WO2023152224A1

WO2023152224A1 - Polyurethane membrane for sensor

Info

Publication number: WO2023152224A1
Application number: PCT/EP2023/053202
Authority: WO
Inventors: Ajay Padsalgikar; Andre Martinez
Original assignee: DSM IP Assets BV
Current assignee: DSM IP Assets BV
Priority date: 2022-02-10
Filing date: 2023-02-09
Publication date: 2023-08-17
Anticipated expiration: 2024-08-10

Abstract

Disclosed herein are membranes, composition for forming membranes, methods for forming membranes, and sensors and devices comprising membranes. The membrane comprises the reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol, wherein the first chain extender diol and second chain extender diol are different and satisfy at least one of aspecified set of relationships.

Description

Polyurethane Membrane for Sensor

Field

The disclosed inventions relate to polyurethane compositions, membranes formed from such polyurethane compositions, and sensors and devices comprising such membranes.

Background

A sensor may comprise an analyte diffusion-limiting membrane. Without an analyte diffusion-limiting membrane, a sensor becomes saturated quickly and at low analyte concentrations. Ideally, a sensor has sufficient oxygen for adequate operation, but saturation of the target analyte at the sensor surface is prevented. An oxygen permeable membrane that restricts analyte flux to the sensing layer is thus often required. Preferred diffusion-limiting membranes are mechanically strong, biocompatible, minimize protein adsorption, have sufficient oxygen diffusivity, and are easily manufactured.

Synthetic membranes formed from polyurethanes are known. Polyurethanes have been chosen due to their ability to form films when blended with a range of solvents and ability to regulate the flux of analytes to sensors.

For instance, US5589563 discloses the casting of membranes from polyurethanes comprising surface modifying endgroups. A polyurethane with a surface modifying endgroups is a polyurethane comprising one or more endgroups at the terminal ends of the backbone of the polyurethane. The surface modifying endgroups and backbone are such that the surface activity of such a polyurethane reflects the surface activity of the surface modifying endgroups rather than the backbone.

Further techniques for forming membranes from polyurethanes are disclosed in US7226978. A membrane formed from a blend of amphiphilic copolymer and hydrophobic polymer is disclosed. It is stated that the blend allows membranes having hydrophilic domains that control the diffusion of an analyte therethrough dispersed in a hydrophobic matrix. Polyurethanes may be employed as the amphiphilic copolymer or hydrophobic polymer.

Another technique for forming membranes is disclosed in US7157528 and US7687586. In these documents a biocompatible multipolymer is disclosed. The multipolymer comprises a hydrophilic soft segment and an oxygen-permeable soft segment.

Further techniques for forming membranes from polyurethanes are disclosed in US8255032. A membrane comprising a blend of silicone-containing polyurethane with hydrophilic polymer is disclosed. The hydrophilic polymer may be polyvinylpyrrolidone, polyhydroxyethyl methacrylate, polyvinylalcohol, polyacrylic acid, polyethers, and copolymers thereof.

Further such membranes are disclosed in US20210077957, US20210079180, and US20210070989.

Despite these documents, there is still a need for compositions for forming synthetic membranes that yield suitable mechanical properties, oxygen and analyte transport properties, and membrane quality.

Summary

Polyurethanes possess various segments, e.g., hard blocks and soft blocks. It was hypothesized that due to the nature of differing polarities of these various segments present in the polyurethane, a better homogeneity could be obtained through the suppression of order in the arrangement of hard block domains. In accordance with the invention, this disruption of order is achieved through the introduction of structural heterogeneity in the hard segment formation. In an embodiment, the desired structural heterogeneity can be achieved by the mixing of structurally dissimilar chain extenders.

In an embodiment, a membrane comprises a polyurethane, the polyurethane comprising the reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol, wherein the first chain extender diol and the second chain extender diol are different and satisfy at least one of the following relationships: a. are both aliphatic, are unsubstituted alkane diols, and differ in the classification of one or both hydroxyl groups; b. are both cyclo-aliphatic, are isomers of one another, and the first chain extender diol and the second chain extender diol differ in the relative position of the hydroxyl groups on the hydrocarbon ring; c. the first chain extender diol is aliphatic but not cycloaliphatic and the second chain extender diol is cycloaliphatic; or d. the first chain extender diol is an unsubstituted alkane diol and the second diol is a substituted alkane diol.

The polyurethanes and membranes disclosed herein may exhibit improved oxygen and/or glucose transport properties, improved mechanical properties, transport or mechanical properties that are more tailorable merely by modifying the amounts of a given set of reactants, improved material homogeneity, easier or more uniform dissolution of the polyurethanes in desired solvents, and simpler or more efficient manufacturing processes. Brief Description of the Drawings

Figure 1 is a plot of water uptake vs. the weight fraction of 1 ,3-BDO based on the total weight of the chain extender associated with Example 1.

Detailed Description

In accordance with the invention, a membrane comprises a polyurethane comprising the reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol.

In an embodiment, a membrane comprises the polyurethane. In an embodiment, a membrane comprises the polyurethane and a free hydrophilic polymer. In an embodiment, the membrane is devoid or substantially devoid of free hydrophilic polymer.

In accordance with an embodiment, a composition for forming a membrane comprises from 80 to 99.5 wt%, based on the total weight of the composition, of a solvent and from 0.5 to 20 wt%, based on the total weight of the composition, of a polyurethane. In an embodiment, a composition for forming a membrane comprises from 90 to 99.5 wt%, based on the total weight of the composition, of a solvent and from 0.5 to 10 wt%, based on the total weight of the composition, of a polyurethane.

By a reaction product it is meant that the diisocyanate and polymeric aliphatic diol, the first chain extender diol and the second chain extender diol, are engaged in a simultaneous or sequential chemical reaction. For example, a reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol is formed i) when the diisocyanate, polymeric aliphatic diol, first chain extender diol, and second chain extender diol are all reacted together in a single solution, or ii) when a pre-polymer is first formed by reacting the diisocyanate and the polymeric aliphatic diol, and then this prepolymer is subsequently reacted with a mixture of the first chain extender diol and the second chain extender diol.

