Source: http://www.google.com/patents/US8030477?dq=6,418,462
Timestamp: 2015-05-06 08:59:26
Document Index: 117925011

Matched Legal Cases: ['Application No. 99', 'Application No. 2000', 'Application No. 99', 'Application No. 99', 'Application No. 2000', 'Application No. 09', 'Application No. 09', 'Application No. 2000', 'Application No. 2000']

Patent US8030477 - Methods for the synthesis of arrays of DNA probes - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsThe synthesis of arrays of DNA probes sequences, polypeptides, and the like is carried out using a patterning process on an active surface of a substrate. An image is projected onto the active surface of the substrate utilizing reflective projection optics. The projection optics project a light image...http://www.google.com/patents/US8030477?utm_source=gb-gplus-sharePatent US8030477 - Methods for the synthesis of arrays of DNA probesAdvanced Patent SearchPublication numberUS8030477 B2Publication typeGrantApplication numberUS 11/524,082Publication dateOct 4, 2011Filing dateSep 20, 2006Priority dateFeb 23, 1998Fee statusPaidAlso published asCA2321070A1, CA2321070C, DE69942272D1, EP1066506A1, EP1066506A4, EP1066506B1, EP2180309A2, EP2180309A3, EP2259046A2, EP2259046A3, US6375903, US20100227780, WO1999042813A1Publication number11524082, 524082, US 8030477 B2, US 8030477B2, US-B2-8030477, US8030477 B2, US8030477B2InventorsFrancesco Cerrina, Michael R. Sussman, Frederick R. Blattner, Sangeet Singh-Gasson, Roland GreenOriginal AssigneeWisconsin Alumni Research FoundationExport CitationBiBTeX, EndNote, RefManPatent Citations (62), Non-Patent Citations (55), Referenced by (2), Classifications (52), Legal Events (1) External Links: USPTO, USPTO Assignment, EspacenetMethods for the synthesis of arrays of DNA probes
US 8030477 B2Abstract
The synthesis of arrays of DNA probes sequences, polypeptides, and the like is carried out using a patterning process on an active surface of a substrate. An image is projected onto the active surface of the substrate utilizing reflective projection optics. The projection optics project a light image onto the active surface of the substrate to deprotect linker molecules thereon. A first level of bases may then be applied to the substrate, followed by development steps, and subsequent exposure of the substrate utilizing a different light image, with further repeats until the elements of a two dimensional array on the substrate surface have an appropriate base bound thereto.
1. A method of projecting a pattern onto a surface comprising the steps of:
(a) providing a substrate with an active surface to which protected linker molecules have been applied;
(b) projecting a two-dimensional light image onto the active surface of the substrate using projection optics comprising reflective optical elements to illuminate pixel sites on the active surface to photodeprotect the linker molecules thereon, wherein the reflective optical elements provide telecentric projection optics and wherein the step of projecting the two-dimensional image onto the active surface of the substrate comprises:
(i) providing a micromirror device comprising a two-dimensional array of electronically addressable micromirrors, each of which can be selectively tilted between one of at least two separate positions, and providing signals to the micromirror device to select a pattern of the micromirrors in the two-dimensional array which are to reflect light onto the active surface; and
(ii) projecting light from a light source onto the micromirror array and reflecting the light from the mirrors of the micromirror array onto the projection optics to project the two-dimensional image onto the active surface,
and further wherein the step of projecting the two-dimensional light image does not use a lithographic mask.
2. The method of claim 1, wherein the reflective optical elements comprise a concave mirror and a convex mirror, the concave mirror reflecting light to the convex mirror which reflects the light back to the concave mirror which reflects the light to the active surface where it is imaged.
3. The method of claim 2, wherein the reflective optical elements further comprise a planar mirror which reflects the light from the concave mirror to the active surface.
4. The method of claim 2, wherein the projection optics further comprise a telecentric aperture placed in front of the convex mirror.
5. The method of claim 2, wherein the radius of curvature of the concave mirror is twice that of the convex mirror.
6. A method of synthesizing arrays of DNA probes comprising carrying out the method of projecting a pattern onto a surface according to claim 2, the method further comprising:
(c) providing a fluid containing an appropriate nucleotide base to the active surface of the substrate and binding the nucleotide base to the photodeprotected linker molecules.
7. The method of claim 1, wherein the substrate is transparent and the light image is projected through a surface of the substrate that is opposite to the active surface.
