CELLS HAVING A SPECTRAL SIGNATURE AND METHODS OF PREPARATIONS AND USE THEREOF
Methods, compositions and articles of manufacture for encoding a cell with semiconductor nanocrystals and/or other fluorophors are provided. The encoded cells can be subjected to functional assays in mixed populations, and an assay result can be determined and associated with individual cells by virtue of their code. The methods are particularly useful in multiplex settings where a plurality of encoded cells are to be assayed.
1 . A composition comprising a plurality of different spectrally encoded cell types, wherein the cell types are labeled with semiconductor nanocrystals.
2 . The composition of claim 1 , wherein the cell types further comprise at least one organic fluorophore or at least one fluorescent protein.
3 . The composition of claim 1 , further comprising a test compound.
4 . The composition of claim 1 , wherein the cells are capable of expressing a detectable enzyme.
5 . The composition of claim 4 , wherein the detectable enzyme is luciferase.
6 . The composition of claim 1 , wherein the semiconductor nanocrystal is associated non-specifically with the cell.
7 . The composition of claim 1 , wherein the semiconductor nanocrystals comprise cationic polymers.
8 . The composition of claim 7 , wherein the semiconductor nanocrystals comprise a core and a shell.
9 . The composition of claim 8 , wherein the core is selected from the group consisting of ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, AlAs, AlP, AlSb, AlS, Ge, Si, Pb, PbS, PbSe, an alloy thereof, and a mixture thereof.
10 . The composition of claim 1 , comprising at least three different encoded cell types.
11 . The composition of claim 1 , comprising at least five different encoded cell types.
12 . The composition of claim 1 , wherein each spectrally encoded cell comprises a plurality of types of semiconductor nanocrystals.
13 . The composition of claim 1 , wherein each spectrally encoded cell comprises one type of semiconductor nanocrystal.
14 . The composition of claim 1 , wherein the cell types are spectrally encoded by phenotype.
15 . The composition of claim 1 , wherein each spectrally encoded cell type has a different excitation wavelength, emission wavelength, emission intensity, FWHM (full width at half maximum peak height), or fluorescence lifetime.
16 . The composition of claim 1 , wherein the cells types are selected from the group consisting of acidophils, acinar cells, pinealocytes, adipocytes, ameloblasts, astrocytes, basal (stem) cells, basophils, hepatocytes, neurons, bulging surface cells, C cells, cardiac muscle cells, centroacinar cells, chief cells, chondrocytes, Clara cells, columnar epithelial cells, corpus luteal cells, decidual cells, dendrites, endrocrine cells, endothelial cells, enteroendocrine cells, eosinophils, erythrocytes, extraglomerular mesangial cells, fetal fibroblasts, fetal red blood cells, fibroblasts, follicular cells, ganglion cells, giant Betz cells, goblet cells, hair cells, inner hair cells, type I hair cells, hepatocytes, endothelial cells, Leydig cells, lipocytes, liver parenchymal cells, lymphocytes, lysozyme-secreting cells, macrophages, mast cells, megakaryocytes, melanocytes, mesangial cells, monocytes, myoepithelial cells, myoid cells, neck mucous cells, nerve cells, neutrophils, oligodendrocytes, oocytes, osteoblasts, osteochondroclasts, osteoclasts, osteocytes, pillar cells, sulcal cells, parathyroid cells, parietal cells, pepsinogen-secreting cells, pericytes, pinealocytes, pituicytes, plasma cells, platelets, podocytes, spermatocytes, Purkinje cells, pyramidal cells, red blood cells, reticulocytes, Schwann cells, Sertoli cells, columnar cells, skeletal muscle cells, smooth muscle cells, somatostatin cells, enteroendocrine cells, spermatids, spermatogonias, spermatozoas, stellate cells, supporting Deiter cells, support Hansen cells, surface cells, surface epithelial cells, surface mucous cells, sweat gland cells, T lymphocytes, theca lutein cells, thymocytes, thymus epithelial cell, thyroid cells, transitional epithelial cells, type I pneumonocytes, and type II pneumonocytes.
17 . A method of distinguishably identifying a cell encoded with a semiconductor nanocrystal in a mixed population of cells, the method comprising:
mixing a cell encoded with a semiconductor nanocrystal with a cell distinct therefrom to form a mixed population, culturing the mixed population, exposing the mixed population to an excitation energy source, and detecting the semiconductor nanocrystal to identify the encoded cell.
18 . The method of claim 18 , wherein a plurality of different cell types are encoded with semiconductor nanocrystals.
19 . The method of claim 18 , wherein the cells exhibit apoptosis, cell migration, cytoplasm to nucleus translocation, retrograde transport, neurite outgrowth, or receptor internalization.
20 . A method of encoding a plurality of different cell types comprising: providing cells; and contacting each cell type with a semiconductor nanocrystal under conditions in which the semiconductor nanocrystal is associated with the cells to provide a plurality of encoded cell types.