The disclosed compositions, membranes, and sensors may have advantages over the prior art in terms of mechanical properties, such as modulus, tensile strength, elongation, or durability, analyte permeability, oxygen permeability, isotropy of mechanical properties, surface quality, use with a wider range of solvents, process reproducibility, process speed, health and safety concerns, such as easier or more expedient removal of residual solvent.

The polyurethane comprises the reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol. In an embodiment, the polyurethane consists of the reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol. In an embodiment, the polyurethane further comprises an endgroup. In an embodiment, the polyurethane is linear.

Diisocyanate

The polyurethane comprises the residue of a diisocyanate. In an embodiment, the diisocyanate is aliphatic. In an embodiment, the diisocyanate is aromatic. In an embodiment, the diisocyanate comprises 4,4'-diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 1 ,4-phenylene diisocyanate, hexamethylene diisocyanate (HDI), tetramethylene-1 ,4-diisocyanate, cyclohexane-1 ,4-diisocyanate, dicyclohexylmethane-4,4'-diisocyanate (HMDI), isophorone diisocyanate (IPDI), or a mixture thereof. In an embodiment, the diisocyanate comprises hexamethylene diisocyanate, dicyclohexylmethane 4,4'-diisocyanate, isophorone diisocyanate, or a mixture thereof. In an embodiment, the diisocyanate consists of hexamethylene diisocyanate, dicyclohexylmethane 4,4'-diisocyanate, isophorone diisocyanate, or a mixture thereof. In an embodiment, the diisocyanate comprises 4,4'- diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, or 1 ,4-phenylene diisocyanate. In an embodiment, the diisocyanate consists of 4,4'- diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 1 ,4-phenylene diisocyanate, or a mixture thereof.

In an embodiment, the molecular weight of the diisocyanate is from 100 to 500 g/mol. In an embodiment, the molecular weight of the diisocyanate is from 150 to 260 g/mol.

In an embodiment, the formulation from which the polyurethane is formed comprises at least 10 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, or at least 40 wt% of a diisocyanate, based on the total weight of the formulation. In an embodiment, the formulation from which the polyurethane is formed comprises at most 50 wt%, at most 40 wt%, at most 35 wt%, at most 30 wt%, at most 25 wt%, or at most 20 wt% of a diisocyanate, based on the total weight of the formulation. In an embodiment, the polyurethane comprises at least 10 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, or at least 40 wt% of the residue of a diisocyanate, based on the polyurethane. In an embodiment, the polyurethane comprises at most 50 wt%, at most 40 wt%, at most 35 wt%, at most 30 wt%, at most 25 wt%, or at most 20 wt% of the residue of a diisocyanate, based on the total weight of the polyurethane.

Polymeric Aliphatic Diol

The polyurethane comprises the residue of a polymeric aliphatic diol. A polymeric aliphatic diol comprises two OH groups and a backbone. The OH groups may be directly attached to the backbone or may be separated by a linker. For example, a hydroxyalkyl terminated polydimethylsiloxane (carbinol terminated) is a polymeric aliphatic diol.

In an embodiment, the polymeric aliphatic diol comprises a poly(alkylene oxide), a polycarbonate, a polysiloxane, a random or block copolymer thereof, or a mixture thereof. In an embodiment, the polymeric aliphatic diol comprises a poly(alkylene oxide), a polycarbonate, a random or block copolymer thereof, or a mixture thereof. In an embodiment, the polymeric aliphatic diol comprises C2-C16 fluoroalkyl or C2-C16 fluoroalkyl ether.

In an embodiment, the polymeric aliphatic diol comprises a polyethylene oxide) diol, a polypropylene oxide) diol, a poly(tetramethylene oxide) diol, a poly(isobutylene) diol, a polyester diol, for example a polyester diol formed from adipic acid or isophtalic acid and a monomeric diol, an alkane diol, such as a hydrogenated polybutadiene diol or a polyethylene diol, a poly(hexamethylene carbonate) diol, a poly(polytetrahydrofuran carbonate) diol, a polysiloxane diol, a random or block copolymer diol of polyethylene oxide) and polypropylene oxide), a random or block copolymer diol of poly(ethylene oxide) and poly(tetramethylene oxide), a random or block copolymer diol of poly(ethylene oxide) and a polysiloxane, or a mixture thereof.

In an embodiment, the polymeric aliphatic diol comprises a poly(ethylene oxide) diol, a polypropylene oxide) diol, a poly(tetramethylene oxide) diol, a poly(isobutylene) diol, a polysiloxane diol, a random or block copolymer diol of polypthylene oxide) and polypropylene oxide), a random or block copolymer diol of polypthylene oxide) and poly(tetramethylene oxide), a random or block copolymer diol of polypthylene oxide) and a polysiloxane, a random or block copolymer diol comprising a polysiloxane, or a mixture thereof.

In an embodiment, the polymeric aliphatic diol comprises a mixture of a polysiloxane diol and one or more of a polypthylene oxide) diol, a polypropylene oxide) diol, a poly(tetramethylene oxide) diol, a random or block copolymer diol of polypthylene oxide) and polypropylene oxide), a random or block copolymer diol of polypthylene oxide) and poly(tetramethylene oxide), and a polyoxazoline diol. In an embodiment, the polymeric aliphatic diol comprises a polycarbonate diol. In an embodiment, the polymeric aliphatic diol comprises a polycarbonate diol that comprises a poly(hexamethylene carbonate) diol or a polypolytetrahydrofuran carbonate) diol. In an embodiment, the polymeric aliphatic diol comprises a polycarbonate diol having a Mn of at least 500 g/mol, at least 750 g/mol, at least 1000 g/mol, or at least 1500 g/mol. In an embodiment, the polymeric aliphatic diol comprises a polycarbonate diol having a Mn of at most 10,000 g/mol, at most 7500 g/mol, at most 5000 g/mol, at most 4000 g/mol, at most 3000 g/mol, or at most 2500 g/mol. In an embodiment, the polymeric aliphatic diol comprises a polysiloxane diol, a polycarbonate diol, or a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol consists of a polysiloxane diol, a polycarbonate diol, a poly(tetramethylene oxide) diol, or a mixture thereof. In an embodiment, the polymeric aliphatic diol comprises a mixture of two or more of a polysiloxane diol, a polycarbonate diol, or a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol consists of a mixture of two or more of a polysiloxane diol, a polycarbonate diol, or a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol comprises a polysiloxane diol and one or more of a polycarbonate diol and a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol consists of a polysiloxane diol and one or more of a polycarbonate diol and a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol comprises 15 wt% or less, 10 wt% or less, 5 wt% or less, 2 wt% or less, based on the total weight of polymeric aliphatic diol, or is devoid of hydrophobic poly(alkylene oxide). Hydrophobic poly(alkylene oxide)s are polypropylene oxide), and poly(tetramethylene oxide). In an embodiment, the polymeric aliphatic diol comprises 15 wt% or less, 10 wt% or less, 5 wt% or less, 2 wt% or less, based on the total weight of polymeric aliphatic diol, or is devoid of polysiloxane. An example of a polysiloxane is polydimethylsiloxane. In an embodiment, the polymeric aliphatic diol comprises 15 wt% or less, 10 wt% or less, 5 wt% or less, 2 wt% or less, based on the total weight of polymeric aliphatic diol, or is devoid of, hydrophobic poly(alkylene oxide) and polysiloxane.

