GB2198738A - Process for producing multiple monolayers of polymeric linkages and devices comprising multiple monolayers - Google Patents
Process for producing multiple monolayers of polymeric linkages and devices comprising multiple monolayers Download PDFInfo
- Publication number
- GB2198738A GB2198738A GB08722724A GB8722724A GB2198738A GB 2198738 A GB2198738 A GB 2198738A GB 08722724 A GB08722724 A GB 08722724A GB 8722724 A GB8722724 A GB 8722724A GB 2198738 A GB2198738 A GB 2198738A
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- Prior art keywords
- multifunctional
- produce
- reagent
- immobilized
- reagents
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- Granted
Links
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical group C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 18
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- LXEJRKJRKIFVNY-UHFFFAOYSA-N terephthaloyl chloride Chemical compound ClC(=O)C1=CC=C(C(Cl)=O)C=C1 LXEJRKJRKIFVNY-UHFFFAOYSA-N 0.000 claims description 2
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- CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 description 3
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
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- LFKYBJLFJOOKAE-UHFFFAOYSA-N imidazol-2-ylidenemethanone Chemical compound O=C=C1N=CC=N1 LFKYBJLFJOOKAE-UHFFFAOYSA-N 0.000 description 2
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
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- 238000002360 preparation method Methods 0.000 description 2
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- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- LIVNPJMFVYWSIS-UHFFFAOYSA-N silicon monoxide Inorganic materials [Si-]#[O+] LIVNPJMFVYWSIS-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- GVTLFGJNTIRUEG-ZHACJKMWSA-N (e)-n-(3-methoxyphenyl)-3-phenylprop-2-enamide Chemical compound COC1=CC=CC(NC(=O)\C=C\C=2C=CC=CC=2)=C1 GVTLFGJNTIRUEG-ZHACJKMWSA-N 0.000 description 1
- IYAYDWLKTPIEDC-UHFFFAOYSA-N 2-[2-hydroxyethyl(3-triethoxysilylpropyl)amino]ethanol Chemical compound CCO[Si](OCC)(OCC)CCCN(CCO)CCO IYAYDWLKTPIEDC-UHFFFAOYSA-N 0.000 description 1
- JBRZTFJDHDCESZ-UHFFFAOYSA-N AsGa Chemical compound [As]#[Ga] JBRZTFJDHDCESZ-UHFFFAOYSA-N 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- JHGSJQBGMSPENR-UHFFFAOYSA-N C1(=CC=C(C=C1)N)N.CN(C=O)C Chemical compound C1(=CC=C(C=C1)N)N.CN(C=O)C JHGSJQBGMSPENR-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229910001218 Gallium arsenide Inorganic materials 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- GPXJNWSHGFTCBW-UHFFFAOYSA-N Indium phosphide Chemical compound [In]#P GPXJNWSHGFTCBW-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 125000004018 acid anhydride group Chemical group 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
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- 239000007864 aqueous solution Substances 0.000 description 1
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- 230000001588 bifunctional effect Effects 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- YENOLDYITNSPMQ-UHFFFAOYSA-N carboxysilicon Chemical compound OC([Si])=O YENOLDYITNSPMQ-UHFFFAOYSA-N 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229920000547 conjugated polymer Polymers 0.000 description 1
- 239000005289 controlled pore glass Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002019 doping agent Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- GQYHUHYESMUTHG-UHFFFAOYSA-N lithium niobate Chemical compound [Li+].[O-][Nb](=O)=O GQYHUHYESMUTHG-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000002186 photoactivation Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001197 polyacetylene Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical group [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 1
- 238000002444 silanisation Methods 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
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- 230000008961 swelling Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 239000005052 trichlorosilane Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y10/00—Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G12/00—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G79/00—Macromolecular compounds obtained by reactions forming a linkage containing atoms other than silicon, sulfur, nitrogen, oxygen, and carbon with or without the latter elements in the main chain of the macromolecule
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/001—Macromolecular compounds containing organic and inorganic sequences, e.g. organic polymers grafted onto silica
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G85/00—General processes for preparing compounds provided for in this subclass
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01B—CABLES; CONDUCTORS; INSULATORS; SELECTION OF MATERIALS FOR THEIR CONDUCTIVE, INSULATING OR DIELECTRIC PROPERTIES
- H01B1/00—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors
- H01B1/06—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of other non-metallic substances
- H01B1/12—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of other non-metallic substances organic substances
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L23/00—Details of semiconductor or other solid state devices
- H01L23/52—Arrangements for conducting electric current within the device in operation from one component to another, i.e. interconnections, e.g. wires, lead frames
- H01L23/522—Arrangements for conducting electric current within the device in operation from one component to another, i.e. interconnections, e.g. wires, lead frames including external interconnections consisting of a multilayer structure of conductive and insulating layers inseparably formed on the semiconductor body
- H01L23/532—Arrangements for conducting electric current within the device in operation from one component to another, i.e. interconnections, e.g. wires, lead frames including external interconnections consisting of a multilayer structure of conductive and insulating layers inseparably formed on the semiconductor body characterised by the materials
- H01L23/53204—Conductive materials