8. The method of claim 1, further comprising collimating the light from the light source to provide a collimated beam projected onto the micromirror array at an oblique angle to a main optical axis that extends from the micromirror array to the substrate, and wherein in one position of each micromirror the light is reflected along the main optical axis onto the projection optics and in a second position of each micromirror the light from the source is reflected at an angle off the main optical axis and away from the substrate.
9. The method of claim 1, further comprising filtering the light from the light source, whereby only desired wavelengths of light are passed through to the micromirror array.
10. The method of claim 9, wherein the light from the light source comprises ultraviolet or near-ultraviolet light and the desired wavelengths that are passed are in the range of ultraviolet or near-ultraviolet wavelengths.
11. The method of claim 9, wherein the light from the light source is filtered by a filter comprising a dichroic mirror that reflects the desired wavelengths and passes wavelengths to be blocked.
12. The method of claim 1, further comprising a computer connected to the micromirror device to provide command signals to control the deflection of the mirrors in the micromirror array to provide a desired pattern for projection onto the active surface.
13. The method of claim 1, wherein the image that is patterned onto the active surface of the substrate is reduced in size with respect to the size of the array of micromirrors.
14. A method of synthesizing arrays of DNA probes comprising carrying out the method of projecting a pattern onto a surface according to claim 1, the method further comprising:
(d) projecting a new two-dimensional light image onto the active surface of the substrate to illuminate pixel sites on the active surface to photodeprotect linker molecules or bound nucleotide bases; and
(e) providing a fluid containing an appropriate nucleotide base to the active surface of the substrate and binding the nucleotide base to the photodeprotected linker molecules or bound nucleotide bases.
16. The method of claim 15, wherein steps (d) and (e) are repeated a selected number of times to build up a selected number of levels of nucleotide bases in a DNA probe array on the substrate.
17. The method of claim 14, wherein the nucleotide base is flowed over the active surface in step (c) and bound to the linker molecules utilizing phosphoramidate DNA synthesis.
18. The method of claim 14, wherein the active surface of the substrate is enclosed in a flow cell comprising a sealed reaction chamber, an input port and an output port.
19. The method of claim 18, wherein the flow cell comprises a housing comprising a lower base, an upper cover section and a gasket mounted on the base, wherein the substrate is a transparent glass slide secured between the upper cover section and the lower base to define the sealed reaction chamber between the substrate and the lower base that is sealed by the gasket, and channels extending through the housing from the input port to the reaction chamber and from the reaction chamber to the output port, the active surface of the substrate facing the sealed reaction chamber. Description
This application is a continuation of prior application Ser. No. 09/637,891 filed Aug. 9, 2000, which is a continuation of prior application Ser. No. 09/253,460 filed Feb. 22, 1999, which application claimed the benefit of provisional patent application Ser. No. 60/075,641, filed Feb. 23, 1998.
This invention was made with United States government support awarded by the following agencies: DOE Grant Nos.: DE-FG07-96ER13938; P0062242-02; DE-FG02-96ER45569; 63040304; P071760302; NSF Grant Nos.: IBN-9706552; ECS-9317745; INT-960289; ONR DOD-Navy Grant# N00014-97-1-0460; DOD-Army Grant # DAAH04-95-1-0456; USDA AGRICCREE Grant No.: 95-37304-2364. The United States has certain rights in this invention.
The sequencing of deoxyribonucleic acid (DNA) is a fundamental tool of modern biology and is conventionally carried out in various ways, commonly by processes which separate DNA segments by electrophoresis. See, e.g., Current Protocols In Molecular Biology, Vol. 1, Chapter 7, �DNA Sequencing,� 1995. The sequencing of several important genomes has already been completed (e.g., yeast, E. coli), and work is proceeding on the sequencing of other genomes of medical and agricultural importance (e.g., human, C. elegans, Arabidopsis). In the medical context, it will be necessary to �re-sequence� the genome of large numbers of human individuals to determine which genotypes are associated with which diseases. Such sequencing techniques can be used to determine which genes are active and which inactive either in specific tissues, such as cancers, or more generally in individuals exhibiting genetically influenced diseases. The results of such investigations can allow identification of the proteins that are good targets for new drugs or identification of appropriate genetic alterations that may be effective in genetic therapy. Other applications lie in fields such as soil ecology or pathology where it would be desirable to be able to isolate DNA from any soil or tissue sample and use probes from ribosomal DNA sequences from all known microbes to identify the microbes present in the sample.
