Low fluorescence assay platforms and related methods for drug discovery
First Claim
1. A multi-well platform, comprising:
- a) a plurality of wells, each well comprising;
i) a wall having less fluorescence than a polystyrene-wall of at least about 90 percent of said wall'"'"'s thickness, and ii) a bottom having a high transmittance portion and having less fluorescence than a polystyrene-bottom of at least about 90 percent of said bottom'"'"'s thickness, said bottom having a thickness less than about 450 microns and said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm;
b) a frame, wherein said wells are disposed in said frame.
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Abstract
One aspect of the present invention is a multi-well platform for fluorescence measurements, comprising a plurality of wells within a frame, wherein the multi-well platform has low fluorescence background. Another aspect of the present invention is a system for spectroscopic measurements, comprising reagents for an assay and a multi-well platform for fluorescence measurements. A further aspect of the present invention is a method for detecting the presence of an analyte in a sample contained in a multi-well platform by detecting light emitted from the sample. Another aspect of the present invention is a method from identifying a modulator of a biological process or target in a sample contained in a multi-well platform by detecting light emitted from the sample. Another aspect of the present invention is a composition identified by this method. A further aspect of the present invention is a method to identify a therapeutic. A further aspect of the present invention is a method of testing a therapeutic for therapeutic activity and toxicology by identifying a therapeutic using a method of the present invention and monitoring the toxicology and efficacy of the therapeutic in an in vivo model.
363 Citations
38 Claims
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1. A multi-well platform, comprising:
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a) a plurality of wells, each well comprising;
i) a wall having less fluorescence than a polystyrene-wall of at least about 90 percent of said wall'"'"'s thickness, and ii) a bottom having a high transmittance portion and having less fluorescence than a polystyrene-bottom of at least about 90 percent of said bottom'"'"'s thickness, said bottom having a thickness less than about 450 microns and said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm;
b) a frame, wherein said wells are disposed in said frame. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
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25. A system for spectroscopic measurements, comprising:
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a) reagents for an assay, b) a device, comprising;
i) a multi-well platform, comprising;
a) a plurality of wells, each well comprising;
(1) a wall having less fluorescence than a polystyrene-wall of at least about 90 percent of said wall'"'"'s thickness, and (2) a bottom having a high transmittance portion and having less fluorescence than a polystyrene-bottom wall of at least about 90 percent of said bottom'"'"'s thickness, said bottom having a thickness less than about 450 microns and said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm, and b) a frame, wherein said wells are disposed in said frame, and ii) a second platform to hold said multi-well platform, iii) wherein said second platform is for detecting a signal from a sample. - View Dependent Claims (26)
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27. A method for detecting the presence of an analyte in a sample contained in a multi-well platform by detecting light emitted from the sample, said method comprising the steps of:
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a) exciting at least one sample with radiation of a first wavelength;
b) wherein at least one sample suspected of containing an analyte is placed into at least one well of a multi-well platform comprising;
i) a plurality of wells, each well comprising;
a) a wall having less fluorescence than a polystyrene-wall of at least about 90 percent of said wall'"'"'s thickness, and (1) a bottom having a high transmittance portion and having less fluorescence than a polystyrene-bottom wall of at least about 90 percent of said bottom'"'"'s thickness, said bottom having a thickness less than about 450 microns and said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm, and ii) a frame, wherein said wells are disposed in said frame, c) measuring the emission of radiation of a second wavelength emitted from said at least one sample, d) wherein the amount of radiation of a second wavelength measured indicates the presence or absence of said analyte. - View Dependent Claims (29, 30)
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28. A method for identifying a modulator of a biological process or target in a sample contained in a multi-well platform by detecting light emitted from the sample, said method comprising the steps of:
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a) contacting a biological process or target in a sample with a test chemical;
b) placing at least one sample suspected of containing a target substance into at least one well of the multi-well platform comprising;
i) a plurality of wells, each well comprising;
a) a wall having less fluorescence than a polystyrene-wall of at least about 90 percent of said wall'"'"'s thickness, and (1) a bottom having a high transmittance portion and having less fluorescence than a polystyrene-bottom wall of at least about 90 percent of said bottom'"'"'s thickness, said bottom having a thickness less than about 450 microns and said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm, and ii) a frame, wherein said wells are disposed in said frame, wherein the number of said wells disposed in said frame is 864 or more wells, c) exciting said sample with radiation of a first wavelength, and d) measuring the emission of radiation of a second wavelength emitted from said sample, e) wherein the amount of radiation of a second wavelength measured indicates the presence or absence of said modulator.