- H01L23/5328—Conductive materials containing conductive organic materials or pastes, e.g. conductive adhesives, inks
-
- H—ELECTRICITY
- H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
- H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
- H10K10/00—Organic devices specially adapted for rectifying, amplifying, oscillating or switching; Organic capacitors or resistors having potential barriers
- H10K10/701—Organic molecular electronic devices
-
- H—ELECTRICITY
- H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
- H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
- H10K85/00—Organic materials used in the body or electrodes of devices covered by this subclass
- H10K85/10—Organic polymers or oligomers
- H10K85/111—Organic polymers or oligomers comprising aromatic, heteroaromatic, or aryl chains, e.g. polyaniline, polyphenylene or polyphenylene vinylene
-
- H—ELECTRICITY
- H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
- H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
- H10K85/00—Organic materials used in the body or electrodes of devices covered by this subclass
- H10K85/30—Coordination compounds
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L2924/00—Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
- H01L2924/0001—Technical content checked by a classifier
- H01L2924/0002—Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L2924/00—Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
- H01L2924/10—Details of semiconductor or other solid state devices to be connected
- H01L2924/11—Device type
- H01L2924/12—Passive devices, e.g. 2 terminal devices
- H01L2924/1204—Optical Diode
- H01L2924/12044—OLED
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Inorganic Chemistry (AREA)
- Nanotechnology (AREA)
- Materials Engineering (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Power Engineering (AREA)
- Computer Hardware Design (AREA)
- General Physics & Mathematics (AREA)
- Mathematical Physics (AREA)
- Theoretical Computer Science (AREA)
- Crystallography & Structural Chemistry (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Peptides Or Proteins (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
An immobilized structure comprising multiple monolayers of effective sequential polymeric linkages can be built, monolayer by monolayer, from the surface of a solid phase, by an alternating reaction sequence conducted with multifunctional reagents. The solid phase has an attached reactive moiety and is reacted with a first multifunctional reagent having one functional group reactive with the moiety of the solid phase and one functional group reactive with the second multifunctional reagent, the resulting intermediate adduct is reacted with the second multifunctional reagent to produce a first monolayer. This sequence of alternating reactions with first and second multifunctional reagents is repeated as often as desired to produce an immobilized structure of multiple monolayers. The process makes it possible to form numerous immobilized multiple monolayer structures wherein the length of each structure extending from a substrate is substantially the same. Structures comprising multiple monolayers of polymeric linkages are useful for immobilizing macromolecules or biomolecules to produce chemical or biochemical sensors. Other uses extend to molecular electronic applications, such as the production of molecular conductive wires and molecular circuitry.
Description
PROCESS FOR PRODUCING MULTIPLE MONOLAYERS
OF POLYMERIC LINKAGES AND DEVICES
COMPRISING MULTIPLE MONOLAYERS
This invention relates to a process for producing multiple monolayers of polymeric linkages wherein the length of each of theresulting multiple monolayer structures can be controlled so that they may be substantially the same.
Structures comprising niultiple monolayers of polymeric linkages are useful for many purposes, for example in chemical or biochemical sensors, and molecular conductive wires.
The assembling of molecular layered structures has gained recognition in the past, primarily in the context of solid phase synthesis of peptides. R. B. Merrifield reports in
Biochemistry, Vol. 3, No. 9 pp. 1385-1390 (1964), the stepwise synthesis of the naturally occurring nonapeptide bradykinin, by attachment of a terminal amino acid to a substrate, a decarboxylation step, and then a coupling step wherein an amino acid residue is attached to the terminal amino acid. The steps are repeated until a peptide with nine amino acid residues is produced.
More recently, this approach to protein synthesis has been expanded to the production of a multilayer film of 1,5-hexadecenyl-trichlorosilane. Lucy Metzer and Jacob Sagiv in
J. Am. Chem. Soc., Vol. 105, pp. 674-676 (1983) report a two-step sequence consisting of monolayer absorption, followed by chemical activation of the exposed surface to provide polar absorption sites for the anchoring of the next monolayer.
The present invention provides a process for producing an immobilized structure comprising multiple monolayers of effective sequential polymeric linkages, which process comprises:
a) providing a solid phase having a first attached reactive moiety;
b) conducting a first coupling reaction by reacting said attached reactive moiety with an excess of a first multifunctional reagent or combination of multifunctional reagents comprising at least one functional group reactive with said reactive moiety and at least one functional group reactive with a second multifunctional reagent or combination of reagents, thereby producing an intermediate adduct attached to said solid phase and comprising a residue from said first reagent or reagents, with at least one second reactive moiety capable of coupling to the second multifunctional reagent;;
c) conducting a second coupling reaction by reacting said intermediate adduct with an excess of the second multifunctional reagent or combination of reagents to produce a first molecular unit of said effective polymeric linkage comprising at least one terminal reactive moiety capable of coupling to said first multifunctional reagent or combination of reagents;
d) alternately repeating said first and second coupling reactions to produce an immobilized structure comprising multiple monolayers of effective sequential polymeric linkages.
