. The system can be equipped with different reaction vessels. For solid-phase synthesis the removable reaction vessels (number/volume: 96/2 ml; 60/5 ml; 40/10 ml) in glass or polypropylene with glass or PTFE frits are rec-
ommended. Owing to the reaction block design all manipulations can be performed under inert gas atmosphere using reaction temperatures between —60 and +150 °C.
The system has a specially designed agitation mechanism. Each reaction tube is circumvented by electric coils that are used to generate a magnetic field. The coils are placed in a movable levitation plate, the center of the magnetic field is about 6 mm above the frit of the reaction tubes. This special set-up ensures that, during agitation, the resin is not crushed between the stirring bar and the frit (Fig. 6.9).
Zenyx Magellan synthesizer In 1996, Zeneca Pharmaceuticals entered into a collaboration with Zenyx Scientific to design and build an instrument for multiple parallel synthesis . The new system was intended to fulfill the following main objectives:
• access to libraries containing up to 1000 single compounds;
• scale: up to 30 mg for primary screening and repository;
• microplates should be used as transfer racks.
The Magellan system is a fully automated synthesizer controlled by a computer. An Excel interface within the control software allows substance data to be imported for the reprogramming of standard protocols. With this system 96 reactions can be performed within one run, using a Stem  reaction block. The set-up is very flexible because the layout of the workstation can easily be changed. The XYZ robot arm is in charge of all pipetting jobs. After cleavage from the resin, the compounds can be delivered directly into disposable vials using a special 96-filter station with 96 individual needles with a filter frit at the end.
Perkin-Elmer Solaris 530 The Solaris™ 530  organic synthesizer for automated combinatorial chemistry was introduced in late 1998 by PE Biosystems, a division of the PE Corporation (Fig. 6.10).
The system is able to synthesize 48 discrete molecules per run in parallel. The portable synthesis module contains an array of 8 x 6 reaction vessels with a volume of 10 ml per vial (Fig. 6.11). A reflux channel is built in the chemically inert module to provide reflux conditions. The dual septa secures an inert atmosphere.
Key features of the system include:
• eight liquid-handling tips;
• seven sensors to monitor critical instrument functions;
• completely enclosed system with flow-through ventilation;
• multiple instrument sensors;
• offline workstation for heating, mixing, and cooling.
An offline incubation workstation enables multiuser access and staggered synthesis runs, which increases throughput. The system is designed for the automated lead optimization using solid-phase synthesis techniques.
Zinsser Sophas In 1998 Zinsser  launched the Sophas system, which is specially designed for solid-phase synthesis. The synthesizer uses a robotic XYZ arm with four independent probes that are manufactured by Rosys . All liquid-handling tasks are controlled via a personal computer. The easy-to-use software is very flexible, can import data from any database, and allows customized layouts to
be defined. The automated workbench offers the opportunity to choose from a set of movable reactors that range from 96-well plates to 25-ml reaction vessels.
Charybdis Technologies Illiad PS2 Charybdis Technologies  was founded in 1996, and provides solutions in the areas of high-throughput organic synthesis, laboratory automation, and chemical discovery. The Iliad PS2 Series are multitasking robotic workstations for solid- and solution-phase chemistry. The two independent XYZ robotic arms work in parallel and are controlled via the OASys software. The heart of all Charybdis synthesizers is the Calypso reaction block system, which consists of a top frame with a specially designed top cover plate and a base frame with a base cover plate. The reaction block accepts any array with the standard footprint of a microplate with well volumes of 50, 25, 10, 5, and 2 ml. The Iliad systems can be upgraded to provide online filtration and agitation.
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