Hydrogels and hydrogel arrays made from reactive prepolymers crosslinked by [2 + 2] cycloaddition

Abstract

Reactive prepolymers incorporating [2+2] photoreactive sites are synthesized. Upon exposure to UV light, these prepolymers undergo [2+2] cycloaddition to crosslink. When crosslinked, the reactive prepolymers form a hydrogel. Selective hydrogel formation is provided through selective exposure of the reactive prepolymer to UV light. Supports and other molecules may be attached or incorporated into the hydrogel through [2+2] cycloaddition with uncrosslinked [2+2] photoreactive sites present in the hydrogel.

What is claimed:  
     
         1 . A reactive prepolymer comprising a copolymer of a first monomer and a 2+2 photocyclizable monomer.  
     
     
         2 . The reactive prepolymer of  claim 1 , wherein said copolymer comprises between one and about 50 said first monomers for each said 2+2 photocyclizable monomer.  
     
     
         3 . The reactive prepolymer of  claim 1 , wherein said copolymer comprises between about 10 and about 20 said first monomers for each said 2+2 photocyclizable monomer.  
     
     
         4 . The reactive prepolymer of  claim 1 , wherein said reactive prepolymer has the structure:  
       
         
           
           
               
               
           
         
       
       wherein 
 x is an integer from 1 to 50;  
 y is an integer from 1 to 50; and  
 R is a moiety that comprises a 2+2 photoreactive site.  
 
     
     
         5 . The reactive prepolymer of  claim 4 , wherein x is between about 10 and about 20 and y is 1.  
     
     
         6 . The reactive prepolymer of  claim 4 , wherein x is about 15 and y is 1.  
     
     
         7 . The reactive prepolymer of  claim 1 , wherein the first monomer is a monomer that is water-soluble and can undergo chain-type polymerization.  
     
     
         8 . The reactive prepolymer of  claim 7 , wherein the first monomer is selected from the group consisting of acrylamide, hydroxyethyl acrylate, vinyl pyridine, acrylic acid, methacrylic acid, and vinyl pyrrolidone, or mixtures thereof.  
     
     
         9 . The reactive prepolymer of  claim 7 , wherein the first monomer is acrylamide.  
     
     
         10 . The reactive prepolymer of  claim 1 , wherein the 2+2 photocyclizable monomer comprises a 2+2 photoreactive site and a polymerizable functionality.  
     
     
         11 . The 2+2 photocyclizable monomer of  claim 10 , wherein a spacer separates the polymerizable functionality and the 2+2 photoreactive site.  
     
     
         12 . The reactive prepolymer of  claim 1 , wherein the 2+2 photocyclizable monomer is selected from the group consisting of N-(6-acryloylhexyl)-2,3-dimethylmaleimide and vinyl cinnamate, or mixtures thereof.  
     
     
         13 . The reactive prepolymer of  claim 1 , wherein the 2+2 photocyclizable monomer comprises a second monomer and a 2+2 photocyclizable compound.  
     
     
         14 . The reactive prepolymer of  claim 13 , wherein the second monomer is selected from the group consisting of acrylic acid, glycidyl methacrylate, and methacrylic acid, or mixtures thereof.  
     
     
         15 . The reactive prepolymer of  claim 13 , wherein the second monomer is glycidyl methacrylate.  
     
     
         16 . The reactive prepolymer of  claim 13 , wherein the second monomer is acrylic acid.  
     
     
         17 . The reactive prepolymer of  claim 13 , wherein the 2+2 photocyclizable compound is selected from the group consisting of glycidyl methacrylate, acrylic acid, hydroxyethyl acrylate, hydroxypropyl acrylate, and acryloyl halides, or mixtures thereof.  
     
     
         18 . The reactive prepolymer of  claim 15 , wherein the 2+2 photocyclizable compound is acrylic acid.  
     
     
         19 . The reactive prepolymer of  claim 16 , wherein the 2+2 photocyclizable compound is glycidyl methacrylate.  
     
     
         20 . The reactive prepolymer of  claim 1 , wherein the 2+2 photocyclizable monomer is prepared by forming a copolymer of the first monomer with a second monomer, and subsequently, condensing a 2+2 photocyclizable compound with the copolymer.  
     
     
         21 . The reactive prepolymer of  claim 20 , wherein the second monomer is selected from the group consisting of acrylic acid, glycidyl methacrylate, and methacrylic acid, or mixtures thereof.  
     
     
         22 . The reactive prepolymer of  claim 20 , wherein the 2+2 photocyclizable compound is selected from the group consisting of glycidyl methacrylate, acrylic acid, hydroxyethyl acrylate, hydroxypropyl acrylate, and acryloyl halides, or mixtures thereof.  
     