The process makes it possible to produce numerous immobilized multiple monolayer structures wherein the length of each structure extending from the substrate is substantially the same.
The inventor also provides immobilized structures prepared in accordance with the process described above.
The expression "effective sequential polymeric linkages" within the context of the invention means at least two molecular units, sequentially bonded, preferably having either conjugated moieties capable of acting as conductive or semiconductive molecular entities through pi () bond delocalization; or unconjugated moieties that are not conductive, and are thus capable of acting as resistive molecular entities. In either of these preferred embodiments, biomolecules or other macromolecules may also be immobilized by physical or cavalent bonding to terminal functional groups of the multiple monolayer structures.
The solid phase in the present invention is one that has a "reactive moiety" available on a surface that is capable of reacting with the first multifunctional reagent whereby to form an immobilized intermediate adduct having a second reactive moiety capable of reacting with the second multifunctional reagent.
In the context of the invention, a "reactive moiety" means a molecular moiety that is capable of reacting with another moiety via classical functional group organic chemistry. Of these may be mentioned such moieties as amino, carboxylic acid, carbonylimidazole, aldehyde, carboxylic acid halide, carboxylic acid ester, carboxylic acid anhydride, alcohol or phenol groups.
Amino groups and carbonylimidazole groups are preferred because of their high reactivity.
The properties of structures produced according to the invention are illustrdted with reference to the accompanying
Drawings, in which:
Figure 1 is a plot of the radioisotopic data obtained after each complete reaction cycle of a sequence adding successive monolayers of phenylurethane.
Figure 2 is a plot of immobilized acetylcholinesterase (AChE) activities after a 6-month period of time relative to bond lengths of phenylurethane linkages.
Figure 3 is a plot of the change in bond lengths of an immobilizing monolayer structure relative to percentage enzyme activity of the enzyme immobilized with the multiple monolayer structure.
In the process of the present invention, an immobilized structure comprising multiple monolayers of effective sequential polymeric linkages is formed, monolayer by monolayer, from the surface of a solid phase, by an alternating reaction sequence conducted with multifunctional reagents.
According to the method of the invention, a solid phase having a first attached reactive moiety is contacted with a first multifunctional reagent or combination of reagents. The method of contact may be by any means that allows the reactants to come into contact with the solid phase.
For example, the substrate having the reactive moiety may be reacted with the chosen first multifunctional reagent or combination of reagents in a conventional manner, in the vapour state or by simply mixing the reactants together in the liquid state. When the reaction is carried out in the liquid state, conventional solvents are often employed. In some instances, the multifunctional reagent may be susceptible to hydrolysis, and thus, an aprotic solvent should be employed. It is generally preferred to employ an excess of the multifunctional reagent to avoid bimolecular termination reactions which produce products on the solid phase which will interfere with the desired building of the polymeric monolayers.
Successful completion of the first coupling reaction will result in an intermediate adduct which contains at least a part of the first reagent and terminates with at least one second reactive moiety. At this time it is often preferred to employ an additional step of removing unreacted first multifunctional reagents, usually by Conventional washing techniques.
In the second coupling step, the substrate, now having the intermediate adduct affixed to it, is reacted in a similar fashion with a second multifunctional reagent or a combination thereof. During this step, at least a portion of the second reagent or combination of reagents is incorporated, producing one monolayer of the desired polymeric linkage, the individual molecular chains in this monolayer each terminating with at least one moiety capable of reacting with the first multifunctional reagent. This cycle is then repeated to produce a second monolayer, and so on. The repeated reaction produces a desired number of monolayers, with the terminal end of the overall structure ending with at least one reactive moiety, which may belong to either one (as desired) of the two types of reactive moiety.
Solid phases having reactive moieties attached to their surfaces useful in the practice of the invention can be any solid material that can act as a substrate for attachment of the multiple monolayers, serve to anchor the reaction products to a solid phase, and permit the unreacted multifunctional reagents in each step to be removed efficiently before the next reaction step with another multifunctional reagent. Selection of the substrate may be governed in part by its physical and chemical properties, such as solubility, functional groups, mechanical stability, surface area swelling propensity, and hydrophobic or hydrophilic properties; as well as its electrical properties, such as conductivity or resistivity.
