US5242828A — Sensing surfaces capable of selective biomolecula…

Claim 1

Independent Claim 147 words

A sensing surface suitable for use in a biosensor, comprising: a film, having two faces, of a free electron metal selected from the group consisting of copper, silver, aluminum and gold; and a densely packed monolayer of an organic molecule X-R-Y coated on one of the faces of said film where X is a group selected from the group consisting of asymmetrical or symmetrical disulfide (-SSR'Y', -SSRY), sulfide (-SR'Y', -SRY), diselenide (-SeSeR'Y', -SeSeRY), selenide (SeR'Y', -SeRY), thiol (-SH), isonitrile, nitro (-NO 2 ), selenol (-SeH), trivalent phosphorous compounds, isothiocyanate, xanthate, thiocarbamate, phosphine, thio acid and dithio acid (-COSH, -CSSH) where R and R' are hydrocarbon chains, optionally interrupted by hetero atoms, of a length exceeding 10 atoms, wherein in the case of an asymmetrical molecule, R' or R may be H, and Y and Y' are active groups for covalently binding ligands or a biocompatible porous matrix.

Claim 2

Dependent Claim 147 words

A sensing surface suitable for use in a biosensor, comprising: a film, having two faces, of a free electron metal selected from the group consisting of copper, silver, aluminum and gold; and a densely packed monolayer of an organic molecule X-R-Y coated on one of the faces of said film where X is a group selected from the group consisting of asymmetrical or symmetrical disulfide (-SSR'Y', -SSRY), sulfide (-SR'Y', -SRY), diselenide (-SeSeR'Y', -SeSeRY), selenide (SeR'Y', -SeRY), thiol (-SH), isonitrile, nitro (-NO 2 ), selenol (-SeH), trivalent phosphorous compounds, isothiocyanate, xanthate, thiocarbamate, phosphine, thio acid and dithio acid (-COSH, -CSSH) where R and R' are hydrocarbon chains, optionally interrupted by hetero atoms, of a length exceeding 10 atoms, wherein in the case of an asymmetrical molecule, R' or R may be H, and Y and Y' are active groups for covalently binding ligands or a biocompatible porous matrix.

Claim 3

Dependent Claim 31 words

The sensing surface according to claim 1, which contains a biocompatible porous matrix which is bound to the densely packed monolayer X-R-Y and via which a desired ligand can be bound.

Claim 4

Dependent Claim 15 words

The sensing surface according to claim 2, wherein the biocompatible porous matrix is a hydrogel.

Claim 5

Dependent Claim 37 words

The sensing surface according to claim 3, wherein the hydrogel is derivatized to contain hydroxyl, carboxyl, amino, aldehyde, carbonyl, epoxy or vinyl groups for immobilizing a desired ligand, and optionally a biospecific ligand bound via said group.

Claim 6

Dependent Claim 34 words

The sensing surface according to claim 3, wherein the hydrogel is a polysaccharide selected from the group consisting of agarose, dextran, carrageenan, alginic acid, starch and cellulose and a derivative of any of these.

Claim 7

Dependent Claim 18 words

The sensing surface according to claim 3, wherein the hydrogel is a polysaccharide or a swellable organic polymer.

Claim 8

Dependent Claim 48 words

The sensing surface according to claim 6, wherein the hydrogel is activated to contain (i) charged groups for bringing about a concentration of biomolecules carrying an opposite charge to that of said charged groups, and (ii) reactive groups for covalently binding the biomolecules concentrated to the sensing surface.

Claim 9

Dependent Claim 26 words

The sensing surface according to claim 7, wherein the charged groups are carboxyl groups and the reactive groups are reactive esters, hydrazides or reactive disulfide-containing derivatives.

Claim 10

Dependent Claim 21 words

The sensing surface according to claim 8, wherein the reactive disulfide-containing derivative is formed via reaction between reactive ester and 2-(2-pyridinyldithio)ethanamine.

Claim 11

Dependent Claim 14 words

The sensing surface according to claim 8, wherein said hydrogel contains a 2-aminoethanethiol derivative.

Claim 12

Dependent Claim 13 words

The sensing surface according to claim 6, wherein the hydrogel consists of dextran.

Claim 13

Dependent Claim 42 words

The sensing surface according to claim 11, wherein the dextran is derivatized to contain carboxyl, amino, aldehyde, carbonyl, epoxy or vinyl groups for immobilizing the desired ligand, and optionally a biospecific ligand bound via said group or hydroxy groups in the dextran.

Claim 14

Dependent Claim 49 words

The sensing surface according to claim 11, wherein the dextran has been activated to contain (i) charged groups for bringing about a concentration of biomolecules carrying an opposite charge to that of said charged groups, and (ii) reactive groups for covalently binding the biomolecules concentrated to the sensing surface.

Claim 15

Dependent Claim 34 words

The sensing surface according to claim 13, wherein the dextran has been activated with carboxyl groups part of which have been activated to the form of reactive esters, hydrazides, thiols or reactive disulfide-containing derivatives.

Claim 16

Dependent Claim 14 words

The sensing surface according to claim 14, wherein said dextran contains a 2-aminoethanethiol derivative.

Claim 17

Dependent Claim 21 words

The sensing surface according to claim 14, wherein the reactive disulfide-containing derivative is formed via reaction between reactive ester and 2-(2-pyridinyldithio)ethanamine.

Claim 18

Dependent Claim 20 words

The sensing surface according to claim 1, which contains a ligand which is bound to the densely packed monolayer X-R-Y.

Claim 19

Dependent Claim 21 words

The sensing surface according to claim 1, wherein R and R' are hydrocarbon chains, optionally interrupted by heteroatoms containing 12-40 atoms.

Claim 20

Dependent Claim 14 words

The sensing surface according to claim 1, wherein Y and Y' are the same.

