Process and apparatus for combinatorial synthesis
First Claim
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1. A synthesizer for combinatorial chemistry comprising:
- a plurality of synthesizer columns adapted to retain solid reaction supports within the columns during a series of reaction steps, each synthesizer column comprising a reagent fluid path selectively controlled by individual inlet and outlet reagent valves disposed on opposite ends of each column, and a mixing fluid path selectively controlled by individual first and second mixing valves disposed on opposite ends of each column;
a common mixing chamber in fluid communication with each of the synthesizer columns when the mixing fluid path is established by flow through the first mixing valves of each synthesizer column, said first mixing valves disposed in-line between each synthesizer column and common mixing chamber;
a pressure controllable fluid reservoir in fluid communication with the mixing fluid path and adapted to provide a motive force to the mixing fluid path to transport a stream of fluidized solid supports into the synthesizer columns for the series of reaction steps as well as out of the synthesizer columns and into a common mixing chamber between reaction steps.
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Abstract
Apparatus and methods are described for split synthesis combinatorial chemistry that provides candidate libraries where an even distribution of theoretical products is obtainable through even mixing during the pooling step, followed by controlled redistribution of the mixed pooled products from the prior addition step into separate synthesis columns, one for each different specie of subunit to be added.
108 Citations
18 Claims
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1. A synthesizer for combinatorial chemistry comprising:
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a plurality of synthesizer columns adapted to retain solid reaction supports within the columns during a series of reaction steps, each synthesizer column comprising a reagent fluid path selectively controlled by individual inlet and outlet reagent valves disposed on opposite ends of each column, and a mixing fluid path selectively controlled by individual first and second mixing valves disposed on opposite ends of each column; a common mixing chamber in fluid communication with each of the synthesizer columns when the mixing fluid path is established by flow through the first mixing valves of each synthesizer column, said first mixing valves disposed in-line between each synthesizer column and common mixing chamber; a pressure controllable fluid reservoir in fluid communication with the mixing fluid path and adapted to provide a motive force to the mixing fluid path to transport a stream of fluidized solid supports into the synthesizer columns for the series of reaction steps as well as out of the synthesizer columns and into a common mixing chamber between reaction steps. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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13. A synthesizer for combinatorial chemistry comprising:
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a plurality of synthesizer columns, each column comprising; a fritted reagent inlet aperture and a non-fritted mixing aperture disposed on a first end of each column, a fritted outlet aperture on a second end of each column, a reagent inlet valve in fluid communication with the fritted reagent inlet aperture and a reagent outlet valve in fluid communication with the fritted outlet aperture; a first mixing valve in fluid communication with the non-fritted mixing aperture and a second mixing valve in fluid communication with the fritted outlet aperture; a common mixing chamber in selective fluid communication with each synthesizer column, wherein the first mixing valve of each synthesizer column is disposed between the synthesizer column and the common mixing chamber; a pressure controllable fluid reservoir in fluid communication with the mixing chamber and adapted to control a fluid flow of fluidized solid supports into the synthesizer columns for the series of reaction steps as well as out of the synthesizer columns and into the common mixing chamber between reaction steps. - View Dependent Claims (14, 15, 16, 17, 18)
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Specification