Three major types of substrates are most preferred: inorganics, natural polymers, and synthetic polymers. Of these may be mentioned polymers such as polyvinyl alcohols, acrylates and acrylic acid polymers such as polyethylene-co-acrylic acid, polyethylene-co-methacrylic acid, polyethylene-co-ethylacrylate, polyethylene-co-methyl acrylate, polypropylene-co-acrylic acid, polypropylene-co-methacrylic acid, polypropylene-co-ethyl acrylate, polypropylene-co-methyl acrylate, polyethylene-co-vinyl acetate, and polypropylene-co-vinyl acetate; those containing acid anhydride groups such as polyethylene-co-maleic anhydride, and polypropylene-co-maleic anhydride; natural polymers such as polypeptides, proteins and carbohydrates; metalloids that have semiconductive properties such as silicon, germanium, and aluminium; and metals such as platinum, gold, nickel, copper, zinc, tin, palladium and silver. Particularly useful are oxides of metals and metalloids such as Pt-PtO, Si-Si-0, Au-Au0, Ti02, and Cu-Cu0. Inorganics having conductive or semiconductive properties are preferred in some embodiments of the invention.
Of these may be mentioned silicon/silicon oxide semiconductor elements, or other semiconductor.elements such as lithium niobate, gallium arsenide, and indium phosphide.
Substrates such as those mentioned above, particularly the metalloids, may be treated to provide an appropriate reactive moiety, or in some instances may be obtained commercially already having the reactive moiety. Materials having reactive surface moieties such as aminosilane linkages, hydroxyl linkages, or carboxysilane linkages are preferred in some embodiments of the invention, and may be produced by well established surface chemistry techniques involving e.g. silanization reactions.
Examples of these materials are those having surface silicon oxide moieties, covalently linked to gamma-aminopropylsilane, and other organic moieties; e.g. N-t3-(triethyoxysilyl) propyl]Phthalamic acid; and bis-(2-Hydroxyethyl)aminopropyltriethoxysilane. Exemplary of readily available materials containing NH2-reactive functionalities are Para-aminophenyl-triethyoxysilane and qamma-aminopropyl silanized Controlled Porous Glass Beads, available from Pierce Chemical Co., P.O. Box 117, Rockford,
Illinois 61105.
The multifunctional reagents useful in the process of the invention are those that can react in alternate manner to produce at least one molecular unit of the desired effective polymeric linkage, the alternate steps of reaction scheme being capable of repetition until the desired number of molecular units is produced. Combinations of first and second multifuctional reagents may be varied to obtain a wide variety of polymeric linkages with electrical properties ranging from nonconductive to semiconductive and conductive. Terminal functional groups of the resulting multiple monolayer structure may be further reacted e.g. with biomolecules or other macromolecules. Combinations of first multifunctional agents may also be used in conjunction with combinations of second multifunctional reagents to produce branched polymeric linkages.
In general, at least a part of the first multifunctional reagent or combination of reagents is incorporated into the immobilized molecular unit, producing an intermediate adduct with at least one terminal functional group that is capable of reacting with the second multifunctional reagent. Upon such reaction with the second multifunctional reagent or reagents, at least a portion of that second reagent is incorporated into the immobilized structure, producing one complete molecular unit with at least one terminal group capable of reacting with a further amount of the first multifunctional reagent. The cycle may then be repeated ad libitum. It is generally preferred that the terminal group or groups of a completed molecular unit be the same reactive moiety as that originally provided on the substrate.
The first multifunctional reagent or combination of reagents in the present process is selected according to the type of multiple monolayer structure it is desired to achieve, and may be heterofunctional or homofunctional. The first reagent or combination thereof is capable of reacting with the reactive moiety attached to the solid phase.
Illustrative of multifunctional reagents suitable for use as the first reagent, whether alone or in combination, may be mentioned those that react with the substrate moiety by nucleophilic displacement and may be represented by the following general formula I:
wherein R is readily displaced by nucleophiles, and is preferably aromatic heterocyclic or halogen.
Further reagents suitable as the first multifunctional reagents are those capable of reacting with the substrate reactive moiety via a'condensation/elimination scheme, and may be represented by the general formulae II and III:
0 0
R2 - C - R1 - C - R3
II wherein R1 is phenylene, polyphenylene, fused ring aromatic, alkylene, alkenylene, aromatic heterocyclic, or metalloorganic;
R2 and R3 which may be the same or different, are each H, halogen, OR4, OH, or SH, wherein R4 is an aliphatic or aromatic hydrocarbon; R5 - N - R1 - N - R6
III wherein R1 has the meaning given above; and R5-N- and R6-N-, which may be the same or different, are each HO-N-, O=N- or,
X-N2+.Preferred first reagents include carbonyl diimidazde, 1,4-dialdobenzene, l,l-dialdoferrocene, 1,4-dinitrosobenzene or benzene -1.4- dicarboxylic acid chloride.
The second multifunctional reagent is one that will react with the terminal functional group or groups of the intermediate adduct produced by the first reaction.
The second multifunctional reagent or reagents may be heterofunctional or homofunctional and can preferably have the formula IV:
an aromatic hydrocarbon group having one ring or a plurality of separate rings, a fused ring aromatic group, a saturated or aliphatic hydrocarbon group, an aromatic heterocyclic group, or a metalloorganic group, X1 and X2 are the same or different and are NH2, NHOH, or OH; and X3 and X4 are the same or different and are NHZ, NHOH, OH, or H. Preferred second reagents include phenylene diamine or 1,4-hydroquinone.