In an embodiment, the polymeric aliphatic diol has a Mn of at least 200 g/mol, at least 250 g/mol, at least 300 g/mol, at least 400 g/mol, or at least 500 g/mol, at least 600 g/mol, at least 700 g/mol, at least 800 g/mol, at least 900 g/mol, or at least 1000 g/mol. In an embodiment, the polymeric aliphatic diol has a Mn of at most 10,000 g/mol, at most 8500 g/mol, at most 6000 g/mol, at most 5000 g/mol, at most 4000 g/mol, at most 3000 g/mol, at most 2000 g/mol, or at most 1500 g/mol.

In an embodiment, the polyurethane is formed from a formulation that comprises at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, or at least 60 wt% of a polymeric aliphatic diol, based on the total weight of the formulation. In an embodiment, the polyurethane is formed from a formulation that comprises at most 80 wt%, at most 70 wt%, at most 60 wt%, or at most 50 wt% of a polymeric aliphatic diol, based on the total weight of the formulation. In an embodiment, the polyurethane comprises at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, or at least 60 wt% of the residue of a polymeric aliphatic diol, based on the total weight of the polyurethane. In an embodiment, the polyurethane comprises at most 80 wt%, at most 70 wt%, at most 60 wt%, or at most 50 wt% of the residue of a polymeric aliphatic diol, based on the total weight of the polyurethane.

Chain Extender Diols

The polyurethane comprises the residue of a first chain extender diol and a second chain extender diol. A chain extender diol is a non-polymeric diol having a molecular weight of 500 g/mol or less. In an embodiment, the chain extender diols are alkane diols having from 2 to 20 carbon atoms, wherein one or more carbon atoms may be substituted with oxygen, silicon, phosphorous, or sulfur. In an embodiment, the chain extender diols are alkane diols having from 2 to 20 carbon atoms, wherein one or more carbon atoms may be substituted with oxygen or silicon. In an embodiment, the chain extender diols are alkane diols having from 2 to 20 carbon atoms, wherein one or more carbon atoms may be substituted with oxygen. In an embodiment, the chain extender diols are unsubstituted alkane diols having from 2 to 20 carbon atoms.

An unsubstituted alkane diol is a diol consisting of single-bonded carbon and hydrogen atoms and two OH groups. A substituted alkane diol would be an alkane diol but for the substitution of one or more carbon atoms with another atom, such as oxygen or silicon, while still retaining at least two carbon atoms. Examples of unsubstituted alkane diols are ethylene glycol, propanediol, butanediol, pentanediol, 1 ,4- cyclohexanedimethanol, and the like. Examples of substituted alkane diols are diethylene glycol, dipropylene glycol, 1 ,3-bis(4-hydroxybutyl)tetramethyldisiloxane (BHTD), 1 ,3- bis(hydroxypropyl)tetramethyldisiloxane, 1 ,3-bis(3-hydroxyisobutyl)tetramethyldisiloxane, 3-ethoxy-1 ,2-propanediol, or 2,2’-Thiodiethanol.

In an embodiment, the first chain extender diol and/or the second chain extender diol has a molecular weight of at least 60 g/mol, at least 70 g/mol, at least 80 g/mol, at least 90 g/mol, or at least 100 g/mol. In an embodiment, the first chain extender diol and/or the second chain extender diol comprises has a molecular weight of at most 500 g/mol, at most from 400 g/mol, at most 300 g/mol, at most 200 g/mol, or at most 150 g/mol. In an embodiment, the first chain extender diol and/or the second chain extender diol comprises ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, 1 ,3- propanediol, 1 ,2-butanediol, 1 ,3-butanediol, 1 ,4-butanediol, 2,3-butanediol, 1 ,2- pentanediol, 1 ,3-pentanediol, 1 ,4-pentanediol, 1 ,5-pentanediol, 1 ,3-hexanediol, 1 ,4- hexanediol, 1 ,5-hexanediol, 1 ,6-hexanediol, 2,4-hexanediol, 2,5-hexanediol, 1 ,2- octanediol, 1 ,3-octanediol, 1 ,4-octanediol, 1 ,5-octanediol, 1 ,6-octanediol, 1 ,7-octanediol, 1 ,8-octanediol, 2,7-octanediol, neopentyl glycol, 1 ,2-cyclohexanediol, 1 ,3-cyclohexanediol, 1 ,4-cyclohexanediol, 1 ,2-cyclohexanedimethanol, 1 ,3-cyclohexanedimethanol, 1 ,4- cyclohexanedimethanol, or 1 ,1 -cyclohexanedimethanol. In an embodiment, the first chain extender diol and/or the second chain extender diol comprises ethylene glycol, propylene glycol, 1 ,3-propanediol, 1 ,2-butanediol, 1 ,3-butanediol, 1 ,4-butanediol, 2,3-butanediol, 1 ,2- pentanediol, 1 ,3-pentanediol, 1 ,4-pentanediol, 1 ,5-pentanediol, 1 ,3-hexanediol, 1 ,4- hexanediol, 1 ,5-hexanediol, 1 ,6-hexanediol, 2,4-hexanediol, 2,5-hexanediol, 1 ,2- octanediol, 1 ,3-octanediol, 1 ,4-octanediol, 1 ,5-octanediol, 1 ,6-octanediol, 1 ,7-octanediol, 1 ,8-octanediol, or 2,7-octanediol.

