Method for drug screening and characterization by calcium flux
AssigneeCedars-Sinai Medical Center
InventorsAnat Ben-Shlomo, Shlomo Melmed, Kolja Wawrowsky
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Abstract
The instrumentation and methods described herein are based on imaging and measuring single cell dose response by fluorescent ion imaging that records live cell responses to drug doses. Dose response curves and other pharmacological parameters can be computed by imaging and measuring oscillation changes for each drug dose and each cell. The instrumentation and methods described herein provide a means of measuring statistical variability of cell populations for improved screening and development methods for drugs.
Claims22
A method of identifying a drug that modulates ion oscillation based upon its effect on ion oscillation in a cell, comprising:
- i. providing a cell sample;
- ii. providing a means of imaging the cell sample;
- iii. administering the drug to said sample, wherein the drug's potential to modulate ion oscillation is unknown prior to administering it to the sample;
- iv. imaging said sample with said means for an interval of time to create a series of images of an ion oscillation response to said drug;
- v. repeating steps i-iv at least five times using different doses of said drug for each repetition;
- vi. measuring the ion oscillation from said images;
- vii. plotting said oscillation for each dose to create an oscillation plot for each single cell of said sample;
- and
- viii. transforming said plots into a dose-response curve for each single cell of said sample;
- ix. analyzing the dose-response curves and/or oscillation plots to determine the effect of each dose of the drug on ion flux in the cells, wherein individual cell responses are used to determine a minimum and a maximum dose of a response, and an average slope and IC50 value are from the sum of disparate individual responses;
- and
- x. determining that the drug modulates ion oscillation if ion flux is detected, and determining that the drug does not modulate ion oscillation if ion flux is not detected.
A method of identifying a drug that modulates ion oscillation based upon its effect on ion oscillation in a cell sample, comprising:
- i. providing a cell sample;
- ii. providing a means of imaging the cell sample;
- iii. administering the drug to said sample, wherein said drug's potential to modulate ion oscillation is unknown prior to administering it to the sample;
- iv. imaging said sample with said means for an interval of time to create a series of images of an ion oscillation response to said drug;
- v. repeating steps i-iv at least five times using different doses of said drug for each repetition;
- vi. measuring the ion oscillation from said images;
- vii. plotting said oscillation for each dose to create an oscillation plot for each single cell of said sample;
- viii. transforming said plots into a dose-response curve for each single cell of said sample;
- ix. repeating steps i-viii at least two times using different cells from said sample;
- and
- x. averaging each single cell dose-response curve to create a dose-response curve for said sample;
- and
- xi. analyzing the dose-response curve and/or oscillation plots to determine the effect of each dose of the drug on ion flux in the sample, wherein individual cell responses are used to determine a minimum and a maximum dose of a response, and an average slope and IC50 value are derived from the sum of disparate individual responses;
- and
- xii. determining that the drug modulates ion oscillation if ion flux is detected, and determining that the drug does not modulate ion oscillation if ion flux is not detected.
Dependencies are inferred from the claim text.