Porous wafer for segmented synthesis of biopolymers

Claim 2

A modular chemically inert wafer for synthesizing biopolymers, comprising: a solid phase support material, derivatized to covalently bind a biopolymer residue; a retaining ring having inner and outer walls, for retaining said support material in a chamber formed by the inner walls and coaxially extending there through said retaining ring; upper and lower porous means positioned at each end of said retaining ring wherein said porous means allow flow through said retaining ring to said support material and prevent migration of said support material from said retaining ring; wherein said solid phase support material, said retaining ring and said porous means are capable of maintaining integrity in the presence of iodine and at pH values above 9.0 and below 3.0; and wherein said wafers are adapted to be abuttably stackable in a multiple relationship.

Claim 3

The wafer of claim 1, wherein said retaining ring comprises an inner, enclosed reaction chamber for receiving and retaining said support material, said retaining ring being open on both ends.

Claim 4

The wafer of claim 2, wherein said porous flow means comprise separate means provided at each end of said retaining ring and extending across said open ends of said retaining ring to enclose said chamber.

Claim 5

The wafer of claim 3, wherein said porous flow means are pressure fitted in said retaining ring.

Claim 6

The wafer of claim 1, further comprising securing means for securing said porous flow means to said retaining ring.

Claim 7

The wafer of claim 5, wherein said securing means is capable of maintaining its integrity in the presence of iodine, at pH values above 9.0 or below 3.0.

Claim 8

The wafer of claim 1, wherein said solid phase support material is selected from the group consisting of silica, controlled pore glass, polystyrene-divinyl-benzene, polyamide-Kieselguhr, benzyl-linked polystyrene resins, spacer-linked styrene resins, polyamide resins, and macroreticular resins.

Claim 9

The wafer of claim 1, wherein said solid phase support material comprises controlled pore glass.

Claim 10

The wafer of claim 1, wherein said solid phase support material comprises a derivatized material with a covalently attached residue.

Claim 11

The wafer of claim 1 wherein the porous flow means comprises said solid phase supporting material.

Claim 12

The wafer of claim 1, wherein said wafer has a void volume less than the volume of said chamber formed by the inner walls of said retaining ring.

Claim 13

The wafer of claim 1, wherein said porous flow means is selected from the group consisting of a fluorocarbon material, fritted glass, scintered glass, titanium and stainless steel.

Claim 14

The wafer as claimed in claim 1, wherein the porosity of said flow means is sufficiently large to allow flow through the wafer and sufficiently small to retain said solid phase support material in the wafer.

Claim 15

A modular chemically inert wafer for synthesizing biopolymers comprising: a solid phase support material, derivatized to covalently bind a biopolymer residue; an inner housing ring having inner and outer walls comprising an inner reaction chamber formed by the inner walls of said ring and coaxially extending there through for receiving and retaining said support material, said retaining ring being open at both ends; an inert porous membrane positioned at and extending across each of said open ends of said inner retaining ring such that an upper surface of said membrane defines the uppermost surface of said wafer, said membrane having a diameter larger than the outermost diameter of said housing ring so that said membrane extends beyond said outer wall; two outer sleeve-like rings having an inner diameter slightly larger than said inner ring and the thickness of said membrane for securing the edges of said membrane between said inner housing ring and said outer sleeve-like rings; wherein said solid phase support, inner housing support, inner housing ring, inert porous membrane and outer ring are capable of maintaining integrity in the presence of iodine and at pH values above 9.0 and below 3.0; and wherein said wafers are adapted to be abuttably stacked in a multiple relationship.

Claim 16

A modular chemically inert wafer for synthesizing biopolymers comprising: a solid phase support material, derivatized to covalently bind a biopolymer residue; an inner housing ring having inner and outer walls comprising an inner reaction chamber formed by the inner walls of said ring and coaxially extending there through for receiving and retaining said support material, said retaining ring being open at both ends; an inert porous membrane positioned at and extending across each of said open ends of said inner retaining ring such that an upper surface of said membrane defines the uppermost surface of said wafer, said membrane having a diameter larger than the outermost diameter of said housing ring so that said membrane extends beyond said outer wall; two outer sleeve-like rings having an inner diameter slightly larger than said inner ring and the thickness of said membrane for securing the edges of said membrane between said inner housing ring and said outer sleeve-like rings; wherein said solid phase support, inner housing support, inner housing ring, inert porous membrane and outer ring are capable of maintaining integrity in the presence of iodine and at pH values above 9.0 and below 3.0; and wherein said wafers are adapted to be abuttably stacked in a multiple relationship.