The first and second reagents are chosen according to the polymeric linkages it is desired to form. When the first multifunctional reagents have the general formula I, the second multifunctional reagents should contain nucleophilic groups that will react, via a further displacement reaction, with the terminal functional moiety or moieties of the intermediate adduct produced from the first coupling reaction. When the first reagents have general formula II or III, the second multifunctional reagents should be ones that will react via condensation/elimination. In general, reaction cycles conducted with a combination of a first reagent acting via nucleophilic displacement with a conjugated second reagent will produce semiconjugated polymeric linkages with potential semiconductivity, while reaction with unconjugated reagents produces non-conjugated linkages.
Reaction cycles conducted with a first reagent acting via condensation/elimination and a conjugated second reagent will produce conjugated polymeric linkages, potentially conductive.
Reaction cycles conducted with an unconjugated second reagents will produce non-conjugated linkages.
Typical schemes for utilizing the various first and second bifunctional reagents are depicted in the following Table:
# # # # # # # # # # # # # # # # # # # # # # # # # # # # TYPICAL SCHEMES FOR SOLIO-PHASE SYNTHETIC LINKAGES
Solid First Second Solid-Phase Synthetic Linkage
Phase Bifunctional Difunctional
Reagent Reagent The following presents a typical scheme for synthesis of a branched multiple monolayer structure wherein the polymer or oligomer produced is potentially semiconductive and could be utilized as a twodimensional molecular wire.
It should be appreciated that various combinations of multiple monolayer units, with varying electrical properties, could be combined to form various electrical component parts on a molecular level. For example, electrical units such as "switches" or "resistors" could be produced in accordance with the invention. The following presents a typical scheme for formation of a molecular switch:
As demonstrated above, semiconjugated or conjugated linkages, in this case polybenzoimines, are provided on conductive substrates with a compound containing a displaceable metal, in this case a metalloporphyrin, capable of acting as a molecular switch, interposed between portions of the linkages.
When a sufficient voltage or other stimulus is applied across this structure, the metal will be displaced from the molecular switch, allowing electric current to be conducted. The first polymeric linkages may be provided on the substrate according to the process of the invention, generating a terminal reactive group capable of reacting with the metalloporphyrin. Additional polymeric monolayers are then built, monolayer by monolayer, from the matalloporphyrin molecular switch, and the terminal ends of the second linkages are then reacted with reactive moieties on the second substrate for attachment thereto.
Compounds suitable for use as molecular switches are those that can react to an applied voltage or other stimulus, such as photoactivation, in such a way as to preclude or to allow the passage of electrons. Useful in this regard are compounds such as the metalloporphyrins, phthalocyanines, and hemiquinones. Plausible schemes also exist for incorporating charge-transfer salts such as TTF-TCNQ (tetrathiafulvalene-tetracyanoquinodimethane). For example, diamino-TTF could be covalently coupled within the backbone of a solid-phase synthesized conjugated polymer, and then TCNQ molecules could be allowed to chelate to the TTF units from solution to form the TTF-TCNQ charge-transfer salt moieties at a specific position in the molecular circuit. For compounds that may act as molecular switches, see Brian M. Hoffman and James A.
Ibers, "Porphyrinic Molecular Metals," Acc. Chem. Res. 1983, 16, 15-21; T.W. Barrett et al., "Electrical Conductivity in
Phthalocyanines Modulated by Circularly Polarized Light," Nature,
Vol. 301, 24 February, 1983; and, 2nd International Workshop on
Molecular Electronic Devices, Naval Research Lab, Washington
D.C., April 13-15 (1983).
Unconjugated areas that act as a molecular resistor could be further combined with a molecular wire section and molecular switch to modulate electric current passing through. A scheme for a simple molecular circuit is presented below, wherein molecular conductive wires of polybenzoimines are conjugated to a metalloporphyrin switch in parallel with an N-propyldiamine resistor:
It should be appreciated that the stepwise monolayer addition of the present method can provide a substrate having numerous multiple monolayer structures originating from its surface, with a narrow distribution of total monolayer lengths.
In some embodiments, the precision obtained is within a few
Angstrom units. This is particularly useful in the area of conductive or semiconductive polymers. Uniformity of oligomer or polymer lengths would be helpful in building molecular level circuits as depicted above, since careful control may be exerted over the length of each of the components making up the circuit.
Such uniformity is not easy to achieve with the technique at present available to the art.
It should also be appreciated that the number of multiple monolayer structures prepared on the surface of a substrate will be governed by the number of initial reactive sites on the substrate surface, as well as other factors, such as steric hindrances between the monolayer linkages themselves. The number of initial sites could be such that enough multiple monolayers may be prepared to form an actual layer across all or a portion of the substrate surface, the thickness of the layer governed by the number of reaction cycles completed, building successive monolayers on each of the respective structures. The present process thus also provides an alternative to conventional film-forming techniques.