The conventional sequencing of DNA using electrophoresis is typically laborious and time consuming. Various alternatives to conventional DNA sequencing have been proposed. One such alternative approach, utilizing an array of oligonucleotide probes synthesized by photolithographic techniques is described in Pease, et al., �Light-Generated Oligonucleotide Arrays for Rapid DNA Sequence Analysis,� Proc. Natl. Acad. Sci. USA, Vol. 91, pp. 5022-5026, May 1994. In this approach, the surface of a solid support modified with photolabile protecting groups is illuminated through a photolithographic mask, yielding reactive hydroxyl groups in the illuminated regions. A 3′ activated deoxynucleoside, protected at the 5′ hydroxyl with a photolabile group, is then provided to the surface such that coupling occurs at sites that had been exposed to light. Following capping, and oxidation, the substrate is rinsed and the surface is illuminated through a second mask to expose additional hydroxyl groups for coupling. A second 5′ protected activated deoxynucleoside base is presented to the surface. The selective photodeprotection and coupling cycles are repeated to build up levels of bases until the desired set of probes is obtained. It may be possible to generate high density miniaturized arrays of oligonucleotide probes using such photolithographic techniques wherein the sequence of the oligonucleotide probe at each site in the array is known. These probes can then be used to search for complementary sequences on a target strand of DNA, with detection of the target that has hybridized to particular probes accomplished by the use of fluorescent markers coupled to the targets and inspection by an appropriate fluorescence scanning microscope. A variation of this process using polymeric semiconductor photoresists, which are selectively patterned by photolithographic techniques, rather than using photolabile 5′ protecting groups, is described in McGall, et al., �Light-Directed Synthesis of High-Density Oligonucleotide Arrays Using Semiconductor Photoresists,� Proc. Natl. Acad. Sci. USA, Vol. 93, pp. 13555-13560, November 1996, and G. H. McGall, et al., �The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates,� Journal of the American Chemical Society. 119, No. 22, 1997, pp. 5081-5090.
FIG. 8 is a cross-sectional view through the reaction chamber flow cell of FIG. 7 taken generally along the lines 8-8 of FIG. 7.
The projection optics 44 may be of standard design, since the images to be formed are relatively large and well away from the diffraction limit. The lenses 45 and 46 focus the light in the beam 41 passed through the adjustable iris 47 onto the active surface of the substrate. The projection optics 44 and the beam splitter 32 are arranged so that the light deflected by the micromirror array away from the main optical axis (the central axis of the projection optics 44 to which the beams 41 are parallel), illustrated by the beams labeled 40 (e.g., 10� off axis) fall outside the entrance pupil of the projection optics 44 (typically 0.5/5=0.1; 10� corresponds to an aperture of 0.17, substantially greater than 0.1). The iris 47 is used to control the effective numerical aperture and to ensure that unwanted light (particularly the off-axis beams 40) are not transmitted to the substrate. Resolution of dimensions as small as 0.5 microns are obtainable with such optics systems. For manufacturing applications, it is preferred that the micromirror array 35 be located at the object focal plane of a lithographic I-line lens optimized for 365 nm. Such lenses typically operate with a numerical aperture (NA) of 0.4 to 0.5, and have a large field capability
The micromirror array device 35 may be formed with a single line of micromirrors (e.g., with 2,000 mirror elements in one line) which is stepped in a scanning system. In this manner the height of the image is fixed by the length of the line of the micromirror array but the width of the image that may be projected onto the substrate 12 is essentially unlimited. By moving the stage 18 which carries the substrate 12, the mirrors can be cycled at each indexed position of the substrate to define the image pattern at each new line that is imaged onto the substrate active surface.