Claim 21

Dependent Claim 22 words

The sensing surface according to claim 1, wherein Y and Y' are hydroxyl, carboxyl, amino, aldehyde, hydrazide, carbonyl, epoxy or vinyl groups.

Claim 22

Dependent Claim 29 words

The sensing surface according to claim 1, wherein the hydrogel is a swellable organic polymer selected from the group consisting of polyvinyl alcohol, polyacrylic acid, polyethylene glycol or polyacrylamide.

Claim 23

Dependent Claim 168 words

A sensing element suitable for use in a biosensor, comprising: a substrate; a film of a free electron metal selected from the group consisting of copper, silver, aluminum and gold disposed on said substrate, said film having a first and second major surface, said first major surface being in contact with said substrate; and a densely packed monolayer of an organic molecule X-R-Y coated on said second major surface of said film where X is a group selected from the group consisting of asymmetrical or symmetrical disulfide (-SSR'Y', -SSRY), sulfide (-SR'Y', -SRY), diselenide (-SeSeR'Y', -SeSeRY), selenide (SeR'Y', -SeRY), thiol (-SH), isonitrile, nitro (-NO 2 ), selenol (-SeH), trivalent phosphorus compounds, isothiocyanate, xanthate, thiocarbamate, phosphine, thio acid and dithio acid (-COSH, -CSSH), where R and R' hydrocarbon chains, optionally interrupted by hetero atoms, of a length exceeding 10 atoms, wherein in the case of an asymmetrical molecule R' or R may be H, and Y and Y' are active groups for covalently binding ligands or a biocompatible porous matrix.

Claim 24

Dependent Claim 168 words

A sensing element suitable for use in a biosensor, comprising: a substrate; a film of a free electron metal selected from the group consisting of copper, silver, aluminum and gold disposed on said substrate, said film having a first and second major surface, said first major surface being in contact with said substrate; and a densely packed monolayer of an organic molecule X-R-Y coated on said second major surface of said film where X is a group selected from the group consisting of asymmetrical or symmetrical disulfide (-SSR'Y', -SSRY), sulfide (-SR'Y', -SRY), diselenide (-SeSeR'Y', -SeSeRY), selenide (SeR'Y', -SeRY), thiol (-SH), isonitrile, nitro (-NO 2 ), selenol (-SeH), trivalent phosphorus compounds, isothiocyanate, xanthate, thiocarbamate, phosphine, thio acid and dithio acid (-COSH, -CSSH), where R and R' hydrocarbon chains, optionally interrupted by hetero atoms, of a length exceeding 10 atoms, wherein in the case of an asymmetrical molecule R' or R may be H, and Y and Y' are active groups for covalently binding ligands or a biocompatible porous matrix.

Claim 25

Dependent Claim 21 words

The sensing surface according to claim 22, wherein R and R' are hydrocarbon chains, optionally interrupted by heteroatoms, containing 12-30 atoms.

Claim 26

Dependent Claim 14 words

The sensing surface according to claim 22, wherein Y and Y' are the same.

Claim 27

Dependent Claim 22 words

The sensing surface according to claim 22, where Y and Y' are hydroxyl, carboxyl, amino, aldehyde, hydrazide, carbonyl, epoxy or vinyl groups.

Claim 28

Dependent Claim 144 words

A sensing surface suitable for use in a biosensor comprising: a film, having two faces, of a free electron metal selected from the group consisting of copper, silver, aluminum and gold; and a monolayer of an organic molecule X-R-Y coated on one of the faces of said film where X is a group selected from the group consisting of asymmetrical or symmetrical disulfide (-SSR'Y', -SSRY), sulfide (-SR'Y', -SRY), diselenide (-SeSeR'Y', -SeSeRY), selenide (SeR'Y', -SeRY), thiol (-SH), isonitrile, nitro (-NO 2 ), selenol (SeH), trivalent phosphorous compounds isothiocyanate, xanthate, thiocarbamate, phosphine, thio acid and dithio acid (-COSH, -CSSH) where R and R' are hydrogen chains, optionally interrupted by hetero atoms, of a length exceeding 10 atoms, wherein in the case of an asymmetrical molecule, R' or R may be H, Y and Y' are active groups for covalently binding ligands or a biocompatible porous matrix.

Claim 29

Dependent Claim 144 words

A sensing surface suitable for use in a biosensor comprising: a film, having two faces, of a free electron metal selected from the group consisting of copper, silver, aluminum and gold; and a monolayer of an organic molecule X-R-Y coated on one of the faces of said film where X is a group selected from the group consisting of asymmetrical or symmetrical disulfide (-SSR'Y', -SSRY), sulfide (-SR'Y', -SRY), diselenide (-SeSeR'Y', -SeSeRY), selenide (SeR'Y', -SeRY), thiol (-SH), isonitrile, nitro (-NO 2 ), selenol (SeH), trivalent phosphorous compounds isothiocyanate, xanthate, thiocarbamate, phosphine, thio acid and dithio acid (-COSH, -CSSH) where R and R' are hydrogen chains, optionally interrupted by hetero atoms, of a length exceeding 10 atoms, wherein in the case of an asymmetrical molecule, R' or R may be H, Y and Y' are active groups for covalently binding ligands or a biocompatible porous matrix.

Claim 30

Dependent Claim 27 words

The sensing surface of claim 26, wherein said monolayer forms an efficient barrier layer which is stable upon storage and which protects said film from chemical corrosion.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1996-09-06	1997-03-08	1997-09-07	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2000-09-06	2001-03-08	2001-09-07	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2004-09-06	2005-03-08	2005-09-07	$7700.00	Window Closed / Lapsed

Sensing surfaces capable of selective biomolecular interactions, to be used in biosensor systems

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