High throughput screening with parallel vibrational spectroscopy
First Claim
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1. An instrument for simultaneous assay of molecular interaction in multiple samples via parallel vibration spectroscopy comprising:
- a) a source of broadband infrared radiation for probing molecular interactions with a modulator of broadband infrared radiation;
b) a multiple-well sample holder comprising a substrate at least partially made of an infrared transparent material and etched to form an array of wells;
c) a light directing optical structure having an optical interface with each sample well, wherein the optical structure directs modulated broadband infrared radiation to each said sample well allowing internal reflection and subsequent exit of the altered light;
d) an infrared imaging radiation detector for simultaneously detecting the altered light; and
e) a computer for analyzing data from the infrared imaging radiation detector.
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Abstract
Rapid spectrum assay of multiple samples with infrared light is made possible by devices and methods that increase total light throughput. Multiple wavelength scan with Fourier analysis is combined with large numbers of sample wells located within infrared light compatible solid materials. In particular, very large scale measurement devices and systems for their use are fabricated from lithography and other techniques used for semiconductor processing.
56 Citations
32 Claims
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1. An instrument for simultaneous assay of molecular interaction in multiple samples via parallel vibration spectroscopy comprising:
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a) a source of broadband infrared radiation for probing molecular interactions with a modulator of broadband infrared radiation; b) a multiple-well sample holder comprising a substrate at least partially made of an infrared transparent material and etched to form an array of wells; c) a light directing optical structure having an optical interface with each sample well, wherein the optical structure directs modulated broadband infrared radiation to each said sample well allowing internal reflection and subsequent exit of the altered light; d) an infrared imaging radiation detector for simultaneously detecting the altered light; and e) a computer for analyzing data from the infrared imaging radiation detector. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A multiple-well sample holder suitable for simultaneous assay of molecular interactions in multiple samples via parallel vibrational spectroscopy, comprising:
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a) a substrate at least partially made of an infrared transparent material having a sample surface and an optical interface, wherein; b) the sample surface of the infrared transparent substrate contains an array of multiple sample wells for accepting fluids, and c) the optical interface contains at least one light directing optical structure that directs broadband infrared radiation through the substrate, allowing internal reflection from the sample surface and the subsequent exit of the altered light; and d) the distance between the sample surface and the optical interface is greater than 1 micron. - View Dependent Claims (9, 10, 11)
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12. A sample holder for the simultaneous assay of molecular interactions in multiple samples via parallel vibrational spectroscopy, comprising:
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a) an array of wells; and b) a prismatic structure contacting each sample well, wherein the prismatic structure comprises a material that is transparent to broadband infrared light of wavelengths between 5 and 10 microns, is at least twice as tall as it is wide and allows the light to enter the optically dense material with an incidence angle that exceeds the critical angle for total internal reflection. - View Dependent Claims (13, 14)
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15. A tool for detecting effects of chemical compounds on cellular activities or for detecting desirable genetic manipulations in vitro, comprising:
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a) a source of broadband infrared radiation having wavelengths longer than 5 nanometers; b) a temperature controlled cell sample holder having an array of wells that hold and maintain metabolizing cells at a constant temperature in a wet environment, wherein each well has at least one surface in optical contact with the cells that is transparent to the infrared radiation; c) at least one prismatic structure having an optical interface with each sample well for directing the broadband infrared radiation into the infrared radiation transparent surfaces with an incidence angle that exceeds the critical angle for total internal reflection that penetrates a layer of cells in contact with the surface; and d) an infrared imaging detector that collects reflected light; and e) a computer for analyzing data from the infrared imaging radiation detector. - View Dependent Claims (16, 17, 18, 19, 20, 21)
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22. A method for studying biomolecules in solution, comprising:
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a) providing a plurality of solution samples comprising biomolecules to be analyzed and at least one reference solution sample; b) inputting each one of the plurality of solution samples into an array of sample wells defined in a multiple well sample holder, wherein the array surface is transparent to broadband infrared radiation and is in optical contact with a prismatic structure that directs infrared light into the array surface with an incidence angle that exceeds the critical angle for total internal reflection that penetrates at least one tenth micron of the solution; c) irradiating the array surface with broadband infrared radiation; d) collecting reflected broadband light spectra from each well in the multiple well sample holder simultaneously using an imaging infrared detector; e) comparing spectra from one or more sample wells to reference spectra from at least one reference sample well; and f) determining if there is any difference between the sample and the reference spectra. - View Dependent Claims (23, 24, 25, 27, 28, 29, 30, 31, 32)
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26. A method for studying biomolecules in solution, comprising:
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a) providing a plurality of solution samples comprising biomolecules to be analyzed, and relevant data from at least one reference sample; b) inputting each one of the plurality of the samples into an array of sample wells defined in a multiple well sample holder, wherein the array surface is transparent to broadband infrared and is in optical contact with a prismatic structure that directs infrared light into the array surface with an incidence angle that exceeds the critical angle for total internal reflection that penetrates at least one tenth micron of the solution; c) irradiating the array surface with broadband infrared radiation; d) collecting the reflected broadband light spectra from each well in the multiple well sample holder simultaneously using an imaging infrared detector; e) comparing the spectra from one or more sample wells to the data from at least one reference sample; and f) determining if there is any difference between the sample spectra and the reference data.
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Specification