A more detailed view of a preferred array synthesizer apparatus which uses the off-axis projection arrangement of FIG. 2 is shown in FIG. 3. In the apparatus of FIG. 3, the source 25 (e.g., 1,000 W Hg arc lamp, Oriel 6287, 66021), provided with power from a power supply 50 (e.g., Oriel 68820), is used as the light source which contains the desired ultraviolet wavelengths. The filter system 26 is composed, for example, of a dichroic mirror (e.g., Oriel 66226) that is used to absorb infrared light and to selectively reflect light of wavelengths ranging from 280 to 400 nm. A water-cooled liquid filter (e.g., Oriel 6127) filled with deionized water is used to absorb any remaining infrared. A colored glass filter (Oriel 59810) or an interference filter (Oriel 56531) is used to select the 365 nm line of the Hg lamp 25 with a 50% bandwidth of either 50 nm or 10 nm, respectively. An F/1 two element fused silica condenser (Oriel 66024) is used as the condenser 28, and with two plano-convex lenses 52 (Melles Griot 01LQP033 and Melles Griot 01LQP023), forms a Kohler illumination system. This illumination system produces a roughly collimated uniform beam 30 of 365 nm light with a diameter just large enough to encompass the 16 mm�12 mm active area of the micromirror array device 35. This beam 30 is incident onto the device 35 at an angle of 20� measured from the normal to the face of the device. The micromirror array device 35 is located approximately 700 mm away from the last filter. When the micromirrors are in a first position, the light in the beam 30 is deflected downwardly and out of the system. For example, in this micromirror device the mirrors in their first position may be at an angle of −10� with respect to the normal to the plane of the micromirrors to reflect the light well away from the optical axis. When a micromirror is controlled to be deflected in a second position, e.g., at an angle of +10� with respect to the normal to the plane of the micromirrors, the light reflected from such micromirrors in the second position emerges perpendicularly to the plane of the micromirror array in the beam 41. The pattern formed by the light reflected from the micromirrors in their second position is then imaged onto the active surface 15 of a glass substrate 12 enclosed in a flow cell 18 using a telecentric imaging system composed of two doublet lenses 45 and 46 and an adjustable aperture 47. Each of the doublet lenses 45 and 46 is composed of a pair of plano-convex lenses (e.g., Melles Griot 01LQP033 and 01LQP037) put together with the curved surfaces nearly touching. The first doublet lens is oriented so that the shorter focal length (01LQP033) side is towards the micromirror array device 35, and the second doublet is oriented so that its longer focal length (01LQP037) side is toward the micromirror array device 35. Doublets composed of identical lenses may be used, in which case either side may face the micromirror array device. The adjustable aperture 47, also called a telecentric aperture, is located at the back focal plane of the first doublet. It is used to vary the angular acceptance of the optical system. Smaller aperture diameters correspond to improve contrast and resolution but with correspondingly decreased intensity in the image. As illustrated in FIG. 3, a standard DNA synthesizer 55 supplied with the requisite chemicals can be connected by the tubes 20 and 21 to the flow cell 18 to provide the desired sequence of chemicals, either under independent control or under control of the computer 38. A typical diameter for the aperture 47 is about 30 nm. An illustrative ray diagram showing the paths of light through the lenses 45 and 46 is shown in FIG. 4 for this type of refractive optical system. Fans of rays originating at the center of the object (the micromirror device face), at the edge, and at an intermediate location are shown. The optical system forms an inverted image of the face of the micromirror array device.
More detailed views of a reaction chamber flow cell 18 that may be utilized with the apparatus of the invention is shown in FIGS. 7 and 8. The exemplary flow cell 18 in these figures includes an aluminum housing 70, held together by bolts 71, having an inlet 73 connected to an input port line 20 and an outlet 75 converted to an output port line 21. As illustrated in the cross-sectional view of FIG. 8, the housing 70 includes a lower base 78 and an upper cover section 79 which are secured together over the substrate with the bolts 71. The substrate 12, e.g., a transparent glass slide, is held between the upper plate 79 and a cylindrical gasket 81 (e.g., formed of Kal Rezθ), which in turn is supported on a nonreactive base block 82 (e.g., Teflonθ), with an inlet channel 85 extending from the inlet 73 to a sealed reaction chamber 88 formed between the substrate 12 and the base block 82 that is sealed by the gasket, and with an outlet channel 89 extending from the reaction chamber 88 to the outlet 75. The bolts 71 can be screwed and unscrewed to detachably secure the substrate 12 between the cover section and the base to allow the substrate to be replaced with minimal displacement of the base of the flow cell. Preferably, as shown in FIG. 8, a rubber gasket 90 is mounted at the bottom of the plate 79 to engage against the substrate at a peripheral region to apply pressure to the substrate against the gasket 81. If desired, the flow cell may also be used as a hybridization chamber during readout.
