Methods and devices for removal of organic molecules from biological mixtures using a hydrophilic solid support in a hydrophobic matrix

Abstract

Methods and devices for removing small negatively charged molecules from a biological sample mixture that uses a solid-phase extraction material that includes a hydrophilic solid support at least partially embedded within a hydrophobic matrix.

1 . An analytical receptacle comprising one or more reservoirs and a surface with a cover film adhered to the surface and enclosing the one or more reservoirs; wherein the cover film comprises a backing and an adhesive disposed on at least one major surface of the backing and in contact with the receptacle surface; wherein at least a portion of the adhesive has a solid-phase extraction material disposed thereon; wherein the solid-phase extraction material comprises hydrophilic particles at least partially embedded in the adhesive.  
     
     
         2 . The analytical receptacle of  claim 1  wherein the particles have an average particle size of at least about 5 nm.  
     
     
         3 . The analytical receptacle of  claim 1  wherein the particles have an average particle size of no greater than about 500 microns.  
     
     
         4 . The analytical receptacle of  claim 1  wherein the particles are disposed on the layer of adhesive at a density of about 0.1 mg per 12 mm 2  surface area to about 5 mg per 12 mm 2  surface area.  
     
     
         5 . The analytical receptacle of  claim 1  wherein the particles are pattern coated on the adhesive.  
     
     
         6 . The analytical receptacle of  claim 1  wherein the particles have a surface area of from about 50 square meters per gram (m 2 /g) to no greater than about 200 m 2 /g.  
     
     
         7 . The analytical receptacle of  claim 1  wherein the particles comprise active groups at a density of at least about 0.01 micromoles per 1735 square millimeters (mmoles/1735 mm 2 ).  
     
     
         8 . The analytical receptacle of  claim 1  wherein the particles possess a fixed positive charge between pH 8.0 and pH 9.0.  
     
     
         9 . The analytical receptacle of  claim 1  wherein the particles separate at least about 70% of negatively charged unincorporated polymerase chain reaction (PCR) reagents from desired PCR products.  
     
     
         10 . The analytical receptacle of  claim 1  wherein the negatively charged unincorporated PCR reagents comprise unincorporated residual primers, unincorporated dye molecules, or unincorporated dNTPs.  
     
     
         11 . The analytical receptacle of  claim 10  wherein the particles separate at least about 90% of the unincorporated residual primers and/or at least about 70% of the unincorporated dNTPs from the desired PCR products.  
     
     
         12 . The analytical receptacle of  claim 10  wherein the particles separates at least about 95% of the unincorporated residual primers, unincorporated dye molecules, and unincorporated dNTPs from the desired PCR products.  
     
     
         13 . The analytical receptacle of  claim 1  wherein at least a portion of the particles is coated with a negatively charged polymer.  
     
     
         14 . The analytical receptacle of  claim 13  wherein the particles, the negatively charged polymer, or both are pattern coated.  
     
     
         15 . The analytical receptacle of  claim 1  wherein the particles bind less than 30% of the desired PCR products.  
     
     
         16 . The analytical receptacle of  claim 10  wherein the particles comprise active groups at a density of at least about 0.01 micromoles per 1735 square millimeters (mmoles/1735 mm 2 ).  
     
     
         17 . The analytical receptacle of  claim 1  wherein the particles separate at least about 70% of negatively charged unincorporated DNA sequencing reagents from desired DNA sequencing products.  
     
     
         18 . The analytical receptacle of  claim 17  wherein the negatively charged unincorporated DNA sequencing reagents comprise unincorporated residual primers, unincorporated dye molecules, unincorporated dNTPs, unincorporated ddNTPs, or unincorporated dye terminators.  
     
     
         19 . The analytical receptacle of  claim 18  wherein the particles separate at least about 95% of the unincorporated residual primers, unincorporated dye molecules, unincorporated dNTPs, or unincorporated dye terminators from the desired DNA sequencing products.  
     
     
         20 . The analytical receptacle of  claim 18  wherein the particles separate at least about 95% of the unincorporated residual primers, unincorporated dye molecules, unincorporated dye terminators, unincorporated dNTPs, and unincorporated ddNTPs from the desired DNA sequencing products.  
     
     
         21 . The analytical receptacle of  claim 17  wherein at least a portion of the particles is coated with a negatively charged polymer.  
     
     
         22 . The analytical receptacle of  claim 21  wherein the particles, the negatively charged polymer, or both are pattern coated.  
     