Along these same lines, the spacing between the various multiple monolayer structures can be controlled by adjusting the availability of reactive moieties on the solid phase. In some embodiments of the present invention, spacing between linkages has been in the order of approximately 23 Angstrom units. In this case, the spacing could be increased to approximately 50
Angstrom units by passivating the available reactive sites on the solid phase by approximately 50%. In a preferred embodiment, wherein multiple monolayers of phenylurethane linkages are produced, the spacing of NH2 groups on the solid phase may be altered by passivating approximately 50% of the available sites with dichlorodimethylsilane before the monolayer synthesis procedure. Thus, the linkages could be packed at approximately 50 Angstrom centres, which might be advantageous in molecular electronic applications.
Electroactive properties of conductive or semiconductive polymers prepared according to the above reaction schemes may be enhanced through the use of conventional p- or n- doping. For example, dopants such as I2, conventionally used to dope polyacetylenes, could be used to dope the conjugated linkages produced by this technique.
After the desired number of monolayers of a particular molecular unit has been prepared, the terminal end of the multiple monolayer structure may be further reacted with a variety of molecules. Useful in this regard are macromolecules, such as chelated crown ethers, or biomolecules such as enzymes, hormones, antigens, antibodies and membrane receptors.
Immobilization of biomolecules through the use of the immobilized monolayer structure enhances the stability of the biomolecules, and is thus an alternative to direct immobilization on a substrate. In some embodiments, the stability of a particular enzyme is directly proportional to the length of the multiple monolayer structure. More than four monolayers is generally preferred, with more than ten monolayers being particularly preferred. One skilled in the art should be able to readily optimize the stability of a biomolecule of interest by testing its stability relative to various monolayer lengths.
It is preferable that covalent bonding techniques be employed when immobilizing biomolecules. Conventional techniques that are applicable have been described in the art, for instance in "Immobilized Enzymes, Antigens, Antibodies, and Peptides,
Preparation and Characterization," edited by Howard H. Westall,
Marcel Dekker, Inc. (1975).
The following presents a preferred reaction scheme according to the present invention for production of a multiple monolayer structure comprising electroactive polyphenylurethane linkages:
Substrate containing a reactive moiety, preferably NHZ, is reacted first with carbonyldiimidazole in a solvent. Solvents particularly useful in this regard are aprotic, so as to avoid the side reaction of hydrolysis of the carbonyldiimidazole.
Preferred solvents include dimethylformamide, dimethylsulfoxide, benzene, chloroform, acetone, and diethyl ether.
Amounts of carbonyldiimidazole employed in this first coupling step may vary widely, and should be an amount sufficient to avoid the production of termination reaction products which will interfere with the desired building of the polymeric monolayers. For this reason, an excess of the reagent may generally be employed: For example, for 1 milliequivalent of amino moiety, amounts from 1 to 10 milliequivalents of carbonyldiimidazole, or even more, can be employed, with 6 to 10 milliequivalents being more preferable. The coupling reaction may be carried out by conventional techniques, such as by simply mixing the reactants. The reaction period may vary widely, and generally is from 15 to 60 minutes. The temperature at which the reaction takes place may also vary widely, and is generally carried out at room temperature for the sake of convenience.
It is preferable to employ an additional step of removing unreacted carbonyldiimidazole. This can usually be accomplished by conventional filtering and washing techniques, preferably by washing with an aqueous solution and then an aprotic solvent to decompose unreacted carbonyldiimidazole and remove residual products from the solid phase.
The above coupling reaction will produce an imidazole derivative attached to the substrate, which is reactive with a second multifunctional reagent, preferably a diamine such as 1,4 phenylenediamine. Here again, it is preferable to employ an excess of this second reagent to minimize bimolecular termination reactions which can produce products on the solid-phase which will interfere with the desired building of the polymeric monolayers.
Contact of the imidazole derivative with the second reagent is effected by conventional techniques. Contact periods can vary widely, with at least 15 minutes being suitable for the reaction.
Completion of the second coupling reaction produces one monolayer of phenylurethane. The alternating reaction scheme may then be repeated any desired number of times to produce the desired length of the overall structure, the terminal group ending with an amino functionality or hemi-carbonyldiimidazole functionality.
In particularly preferred embodiments, the thus produced multiple monolayer structure is used to immobilize certain enzymes or other proteins. The immobilization may take place using conventional techniques. For example, contact of the first multifunctional reagent with the terminal moiety of the multiple monolayer structure will produce the intermediate adduct, that in turn may react with amino groups contained in the enzyme. Thus, covalent bonding of the enzyme to the monolayer structure is achieved.
Illustrative of the many uses of the immobilized multiple monolayer structures as described hereinabove may be mentioned applications in the area of biological and chemical sensors. Any number of such materials as antibodies, enzymes, hormones, or membrane receptors,..can be attached to the multiple monolayer structures, to produce the optimum molecular design for a particular sensing unit. In some embodiments of the present invention, the stability of a particular immobilized enzyme can be increased many times by increasing the distance between the substrate and the enzyme through the use of the multiple monolayer structure.