An exemplary process for forming DNA probes is illustrated with respect to the schematic diagrams of FIGS. 9-14. FIG. 9 illustrates the coating of the substrate 12, having a silane layer 95 forming the active surface 15 thereof, with the photolabile linker molecule MENPOC-HEG coated on the silane layer using standard phosphoramidite chemistry. MENPOC-HEG-CEP=18-O-[(R,S)-(1-(3,4-(Methylenedioxy)-6-nitrophenyl)ethoxy)carbonyl]-3,6,9,12,15,18-hexaoxaoctadec-1-yl O′-2-cyanoethyl-N,N-Diisopropylphosphoramidite. The silane layer was made from N-(3-(triethoxysilyl)-propyl)-4-hydroxybutyramide. At the step shown in FIG. 9, the substrate can be exposed to light and active free OH groups will be exposed in areas that have been exposed to light.
FIG. 10 illustrates the photo-deprotection of the MENPOC-HEG linker and the production of free OH groups in the area 100 that is exposed to light. FIG. 11 illustrates the coupling of FluorePrimeθ fluorescein amidite to free OH groups produced from photo-deprotection of MENPOC-HEG. FIG. 12 illustrates the coupling of DMT-nucleotide to free OH groups produced from photo-deprotection of MENPOC-HEG linker. FIG. 13 illustrates the step of acid deprotection of DMT-nucleotides in the area 100 exposed to light. FIG. 14 illustrates the hybridization of poly-A probe labeled with fluorescein with poly-T oligonucleotides synthesized from DMT-nucleotide-CEPs.
Patent CitationsCited PatentFiling datePublication dateApplicantTitleUS4146329Sep 14, 1977Mar 27, 1979The United States Of America As Represented By The Secretary Of The NavyAutoalignment system for high power laserUS4163150Sep 28, 1977Jul 31, 1979Ernst Leitz Wetzlar GmbhProcess and apparatus for automatically realizing Kohler's principle of illuminationUS4301363Aug 30, 1979Nov 17, 1981Canon Kabushiki KaishaAlignment deviceUS4571603Jan 10, 1984Feb 18, 1986Texas Instruments IncorporatedDeformable mirror electrostatic printerUS4596992Aug 31, 1984Jun 24, 1986Texas Instruments IncorporatedLinear spatial light modulator and printerUS4615595Oct 10, 1984Oct 7, 1986Texas Instruments IncorporatedFrame addressed spatial light modulatorUS4662746Oct 30, 1985May 5, 1987Texas Instruments IncorporatedSpatial light modulator and methodUS5028939Jun 26, 1989Jul 2, 1991Texas Instruments IncorporatedSpatial light modulator systemUS5083857Jun 29, 1990Jan 28, 1992Texas Instruments IncorporatedMulti-level deformable mirror deviceUS5096279Nov 26, 1990Mar 17, 1992Texas Instruments IncorporatedSpatial light modulator and methodUS5143854Mar 7, 1990Sep 1, 1992Affymax Technologies N.V.Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereofUS5149172Jul 25, 1990Sep 22, 1992Parry DavisChild safety seatUS5159172 *Aug 7, 1990Oct 27, 1992International Business Machines CorporationOptical projection systemUS5202231Jun 18, 1991Apr 13, 1993Drmanac Radoje TMethod of sequencing of genomes by hybridization of oligonucleotide probesUS5252743Nov 13, 1990Oct 12, 1993Affymax Technologies N.V.Spatially-addressable immobilization of anti-ligands on surfacesUS5318679Jan 25, 1993Jun 7, 1994H & N Instruments, Inc.Synthesis of chain chemical compoundsUS5324483Feb 2, 1993Jun 28, 1994Warner-Lambert CompanyApparatus for multiple simultaneous synthesisUS5405783Mar 12, 1992Apr 11, 1995Affymax Technologies N.V.Large scale photolithographic solid phase synthesis of an array of polymersUS5412087Apr 24, 1992May 2, 1995Affymax Technologies N.V.Spatially-addressable immobilization of oligonucleotides and other biological polymers on surfacesUS5424186Dec 6, 1991Jun 13, 1995Affymax Technologies N.V.Very large scale immobilized polymer synthesisUS5445934Sep 30, 1992Aug 29, 1995Affymax Technologies N.V.Array of oligonucleotides on a solid substrateUS5451683Apr 23, 