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Reading dry chemical arrays through the substrateRelated Patent Categories: Chemistry: Analytical And Immunological Testing, Optical ResultReading dry chemical arrays through the substrate description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060166369, Reading dry chemical arrays through the substrate. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION [0001] This invention relates to arrays, particularly biopolymer arrays such as DNA or protein arrays, which are useful in diagnostic, screening, gene expression analysis, and other applications. BACKGROUND OF THE INVENTION [0002] Polynucleotide arrays (such as DNA or RNA arrays) and peptide array, are known and may be used, for example, as diagnostic or screening tools. Such arrays include regions (sometimes referenced as spots or features) of usually different sequence polynucleotides or peptides arranged in a predetermined configuration on a substrate. The array is "addressable" in that different features have different predetermined locations ("addresses") on a substrate carrying the array. [0003] Biopolymer arrays can be fabricated using in situ synthesis methods or deposition of the previously obtained biopolymers. The in situ fabrication methods include those described in U.S. Pat. No. 5,449,754 for synthesizing peptide arrays, and in U.S. Pat. No. 6,180,351 and WO 98/41531 and the references cited therein for polynucleotides. In situ methods also include photolithographic techniques such as described, for example, in WO 91/07087, WO 92/10587, WO 92/10588, and U.S. Pat. No. 5,143,854. The deposition methods basically involve depositing biopolymers at predetermined locations on a substrate which are suitably activated such that the biopolymers can link thereto. Biopolymers of different sequence may be deposited at different feature locations on the substrate to yield the completed array. Procedures known in the art for deposition of biopolymers, particularly DNA such as whole oligomers or cDNA, are described, for example, in U.S. Pat. No. 5,807,522 (touching drop dispensers to a substrate), and in PCT publications WO 95/25116 and WO 98/41531, and elsewhere (use of a pulse jet in the form of a piezoelectric inkjet head). [0004] Further details of large scale fabrication of biopolymer arrays by depositing either previously obtained biopolymers or by the in situ method, are disclosed in U.S. Pat. No. 6,242,266, U.S. Pat. No. 6,232,072, U.S. Pat. No. 6,180,351, and U.S. Pat. No. 6,171,797. [0005] In array fabrication, the quantities of DNA available for the array are usually very small and expensive. Sample quantities available for testing are usually also very small and it is therefore desirable to simultaneously test the same sample against a large number of different probes on an array. These conditions require the manufacture and use of arrays with large numbers of very small, closely spaced features. [0006] The arrays, when exposed to a sample, will exhibit a binding pattern. The array can be read by observing this binding pattern by, for example, labeling all targets such as polynucleotide targets (for example, DNA), in the sample with a suitable label (such as a fluorescent compound), scanning an illuminating beam across the array and accurately detecting the fluorescent signal from the different features of the array. Assuming that the different sequence polynucleotides were correctly deposited in accordance with the predetermined configuration, then the observed binding pattern will be indicative of the presence and/or concentration of one or more polynucleotide components in the sample. Peptide or arrays of other chemical moieties can be used in a similar manner. Conventionally, the illuminating and detecting have been performed on a dry array from a forward direction facing a front surface of the array carrying the array features, so that the illuminating and detected light need not pass through the substrate. In an alternative known arrangement, a transparent substrate forms part of a chamber in a housing with the array on a front substrate surface facing inward to the chamber. After exposure to a liquid containing the sample, the chamber is flushed and again filled with a liquid and the liquid containing chamber positioned in the array reading apparatus. In this situation, aside from the flushing and re-filling of the chamber, care must be taken that liquid does not leak from the chamber while positioned in the reading apparatus. The illuminating and detecting in this case has, of necessity, been performed in a backward direction through the substrate and onto the array while it is immersed in the liquid. [0007] Techniques and apparatus for scanning chemical arrays are described, for example, in U.S. Pat. No. 5,763,870 and U.S. Pat. No. 5,945,679. Apparatus which reads an array by scanning an illuminating beam by the foregoing technique are often referred to as scanners and the technique itself often referred to as scanning. Conventionally, such scanning has been done by illuminating array features on a front surface of the substrate one pixel at a time. [0008] Array scanners typically use a laser beam as a light source, which is scanned over pixels covering the array features. A detector (typically a fluorescence detector) with a very high light sensitivity is normally desirable to achieve maximum signal-to-noise in detecting hybridized molecules, particularly in array scanners used for DNA sequencing or gene expression studies. At present, photomultiplier tubes ("PMTs") are still the detector of choice although charge coupled devices ("CCDs") and avalanche photodiodes ("APDs") can also be used. PMTs and APDs are typically used for temporally sequential scanning of array features, while CCDs permit scanning many features in parallel (for example, one line of features simultaneously, in which case an illuminating line may be used). [0009] When a sample component only weakly binds to an array feature (due to a low concentration of that component in the sample) the resulting fluorescence signal from that feature will be low. To be able to detect such low signal features, it is important to detect the resulting low signal with a high signal to noise ratio. It is also desirable to have a reading method where a liquid filled chamber containing the array is not positioned within the scanner. SUMMARY OF THE INVENTION [0010] The present invention then, provides in one aspect a method of interrogating an addressable array unit having a transparent substrate with a back surface, and an array with a plurality of different chemical features on a front surface. The method includes illuminating the features while the array is dry, with an interrogating light which is directed through the substrate from the back surface and onto the chemical features on the front surface. Light emitted from respective features in response to the interrogating light is detected, which detected light has passed from the front surface, through the substrate and out the back surface. The detected emitted light is emitted from locations of the features which