Claim 17

A segmented wafer synthesis device for the synthesis of multiple defined-sequence biopolymers, comprising: a solvent/reagent delivery system; at least one column connected to said solvent/reagent delivery system to provide solvent and reagent flow through said column; and at least one wafer as claimed in claim 1 positioned in said column at which polymeric synthesis occurs.

Claim 18

The synthesis device of claim 15, further comprising at least four columns for receiving four reagents, and a plurality of wafers in each column, wherein each of said wafers provides for the synthesis of a defined-sequence biopolymer.

Claim 19

A segmented wafer synthesis device for the synthesis of multiple defined-sequence biopolymers, comprising: a solvent/reagent delivery system; and a plurality of stacked wafers as claimed in claim 1, each of said wafers including a biopolymeric synthesis material and being connected to the next adjacent wafer to form a column, wherein said solvent/reagent delivery system is connected to said column to provide flow through said column.

Claim 20

A process for synthesizing biopolymers comprising the steps of: providing at least one wafer as defined in claim 1; passing reagents and washing solvents through said at least one wafer to sequentially add at least one biopolymer residue to at least one biopolymer residue bound to said support material; releasing the completed synthesized biopolymer from said solid support; and collecting the synthesized biopolymer in substantially purified form.

Claim 21

The process of claim 18 wherein said reagents and washing solvents are passed through more than one wafer at a time.

Claim 22

The process of claim 19 wherein the support material in successive wafers is of varying capacity.

Claim 23

The process according to claim 19 wherein said wafers are abuttably stacked in a columnar relationship.

Claim 24

The process according to claim 19 wherein said wafers are abuttably stacked to form a column.

Claim 25

A process for synthesizing biopolymers, comprising the steps of: assembling a chemically inert wafer; using the phosphoramidite method of synthesizing polynucleotides comprising detritylation, condensation, oxidation and capping; repeating said method to sequentially add nucleotides until the desired biopolymer is completely synthesized; and releasing the completed biopolymer from the solid support, removing protecting groups and recovering said biopolymer in substantially purified form.

Claim 26

A process for synthesizing biopolymers, comprising the steps of: assembling a chemically inert wafer; using the phosphoramidite method of synthesizing polynucleotides comprising detritylation, condensation, oxidation and capping; repeating said method to sequentially add nucleotides until the desired biopolymer is completely synthesized; and releasing the completed biopolymer from the solid support, removing protecting groups and recovering said biopolymer in substantially purified form.

Claim 27

A process for synthesizing biopolymers comprising the steps of: making a first stack of more than one modular chemically inert wafer wherein each said wafer is abuttably positioned next to at least one other wafer; adding at least one biopolymer residue to at least one biopolymer residue bound to support material of said wafer; removing at least one wafer from said first stack of wafers and placing said removed wafer in a second stack of wafers; repeating the making of a stack, the adding and removing steps until each desired biopolymer is completely synthesized wherein a different biopolymer residue is added in each stack; releasing said completed biopolymer from the solid support deprotecting said biopolymers; and recovering said biopolymer in substantially purified form.

Claim 28

A process for synthesizing biopolymers comprising the steps of: making a first stack of more than one modular chemically inert wafer wherein each said wafer is abuttably positioned next to at least one other wafer; adding at least one biopolymer residue to at least one biopolymer residue bound to support material of said wafer; removing at least one wafer from said first stack of wafers and placing said removed wafer in a second stack of wafers; repeating the making of a stack, the adding and removing steps until each desired biopolymer is completely synthesized wherein a different biopolymer residue is added in each stack; releasing said completed biopolymer from the solid support deprotecting said biopolymers; and recovering said biopolymer in substantially purified form.

Claim 29

A modular chemically inert wafer for synthesizing biopolymers, comprising: a solid phase support material, derivatized to covalently bind a biopolymer residue; a retaining ring having inner and outer walls, for retaining said support material in a chamber formed by the inner walls and coaxially extending there through said retaining ring; upper and lower porous means positioned at each end of said retaining ring wherein said porous means allow flow through said retaining ring to said support material and prevent migration of said support material from said retaining ring; wherein said solid phase support material, said retaining ring, and said upper and lower porous means are capable of maintaining integrity in the presence of iodine, at pH values above 9.0 or below 3.0; and wherein said wafers are adapted to be abuttably stackable in a multiple relationship.