In an embodiment, the first chain extender and the second chain extender are both aliphatic, are unsubstituted alkane diols, and differ in the classification of one or both hydroxyl groups. In an embodiment, the first chain extender is 1 ,4-butanediol and the second chain extender is propylene glycol. In an embodiment, the first chain extender and the second chain extender are both aliphatic, are unsubstituted alkane diols, are isomers, and differ in the classification of one or both hydroxyl groups. In an embodiment, the first chain extender is 1 ,4-butanediol and the second chain extender is 1 ,3-butanediol.

In an embodiment, the first chain extender diol and the second chain extender diol differ in the classification (primary, secondary, or tertiary) of one or both hydroxyl groups. In an embodiment, the first chain extender diol comprises two primary hydroxyl groups, one primary and one secondary hydroxyl group, one primary and one tertiary hydroxyl group, two secondary hydroxyl groups, or one secondary and one tertiary hydroxyl group. In an embodiment, the second chain extender diol comprises two primary hydroxyl groups, one primary and one secondary hydroxyl group, one primary and one tertiary hydroxyl group, two secondary hydroxyl groups, or one secondary and one tertiary hydroxyl group.

In an embodiment, the first chain extender diol and the second chain extender diol are both cycloaliphatic and differ in the position of the hydroxyl group on the ring. In an embodiment, the first chain extender is 1 ,4-cyclohexanediol and the second chain extender is 1 ,2-cyclohexanediol or 1 ,3-cyclohexanediol.

In an embodiment, the first chain extender diol is an unsubstituted alkane diol and the second diol is a substituted alkane diol. In an embodiment, the first chain extender is 1 ,4-butanediol and the second chain extender is 1 ,3-bis(4- hydroxybutyl)tetramethyldisiloxane.

In an embodiment, the polyurethane is formed from a formulation that comprises at least 1 wt%, at least 2 wt%, at least 5 wt%, at least 8 wt%, or at least 10 wt% of chain extender diols, based on the total weight of the formulation. In an embodiment, the polyurethane is formed from a formulation that comprises at most 20 wt%, at most 15 wt%, at most 12 wt%, at most 10 wt%, at most 8 wt%, or at most 5 wt%, of chain extender diols, based on the total weight of the formulation. In an embodiment, the polyurethane comprises at least 1 wt%, at least 2 wt%, at least 5 wt%, at least 8 wt%, or at least 10 wt% of the residue of chain extender diols, based on the total weight of the polyurethane. In an embodiment, the polyurethane comprises at most 20 wt%, at most 15 wt%, at most 12 wt%, at most 10 wt%, at most 8 wt%, or at most 5 wt%, of the residue of a chain extender diols, based on the total weight of the polyurethane.

Endgroups

In an embodiment, the polyurethane comprises one or more endgroups. An endgroup is a moiety present at a terminal end of a molecule. In an embodiment, the polyurethane is linear and comprises an endgroup at each terminus of the backbone. In an embodiment, the endgroup is linear. In an embodiment, the endgroup is branched. In an embodiment, the polyurethane comprises an average of at least 0.1 endgroups, at least 0.25 endgroups, at least 0.5 endgroups, at least 1 endgroup, at least 1.5 endgroups, at least 1 .8 endgroups, about 2 endgroups, or at least 2 endgroups. In an embodiment, the polyurethane comprises an average of at most 4 endgroups an average of at most 2 endgroups, or an average of at most 2 endgroups.

An endgroup may be formed by reacting a terminal isocyanate group present after forming the polymer backbone with a coreactive group on a monofunctional moiety. For instance, a terminal isocyanate group may be reacted with 1 -octanol or octylamine to form a C₈ alkyl endgroup. Endgroups may also result from the inclusion of chain stoppers, such as monofunctional alcohols, in a formulation used in the formation of a polyurethane. For instance, a formulation for forming a polyurethane may comprise a diisocyanate, a polymeric aliphatic diol, a chain extender, and a monofunctional alcohol.

In an embodiment, the endgroup comprises a hydrophobic poly(alkylene oxide), a hydrophilic poly(alkylene oxide), a copolymer comprising a hydrophilic poly(alkylene oxide) and a hydrophobic poly(alkylene oxide), a polysiloxane, C₂-C₂o alkyl, C₂-Ci₆ fluoroalkyl, C₂-Ci6 fluoroalkyl ether, or copolymers thereof. In an embodiment, the polysiloxane is a poly(dimethylsiloxane). In an embodiment, the hydrophilic poly(alkylene oxide) is polyethylene oxide). In an embodiment, the hydrophobic poly(alylene oxide) is polypropylene oxide) or poly(tetramethylene oxide). In an embodiment, the endgroup comprises a hydrophobic poly(alkylene oxide), a hydrophilic poly(alkylene oxide), a copolymer comprising a hydrophilic poly(alkylene oxide) and a hydrophobic poly(alkylene oxide), C₂-C₂₀ alkyl, C₂-Ci₆ fluoroalkyl, C₂-Ci₆ fluoroalkyl ether, or copolymers thereof. Such endgroups may be formed with monofunctional alcohols, including carbinols, or amines of the foregoing.