1993Sep 19, 1995Affymax Technologies N.V.Spatially-addressable immobilization of anti-ligands on surfacesUS5482867Apr 23, 1993Jan 9, 1996Affymax Technologies N.V.Spatially-addressable immobilization of anti-ligands on surfacesUS5489678Feb 16, 1995Feb 6, 1996Affymax Technologies N.V.Photolabile nucleoside and peptide protecting groupsUS5504614Jan 31, 1995Apr 2, 1996Texas Instruments IncorporatedMethod for fabricating a DMD spatial light modulator with a hardened hingeUS5510270Sep 30, 1992Apr 23, 1996Affymax Technologies N.V.Synthesis and screening of immobilized oligonucleotide arraysUS5535047Apr 18, 1995Jul 9, 1996Texas Instruments IncorporatedActive yoke hidden hinge digital micromirror deviceUS5556752Oct 24, 1994Sep 17, 1996Affymetrix, Inc.Surface-bound, unimolecular, double-stranded DNAUS5578832Sep 2, 1994Nov 26, 1996Affymetrix, Inc.Method and apparatus for imaging a sample on a deviceUS5583688Dec 21, 1993Dec 10, 1996Texas Instruments IncorporatedMulti-level digital micromirror deviceUS5593839Jun 2, 1995Jan 14, 1997Affymetrix, Inc.Computer-aided engineering system for design of sequence arrays and lithographic masksUS5599695Feb 27, 1995Feb 4, 1997Affymetrix, Inc.Printing molecular library arrays using deprotection agents solely in the vapor phaseUS5600383Jun 7, 1995Feb 4, 1997Texas Instruments IncorporatedMulti-level deformable mirror device with torsion hinges placed in a layer different from the torsion beam layerUS5604624Jun 5, 1995Feb 18, 1997Corning IncorporatedOptical system for projection displayUS5631734Feb 10, 1994May 20, 1997Affymetrix, Inc.Method and apparatus for detection of fluorescently labeled materialsUS5653939Aug 7, 1995Aug 5, 1997Massachusetts Institute Of TechnologyOptical and electrical methods and apparatus for molecule detectionUS5677195Nov 20, 1992Oct 14, 1997Affymax Technologies N.V.Combinatorial strategies for polymer synthesisUS5691541May 14, 1996Nov 25, 1997The Regents Of The University Of CaliforniaMaskless, reticle-free, lithographyUS5695940Jun 5, 1995Dec 9, 1997Hyseq, Inc.Method of sequencing by hybridization of oligonucleotide probesUS5696631Feb 22, 1996Dec 9, 1997Anvik CorporationUnit magnification projection lens systemUS5734498May 9, 1994Mar 31, 1998The Regents Of The University Of CaliforniaIlluminator elements for conventional light microscopesUS5744101Feb 14, 1995Apr 28, 1998Affymax Technologies N.V.Photolabile nucleoside protecting groupsUS5744305Jun 6, 1995Apr 28, 1998Affymetrix, Inc.Arrays of materials attached to a substrateUS5753788May 19, 1995May 19, 1998Affymetrix, Inc.Photolabile nucleoside protecting groupsUS5768009Apr 18, 1997Jun 16, 1998E-BeamLight valve target comprising electrostatically-repelled micro-mirrorsUS5815310Dec 12, 1995Sep 29, 1998Svg Lithography Systems, Inc.High numerical aperture ring field optical reduction systemUS5831070Apr 19, 1996Nov 3, 1998Affymetrix, Inc.Printing oligonucleotide arrays using deprotection agents solely in the vapor phaseUS5870176Jun 18, 1997Feb 9, 1999Sandia CorporationMaskless lithographyUS5959098Apr 17, 1996Sep 28, 1999Affymetrix, Inc.Substrate preparation processUS6060224Jan 14, 1999May 9, 2000Sweatt; William C.Method for maskless lithographyUS6225625Jun 1, 1995May 1, 2001Affymetrix, Inc.Signal detection methods and apparatusUS6271957May 26, 1999Aug 7, 2001Affymetrix, Inc.Methods involving direct write optical lithographyUS6295153Jun 4, 1999Sep 25, 2001Board Of Regents, The University Of Texas SystemDigital optical chemistry micromirror imagerUS6375903Feb 22, 1999Apr 23, 2002Wisconsin Alumni Research FoundationMethod and apparatus for synthesis of arrays of DNA probesUS6426184Feb 10, 1999Jul 30, 2002The Regents Of The University Of MichiganMethod and apparatus for chemical and biochemical