In addition, molecular wires may be produced by building and varying, with a precision of within a few Angstrom units, the bond lengths of electroactive linkages attached to electrode and semiconductor surfaces. Along these same lines, combinations of these monolayer structures with compounds acting as switches may be useful in making molecular scale electronic circuits.
The following examples depict specific embodiments of the present invention.
EXAMPLE 1
Preparation of Multiple Monolaver Structures
Consisting of Polvohenylurethane Linkages: 1 gram of Controlled Porous Glass Beads (CPG) was washed with 4 to 5 volumes of dry dimethylformamide (DMF) on a sintered glass funnel, then transferred to a flask and 5.0 ml of 0.25M carbonyldiimidazole (CDI) in DMF was added. The mixture was shaken for i5 minutes at room temperature, and then filtered and washed with water, and 4 to 5 volumes of DMF. The CDI-treated
CPG was transferred td a flask and 5.0 ml of 0.25M14C p-phenylene diamine was added (100 to 500 DPM/micromole diamine) and shaken for 80 minutes. The mixture was filtered and washed with DMF until no 14C was evident in the filtrate.
The process was repeated up to eighteen cycles. A sample from each cycle was counted for 14C and analyzed for NH2 end groups. Radioisotopic data indicated that for each complete reaction sequence, one monolayerwas successfully added to the structure, with a correlation coefficient of 0.94. For a build-up of the first eight monolayers, a similar correlation coefficient of 0.9932 was obtained (see Figure 1).
The surface area per gram of CPG beads was known to be approximately 70 m2/gram. By using routine calculation procedures, it was possible to calculate that the packing density of the phenylurethane linkages was a nominal one-linkage/528A2, with a 23A interspacial distance between adjacent linkages.
CPG = Pierce 23909 controlled pore glass, aminopropyl
DMF = Pierce 20673 Dimethylformamide
p-Phenylenediamine = Aldrich P-2, 396-2 recrystallized from toluene mp 143-144
14C p-Phenylenediamine = Pathfinder 15.03 Hc/micromole
CDI - Pierce 20220 = N,N'- carbonyldiimidazole
EXAMPLE 2
Acetylcholinesterase Immobilization & Stability Studies
Using the aforementioned series of glass beads with variable bond lengths of phenylurethane linkages, eel-type acetylcholinesterase was immobilized at the amino groups at the ends of these linkages with carbonyl diimidazole (CDI). The immobilized enzyme-glass beads were stored in a refrigerator (ca.
100 C). Periodic assays were carried out to determine how much of the initial enzyme activity was retained over a period of six months. The data are summarized below:
Bond Lengths Versus Percentage Activity of AChE Enzyme
No. of Monolayers ......... 2 4 6 8
Bond Length (Angstroms) .... 21 35 49 60 A
Percentage Activity
After Six Months .......... 30 50 60 65%
The effect of immobilizing bond length on enzyme stability is very pronounced. After six months, the shortest linkage (21A) retained 30% of enzyme activity versus 65% activity for the longest linkage (60A), an increase greater than twofold (see Figure 2).
It should be appreciated that there is a mathematical correlation between the immobilizing bond length and long-term stability of the immobilized enzyme. In fact, the correlation between the percentage of enzyme activity values and the logarithm of the immobilizing bond lengths (or number of monolayers) is a linear relationship. In another data manipulation, the percent enzyme activity was plotted against the percentage change in total bond length per successive monolayer of phenylurethane. This plot is very linear, with a statistical correlation coefficient of 0.9992 (Figure 3).
Claims (14)
1. A process for producing an immobilized structure comprising multiple monolayers of effective sequential polymeric linkages, which process comprises:
a) providing a solid phase having a first attached reactive moiety;
b) conducting a first coupling reaction by reacting said attached reactive moiety with an excess of a first multifunctional reagent or combination of multifunctional reagents comprising at least one functional group reactive with said reactive moiety and at least one functional group reactive with a second multifunctional reagent or combination of reagents, thereby producing an intermediate adduct attached to said solid phase and comprising a residue from said first reagent or reagents, with at least one second reactive moiety capable of coupling to the second multifunctional reagent;;
c) conducting a second coupling reaction by reacting said intermediate adduct with an excess of the second multifunctional reagent or combination of reagents to produce a first molecular unit of said effective polymeric linkage comprising at least one terminal reactive moiety capable of coupling to said first multifunctional reagent or combination of reagents;
d) alternately repeating said first and second coupling reactions to produce an immobilized structure comprising multiple monolayers of effective sequential polymeric linkages.
2. A process as claimed in claim 1 wherein at least two immobilized multiple monolayer structures having substantially the same number of polymeric linkages are produced.
