Methods and reagents for selection of biological molecules

Abstract

Coated Ferromagnetic Density Particles or Density Particles with binding agents bound thereto capable of binding biological molecules and methods of use and apparatus for means are disclosed. Coated particles coupled to specific binding agents can be used for molecular biology and proteomic applications in research and diagnostics.

We claim: 
     
         1 . A method for isolating biological molecules from a fluid sample, comprising:
 providing a plurality of ferromagnetic metal particles of a density effective to be substantially mixed through a fluid sample and to be separated in a fluid sample by a magnetic field, said particles being coated with at least one binding agent specific to having at least one preselected biological molecule binding thereto;   mixing said particles through at least a portion of a fluid sample containing a preselected population of a biological molecule without substantially physically damaging said preselected population, said mixing being effected by causing said particles to move at least once through a substantial part of said sample to cause said preselected population to bind thereto; and   magnetically separating said particles with said bound biological molecule from said sample.   
     
     
         2 . The method of  claim 1 , wherein said at least one binding agent is specific to having at least one complementary molecular pair for RNA, DNA, protein, glycoprotein, lipid and carbohydrate binding thereto. 
     
     
         3 . The method of  claim 2 , wherein said complementary molecular pair comprises at least one of antibody/antigen, nucleic acid/complementary nucleic acid, lectin/carbohydrate, and avidin/biotin. 
     
     
         4 . The method of  claim 1 , further comprising at least one blocking agent coating over sites on said ferromagnetic metal particles. 
     
     
         5 . The method of  claim 1 , wherein said particles are of a size of about 0.5 to about 3 microns in diameter. 
     
     
         6 . The method of  claim 1  wherein said particles are made from a group consisting of nickel, cobalt, iron, nickel alloys, cobalt alloys, iron alloys and combinations thereof. 
     
     
         7 . The method as defined in  claim 1 , wherein said ferromagnetic particles have a density of about 6 to 9 gm/cm 3 . 
     
     
         8 . The method as defined in  claim 1 , wherein the fluid sample comprises at least one of diluted whole blood, undiluted whole blood, diluted serum, undiluted serum, diluted plasma, undiluted plasma and bone marrow. 
     
     
         9 . The method as defined in  claim 1 , further including the steps of purifying protein, RNA, DNA, by a chromatography method wherein said chromatography method is selected from a group consisting of ion exchange, affinity chromatography, and high-performance liquid chromatography. 
     
     
         10 . A method for isolating biological molecules from a fluid sample, comprising:
 providing a plurality of metal particles having a density effective to be substantially mixed and separated by gravity settling within a fluid sample, said metal particles being coated with at least one binding agent specific to having at least one preselected biological molecule binding thereto;   mixing said metal particles within at least a portion of the fluid sample, said mixing being effected by causing said metal particles to move at least once through a substantial part of said fluid sample to cause said preselected population to bind thereto; and   separating said metal particles with said bound biological molecule from said fluid sample by gravity settling.   
     
     
         11 . The method of  claim 10 , wherein said at least one binding agent is specific to having at least one complementary molecular pair for RNA, DNA, protein, glycoprotein, lipid and carbohydrate binding thereto. 
     
     
         12 . The method of  claim 11 , wherein said complementary molecular pair comprises at least one of antibody/antigen, nucleic acid/complementary nucleic acid, lectin/carbohydrate, and avidin/biotin. 
     
     
         13 . The method of  claim 10 , further comprising at least one blocking agent coating over sites on said metal particles. 
     
     
         14 . The method of  claim 10 , wherein said ferromagnetic metal particles are of a size of about 2.0 to about 10 microns in diameter. 
     
     
         15 . The method of  claim 10  whereas said metal particles are made from a group consisting of nickel, cobalt, iron, nickel alloys, cobalt alloys, iron alloys and combinations thereof. 
     
     
         16 . The method as defined in  claim 10 , wherein said metal particles have a density of about 6 to 9 gm/cm 3 . 
     
     
         17 . The method as defined in  claim 10 , wherein the fluid sample is from a group consisting of diluted whole blood, undiluted whole blood, diluted serum, undiluted serum, diluted plasma, undiluted plasma and bone marrow. 
     
     
         18 . The method as defined in  claim 10 , further including the steps of purifying protein, RNA, DNA, by a chromatography method wherein said chromatography method is selected from a group consisting of ion exchange, affinity chromatography, and high-performance liquid chromatography. 
     
     
         19 . The method of  claim 10  wherein said gravity settling is an accelerated gravity settling by centrifugation.