In an embodiment, the endgroup comprises C₂-Ci₆ fluoroalkyl or C₂-Ci₆ fluoroalkyl ether. Such endgroups may be formed with monofunctional alcohols or amines comprising C₂-Ci₆ fluoroalkyl or C₂-Ci₆ fluoroalkyl ether. In an embodiment, the endgroup is formed from a monofunctional alcohol or amine comprising C₂-Ci₆ fluoroalkyl or C₂-Ci₆ fluoroalkyl ether. In an embodiment, the endgroup is formed from 1 H,1 H-Perfluoro-3,6-dioxaheptan-1-ol, 1 H, 1 H-Nonafluoro-1 -pentanol, 1 H,1 H-Perfluoro-1-hexyl alcohol, 1 H,1 H-Perfluoro-3,6,9-trioxadecan-1-ol, 1 H,1 H- Perfluoro-1 -heptyl alcohol, 1 H,1 H-Perfluoro-3,6-dioxadecan-1-ol, 1 H, 1 H-Perfluoro-1 -octyl alcohol, 1 H, 1 H-Perfluoro-1 -nonyl alcohol, 1 H,1 H-Perfluoro-3,6,9-trioxatridecan-1-ol, 1 H,1 H-Perfluoro-1-decyl alcohol, 1 H, 1 H-Perfluoro-1 -undecyl alcohol, 1 H, 1 H-Perfluoro-1 - lauryl alcohol, 1 H, 1 H-Perfluoro-1 -myristyl alcohol, or 1 H, 1 H-Perfluoro-1 -palmityl alcohol.

In an embodiment, the endgroup is monomeric and has a molecular weight of 200 g/mol or more, 300 g/mol or more, or 500 g/mol or more. In an embodiment, the endgroup is monomeric and has a molecular weight of 1 ,000 g/mol or less or 800 g/mol or less. In an embodiment, the endgroup is polymeric and has a Mn of 10,000 g/mol or less, 8,000 g/mol or less, 6,000 g/mol or less, or 4,000 g/mol or less. In an embodiment, the endgroup is polymeric and has a Mn of 500 g/mol or more, 1 ,000 g/mol or more, or 2,000 g/mol or more.

In an embodiment, the endgroup is present in an amount of at least 0.1 wt%, at least 0.2 wt%, at least 0.3 wt%, or at least 0.5 wt%, based on the total weight of the formulation from which the polyurethane is formed. In an embodiment, the endgroup is present in an amount of at most 3 wt%, at most 2 wt% or at most 1 wt%, based on the total weight of the formulation from which the polyurethane is formed. In an embodiment, the endgroup is present in an amount of at least 0.1 wt%, at least 0.2 wt%, at least 0.3 wt%, or at least 0.5 wt%, based on the total weight of the polyurethane. In an embodiment, the endgroup is present in an amount of at most 3 wt%, at most 2 wt% or at most 1 wt%, based on the total weight of the polyurethane.

Formation of Polyurethanes

The polyurethanes may be formed as generally known in the art. A catalyst may be employed. In an embodiment, the catalyst is stannous octoate or dibutyltin dilaurate. Amine catalysts may also be used.

Optional Free Hydrophilic Polymer

In an embodiment, the membrane or composition for forming a membrane comprises a free hydrophilic polymer. A free hydrophilic polymer is a hydrophilic polymer that is not bound to the polyurethane by covalent bonds. In an embodiment, the free hydrophilic polymer comprises polyethylene oxide), polyvinylpyrrolidone, polyacrylic acid, polyvinyl alcohol, polyoxazoline, such as a poly(2-methyl-2-oxazoline) or a poly(2-ethyl-2- oxazoline), or hyaluronic acid. In an embodiment, the free hydrophilic polymer has a number average molecular weight of at least 5,000 g/mol, at least 10,000 g/mol, at least 50,000 g/mol, at least 100,000 g/mol, or at least 200,000 g/mol. In an embodiment, the free hydrophilic polymer has a number average molecular weight of at most 10,000,000 g/mol, at most 5,000,000 g/mol, at most 2,000,000 g/mol, at most 1 ,000,000 g/mol, at most 500,000 g/mol, or at most 200,000 g/mol.

Solvent

The compositions comprise a solvent. To form a membrane, the solvent is evaporated after casting a film from the composition comprising the polyurethane, the optional free hydrophilic polymer, and the solvent. In an embodiment, the solvent comprises tetrahydrofuran (THF), methyl-tetrahydrofuran (methyl-THF), dimethylacetamide (DMAc), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or a mixture thereof. In an embodiment, the solvent comprises tetra hydrofuran (THF) or methyl-tetrahydrofuran (methyl-THF).

A co-solvent may also be present. A co-solvent comprises less than 50 wt% of the total amount of solvent. In an embodiment, a co-solvent is present and is methanol, ethanol, isobutanol, propanol, methyl ethyl ketone, or a mixture thereof. In an embodiment, the solvent comprises 50 wt% or more of tetrahydrofuran (THF), methyl- tetrahydrofuran (methyl-THF), or a mixture thereof and less than 50 wt% of methanol, ethanol, isobutanol, propanol, methyl ethyl ketone, or a mixture thereof.

In an embodiment, the solvent comprises 40 wt% or more of tetrahydrofuran (THF), methyl-tetrahydrofuran (methyl-THF), or a mixture thereof, and methanol, ethanol, isobutanol, propanol, methyl ethyl ketone, or a mixture thereof at an amount of from 1 to 60 wt%, based on the total amount of solvent in the composition.

In an embodiment, the solvent is present in an amount of from 80 to 99.5 wt% of the composition, from 85 wt% to 99.5 wt%, or from 90 wt% to 99 wt%. In an embodiment, the co-solvent is present at less than 50 wt% of the total amount of solvent, less than 40 wt%, less than 30 wt%, less than 20 wt%, or less than 10 wt%. In an embodiment, the solvent comprises at least 40 wt% of THF, methyl-THF, or a mixture thereof.

Membranes

Membranes are typically formed by casting the composition comprising the polyurethane, the optional free hydrophilic polymer, and the solvent directly onto a substrate, such as a sensor, or onto a support liner. The solvent is then evaporated, optionally by use of vacuum or elevated temperatures. Typical temperatures are from 40 to 90 °C. Additives, such as a mold release agent, may be present to facilitate the casting process. In an embodiment, the composition further comprises a mold release agent.

In an embodiment, the membrane consists or substantially consists of the polyurethane. In an embodiment, the membrane comprises from 85 to 99.5 wt%, based on the total weight of the membrane, of the polyurethane, and from 0.5 to 15 wt%, based on the total weight of the membrane, of the free hydrophilic polymer.

