Method For Selecting Desired Level Of Dye Loading And Controlling Loading Of Polymer Microparticles

Abstract

Solute-loaded polymer microparticles are obtained by immersing microparticles in a bath comprising a selected solute dissolved in a ternary solvent system. A first solvent of the ternary system is a strong solvent for both the solute and the polymer from which the microparticle was formed. A second solvent is a weak solvent or non-solvent for the solute and the polymer (tuning solvent). A third solvent is a weak solvent or non-solvent for the solute and polymer, but serves as a co-solvent with respect to the first and second solvents in that it is miscible with both the first and second solvents. The amount of solute incorporated into the microparticles is controlled by adjusting the ratio of solute with respect to the microparticle polymer, and by adjusting the composition of the ternary solvent system, principally the amount of tuning solvent. The method is particularly useful for providing libraries of combinatorially encoded microparticles containing distinguishable dye loadings, particularly distinguishable fluorescent dye loadings.

1 .- 39 . (canceled) 
     
     
         40 . A method of dye-loading polymer microparticles comprising:
 a. providing:
 i. a first solvent in which at least one dye and polymer are soluble; 
 ii. a second solvent in which the dye and the polymer are not soluble and wherein the second solvent is immiscible with the first solvent; and 
 iii. a third solvent miscible with the first solvent; 
   b. forming a suspension of the polymer microparticles in a mixture comprising the second solvent and the third solvent   c. adding to the suspension a solution comprising the first solvent and the dye;   d. incubating the resultant suspension for a period of time so that the degree of absorption of the dye into the microparticles is controlled by the amount of second solvent added to suspension; and   e. recovering the dye-loaded microparticles   
     
     
         41 . The method of  claim 40 , wherein the microparticles are substantially uniform in the amount of dye loaded. 
     
     
         42 . The method of  claim 40 , wherein the method is performed without vigorous mixing. 
     
     
         43 . The method of  claim 40 , wherein the resultant suspension is a homogenous ternary solvent mixture. 
     
     
         44 . The method of  claim 40 , wherein the microparticles are crosslinked microparticles. 
     
     
         45 . The method of  claim 40 , wherein the microparticles are core-shell microparticles. 
     
     
         46 . The method of  claim 40 , wherein the first solvent is an organic solvent. 
     
     
         47 . The method of  claim 40 , wherein the second solvent is an aqueous solvent. 
     
     
         48 . The method of  claim 40 , wherein the third solvent is an alcohol. 
     
     
         49 . The method of  claim 40 , wherein the third solvent is miscible with the second solvent. 
     
     
         50 . The method of  claim 40 , wherein the dye is not soluble in the third solvent. 
     
     
         51 . The method of  claim 40 , wherein the concentration of dye in the suspension is from about 1 μg/g of microparticles to about 100 μg/g of microparticles. 
     
     
         52 . The method of  claim 40 , wherein the dye does not precipitate out of the solvent. 
     
     
         53 . The method of  claim 40 , wherein the method is performed without any liquid-liquid phase separation between the solvents. 
     
     
         54 . A method of dye-loading polymer microparticles comprising:
 a. providing:
 i. an organic solvent in which at least one dye and the polymer are soluble; 
 ii. a polar aqueous solvent in which the dye and the polymer are not soluble; 
 iii. an alcohol; and 
   b. forming a suspension of the polymer microparticles in a mixture comprising the polar aqueous solvent and the alcohol;   c. adding to the suspension a solution comprising the organic solvent and the dye;   d. incubating the resultant suspension for a period of time so that the degree of absorption of the dye into the microparticles is controlled by the amount of polar aqueous solvent added to the suspension; and   e. recovering the dye loaded microparticles.