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31. A composition identified by a method comprising the steps of:
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a) contacting a test chemical suspected of having modulating activity of a biological process or target with a biological process or target in a multi-well platform comprising;
i) a plurality of wells, each well comprising a) a wall having less fluorescence than a polystyrene-wall of at least about 90 percent of said wall'"'"'s thickness, (1) a bottom having a high transmittance portion and having less fluorescence than a polystyrene-bottom wall of at least about 90 percent of said bottom'"'"'s thickness, said bottom having a thickness less than about 450 microns and said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm, and b) a frame, wherein said wells are disposed in said frame, b) exciting said sample with radiation of a first wavelength, and c) measuring the emission of radiation of a second wavelength emitted from said sample, d) wherein said test chemical has a modulating activity with respect to said process or target. - View Dependent Claims (32)
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33. A multi-well platform for fluorescence measurements, said multi-well platform comprising:
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a) a frame forming a side wall of a well, b) a bottom, said bottom wall being substantially transparent to the transmission of visible, ultraviolet, or infrared light, and c) wherein said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm, d) further wherein said wells are chamfered and the number of said wells is 864 or more. - View Dependent Claims (34, 35)
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36. A method of testing a therapeutic for therapeutic activity and toxicology comprising the steps of:
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a) identifying a therapeutic using the method comprising the steps of;
i) contacting a test chemical suspected of having modulating activity of a biological process or target with a biological process or target in a multi-well platform comprising;
a) a plurality of wells, each well comprising;
(1) a wall having less fluorescence than a polystyrene-wall of at least about 90 percent of said wall'"'"'s thickness, and (2) a bottom having a high transmittance portion and having less fluorescence than a polystyrene-bottom wall of at least about 90 percent of said bottom'"'"'s thickness, said bottom having a thickness less than about 450 microns and said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm, and b) a frame, wherein said wells are disposed in said frame, ii) exciting said sample with radiation of a first wavelength, iii) measuring the emission of radiation of a second wavelength emitted from said sample, and iv) wherein said test chemical has a modulating activity with respect to said process or target, b) monitoring the toxicology of said therapeutic in an in vivo model, and c) monitoring the efficacy of said therapeutic in an in vivo model.
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37. A therapeutic chemical composition identified by a method comprising the steps of:
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a) identifying a therapeutic using the method comprising the steps of;
i) contacting a test chemical suspected of having modulating activity of a biological process or target with a biological process or target in a multi-well platform comprising;
a) a plurality of wells, each well comprising (1) a wall having less fluorescence than a polystyrene-wall of at least about 90 percent of said wall'"'"'s thickness, and (2) a bottom having a high transmittance portion and having less fluorescence than a polystyrene-bottom wall of at least about 90 percent of said bottom'"'"'s thickness, said bottom having a thickness less than about 450 microns and said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm, and b) a frame, wherein said wells are disposed in said frame, wherein the number of said wells disposed in said frame is 864 or more wells, ii) exciting said sample with radiation of a first wavelength, and iii) measuring the emission of radiation of a second wavelength emitted from said sample, iv) wherein said test chemical has a modulating activity with respect to said process or target, and b) monitoring the toxicology of said therapeutic in an in vitro or in vivo model, and c) monitoring the efficacy of said therapeutic in an in vitro or in vivo model. - View Dependent Claims (38)
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Specification