Robust, self-assembled, biocompatible films

Abstract

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.