Electrochemical solid phase synthesis of polymers
AssigneeCombiMatrix Corporation
InventorDonald D. Montgomery
Life of this patent
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Abstract
A solid phase synthesis method for the preparation of diverse sequences of separate polymers or nucleic acid sequences using electrochemical placement of monomers of nucleic acids at a specific location on a substrate containing at least one electrode that is preferably in contact with a buffering or scavenging solution to prevent chemical crosstalk between electrodes due to diffusion of electrochemically generated reagents.
Claims44
A method for electrochemical placement of a material at a specific location on a porous substrate, which comprises the steps of:
- providing a substrate having at its surface at least one electrode that is proximate to at least one molecule bearing at least one protected chemical functional group,
- placing a buffering solution in contact with the electrode and the porous substrate to prevent electrochemically generated reagents from leaving the locality of the electrode, wherein a buffering solution is one having the capacity to prevent pH changes upon addition of small amounts of acids or bases,
- applying a potential to said electrode sufficient to generate electrochemical reagents capable of deprotecting at least one of the protected chemical functional groups of said molecule, and
- bonding the deprotected chemical functional group with a monomer or a pre-formed molecule.
A method for electrochemical synthesis of an array of separately formed polymers on a porous substrate, which comprises the steps of:
- placing a buffering solution in contact with an array of electrodes that is proximate to a substrate surface, said surface being proximate to one of more molecules bearing at least one protected chemical functional group attached thereto, wherein a buffering solution is one having the capacity to prevent pH changes upon addition of small amounts of acids or bases;
- selectively deprotecting at least one protected chemical functional group on at least one of said molecules;
- bonding a first monomer having at least one protected chemical functional group to one or more deprotected chemical functional groups of aid molecule;
- selectively deprotecting a chemical functional group on the bonded molecule or another of said molecules bearing at least one protected chemical functional group;
- bonding a second monomer having at least one protected chemical functional group to a deprotected chemical functional group of the bonded molecule or said other deprotected molecule;
- and
- repeating the selective deprotection of a chemical functional group on a bonded protected monomer or a bonded protected molecule and the subsequent bonding of an additional monomer to said deprotected chemical functional group until at least two separate polymers of desired length are formed on the substrate surface.
A method for electrochemical synthesis of an array of separately formed oligonucleotides on a porous substrate, which comprises the steps of:
- placing a buffering solution in contact with an array of electrodes that is proximate to a substrate surface, said surface being proximate to one of more molecules bearing at least one protected chemical functional group attached thereto, wherein a buffering solution is one having the capacity to prevent pH changes upon addition of small amounts of acids or bases;
- selectively deprotecting at least one protected chemical functional group on at least one of said molecules;
- bonding a first nucleotide having at least one protected chemical functional group;
- bonding a second nucleotide having at least one protected chemical functional group to a deprotect chemical functional group of the nucleotide bonded molecule or said other deprotected molecule, and
- repeating the selective deprotection of a chemical functional group on a bonded protected nucleotide or a protected bonded molecule and the subsequent bonding of an additional nucleotide to said deprotected chemical functional group until at least two separate oligonucleotides of desired length are formed on the substrate surface.
A method for electrochemical placement of a material at a specific location on a porous substrate, which comprises the steps of:
- providing a substrate having at its surface at least one electrode that is proximate to at least one molecule that is reactive with an electrochemically generated reagent,
- placing a substrate having at is surface at least one electrode that is proximate to at least one molecule that is reactive with an electrochemically generated reagent, and further placing a buffering solution in contact with the electrode and the porous substrate to prevent electrochemically generated reagents from leaving the locality of the electrode, wherein a buffering solution is one having the capacity to prevent pH changes upon addition of small amounts of acids or bases,
- applying a potential to said electrode sufficient to generate electrochemical reagents capable of reacting to the at least one molecule proximate to the electrode, and
- producing a chemical reaction thereby.
Dependencies are inferred from the claim text.