are spaced from the front surface a distance of less than one-eighth of the wavelength of the illuminating light (and optionally less than one-twentieth, less than one-fourtieth, or less than one-fiftieth of the wavelength of the illuminating light). The foregoing wavelengths are measured in a gas (such as air or nitrogen), or a vacuum, whichever one is in contact with the dry array during reading. For example, for many illuminating light peak emissions (such as about 530 nm or 630 nm) and different emitted light peak emissions (such as 550 nm to 610 nm, or 650 nm to 730 nm), the light may be emitted from locations which are less than 50 nm, less than 20 nm, or even less than 10 nm from the front surface of the substrate. Optionally, a method of the present invention may include, prior to the illuminating and detecting, exposing the array to a sample in a liquid, then drying the array. In an alternative configuration, the detected emitted light may be from locations which are spaced from the front surface by any of the foregoing fraction of the detected emitted light wavelength rather than the interrogating light wavelength (or the locations may satisfy the spacing requirements based on any of the foregoing fractions of both the interrogating and detected emitted light wavelengths). [0011] In another aspect of the present invention, a dry array on a substrate may be illuminated and emitted light detected, both as described above. In this aspect though, the detected emitted light is emitted from locations of the features which are spaced from the front surface a distance such that the average detected signal from the dry array is at least 10% (or at least 20%, 40%, 60%, 80%, or at least 100%) greater than would be detected under the same conditions except with the interrogating light and detected emitted light not passing through the substrate. By "same conditions" in this context includes the same array/substrate and same instrument (and therefore with the same interrogating light illumination and emitted light detection, as well as the same depth of field for the detected emitted light, and with the focal plane adjusted to the same position relative to the front surface of the substrate). [0012] In a method of the present invention, the interrogating light may be directed toward the back surface at an angle of less than 45 degrees to a normal to the back surface (such as less than 25, 15, or less than 5 degrees), and more than 0, 1, 2 or 4 degrees. The same ranges may be used for the detected light leaving the back surface. [0013] Another aspect of the present invention provides a package having an addressable array unit having a transparent substrate with a back surface, and an array with a plurality of different chemical features on a front surface, which chemical features may have a thickness (measured when the array is dry) of less than 100 nm (or any other thickness mentioned herein.). Since the array may not have been exposed to a sample at this point (for example, to a sample containing many fluorescently labeled polynucleotides of different sequence which hybridize to respective polynucleotide array features), this thickness may only provide an indication of the distance by which the light emitting features will be spaced from the front surface of the substrate during reading of the dry array. The package further includes instructions to interrogate the array by a method of the present invention. For example, an identifier carried on the array substrate, or a housing carrying the substrate, may provide such instructions. [0014] The present invention further provides a method for use with an addressable array unit having a transparent substrate with a back surface, and an array with a plurality of different chemical features on a front surface. The method includes reading (such as machine reading) an identifier associated with the array unit (such as by being present on the substrate carrying the array, a housing carrying the substrate, or in or on a same package with the array substrate). An instruction that the array should be interrogated and read through the substrate from the back surface, is retrieved (such as by a processor) based on the read identifier. The instruction may be retrieved from the read identifier itself, or from a memory using data from the read identifier (for example, the whole or part of the retrieved identifier). The retrieved instruction may be used to check that the array is properly oriented within an array reader such that the array can be interrogated and read by the reader through the substrate from the back surface. [0015] Another aspect of the present invention provides an apparatus for reading an array which illuminates the array and detects light emitted in response thereto, through the substrate in a manner as already described. The apparatus includes a light source to provide the interrogating light, and a detector to receive the emitted light. A processor receives the data from the detector and may save the results (either further processed or raw) in a memory. The processor may also execute any other method of the present invention, such as retrieving the instruction based on the read identifier, and checking that the array is properly oriented such as based on signals received from the detector or another means (for example, based on whether an indicia, such as the identifier or other indicia, is facing in the correct direction corresponding to proper orientation of the array in the apparatus. The present invention further provides a computer program product for use with such a chemical array reader apparatus. The computer program product comprises a computer readable storage medium having a computer program stored thereon which, when loaded into the processor, causes the reader to execute a method as describe herein. [0016] While the methods and apparatus have been described in connection with arrays of various moieties, such as polynucleotides or DNA, it will be understood throughout this description that other moieties can be used and may include any chemical moieties such as other biopolymers or polymers. [0017] The present invention can provide any one or more of the following or other benefits. For example, a good signal to noise ratio can be obtained while not requiring fluid filled chambers to be mounted in an array reader. BRIEF DESCRIPTION OF THE DRAWINGS [0018] Embodiments of the invention will now be described with reference to the drawings, in which: [0019] FIG. 1 is a perspective view of an array package including a substrate carrying a typical array, as may be used in the present invention; [0020] FIG. 2 is an enlarged view of a portion of FIG. 1 showing some of the identifiable individual features of a single array of FIG. 1; Continue reading about Reading dry chemical arrays through the substrate... Full patent description for Reading dry chemical arrays through the substrate Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Reading dry chemical arrays through the substrate patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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