     
         23 . A hydrogel formed by an ultraviolet irradiation of the reactive prepolymer of  claim 1 .  
     
     
         24 . A hydrogel formed by an ultraviolet irradiation of the reactive prepolymer of  claim 2 .  
     
     
         25 . A hydrogel formed by ultraviolet irradiation of the reactive prepolymer of  claim 8 .  
     
     
         26 . A hydrogel formed by ultraviolet irradiation of the reactive prepolymer of  claim 10 .  
     
     
         27 . A hydrogel formed by ultraviolet irradiation of the reactive prepolymer of  claim 12 .  
     
     
         28 . A hydrogel formed by ultraviolet irradiation of the reactive prepolymer of  claim 13 .  
     
     
         29 . A hydrogel formed by ultraviolet irradiation of the reactive prepolymer of  claim 18 .  
     
     
         30 . A hydrogel formed by ultraviolet irradiation of the reactive prepolymer of  claim 19 .  
     
     
         31 . A hydrogel formed by ultraviolet irradiation of the reactive prepolymer of  claim 20 .  
     
     
         32 . A microarray comprising a solid support and the hydrogel of  claim 23 .  
     
     
         33 . A microarray comprising a solid support and the hydrogel of  claim 25 .  
     
     
         34 . A microarray comprising a solid support and the hydrogel of  claim 26 .  
     
     
         35 . A microarray comprising a solid support and the hydrogel of  claim 27 .  
     
     
         36 . A microarray comprising a solid support and the hydrogel of  claim 28 .  
     
     
         37 . A microarray comprising a solid support and the hydrogel of  claim 29 .  
     
     
         38 . A microarray comprising a solid support and the hydrogel of  claim 30 .  
     
     
         39 . A microarray comprising a solid support and the hydrogel of  claim 31 .  
     
     
         40 . A continuous film comprising a solid support and the hydrogel of  claim 23 .  
     
     
         41 . A continuous film comprising a solid support and the hydrogel of  claim 25 .  
     
     
         42 . A continuous film comprising a solid support and the hydrogel of  claim 26 .  
     
     
         43 . A continuous film comprising a solid support and the hydrogel of  claim 27 .  
     
     
         44 . A continuous film comprising a solid support and the hydrogel of  claim 28 .  
     
     
         45 . A continuous film comprising a solid support and the hydrogel of  claim 29 .  
     
     
         46 . A continuous film comprising a solid support and the hydrogel of  claim 30 .  
     
     
         47 . A continuous film comprising a solid support and the hydrogel of  claim 31 .  
     
     
         48 . A method of making a reactive prepolymer comprising copolymerizing a first monomer with a 2+2 photocyclizable monomer, wherein the 2+2 photocyclizable monomer comprises a polymerizable functionality and a 2+2 photoreactive site.  
     
     
         49 . A method of making a reactive prepolymer comprising: 
 (a) providing a first monomer;    (b) copolymerizing said first monomer with a second monomer; and    (c) covalently attaching said second monomer to a 2+2 photocyclizable compound to form a 2+2 photocyclizable monomer.    
     
     
         50 . A method of making a hydrogel comprising: 
 (a) providing a first monomer;    (b) providing a 2+2 photocyclizable monomer;    (c) polymerizing two or more first monomers with two or more 2+2 photocyclizable monomers, wherein the 2+2 photocyclizable monomers comprise a polymerizable functionality and a 2+2 photoreactive site; and    (d) cyclizing at least two of the 2+2 photocyclizable monomers with ultraviolet light to form the hydrogel.    
     
     
         51 . The method of  claim 50 , wherein said hydrogel has a ratio between about one 2+2 photocyclizable monomer to about every 20 first monomers and about one 2+2 photocyclizable monomer to about every 30 first monomers.  
     
     
         52 . The method of  claim 51 , wherein between 20% and 65% of said 2+2 photocyclizable monomer is crosslinked.  
     
     
         53 . The method of  claim 51 , wherein between 30% and 50% of said 2+2 photocyclizable monomer is crosslinked.  
     
     
         54 . The method of  claim 50 , wherein said hydrogel is between about 2 nanometers and about 5 micrometers in thickness.  
     
     
         55 . The method of  claim 50 , wherein said hydrogel is between about 2 nanometers and about 100 nanometers in thickness.  
     
     
         56 . The method of  claim 50 , wherein said hydrogel is cyclized to a solid support.  
     
