Particles containing detectable elemental code
The invention relates to a new type of element encoded particles suitable for the attachment of bio molecules to enable massively multiplex bio-analytical methods, and to calibrate and tune the elemental flow cytometer mass spectrometer (FC-MS).
1. A method of producing polymeric particles incorporating in the particles two or more staining elements to facilitate determination of said particles by FC-MS, said method comprising:
(a) combining two or more staining element-containing complexes with a solvent mixture comprising at least one organic monomer in which the two or more staining element-containing complexes are soluble and at least one different solvent in which said at least one organic monomer and said two or more staining element-containing complexes are less soluble, wherein at least one of said two or more staining element-containing complexes comprises a tris-4,4,4-trifluoro-1-(2-naphthyl-1,3-butanedione) ligand,
(b) emulsifying the mixture of step (a) for a period of time sufficient to provide a uniform emulsion;
(c) initiating polymerization and continuing reaction until a substantial portion of monomer is converted to polymer; and
(d) incubating the product of step (c) for a period of time sufficient to obtain a latex suspension of stained polymeric particles with the two or more staining element-containing complexes incorporated in the particles therein, wherein said two or more staining element-containing complexes are selected such that upon FC-MS interrogation of each individual particle of said stained polymeric particles, a distinct MS signal is obtained from said two or more staining element-containing complexes, wherein the intensity of said distinct MS signal is proportional to the amount of said two or more staining element-containing complexes in said individual particle of said stained polymeric particles.
2. The method of claim 1 , wherein the staining element-containing complexes comprise organic or inorganic metal complexes, or colloidally stable inorganic nanoparticles.
3. The method of claim 1 , further comprising preparing a series of said mixtures of the at least one organic monomer having different concentrations of one or more staining elements of said two or more staining element-containing complexes in order to produce different sets of stained polymeric particles.
4. The method of claim 1 , wherein said at least one organic monomer is styrene and/or methyl methacrylate.
5. The method of claim 1 , wherein said different solvent in which the at least one organic monomer and said two or more staining element-containing complexes are less soluble comprises water, sodium dodecyl sulfate, and sodium bicarbonate.
6. The method of claim 1 , wherein the step of initiating polymerization comprises the addition of 2,2′-azobis-(2-methylbutyronitrile) to said solvent mixture comprising at least one organic monomer in which said at least one staining element-containing complex is soluble.
7. The method of claim 1 , wherein said solvent mixture comprising at least one organic monomer further comprises methacrylic acid.
8. The method of claim 1 , wherein the latex suspension of polymeric particles obtained has a polydispersity index of no greater than 0.15.