Electrochemical solid phase synthesis
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 or 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.
Claims38
A method for electrochemical synthesis of a polymeric material at specific location on a 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,
- 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 preformed molecule.
A method for electrochemical synthesis of an array of separately formed polymers on a substrate, which comprises the steps of:
- providing an array of electrodes that is proximate to a substrate surface, said surface being proximate to one or more molecules bearing at least one protected chemical functional group attached thereto,
- providing a buffering or scavenging solution in contact with the substrate at a concentration from about 1 mM to about 100 mM;
- 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 said 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 molecule or a bonded protected molecule and the subsequent bonding or an additional monomer to said deprotected functional group until at least two separate polymers of desired length are formed on the substrate surface wherein during said selective deprotection steps, and electric potential is applied to one or more selected electrodes sufficient to generate electrochemical reagents at the selected electrodes capable of deprotecting the chemical functional groups on said proximate molecules or monomers.
A method for electrochemical synthesis of an array of separately formed oligonucleotides on a substrate, which comprises the steps of:
- providing 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, and further providing a buffering or a scavenging solution in contact with the substrate at a concentration from about 1 mM to about 100 mM;
- 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 deprotected 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 protected bonded 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 wherein during said selective deprotection steps, an electric potential is applied to one or more selected electrodes sufficient to generate electrochemical reagents at the selected electrodes capable of deprotecting the chemical functional groups on said proximate molecules or nucleic acids.
A method according to claim wherein said “getter” structure is a second substantially ring-shaped electrode.
A method for electrochemical placement of a material at a specific location on a 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,
- providing a buffering or a scavenging solution in contact with the substrate at a concentration from about 1 mM to about 100 mM;
- applying a potential to the 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.