Robust, self-assembled, biocompatible films
The present invention provides a composite material including a substrate having an oxide surface, and, a continuous monolayer on the oxide surface, the monolayer including a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group that attaches to the oxide surface, an alkyl/alkenyl/alkynyl portion of at least three carbon atoms, a polyalkylene glycol spacer group, and either a reactive site (e.g., a recognition ligand) or a site resistant to non-specific binding (e.g., a methoxy or the like) at the terminus of each modified SAM. The present invention further provides a sensor element, a sensor array and a method of sensing, each employing the composite material. Patterning is also provided together with backfilling to minimize non-specific binding.
1 . A composite material comprising:
a substrate having an oxide surface; and,
a monolayer thereon said oxide surface, said monolayer including: a first species of the formula X-Q-Z 1 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, and Z 1 is a functional moiety that provides a site for attachment of a recognition ligand (R), and, a second species of the formula X-Q-Z 2 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, Z 2 is a functional moiety that provides a site for attachment of a terminal moiety (T) that provides resistance to non-specific binding by the composite material.
2 . The composite material of claim 1 wherein any said alkane, alkene or alkyne group has greater than about 3 carbons.
3 . The composite material of claim 1 wherein all of the spacer groups have the same length of carbon atoms.
4 . The composite material of claim 1 wherein the spacer groups are alkane groups each having the same length of carbon atoms.
5 . The composite material of claim 1 further including a polyalkylene glycol spacer group having from about 3 to 7 repeating units between both functional moiety Z 1 and the recognition ligand (R) and functional moiety group Z 2 and the terminal moiety (T) that is resistant to non-specific binding.
6 . The composite material of claim 5 wherein said polyalkylene glycol is polyethylene glycol.
7 . The composite material of claim 6 wherein said polyethylene glycol has from 3 to 7 repeating units.
8 . The composite material of claim 1 wherein said substrate surface has defined portions of the surface including only a monolayer thereon said oxide surface of said second species of the formula X-Q-Z 2 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, and Z 2 is a functional moiety that provides a site for attachment of a terminal moiety (T) that provides resistance to non-specific binding by the composite material.
9 . The composite material of claim 1 wherein said substrate is selected from the group consisting of silicon dioxide, quartz, indium-tin oxide (ITO) and aluminum zinc oxide (AZO), mesoporous silica particles, metal oxide coated metal nanoparticles, metal oxide coated metal particles and metal oxide coated glass particles.
10 . The composite material of claim 7 wherein said substrate is silicon dioxide, Q is a —(CH 2 ) 3 — group, Z 1 is a —NH— group, T is a methoxy group or a hydroxy group and R is a biotin group, an iodomethyl carbonyl group or a carboxymethyl-2-oxoethyl ether group.
11 . The composite material of claim 7 wherein said substrate is silicon dioxide, Q is a —(CH 2 ) 11 — group, Z 1 is a —NH— group, T is a methoxy group or a hydroxy group and R is a biotin group, an iodomethyl carbonyl group or a carboxymethyl-2-oxoethyl ether group.
12 . The composite material of claim 10 wherein the ratio of said terminal moiety (T) to said recognition ligand (R) is from about 90:10 to about 99.9 to 0.1.
13 . The composite material of claim 10 wherein the ratio of said terminal moiety (T) to said recognition ligand (R) is from about 95:5 to about 99.9 to 0.1.
14 . The composite material of claim 11 wherein the ratio of said terminal moiety (T) to said recognition ligand (R) is from about 90:10 to about 99.9 to 0.1.
15 . The composite material of claim 11 wherein the ratio of said terminal moiety (T) to said recognition ligand (R) is from about 95:5 to about 99.9 to 0.1.