3. A process as claimed in claim 1 or 2 wherein said first multifunctional reagent has the general formula I, II, or
III:
in which R is readily displaced by nucleophiles and is heterocyclic aromatic or halogen;
R1 is phenylene polyphenylene, fused ring aromatic, alkylene, alkenylene, aromatic heterocyclic, or metalloorganic; R2 and R3, which may be the same or different, are each H, halogen, OR4, OH, or SH wherein R4 is an aliphatic or aromatic hydrocarbon; and R2-N- and R6 N- which may be the same or different, are each HO-N-, 0=N- or X-N2+.
4. A process as claimed in claim 3 wherein said first multifunctional reagent is carbonyldiimidazole, 1,4-dialdobenzene, l,l'-dialdoferrocene, 1,4-dinitrosobenzene, or benzene 1,4-dicarboxylic acid chloride.
5. A process as claimed in any one of the preceding claims wherein the second multifunctional reagent has the formula
wherein R7 is an aromatic hydrocarbon group having one ring or a plurality of separate rings, a fused ring aromatic group, a saturated or unsaturated aliphatic hydrocarbon group, an aromatic heterocyclic group, or a metallo organic group; X, and X2 are the same or different and are NH2, NHOH, or OH, and X3 and X4 are the same or different and are NH2, NHOH, OH or H.
6. A process as claimed in claim 5 wherein said second multifunctional reagent is phenylene diamine or 1,4-hydroquinone.
7. A process as claimed in claim 1 wherein said substrate contains an amino functionality and said first and second coupling steps are conducted with an excess of a mixture of 1,4-dialdobenzene and phenylenetriamine to produce a branched multiple monolayer structure.
8. A process as claimed in any of claims 1 to 6 which further comprises:
a) reacting said immobilized structure with a compound capable of acting as a molecular switch;
b) reacting said attached molecular switch with said first and second multifunctional reagents alternately to produce a second immobilized structure attached to said switch, said second structure comprising multiple monolayers of effective sequential polymeric linkages; and
c) reacting said second structure with a second solid phase for attachment thereto.
9. A process for immobilizing an enzyme which comprises:
a) providing a solid phase having an attached amino functionality;
b) conducting a first coupling reaction by reacting said attached amino functionality with an excess of carbonyldiimidazole to produce an intermediate adduct which comprises a carbonyl-containing residue derived from said carbonyldiimidazole, and a reactive moiety capable of coupling to a second multifunctional reagent containing at least one amino functionality;
c) conducting a second coupling reaction by reacting said intermediate compound with an excess of said second multifuctional reagent to produce a first phenylurethane molecular unit;
d) repeating said first and second coupling reactions to produce an immobilized structure with at least four monolayers of phenylurethane linkages and a terminal amino functionality; ;
e) reacting said terminal amino functionality with carbonyldiimidazole to produce a terminal intermediate adduct capable of coupling to an enzyme;
f) reacting said resulting intermediate adduct with an enzyme to produce an enzyme immobilized onto a multiple monolayer structure.
10. A process as claimed in claim 9 wherein the enzyme is acetylcholinesterase.
11. A process as claimed in claim 1 and substantially as hereinbefore described with reference to Example 1.
12. A multiple monolayer structure produced by a process as claimed in any of claims 1 to 8 and 11.
13. A process as claimed in claim 9 and substantially as hereinbefore described with reference to Example 2.
14. An immobilized enzyme produced by a process as claimed in claim 9 or 13.
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US91633786A | 1986-10-07 | 1986-10-07 |
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GB2266182A (en) * | 1992-03-31 | 1993-10-20 | Sharp Kk | Bimolecular switch |
Citations (2)
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EP0115771A2 (en) * | 1983-01-07 | 1984-08-15 | The Dow Chemical Company | Dense star polymers and a process for producing dense star polymers |
EP0208258A1 (en) * | 1985-07-05 | 1987-01-14 | COMPAGNIE GENERALE D'ELECTRICITE Société anonyme dite: | Process for the preparation of macromolecular structures, and compounds obtained |
-
1987
- 1987-09-28 GB GB8722724A patent/GB2198738B/en not_active Expired - Fee Related
- 1987-10-07 JP JP62253483A patent/JPS63101403A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0115771A2 (en) * | 1983-01-07 | 1984-08-15 | The Dow Chemical Company | Dense star polymers and a process for producing dense star polymers |
EP0208258A1 (en) * | 1985-07-05 | 1987-01-14 | COMPAGNIE GENERALE D'ELECTRICITE Société anonyme dite: | Process for the preparation of macromolecular structures, and compounds obtained |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2266182A (en) * | 1992-03-31 | 1993-10-20 | Sharp Kk | Bimolecular switch |
GB2266182B (en) * | 1992-03-31 | 1996-08-28 | Sharp Kk | Improvements relating to information technology |
Also Published As
Publication number | Publication date |
---|---|
JPS63101403A (en) | 1988-05-06 |
GB2198738B (en) | 1990-12-12 |
GB8722724D0 (en) | 1987-11-04 |
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Legal Events
Date | Code | Title | Description |
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732 | Registration of transactions, instruments or events in the register (sect. 32/1977) | ||
PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19960928 |