     
         57 . A method of making a hydrogel comprising: 
 (a) providing a first monomer;    (b) providing a second monomer;    (c) polymerizing at least two first monomers to at least two second monomers;    (d) covalently attaching a 2+2 photocyclizable compound to at least two of the second monomers, wherein said covalent attachment is by a condensation reaction;    (e) providing an additional crosslinking agent; and    (f) cyclizing at least two of the 2+2 photocyclizable compounds with at least one additional crosslinking agent using ultraviolet light to form the hydrogel.    
     
     
         58 . The method of  claim 57 , wherein said additional crosslinking agent is pentaerythritol tetraacrylate.  
     
     
         59 . The method of  claim 57 , wherein said hydrogel has a ratio between about one 2+2 photocyclizable compound to about every 20 first monomers and about one 2+2 photocyclizable compound to about every 30 first monomers.  
     
     
         60 . The method of  claim 59 , wherein between 20% and 65% of said 2+2 photocyclizable compound is crosslinked.  
     
     
         61 . The method of  claim 59 , wherein between 30% and 50% of said 2+2 photocyclizable compound is crosslinked.  
     
     
         62 . The method of  claim 57 , wherein said hydrogel is between about 2 nanometers and about 5 micrometers in thickness.  
     
     
         63 . The method of  claim 57 , wherein said hydrogel is between about 2 nanometers and about 100 nanometers in thickness.  
     
     
         64 . The method of  claim 57 , wherein said hydrogel is cyclized to a solid support.  
     
     
         65 . A method of making a hydrogel comprising: 
 (a) providing a first monomer;    (b) providing a second monomer;    (c) polymerizing at least two first monomers to at least two second monomers;    (d) covalently attaching a 2+2 photocyclizable compound to at least two of the second monomers, wherein said covalent attachment is by a condensation reaction;    (e) providing the reactive prepolymer of claim  48 ; and    (f) cyclizing at least one of the 2+2 photocyclizable compounds with at least one reactive prepolymer of  claim 48  using ultraviolet light to form the hydrogel.    
     
     
         66 . The method of  claim 65 , wherein said hydrogel has a ratio between about one 2+2 photocyclizable compound to about every 20 first monomers and about one 2+2 photocyclizable compound to about every 30 first monomers.  
     
     
         67 . The method of  claim 66 , wherein between 30% and 50% of said 2+2 photocyclizable compound is crosslinked.  
     
     
         68 . The method of  claim 66 , wherein said hydrogel is between about 2 nanometers and about 5 micrometers in thickness.  
     
     
         69 . The method of  claim 65 , wherein said hydrogel is cyclized to a solid support.  
     
     
         70 . A method of making a hydrogel array comprising: 
 (a) placing a reactive prepolymer including at least two 2+2 photocyclizable sites on a solid support; and    (b) cyclizing at least two of the 2+2 photocyclizable sites present in the reactive prepolymer to form a hydrogel array, wherein said hydrogel array is formed by selective irradiation with ultraviolet light.    
     
     
         71 . The method of  claim 70 , wherein said selective irradiation is with ultraviolet light having a wavelength of about 365 nanometers.  
     
     
         72 . The method of  claim 70 , wherein said selective irradiation occurs at areas on an array that are not blocked to ultraviolet irradiation by a mask.  
     
     
         73 . The method of  claim 70 , wherein said selective irradiation occurs at areas on an array irradiated by an ultraviolet laser.  
     
     
         74 . The method of  claim 70 , wherein a hydrogel location of said hydrogel array is between about 2 nanometers and about 5 micrometers in thickness.  
     
     
         75 . The method of  claim 70 , wherein a hydrogel location of said hydrogel array is about 200 micrometers in diameter.  
     
     
         76 . The method of  claim 70 , wherein a hydrogel location of said hydrogel array is about 100 micrometers in diameter.  
     
     
         77 . The method of  claim 70 , wherein a hydrogel location of said hydrogel array is about 50 micrometers in diameter.  
     
     
         78 . A method of making a continuous hydrogel film comprising: 
 (a) placing a reactive prepolymer including at least two 2+2 photocyclizable sites on a solid support; and    (b) cyclizing at least two of the 2+2 photocyclizable sites present in the reactive prepolymer to form a continuous hydrogel film, wherein said continuous hydrogel film is formed by irradiation with ultraviolet light.    
     
     
         79 . The method of  claim 78 , wherein said irradiation is with ultraviolet light having a wavelength of about 365 nanometers.  
     
     
         80 . The method of  claim 78 , wherein said continuous hydrogel film is between about 2 nanometers and about 5 micrometers in thickness.