16 . A sensor element for use in a system for detection of a target species, said element comprising:
a waveguide substrate having an oxide surface; and, one or more recognition groups thereon wherein said one or more recognition groups are in a monolayer upon said oxide surface, said monolayer including: a first species of the formula X-Q-Z 1 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, and Z 1 is a functional moiety that provides a site for attachment of one or more recognition ligands (R), and, a second species of the formula X-Q-Z 2 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, Z 2 is a functional moiety that provides a site for attachment of a terminal moiety (T) that provides resistance to non-specific binding upon the waveguide substrate.
17 . The sensor element of claim 16 wherein said alkane, alkene or alkyne group has greater than about 11 carbons and said sensor system further includes a polyalkylene glycol spacer group having from about 3 to 7 repeating units between functional moiety Z and a recognition moiety.
18 . The sensor element of claim 16 wherein said substrate is selected from the group consisting of silicon dioxide, quartz, indium-tin oxide (ITO), aluminum zinc oxide (AZO), mesoporous silica particles, metal oxide coated metal nanoparticles, metal oxide coated metal particles and metal oxide coated glass particles.
19 . A method of detecting a target species comprising:
contacting a sample including a potential target species with a sensor element including a substrate having an oxide surface and a monolayer upon said oxide surface, said monolayer including a first species of the formula X-Q-Z 1 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, and Z 1 is a functional moiety that provides a site for attachment of a recognition ligand (R) adapted for binding to a pre-selected target species, and, a second species of the formula X-Q-Z 2 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, Z 2 is a functional moiety that provides a site for attachment of a terminal moiety (T) that provides resistance to non-specific binding upon the sensor element; and,
detecting a signal arising in response to binding between said recognition ligand and any said pre-selected targeted species.
20 . The method of claim 19 wherein said alkane, alkene or alkyne group has greater than about 11 carbons and said sensor system further includes a polyalkylene glycol spacer group having from about 3 to 6 repeating units between functional moiety Z and a recognition ligand.
21 . The method of claim 19 wherein said substrate is selected from the group consisting of silicon dioxide, quartz, indium-tin oxide (ITO), aluminum zinc oxide (AZO), mesoporous silica particles, metal oxide coated metal nanoparticles, metal oxide coated metal particles and metal oxide coated glass particles.
22 . A sensor array on an oxide substrate, the array comprising:
a substrate having an oxide surface;
a monolayer thereon said oxide surface, said monolayer including discrete portions upon said oxide surface where: a first species of the formula X-Q-Z 1 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, and Z 1 is a functional moiety that provides a site for attachment of one or more recognition ligands (R) for one or more corresponding pre-selected target species, wherein each different recognition ligand for a corresponding pre-selected target species is located within a different discrete portion upon said oxide surface, and, a second species of the formula X-Q-Z 2 where X includes a silicon atom from a trifunctional alkyl/alkenyl/alkynyl silane group for attachment to the oxide surface, Q represents a central portion of the trifunctional alkyl/alkenyl/alkynyl silane group and serves as a spacer group of an alkane, or a combination of an alkane and one or more of an alkene or an alkyne group having greater than about 3 carbons, the spacer group promoting self assembly of a plurality of said species, Z 2 is a functional moiety that provides a site for attachment of a terminal moiety (T) that provides resistance to non-specific binding, and, where the monolayer in areas other than said discrete portions upon said oxide surface include only said second species of the formula X-Q-Z 2 .
23 . The sensor array of claim 22 wherein said alkane, alkene or alkyne group has greater than about 3 carbons and said sensor array further includes a polyalkylene glycol spacer group having from about 3 to 7 repeating units between both functional moiety Z 1 and any recognition ligand (R) and functional moiety group Z 2 and any terminal moiety (T) that is resistant to non-specific binding.
24 . The sensor array of claim 22 wherein said substrate is selected from the group consisting of silicon dioxide, quartz, indium-tin oxide (ITO), aluminum zinc oxide (AZO), mesoporous silica particles, metal oxide coated metal nanoparticles, metal oxide coated metal particles and metal oxide coated glass particles.