reactions using photo-generated reagentsEP0961174A2May 28, 1999Dec 1, 1999Affymetrix, Inc.Compositions and methods involving direct write optical lithographyJPH0855793A Title not availableJPH09312255A Title not availableWO1990015070A1Jun 7, 1990Dec 13, 1990Affymax Tech NvVery large scale immobilized peptide synthesisWO1993022678A2Apr 23, 1993Nov 11, 1993Massachusetts Inst TechnologyOptical and electrical methods and apparatus for molecule detectionWO1999041007A2Feb 10, 1999Aug 19, 1999Univ HoustonMethod and apparatus for chemical and biochemical reactions using photo-generated reagentsWO1999063385A1Jun 4, 1999Dec 9, 1999Univ TexasDigital optical chemistry micromirror imager* Cited by examinerNon-Patent CitationsReference1"Digital Optical Chemistry," Online! XP002308688 www. Archive.org, retrieved from the Internet: URL:http://web.archive.org/web/19981202230253/http://pompous.swmed.edu/doc.htm, Dec. 2, 1998.2"The Digital Optical Chemistry System," found at http://innovation.swmed.edu/research/bioeng/res-bio-doc.html, printed Feb. 15, 2006.3"The Digital Optical Chemistry System," found at http://innovation.swmed.edu/research/bioeng/res�bio�doc.html, printed Feb. 15, 2006.4Appeal Brief in U.S. Appl. No. 09/639,602, Mar. 26, 2010.5Brunner , Impact of lens aberrations on optical lithography, J. RES. DEVELOP., Jan./Mar. 1997, pp. 57-67, vol. 41, No. 112.6Cerrina Miscellaneous Motion 1 (for Rehearing) RE: Interference for U.S. Patent No. 6,375,903, Nov. 6, 2007.7Decision -Rehearing-Bd.R. 125(c) RE: Interference for U.S. Patent No. 6,375,903, Nov. 8, 2007.8Decision to Grant a European Patent from the European Patent Office for EP Application No. 99 908 351.2, Mar. 25, 2010.9Decision-Interlocutory Motions-Bd.R. 125(b) RE: Interference for U.S. Patent No. 6,375,903, Oct. 23, 2007.10Decision-Interlocutory Motions-Bd.R. 125(b) RE: Interference for U.S. Patent No. 6,375,903, Oct. 9, 2007.11English Translation of Japanese Final Office Action in Japanese Patent Application No. 2000-532704, Nov. 5, 2009.12Examination Communication from the European Patent Office for EP Application No. 99 908 351.2, Jul. 3, 2008.13Examination Communication from the European Patent Office for EP Application No. 99 908 351.2, Oct. 31, 2007.14Examiners Answer to Appeal Brief in U.S. Appl. No. 09/639,602, Aug. 4, 2010.15Final Office Action received in Japanese Patent Application No. 2000-532704, Aug. 26, 2010.16Final Office Action received in U.S. Appl. No. 09/639,602, Jun. 30, 2004.17Final Office Action received in U.S. Appl. No. 09/639,602, Nov. 29, 2006.18Final Office Action received in U.S. Appl. No. 09/639,602, Sep. 17, 2009.19 *Gao et al U.S. Appl. No. 60/074,368, filed Feb. 11, 1998.20Goodall, F.N., et al., "Excimer Laser Photolithography with 1:1 Wynne-Dyson Optics," SPIE vol. 922, Optical/Laser Microlithography, 1988.21Hornbeck, L.J., "Digital Light Processing and MEMs: Reflecting the Digital Display Needs of the Networked Society," SPIE/EOS European Symposium on Lasers, Optics, and Vision for Productivity and Manufacturing I, Besancon, France, Jun. 10-14, 1996.22Judgment Request for Adverse-Bd.R. 127(b) RE: Interference for U.S. Patent No. 6,375,903, Nov. 27, 2007.23Kerth, R.T., et al., "Excimer Laser Projection Lithography on a Full-Field Scanning Projection System," IEEE Electron Device Letters, vol. EDL-7(5), pp. 299-301, 1986.24McGall, G.H., et al., "Light-Directed Synthesis of High-Density Oligonucleotide Arrays Using Semiconductor Photoresists," Proc. Nat'l Acad. Sci. USA, vol. 93, pp. 13555-13560, Nov. 1996.25McGall, G.H., et al., "The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates," Journal of the American Chemical Society, vol. 119, No. 22, pp. 5081-5090, 197.26Motion 1 Re: Interference