DOMINO BLOCK

The Domino Block is designed for parallel solid-phase synthesis: it substantially simplifies liquid exchange in reaction vessels (Krchnak & Padera, Bioorg. Med. Chem. Lett. 1998, 8, 3261). The only operation necessary for washing the resin in the 48 reaction vessels is turning a handle of a valve. The name Domino Block reflects the resemblance of this liquid distribution manifold to a domino piece.

The Domino Block is Teflon-made liquid distribution manifold (footprint of a standard 96-well plate) that connects all reaction vessels to one common port of a distribution valve. This common port is used to introduce and remove the solvent. Plastic polypropylene syringes equipped with a porous disk at the bottom are used as reaction vessels. The syringes, charged with resin, are attached via a male Luer fitting to the Domino Block arrayed with a female Luer lock fittings. Three different Domino Blocks are available. Domino Blocks for 24 syringes (4 rows of 6 syringes) accommodate 2.5 and 5 mL syringes, Domino Blocks for 12 syringes (3 rows of 4 syringes) accommodate syringe size up to 20 mL amd Domino Blocks for 6 syringes (2 rows of 3 syringes) designed for 50 mL syringes. This Domino Block has a special holder to prevent losing syringes during shaking.

The concept of liquid exchange is based on a simple principle. At first, a single outlet reaction vessels (e.g. a plastic syringes), loaded with resin, are connected to an evacuated waste container. The difference in pressure between the reaction vessel (atmospheric pressure) and the evacuated waste container draws the liquid from the reaction vessel into the waste container and creates a vacuum inside the reaction vessel. The evacuated reaction vessels are then connected to a solvent reservoir. The pressure difference causes the evacuated reaction vessels to be filled with the solvent from the reservoir. The role of the Domino Block is to enable the liquid exchange in a number of reaction vessels at the same time.

The Domino Block synthesizer with four Domino Blocks is shown in the cartoon. To operate four Domino Blocks at the same time, common ports of 4-port distribution valves V1 and  V2 were connected. Four ports of the Domino Block selection valve V1 were connected to four Domino Blocks. Four Domino Blocks were placed on a Titer-plate shaker (Lab-Line Instruments) that provided adequate mixing of the the resin in reaction vessels. One port of the distribution valve V2 was connected to the evacuated waste container, and the opposite port was connected to the common port of valve V3. Four ports of this valve were connected to four solvent reservoirs.
To empty reaction vessels, valve V2 was connected to the evacuated waste container.  After the syringes were emptied, which typically took less than 10 sec, the valve V2 was turned to the port "Air/gas inlet" for a fraction of a second. A small amount of air/inert gas was introduced into syringes via this port.

Then the valve V2 was turned to the Solvent position. Domino Block was connected with one of the solvent containers. The evacuated reaction vessels were filled with this solvent. 
While the solvent was exchanged in reaction vessels on one Domino Block, the resin in the other three Domino Blocks was shaken with the washing solvent. It is necessary that the resin beads were exposed to the fresh solvent for at least one minute to allow diffusion of soluble compounds out of the beads. In the meantime, the solvent in the next three Domino Blocks can be changed. Since the entire washing cycle requires only switching the connection between the evacuated waste container and solvent reservoir, the washing process can be easily automated.
All reaction vessels can receive a common reagent from a syringe attached to the Reagent port. After washing the resin beads with the last wash solvent, the reaction vessels were emptied by connecting them to the evacuated waste container. Then the valve was turned to the Reagent position. The solution in the reagent syringe was drawn into reaction vessels. During the reaction, the Domino Blocks with reaction vessels can be left on the shaker. Alternatively, the reaction vessels can be removed from the Domino Block and rotated on a tumbler, or they can be placed into an oven to perform the reaction at elevated temperature.
The Domino Block does not need to be fully loaded with syringes. Unused positions can be closed, and the synthesizer can operate with as little as one reaction vessel at a time