Claim 30

A modular chemically inert wafer for synthesizing biopolymers, comprising: a solid phase support material, derivatized to covalently bind a biopolymer residue; a retaining ring having inner and outer walls, for retaining said support material in a chamber formed by the inner walls and coaxially extending there through said retaining ring; upper and lower porous means positioned at each end of said retaining ring wherein said porous means allow flow through said retaining ring to said support material and prevent migration of said support material from said retaining ring; wherein said solid phase support material, said retaining ring, and said upper and lower porous means are capable of maintaining integrity in the presence of iodine, at pH values above 9.0 or below 3.0; and wherein said wafers are adapted to be abuttably stackable in a multiple relationship.

Claim 31

A biopolymer synthesizer comprising: a plurality of reservoirs for synthesis solvents and reagents; a plurality of reservoirs for biopolymer residue derivatives to be sequentially condensed to form the biopolymer; a plurality of columns equal to the number of derivative reservoirs, wherein said columns are comprised of at least one chemically inert wafer, said wafer including a solid phase support material derivatized to covalently bind a biopolymer residue, an upper and lower porous means to allow said derivatives and solvent/reagents to flow through said column and a retaining means with inner and outer walls forming a reaction chamber with said porous means; said derivative reservoirs and solvent/reagent reservoirs being connected to said columns through means for delivering said derivatives and solvent/reagent through controllable valves to supply said derivatives and solvent/reagents to said columns.

Claim 32

A biopolymer synthesizer comprising: a plurality of reservoirs for synthesis solvents and reagents; a plurality of reservoirs for biopolymer residue derivatives to be sequentially condensed to form the biopolymer; a plurality of columns equal to the number of derivative reservoirs, wherein said columns are comprised of at least one chemically inert wafer, said wafer including a solid phase support material derivatized to covalently bind a biopolymer residue, an upper and lower porous means to allow said derivatives and solvent/reagents to flow through said column and a retaining means with inner and outer walls forming a reaction chamber with said porous means; said derivative reservoirs and solvent/reagent reservoirs being connected to said columns through means for delivering said derivatives and solvent/reagent through controllable valves to supply said derivatives and solvent/reagents to said columns.

Claim 33

A biopolymer synthesizer according to claim 26 for polynucleotide synthesis wherein there are four monomer derivative reservoirs and four columns.

Claim 34

A biopolymer synthesizer according to claim 26 wherein said column is formed by stacking a plurality of said chemically insert wafers, said stack of wafers forming serially interconnected chambers for holding solid phase support material.

Claim 35

A biopolymer synthesizer according to claim 26, further comprising a means for mechanical reassortment of wafers into stacked relationship after each cycle of residue addition.

Claim 36

A process for simultaneous chemical synthesis of a multiplicity of biopolymer sequences, comprising the steps of: assembly of modular chemically inert wafers in abuttably stacked relationship to form a multiplicity of wafer columns; sequentially passing reagents through wafer columns to effect addition of a different biopolymer residue to growing biopolymers contained within each column; reassortment of wafers into a new abuttably stacked relationship to provide for synthesis of a multiplicity of biopolymer sequences; repetition of residue addition steps comprising assembly of columns, biopolymer residue addition, and reassortment of wafers, until synthesis of the desired multiplicity of biopolymer sequences has been achieved.

Claim 37

A process for simultaneous chemical synthesis of a multiplicity of biopolymer sequences, comprising the steps of: assembly of modular chemically inert wafers in abuttably stacked relationship to form a multiplicity of wafer columns; sequentially passing reagents through wafer columns to effect addition of a different biopolymer residue to growing biopolymers contained within each column; reassortment of wafers into a new abuttably stacked relationship to provide for synthesis of a multiplicity of biopolymer sequences; repetition of residue addition steps comprising assembly of columns, biopolymer residue addition, and reassortment of wafers, until synthesis of the desired multiplicity of biopolymer sequences has been achieved.

Claim 38

A process for simultaneous chemical synthesis of a multiplicity of biopolymer sequences as described in claim 30; wherein the biopolymer is selected from among the group consisting of polynucleotides, polypeptides, polysaccharides, glycopeptides, lipopolysaccharides, lipopeptides, functional analogs and structural analogs.

Claim 39

A column for synthesizing biopolymers comprising: a plurality of snappers each containing a wafer in the center; each snapper containing a groove for a sealing ring; said snappers forming a fluid tight column by compression; and said snappers capable of disengaging and repeatedly forming new columns.

Claim 40

A column for synthesizing biopolymers comprising: a plurality of snappers each containing a wafer in the center; each snapper containing a groove for a sealing ring; said snappers forming a fluid tight column by compression; and said snappers capable of disengaging and repeatedly forming new columns.