In an embodiment, a membrane is permeable to both glucose and oxygen. In an embodiment, the membrane or a membrane formed from the composition has a glucose transmission rate of from 1x10^-10 to 1x10^-6 cm²/sec. In an embodiment, the membrane or a membrane formed from the composition has an oxygen transmission rate of from 1x10^-7 to 1x1 CT² cm²/sec. In an embodiment, the membrane or a membrane formed from the composition has an oxygen transmission rate of from 1x10^-5 to 1x10^-3 cm²/sec.

In an embodiment, the membrane has a thickness of from 1 to 100 pm.

In an embodiment, the membrane has a residual solvent content of less than 50 ppm after drying the membrane under nitrogen for 24 hours followed by drying in a convection oven at 50 °C for one hour.

Applications

The disclosed membranes find utility in medical devices and sensors. Such sensors may detect a wide range of analytes, including glucose, lactic acid, galactose, alcohol, medicinal or recreational drugs, cholesterol, antigens, antibodies, viruses, vitamins, minerals, nutrients, proteins, amino acids, hormones or neurotransmitters. In an embodiment, a sensor for measuring glucose, lactic acid, glutamate, pyruvate, choline, acetylcholine, nitric oxide, sodium, potassium, calcium, chloride, bicarbonate, urea, creatine, or dopamine in the blood stream or another bodily fluid comprises a membrane as disclosed.

In an embodiment, the membrane comprises an enzyme that is reactive with an analyte. In an embodiment, a sensor comprises the membrane and a second membrane, the second membrane comprising an enzyme that is reactive with an analyte.

The medical devices or sensors may be implantable in the body. In an embodiment, a continuous analyte monitoring system comprises the membrane. In an embodiment, a continuous glucose monitoring system comprises the membrane.

The Examples below further elucidate embodiments of the invention, but of course, should not be construed as in any way limiting the scope of the claims. Examples

The properties of the materials used in the examples were measured using the following procedures.

Oxygen Permeability

Film samples are cut to the appropriate size and masked with foil to seal any leaks. The film thickness is measured. Film samples are soaked in deionized water for 24 hours prior to the testing. The film is mounted onto a Mocon OxTran 2/20 system and allowed to equilibrate to a constant gas transmission rate, utilizing pure oxygen as the test gas and pure nitrogen as the carrier gas. The humidity is 90%. The equilibrium gas transmission rate is recorded and the gas permeability in Barrer is calculated. Data is averaged from two samples.

Tensile Properties

Tensile testing was performed in accordance with ASTM D 1708, Standard Test Method for Tensile Properties of Plastics by use of Microtensile Samples. Samples were cut from cast films using a microtensile die and loaded on an Instron testing machine between an upper and lower clamp. The stress and strain were zeroed prior to the start of testing. The upper clamp rises until the sample breaks at which point the test is complete. Strain and % elongation were monitored over the course of the test and the maximum of each is reported. Data is averaged from five samples.

Equilibrium Water Uptake and Water Content

A 3 cm diameter circular sample of a membrane is dried in an oven at 50 °C for 24 hours and weighed. The membrane is then immersed in distilled water. Periodically the sample is removed, patted dry to remove surface water, and weighed again. At each timepoint, water uptake and water content are calculated as below. The measurement after 7 days is taken as equilibrium. Data is averaged from three samples.

Equilibrium Water Uptake (%) = (wet weight - dry weight) I (dry weight) x 100% Equilibrium Water Content (%) = (wet weight - dry weight) I (wet weight) x 100%

Example 1

The polyurethanes are formed from the stated formulations without the aid of a catalyst or a mold release agent. Each polyurethane comprises about 30 wt% of hard segment, being 4,4'-methylenediphenyl diisocyanate and chain extender. The chain extender comprises 1 ,4-butanediol (1 ,4-BDO) and optionally 1 ,3-butanediol (1 ,3-BDO). Each polyurethane comprises about 70 wt% of soft segment, being polyethylene glycol (PEG) and polydimethylsiloxane (PDMS). The composition of each polyurethane is shown in Table 1.1.

Table 1.1 - Polyurethane Composition by Weight Percent

Oxygen permeability and tensile properties are measured. The results are shown in Table 1 .2 and 1 .3. The amounts of 1 ,4-BDO (1 ,4-butanediol) and 1 ,3-BDO (1 ,3- butanediol) are reported as a weight percent of total chain extender content.

Table 1 .2 - Example 1 Polyurethanes and Measured Properties

Table 1.3 - Example 1 Polyurethanes and Measured Properties

Water content trended positively with increasing proportion of 1 ,3-butanediol, as does water uptake (Fig. 1). Tensile stress at break and maximum elongation were impacted by adjusting the proportion of the butanediol isomers.

The following non-limiting and non-exhaustive description of exemplary embodiments is intended to further describe certain embodiments of the invention.

1. A membrane comprising a polyurethane, the polyurethane comprising the reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol, wherein the first chain extender diol and the second chain extender diol are different and satisfy at least one of the following relationships: a. are both aliphatic, are unsubstituted alkane diols, and differ in the classification of one or both hydroxyl groups; b. are both cyclo-aliphatic, are isomers of one another, and the first chain extender diol and the second chain extender diol differ in the relative position of the hydroxyl groups on the hydrocarbon ring; c. the first chain extender diol is aliphatic but not cycloaliphatic and the second chain extender diol is cycloaliphatic; or d. the first chain extender diol is an unsubstituted alkane diol and the second diol is a substituted alkane diol.

