Ultra high throughput sampling and analysis systems and methods
First Claim
1. A method of sampling compounds into a microfluidic channel, comprising:
- providing a plurality of different compounds reversibly immobilized on a first surface of a substrate;
providing a capillary element having a microfluidic channel disposed therethrough, the capillary element having at least one open end, and a volume of solubilizing fluid present at the open end of the capillary element;
moving the solubilizing fluid at the open end of the capillary element into contact with a first compound on the surface of the substrate;
sensing when the solubilizing fluid contacts the surface of the substrate, the solubilizing fluid dissolving at least a portion of the first compound; and
drawing at least a portion of the dissolved first compound into the capillary element.
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Accused Products
Abstract
Ultra-high throughput systems and methods are used for sampling large numbers of different materials from surfaces of substantially planar library storage components. The systems and methods typically employ: microfluidic devices having integrated capillary elements for carrying out the analysis of the sampled materials; library storage components, e.g., planar solid substrates, capable of retaining thousands, tens of thousands and hundreds of thousands of different materials in small areas; sensing systems for allowing rapid and accurate sampling of the materials by the microfluidic devices, and associated instrumentation for control and analysis of the overall operation of these systems.
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Citations
51 Claims
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1. A method of sampling compounds into a microfluidic channel, comprising:
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providing a plurality of different compounds reversibly immobilized on a first surface of a substrate;
providing a capillary element having a microfluidic channel disposed therethrough, the capillary element having at least one open end, and a volume of solubilizing fluid present at the open end of the capillary element;
moving the solubilizing fluid at the open end of the capillary element into contact with a first compound on the surface of the substrate;
sensing when the solubilizing fluid contacts the surface of the substrate, the solubilizing fluid dissolving at least a portion of the first compound; and
drawing at least a portion of the dissolved first compound into the capillary element. - 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, 25, 26, 27)
moving the capillary element to a position adjacent to the first compound, and expelling a volume of the solubilizing fluid from the microfluidic channel disposed within the capillary element to contact the first compound.
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8. The method of claim 1, wherein the sensing step comprises sensing an electrical signal that is indicative of contact between the solubilizing fluid and the surface of the substrate.
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9. The method of claim 1, wherein the sensing step comprises sensing an electrical signal that is indicative of a distance between the solubilizing fluid and the surface of the substrate.
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10. The method of claim 8, wherein the step of sensing an electrical signal comprises detecting completion of an electrical circuit between the fluid at the end of the capillary element and the substrate surface.
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11. The method of claim 10, wherein the capillary element is filled with fluid, and the completion of the electrical circuit comprises providing an electrical current through the fluid filled capillary element and detecting completion of the electrical circuit between the capillary element and the substrate.
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12. The method of claim 8, wherein the step of sensing an electrical signal indicative of contact between the fluid and the surface of the substrate comprises detecting a change in a level of capacitance between the fluid and the surface of the substrate, which change occurs when the fluid is sufficiently proximal to or contacting the surface of the substrate.
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13. The method of claim 12, wherein the step of detecting a change in a level of capacitance comprises detecting a change in phase of an electrical current with respect to an applied voltage between the fluid and the surface of the substrate when the fluid is brought into sufficient proximity or contact with the surface of the substrate.
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14. The method of claim 12, wherein the change in phase is measured relative to a reference signal.
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15. The method of claim 1, wherein the sensing step comprises optically detecting contact between the fluid and the surface of the substrate.
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16. The method of claim 15, wherein the optically detecting step comprises detecting a sufficient change in fluorescence emitted from the surface of the substrate.
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17. The method of claim 15, wherein the optically detecting step comprises imaging at least one of the surface of the substrate and the open end of the capillary element, and determining when the solubilizing fluid contacts the surface of the substrate.
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18. The method of claim 17, wherein the substrate is transparent, and step of imaging one of the surface of the substrate or the open end of the capillary element comprises directing an imaging system at the surface of the substrate or capillary element from beneath the substrate, relative to the capillary element.
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19. The method of claim 17, wherein the step of imaging one of the surface of the substrate and the capillary element comprises directing an imaging system at at least one of the substrate surface and capillary element from a side.
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20. The method of claim 1, further comprising repeating the moving, sensing and drawing steps with at least a second compound on the surface of the substrate.
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21. The method of claim 1, further comprising repeating the moving, sensing and drawing steps with at least 10 different compounds separately reversibly immobilized on the substrate surface.
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22. The method of claim 1, further comprising repeating the moving, sensing and drawing steps with at least 100 different compounds separately reversibly immobilized on the substrate surface.
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23. The method of claim 1, further comprising repeating the moving, sensing and drawing steps with at least 1000 different compounds separately reversibly immobilized on the substrate surface.
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24. The method of claim 1, further comprising repeating the moving, sensing and drawing steps with at least 10,000 different compounds separately reversibly immobilized on the substrate surface.
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25. The method of claim 1, further comprising repeating the moving, sensing and drawing steps with at least 100,000 different compounds separately reversibly immobilized on the substrate surface.
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26. The method of claim 1, further comprising repeating the moving, sensing and drawing steps with the first compound.
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27. The method of claim 1, further comprising repeating the moving, sensing and drawing steps with the first compound from 1 to 10 times.
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28. A method of sampling a plurality of different compounds into a microfluidic channel, comprising:
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providing a sample substrate having at least a first surface, the substrate comprising a plurality of different compounds immobilized in a gridded array of one or more rows of different compounds, the different compounds being substantially uniformly spaced within the one or more rows whereby each compound is in a separate discrete region of the first surface of the substrate, the plurality of different compounds being present at a density of a least about 10 different compounds/cm2 of substrate surface;
determining an approximate location of a plurality of the different compounds in the separate discrete regions of the first surface of the substrate which comprises locating at least first and second compound locations on the first surface of the substrate and interpolating an approximate location for substantially all of the different compounds between the first and second compound locations;
separately solubilizing a first compound on the surface;
drawing a portion of the solubilized first compound into a microfluidic channel disposed in a capillary element; and
repeating the solubilizing and drawing steps with at least a second compound on the first surface of the substrate. - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51)
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Specification