Polymer backbone element tags
Element tags based on novel metal-polymer conjugates are provided for elemental analysis of analytes, including ICP-MS. A polymer backbone is functionalized to irreversibly bind metals that are selected prior to use by the user. The polymer is further functionalized to attach a linker which allows for attachment to antibodies or other affinity reagents. The polymer format allows attachment of many copies of a given isotope, which linearly improves sensitivity. The metal-polymer conjugate tags enable multiplexed assay in two formats: bulk assay, where the average biomarker distribution in the sample is diagnostic, and single cell format to distinguish a rare (for example a diseased) cell in a complex sample (for example, blood).
1. A kit comprising:
an isotopic composition comprising multiple lanthanide atoms of a single isotope of a lanthanide; and
an element tag comprising a linear or branched polymer comprising a plurality of chelating groups, wherein each chelating group of the element tag includes at least one lanthanide atom of the isotopic composition or is capable of binding at least one lanthanide atom of the isotopic composition;
wherein:
the isotopic composition does not comprise a natural mixture of isotopes, and
the kit does not comprise any radioactive lanthanide.
2. The kit of claim 1 , wherein the element tag is functionalized to bind a biomolecule.
3. The kit of claim 1 , wherein the element tag is covalently attached to a biomolecule.
4. The kit of claim 1 , wherein the kit further comprises a biomolecule.
5. The kit of claim 4 , wherein the biomolecule is an oligonucleotide.
6. The kit of claim 4 , wherein the biomolecule is an antibody.
7. The kit of claim 1 , wherein each chelating group includes at least one lanthanide atom of the isotopic composition.
8. The kit of claim 1 , wherein the isotopic composition is a lanthanide solution provided separate from the element tag, and wherein each chelating group of the element tag is capable of binding at least one lanthanide atom of the isotopic composition.
9. The kit of claim 1 , further comprising an additional isotopic composition, wherein the additional isotopic composition comprises multiple additional lanthanide atoms of an additional single isotope of a lanthanide that is different from the single isotope of the lanthanide of the isotopic composition.
10. The kit of claim 9 , further comprising an additional element tag comprising an additional linear or branched polymer comprising a plurality of additional chelating groups.
11. The kit of claim 10 , wherein each chelating group of the linear or branched polymer of the element tag includes at least one lanthanide atom of the isotopic composition, and wherein each additional chelating group of the additional linear or branched polymer of the additional element tag includes at least one additional lanthanide atom of the additional isotopic composition.
12. The kit of claim 11 , wherein each element tag is covalently bound to a different antibody.
13. The kit of claim 1 , wherein each chelating group is capable of binding at least one lanthanide atom of the isotopic composition, and each chelating group is selected from the group consisting of Diethylenetriaminepentaacetate (DTPA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a DTPAderivative, and a DOTA derivative.
14. The kit of claim 1 , wherein each chelating group has a negative charge, when bound to a lanthanide atom.
15. The kit of claim 1 , further comprising a reagent for covalent attachment of the element tag to an antibody.