2. A method of forming a sensor comprising: a. providing a composition comprising a solvent and a polyurethane comprising the reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol, wherein the first chain extender diol and the second chain extender diol are different and satisfy at least one of the following relationships: i. are both aliphatic, are unsubstituted alkane diols, and differ in the classification of one or both hydroxyl groups; ii. are both cyclo-aliphatic, are isomers of one another, and the first chain extender diol and the second chain extender diol differ in the relative position of the hydroxyl groups on the hydrocarbon ring;

Hi. the first chain extender diol is aliphatic but not cycloaliphatic and the second chain extender diol is cycloaliphatic; or iv. the first chain extender diol is an unsubstituted alkane diol and the second diol is a substituted alkane diol; b. forming a film from the composition on a component of the sensor; and c. evaporating the solvent. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polyurethane comprises, the reaction product of: a. from 10 to 40 wt% of a diisocyanate, b. from 20 to 80 wt% of a polymeric aliphatic diol, c. from 1 to 10 wt% of a first chain extender diol, and d. from 1 to 10 wt% to of a second chain extender diol, all based on the total weight of the polyurethane. The membrane or method according to any one of the preceding exemplary embodiments, wherein the weight ratio of the first chain extender diol to the second chain extender diol is from 1 :4 to 4:1 . The membrane or method according to any one of the preceding exemplary embodiments, wherein the weight ratio of the first chain extender diol to the second chain extender diol is from 1 :3 to 3:1 . The membrane or method according to any one of the preceding exemplary embodiments, wherein the weight ratio of the first chain extender diol to the second chain extender diol is from 1 :2 to 2:1 . The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender and the second chain extender are both aliphatic, are unsubstituted alkane diols, and differ in the classification of one or both hydroxyl groups. The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender and the second chain extender are both cyclo-aliphatic, are isomers of one another, and the first chain extender diol and the second chain extender diol differ in the relative position of the hydroxyl groups on the hydrocarbon ring. The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender and the second chain extender the first chain extender diol is aliphatic but not cycloaliphatic and the second chain extender diol is cycloaliphatic. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender and the second chain extender the first chain extender diol is an unsubstituted alkane diol and the second diol is a substituted alkane diol. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender diol and the second chain extender diol are alkane diols having from 2 to 20 carbon atoms, wherein one or more carbon atoms may be substituted with oxygen, silicon, phosphorous, or sulfur. 12. The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender diol and the second chain extender diol are unsubstituted alkane diols.

13. The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender diol comprises two primary hydroxyl groups and the second chain extender diol comprises a primary hydroxyl group and a secondary or tertiary hydroxyl group.

14. The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender diol is 1 ,4-butanediol.

15. The membrane or method according to any one of the preceding exemplary embodiments, wherein the second chain extender diol is 1 ,3-butanediol.

16. The membrane or method according to any one of the preceding exemplary embodiments, wherein diisocyanate is aliphatic.

17. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a polysiloxane diol and one or both of a polyethylene oxide diol or a polyoxazoline diol.

18. The membrane or method according to any one of the preceding exemplary embodiments, wherein the membrane is devoid of free hydrophilic polymer.

19. The membrane or method according to any one of preceding exemplary embodiments, wherein the diisocyanate is an aliphatic diisocyanate.

20. The membrane or method according to any one of the preceding exemplary embodiments, wherein the diisocyanate comprises 4,4'-diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 1 ,4-phenylene diisocyanate, hexamethylene diisocyanate (HDI), tetramethylene- 1 ,4-diisocyanate, cyclohexane-1 ,4- diisocyanate, dicyclohexylmethane-4,4'-diisocyanate (HMDI), isophorone diisocyanate (IPDI), or a mixture thereof.

21 . The membrane or method according to any one of the preceding exemplary embodiments, wherein the diisocyanate comprises hexamethylene diisocyanate, dicyclohexylmethane 4,4'-diisocyanate, isophorone diisocyanate, or a mixture thereof.

22. The membrane or method according to any one of the preceding exemplary embodiments, wherein the diisocyanate consists of hexamethylene diisocyanate, dicyclohexylmethane 4,4'-diisocyanate, isophorone diisocyanate, or a mixture thereof.

23. The membrane or method according to any one of preceding exemplary embodiments, wherein the diisocyanate is an aromatic diisocyanate.

24. The membrane or method according to any one of preceding exemplary embodiments, wherein the diisocyanate comprises 4,4'-diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, or 1 ,4-phenylene diisocyanate. . The membrane or method according to any one of preceding exemplary embodiments, wherein the diisocyanate consists of 4,4'-diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 1 ,4-phenylene diisocyanate, or a mixture thereof. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the diisocyanate has a molecular weight of from 100 to 500 g/mol, or from 150 to 260 g/mol. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polyurethane comprises at least 10 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, or at least 40 wt% of the residue of a diisocyanate, based on the total weight of the polyurethane. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polyurethane comprises at most 50 wt%, at most 40 wt%, at most 35 wt%, at most 30 wt%, at most 25 wt%, or at most 20 wt% of the residue of a diisocyanate, based on the total weight of the polyurethane. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a hydrophilic polymeric aliphatic diol. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a polyethylene oxide) diol or a polyoxazoline diol. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a poly(alkylene oxide), a polycarbonate, a polysiloxane, a random or block copolymer thereof, or a mixture thereof. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises C₂-Ci₆ fluoroalkyl or C₂- Ci6 fluoroalkyl ether. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a poly(alkylene oxide), a polycarbonate, a random or block copolymer thereof, or a mixture thereof. . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a polyethylene oxide) diol, a polypropylene oxide) diol, a poly(tetramethylene oxide) diol, a poly(isobutylene) diol, a poly(hexamethylene carbonate) diol, a poly(polytetrahydrofuran carbonate) diol, a polysiloxane diol, a random or block copolymer diol of polyethylene oxide) and polypropylene oxide), a random or block copolymer diol of polyethylene oxide) and poly(tetramethylene oxide), a random or block copolymer diol of polyethylene oxide) and a polysiloxane, or a mixture thereof.

35. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a polycarbonate diol that comprises a poly(hexamethylene carbonate) diol or a poly(polytetrahydrofuran carbonate) diol.

36. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a polycarbonate diol.

37. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a polysiloxane diol or a random or block copolymer diol comprising a polysiloxane.

38. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol has a Mn of at least 200 g/mol, at least 250 g/mol, at least 300 g/mol, at least 400 g/mol, or at least 500 g/mol, at least 600 g/mol, at least 700 g/mol, at least 800 g/mol, at least 900 g/mol, or at least 1000 g/mol.

39. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol has a Mn of at most 10,000 g/mol, at most 8500 g/mol, at most 6000 g/mol, at most 5000 g/mol, at most 4000 g/mol, at most 3000 g/mol, at most 2000 g/mol, or at most 1500 g/mol.

40. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol comprises a polyethylene oxide) diol and a polysiloxane diol.

41 . The membrane or method according to any one of the preceding exemplary embodiments, wherein the polymeric aliphatic diol consists of a polyethylene oxide) diol and a polysiloxane diol.

42. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polyurethane comprises at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, or at least 60 wt% of a residue of a polymeric aliphatic diol, based on the total weight of the polyurethane.

43. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polyurethane comprises at most 80 wt%, at most 70 wt%, at most 60 wt%, or at most 50 wt% of a residue of a polymeric aliphatic diol, based on the total weight of the polyurethane. 44. The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender diol and the second chain extender diol have molecular weights of at least 60 g/mol, at least 70 g/mol, at least 80 g/mol, at least 90 g/mol, or at least 100 g/mol.

45. The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender diol and the second chain extender diol have molecular weights of at most 500 g/mol, at most from 400 g/mol, at most 300 g/mol, at most 200 g/mol, or at most 150 g/mol.

46. The membrane or method according to any one of the preceding exemplary embodiments, wherein the first chain extender diol or second chain extender diol comprises ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, 1 ,3- propanediol, 1 ,3-butanediol, 1 ,4-butanediol, 1 ,5-pentanediol, 1 ,6-hexanediol, or 1 ,8- octanediol.

47. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polyurethane comprises at least 1 wt%, at least 2 wt%, at least 5 wt%, at least 8 wt%, or at least 10 wt% of the residue of chain extenders, based on the total weight of the polyurethane.

48. The membrane or method according to any one of the preceding exemplary embodiments, wherein the polyurethane comprises at most 20 wt%, at most 15 wt%, at most 12 wt%, at most 10 wt%, at most 8 wt%, or at most 5 wt%, of the residue of chain extenders, based on the total weight of the polyurethane.

49. The membrane or method according to any one of the preceding exemplary embodiments, wherein the membrane or composition is devoid of free hydrophilic polymer.

50. The membrane according to any one of the preceding exemplary embodiments, wherein the membrane has an oxygen permeability of from 1x10^-5 to 1x10^-3 or 1x10^-4 cm²/sec

51 . The membrane according to any one of the preceding exemplary embodiments, wherein the membrane has a glucose permeability of from 2x10^-8 to 1x10^-6 or 5x10^-7 cm²/sec

52. The membrane according to any one of the preceding exemplary embodiments, wherein the membrane has a ratio of oxygen permeability to glucose permeability of from 100 to 500.

53. The membrane according to any one of the preceding exemplary embodiments, wherein the equilibrium water uptake is from 30, 31 , 32, 33, 34, or 35 % to 45, 44, 43, or 42 %. 54. A sensor comprising the membrane of any one of the previous exemplary embodiments.

55. A glucose monitoring device comprising the sensor of the previous exemplary embodiment.

The use of the terms “a” and “an” and “the” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. While certain optional features are described as embodiments of the invention, the description is meant to encompass and specifically disclose all combinations of these embodiments unless specifically indicated otherwise or physically impossible.

Claims

2. The membrane according to any one of the preceding claims, wherein the polyurethane comprises, the reaction product of: a. from 10 to 40 wt% of a diisocyanate, b. from 20 to 80 wt% of a polymeric aliphatic diol, c. from 1 to 10 wt% of a first chain extender diol, and d. from 1 to 10 wt% to of a second chain extender diol, all based on the total weight of the polyurethane.

3. The membrane according to any one of the preceding claims, wherein the weight ratio of the first chain extender diol to the second chain extender diol is from 1 :4 to 4: 1 .

4. The membrane according to any one of the preceding claims, wherein the weight ratio of the first chain extender diol to the second chain extender diol is from 1 :2 to 2: 1 .

5. The membrane according to any one of the preceding claims, wherein the first chain extender diol and the second chain extender diol are alkane diols having from 2 to 20 carbon atoms, wherein one or more carbon atoms may be substituted with oxygen, silicon, phosphorous, or sulfur.

6. The membrane according to any one of the preceding claims, wherein the first chain extender diol and the second chain extender diol are unsubstituted alkane diols.

7. The membrane according to any one of the preceding claims, wherein the first chain extender diol comprises two primary hydroxyl groups and the second chain extender diol comprises a primary hydroxyl group and a secondary or tertiary hydroxyl group.

8. The membrane according to any one of the preceding claims, wherein the first chain extender diol is 1 ,4-butanediol.

9. The membrane according to any one of the preceding claims, wherein the second chain extender diol is 1 ,3-butanediol.

10. The membrane according to any one of the preceding claims, wherein diisocyanate is aliphatic.

11 . The membrane according to any one of the preceding claims, wherein the polymeric aliphatic diol comprises a polysiloxane diol and one or both of a polyethylene oxide diol or a polyoxazoline diol.

12. The membrane according to any one of the preceding claims, wherein the membrane is devoid of free hydrophilic polymer.

13. A sensor comprising the membrane of any one of the previous claims.

14. A glucose monitoring device comprising the sensor of the previous claim.

15. A method of forming a sensor comprising: a. providing a composition comprising a solvent and a polyurethane comprising the reaction product of a diisocyanate, a polymeric aliphatic diol, a first chain extender diol, and a second chain extender diol, wherein the first chain extender diol and the second chain extender diol are different and satisfy at least one of the following relationships: i. are both aliphatic, are unsubstituted alkane diols, and differ in the classification of one or both hydroxyl groups; ii. are both cyclo-aliphatic, are isomers of one another, and the first chain extender diol and the second chain extender diol differ in the relative position of the hydroxyl groups on the hydrocarbon ring;

Hi. the first chain extender diol is aliphatic but not cycloaliphatic and the second chain extender diol is cycloaliphatic; or iv. the first chain extender diol is an unsubstituted alkane diol and the second diol is a substituted alkane diol; b. forming a film from the composition on a component of the sensor; and c. evaporating the solvent.