Super-resolution fluorescence localization microscopy
AssigneeNew York University
InventorsEli Rothenberg, David Fenyo, Dylan Reid, Mario Delmar, Marina Cerrone, Esperanza Agullo-Pascual
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Abstract
The present invention relates generally ultrasensitive assays for use in diagnostics and in methods of drug screening and personalizing therapy for an individual patient. Specifically, the present invention relates to improved imaging and computational methods for detecting molecular phenotypes.
Claims21
A method of determining the prognosis for an individual with a genetic predisposition for a determined phenotype comprising:
- (a) isolating at least two autologous stem cells from said individual;
- (b) inducing differentiation of said stem cells into differentiated cells;
- (c) imaging said differentiated cells to determine a property of the proteome;
- and
- (d) comparing a property of the proteome to a physical model to determine variance from a property reference value.
A method of screening a compound or therapeutic agent for efficacy against an individual's distinct molecular phenotype of a genetic disease or abnormality, said method comprising the steps of:
- (a) Obtaining one or more autologous stem cells from said individual;
- (b) Placing said one or more stem cells in an environment such that the stem cells will mature into derived cells expressing the individual's distinct molecular phenotyupe;
- (c) Imaging said derived cells to determine protein localization;
- (d) Treating said derived cells with the compound or therapeutic agent;
- (e) Imaging the treated derived cells using super-resolution fluorescence microscopy to determine protein localization;
- and
- (f) Comparing the protein localization of the derived cells with the protein localization of the treated derived cells,
- wherein the statistically significant change in localization such that the localization is closer to the healthy phenotype indicates efficacy of the comound or therapeutic agent against the individual's distinct molecular phenotype.
A method of screening a compound or therapeutic agent for efficacy against an distinct molecular phenotype of a cell relating to a protein biomarker, said method comprising the steps of:
- (a) obtaining at least one cell;
- (b) imaging said cell at a resolution of about 20 nm or greater to determine the density of the protein biomarker;
- (c) treating said cell with the compound or therapeutic agent;
- (d) imaging the treated cell using at a resolution of about 20 nm or greater to determine density of the protein biomarker;
- and
- (e) comparing the biomarker density of the cells with the biomarker density of the treated cells,
- wherein a change in the density of the protein biomarker indicates efficacy of the compound or therapeutic agent against the individual's distinct molecular phenotype.
A system comprising:
- a processor;
- and
- a tangible computer-readable medium operatively connected to the processor and an image capture mechanism and including computer code configured to:
- detect of molecules using an optimized method that reliably can detect molecular features;
- build a physical model of the interactions and determining the model parameters using computer simulations and randomly generated images with the same number and density of the proteins of the real image;
- apply statistical methods to further reduce these model parameters in dimensionality;
- and
- obtain information regarding a phenotype.
Dependencies are inferred from the claim text.