for U.S. Patent No. 6,375,903, Nov. 10, 2006.27Motion Re: Interference for U.S. Patent No. 6,375,903, Nov. 13, 2006, 26 pages.28Motion Re: Interference for U.S. Patent No. 6,375,903, Nov. 13, 2006, 29 pages.29Neff, J.A., et al., "Two-Dimensional Spatial Light Modulators: A Tutorial," Proceedings of the IEEE, vol. 78, No. 5, pp. 826-855, May 1990.30Non-Final Office Action received in 6,375,903, Jun. 18, 2001.31Non-Final Office Action received in 6,375,903, Mar. 21, 2000.32Non-Final Office Action received in Patent Application No. 09/637,891, Jul. 1, 2003.33Non-Final Office Action received in Patent Application No. 09/637,891, Jul. 14, 2005.34Non-Final Office Action received in U.S. Appl. No. 09/639,602, Aug. 13, 2003.35Non-Final Office Action received in U.S. Appl. No. 09/639,602, Feb. 28, 2006.36Non-Final Office Action received in U.S. Appl. No. 09/639,602, Jan. 16, 2004.37Non-Final Office Action received in U.S. Appl. No. 09/639,602, Jun. 3, 2008.38Non-Final Office Action received in U.S. Appl. No. 09/639,602, Mar. 5, 2009.39Non-Final Office Action received in U.S. Appl. No. 09/639,602, Sep. 11, 2007.40Office Action received in Japanese Patent Application No. 2000-532704, Dec. 22, 2008.41Official Decision of grant for patent in Japanese Patent Application No. 2000-532704, Feb. 10, 2011.42Offner, A., "New Concepts in Projection Mask Aligners," Optical Engineering, vol. 14, pp. 130-132, 1975.43Opposition 1 Re: Interference for U.S. Patent No. 6,375,903, Jan. 31, 2007.44Opposition 2 Re: Interference for U.S. Patent No. 6,375,903, Jan. 31, 2007.45Opposition to Quate motion Re: Interference for U.S. Patent No. 6,375,903, Jan. 31, 2007.46Paufler et al., High-throughput optical direct write lithography, Solid State Technology, Jun. 1997,pp. 175,176,178,180,182.47Pease, et al., "Light-Generated Oligonucleotide Arrays for Rapid DNA Sequence Analysis," Proc. Nat'l. Acad. Sci. USA, vol. 91, pp. 5022-5026, May 1994.48Pre-Brief Appeal Conference Decision in U.S. Appl. No. 09/639,602, Jan. 27, 2010.49Pre-Brief Appeal Conference Request in U.S. Appl. No. 09/639,602, Dec. 16, 2009.50Reply 1 Re: Interference for U.S. Patent No. 6,375,903, Mar. 1, 2007.51Reply 2 Re: Interference for U.S. Patent No. 6,375,903, Mar. 1, 2007.52Reply Brief in U.S. Appl. No. 09/639,602, Oct. 4, 2010.53Ruff, B., et al., "Broadband Deep-UV High NA Photolithography System," SPIE vol. 1088, Optical/Laser Microlithography II, 1989.54U.S. Appl. No. 09/639,602, filed Aug. 15, 2000, Cerrina et al.55Wallraff et al., DNA sequencing on a chip, Chemtech, Feb. 1997, pp. 22-32.* Cited by examinerReferenced byCiting PatentFiling datePublication dateApplicantTitleEP2722105A1Oct 22, 2012Apr 23, 2014Universit�t WienMethod of in situ synthesizing microarraysWO2014064104A1Oct 22, 2013May 1, 2014Universit�t WienMethod of in situ synthesizing microarraysClassifications U.S. Classification536/25.3, 422/82.05, 435/283.1, 435/288.7, 359/298, 422/68.1, 435/6.1International ClassificationB01J19/00, C12M1/36, G02B26/08, C07H21/00, G03F7/20, C40B40/06, C07B61/00, C40B60/14, C12M1/34, G01N21/05, G01N37/00, G01N33/53, C08K3/00, G01N21/17, C12Q1/68Cooperative ClassificationC07B2200/11, B01J2219/0059, C40B60/14, B82Y30/00, B01J19/0046, G02B26/0841, B01J2219/00605, B01J2219/00637, B01J2219/00596, B01J2219/00689, B01J2219/00527, B01J2219/00626, G03F7/2002, B01J2219/00439, C40B40/00, C40B40/06, C07H21/00, B01J2219/00659, B01J2219/00585, B01J2219/00722, B01J2219/00641, B01J2219/00711, B01J2219/00529, B01J2219/00612, B01J2219/00608European ClassificationB01J19/00C, B82Y30/00, G03F7/20A, C07H21/00, G02B26/08M4ELegal EventsDateCodeEventDescriptionMar 27, 2015FPAYFee paymentYear of fee payment: 4RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services