     
         23 . The analytical receptacle of  claim 17  wherein the particles comprise active groups at a density of at least about 0.01μ moles/1735 mm 2 .  
     
     
         24 . The analytical receptacle of  claim 17  wherein the particles bind less than 30% of the desired DNA sequencing products.  
     
     
         25 . A method of removing small negatively charged organic molecules from a biological sample mixture, the method comprising: 
 providing an analytical receptacle comprising one or more reservoirs and a surface with a cover film adhered to the surface and enclosing the one or more reservoirs; wherein the cover film comprises a backing and an adhesive disposed on at least one major surface of the backing and in contact with the receptacle surface, wherein at least a portion of the adhesive has a solid-phase extraction material disposed thereon, wherein the solid-phase extraction material comprises hydrophilic particles at least partially embedded in the adhesive;    providing a biological sample mixture; and    contacting the biological sample mixture with the solid-phase extraction material to remove at least a portion of the small negatively charged organic molecules from the biological sample mixture.    
     
     
         26 . An analytical receptacle comprising one or more reservoirs comprising a surface with an adhesive disposed on at least a portion of the surface; 
 wherein at least a portion of the adhesive has a solid-phase extraction material disposed thereon;    wherein the solid-phase extraction material comprises hydrophilic particles at least partially embedded in the adhesive.    
     
     
         27 . A method of removing small negatively charged organic molecules from a biological sample mixture, the method comprising: 
 providing an analytical receptacle comprising one or more reservoirs comprising a surface with an adhesive disposed on at least a portion of the surface, wherein at least a portion of the adhesive has a solid-phase extraction material disposed thereon, wherein the solid-phase extraction material comprises hydrophilic particles at least partially embedded in the adhesive;    providing a biological sample mixture; and    contacting the biological sample mixture with the solid-phase extraction material to remove at least a portion of the small negatively charged organic molecules from the biological sample mixture.    
     
     
         28 . An analytical receptacle comprising one or more reservoirs comprising a solid phase extraction material comprising solid hydrophilic particles at least partially embedded in a hydrophobic matrix, wherein the hydrophobic matrix is disposed on at least a portion of a surface of the one or more reservoirs, and wherein the solid support material comprises molecules that are different than the hydrophobic matrix.  
     
     
         29 . A method of removing small negatively charged organic molecules from a biological sample mixture, the method comprising: 
 providing an analytical receptacle comprising one or more reservoirs comprising a solid phase extraction material comprising solid hydrophilic particles at least partially embedded in a hydrophobic matrix, wherein the hydrophobic matrix is disposed on at least a portion of a surface of the one or more reservoirs, and wherein the solid support material comprises molecules that are different than the hydrophobic matrix;    providing a biological sample mixture; and    contacting the biological sample mixture with the solid-phase extraction material to remove at least a portion of the small negatively charged organic molecules from the biological sample mixture.    
     
     
         30 . A film comprising: 
 a substrate;    an adhesive disposed on at least one major surface of the substrate; and    particles comprising hydrophilic solid-phase extraction material at least partially embedded in at least a portion of the adhesive.    
     
     
         31 . A method of removing small negatively charged organic molecules from a biological sample mixture, the method comprising: 
 providing a substrate, an adhesive disposed on at least one major surface of the substrate, and particles comprising hydrophilic solid-phase extraction material at least partially embedded in at least a portion of the adhesive;    providing a biological sample mixture; and    contacting the biological sample mixture with the solid-phase extraction material to remove at least a portion of the small negatively charged organic molecules from the biological sample mixture.    
     
     
         32 . A film comprising: 
 a substrate;    a hydrophobic matrix disposed on at least a portion of the substrate; and    particles comprising hydrophilic solid-phase extraction material at least partially embedded in at least a portion of the hydrophobic matrix, wherein the hydrophilic solid-phase extraction material comprises molecules that are different than the hydrophobic matrix.    
     
     
         33 . A method of removing small negatively charged organic molecules from a biological sample mixture, the method comprising: 
 providing a solid-phase extraction material comprising a hydrophilic solid support at least partially embedded within a hydrophobic matrix, wherein the hydrophilic solid support comprises molecules that are different than the hydrophobic matrix;    providing a biological sample mixture; and    contacting the biological sample mixture with the solid-phase extraction material to remove at least a portion of the small negatively charged organic molecules from the biological sample mixture.