Method and apparatus for making miniaturized diagnostic arrays
First Claim
1. A method of forming diagnostic arrays having a number of discrete probes to produce a test strip on a substrate surface suitable for exposure to a sample of unknown substance, comprising the steps of:
- (a) positioning a test strip substrate on a controllably movable substrate support;
(b) positioning over the substrate, a first replaceable set of electro-mechanical fluid ejection devices each having an outlet in fixed spatial relationship relative to each other with said outlets oriented toward the surface of the substrate;
(c) placing activator and test probe fluids in respective reservoirs of a first set of reservoirs, each reservoir being in communication with one of the ejection devices in said first replacement set; and
(d) activating the ejection devices in said first replaceable set and moving said test strip substrate relative to said ejection devices to form and position drops of activator fluid from said first set of reservoirs on the test strip substrate surface in a pattern of discrete sites established by the ejection devices in said first replaceable set, and moving said test strip relative to said ejection devices to form and position drops of test probe fluids from said first set of reservoirs on the test strip surface, on said pattern of sites to form a pattern of discrete test probes, wherein each probe is formed from at least one test probe fluid whereby a test strip having a desired pattern of test probes is prepared for use.
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Accused Products
Abstract
Arrays of electro-mechanical dispensers are used to form extremely small drops of fluid and locate them precisely on substrate surfaces in miniature arrays. The printed arrays may consist of DNA, immunoassay reagents or the like. A positioning support such as an X-Y table moves the dispensing devices and substrate surfaces relative to each other to locate the drops on the substrates in predetermined patterns. Arrays of probes as dense as one thousand per square centimeter with center-to-center spacing as small as twenty-five micrometers are formed.
441 Citations
29 Claims
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1. A method of forming diagnostic arrays having a number of discrete probes to produce a test strip on a substrate surface suitable for exposure to a sample of unknown substance, comprising the steps of:
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(a) positioning a test strip substrate on a controllably movable substrate support; (b) positioning over the substrate, a first replaceable set of electro-mechanical fluid ejection devices each having an outlet in fixed spatial relationship relative to each other with said outlets oriented toward the surface of the substrate; (c) placing activator and test probe fluids in respective reservoirs of a first set of reservoirs, each reservoir being in communication with one of the ejection devices in said first replacement set; and (d) activating the ejection devices in said first replaceable set and moving said test strip substrate relative to said ejection devices to form and position drops of activator fluid from said first set of reservoirs on the test strip substrate surface in a pattern of discrete sites established by the ejection devices in said first replaceable set, and moving said test strip relative to said ejection devices to form and position drops of test probe fluids from said first set of reservoirs on the test strip surface, on said pattern of sites to form a pattern of discrete test probes, wherein each probe is formed from at least one test probe fluid whereby a test strip having a desired pattern of test probes is prepared for use. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A method of forming diagnostic arrays having a number of discrete test probes on a substrate surface comprising the steps of:
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(a) positioning a substrate on a substrate support; (b) positioning a plurality of electro-mechanical fluid ejection devices having outlets in fixed spacial relationship relative to each other with said outlets oriented toward the substrate; (c) providing plurality of fluid reservoirs greater in number than the plurality of electro-mechanical fluid ejection devices and a fluid handling system which selectively places each of the plurality of reservoirs in fluid communication with selected ones of the plurality of fluid ejection devices; (d) placing a fluid in each of a plurality of reservoirs; (e) placing a selected one of the plurality of fluid ejection devices in fluid communication with one fluid reservoir of said plurality of fluid reservoirs; (f) activating said selected one of the plurality of fluid ejection devices and moving said substrate support relative to said selected ejection devices to form and position drops of fluid from said one fluid reservoir into a pattern of discrete test probes on said substrate; (g) placing the selected one of the plurality of fluid ejection devices in fluid communication with another fluid reservoir of said plurality of fluid reservoirs; and (h) activating said selected one of the plurality of fluid ejection devices and moving said substrate support relative to said selected ejection devices to form and position drops of fluid from said another fluid reservoir into a pattern of discrete test probes on said substrate; (i) whereby a plurality of fluids can be dispensed from said reservoirs to form discrete test probes on said substrate without having the number of fluid ejection devices corresponding to the number of fluid reservoirs. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15, 16, 17)
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18. Apparatus for forming diagnostic arrays comprising a number of discrete probes to produce a test strip on a substrate surface suitable for exposure to a sample of unknown substance comprising:
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(a) a substrate support; (b) a test strip substrate positioned on said support; (c) a plurality of electro-mechanical fluid ejection devices having outlets positioned in fixed spatial relationship relative to each other with said outlets oriented toward the test strip substrate and moveable with respect to said substrate support; (d) a plurality of test probe fluid reservoirs greater in number than said plurality of electro-mechanical ejection devices; (e) a fluid handling means for selectively placing each one of said plurality of fluid reservoirs individually in communication with at least one of said ejection devices; (f) means for activating said at least one ejection devices to propel drops of test probe fluid from a selected one of said plurality of test probe fluid reservoirs toward the substrate; and (g) means for moving said ejection devices and the substrate relative to each other to form a pattern of discrete test probes formed from selected ones of the plurality of test probe fluid reservoirs on the substrate. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
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Specification