Agilent Technologies, Inc.

Hewlett-packard Company

Carl Zeiss Jena Gmbh

Andreas N Dorsel

Kenneth Lawrence Staton

John W Sadler

Nicholas Michael Sampas

John Frederick Corson

Kyle J Schleifer

Debra A Sillman

Bo U Curry

Glenda Choate Delenstarr

Herbert F Cattell

George Tsai

Arthur Schleifer

Steven M Lefkowitz

Frank Diedrich

Elecia White

Karl-Heinz Donnerhacke

Beate Moeller

Charles Ladd

David A King

Gary B Gordon

Mark Andrew Troll

Jayati Ghosh

Mel N Kronick

Charles Z Hotz

Russell Alan Parker

Scott D Connell

Jeffrey M McMillan

J Robert Mitchell

Andre B Chow

Cassandra Dey

Guenter Maschke

A method, apparatus for executing the method, and computer program products for use in such an apparatus. The method includes scanning an interrogating light across multiple sites on an array package including an addressable array of multiple features of different moieties, which scanned sites include multiple array features. Signals from respective scanned sites emitted in response to the interrogating light are detected. The interrogating light power is altered for a first site on the array package during the array scan, based on location of the first site or on a determination that the emitted signal from the first site will be outside a predetermined value absent the altering (which allows for protecting a detector against expected overly bright sites), or is altered during the array scan based on the detected interrogating light power (which allows for compensating for light source drift during an array scan).

Interrogating multi-featured arrays

Array scanning methods that focus on the far side and devices configured for use in the same are provided. In reading arrays according to the subject methods, an array is placed in a reading position of a scanning device so that the nominal focal plane of the scanning device is present within the array substrate at a predetermined fixed substrate thickness fraction distance from the far-side of the array, and the array is then read by the device. As such, the subject scanner devices of the present invention are configured to hold an array substrate in a reading position of the device in which the device's nominal focal plane is present within the array substrate. The subject methods and devices find use in a variety of different applications, including both genomic and proteomic applications.

Biopolymeric array scanning devices that focus on the far side of an array and methods for using the same

Methods for correcting systematic errors in the measured position of deposited features of a nucleic acid array on a substrate. Systematic errors are modeled by an algorithmic model based on measuring the positions (and possibly other properties) of a subset of the features, and a model is constructed for predicting deviations in feature position from an ideal grid. Deviations arising in the deposition process, the scanning process, or both may be corrected.

Method of extracting locations of nucleic acid array features

A method, apparatus, and computer program product for reading fluorescence signals from an array of chemical moieties (such as different sequence peptides or polynucleotides, for example different DNA sequences). In the method the spatial sequence of scanned locations need not be the same as the temporal sequence. For example, a later illuminated line may be spatially closer to an earlier illuminated line than is a temporally intervening illuminated line.

Reading multi-featured arrays

A method and apparatus of interrogating an addressable array unit, which includes a substrate, a light reflecting layer on a front side of the substrate, and a plurality of features on a front side of the array. The method may include, for each of multiple features, illuminating the feature simultaneously with reflected and non-reflected interrogating light. A light emitted from respective features is detected. Either or both, constructive interference of interrogating light at the features, or constructive interference of light emitted from the features, can be obtained to allow lowering of light power from the source, enhanced signal, or reduced noise, or combinations of the foregoing. High depth discrimination may also be obtained without the need for a confocal detection system with conventional pinhole.

Apparatus for interrogating an addressable array

An optical scanning system adapted to physically adjust scanner settings in response to control feature readings is disclosed. The scanner and methodology finds particular use in reading of biopolymer arrays. The system may operate in any of a number of ways such that optimal data from scans is obtained. It may also be possible to use the system as a tool to aid in manufacture of arrays by providing feedback to a manufacturer regarding the signal produce for a given batch of samples tested.

Array scanner control system

Automated methods and systems for determining an in-focus-distance for a position on the surface of a molecular array substrate using a molecular array scanner are provided. A signal from a first position of an array substrate is detected and noise is filtered out of the detected signal using a symmetrical filter to produce an in-focus-distance. In one embodiment, the in-focus-distance is utilized as an estimated in-focus-distance at a second position of the array substrate. The method finds use in maintaining the focus of a light source while scanning the array by the scanner. Also provided are methods of assaying a sample using the methods and systems of the invention, and kits for performing the invention. The subject invention finds use in a variety of different applications, including both genomics and proteomics applications.

Method for improved focus control in molecular array scanning by using a symmetrical filter to determine in-focus-distance

A maximum sensitivity optical scanning system is disclosed. It finds use in a variety of applications, including the reading of biopolymeric arrays. It operates by scanning sample at a setting selected to result in signal saturation for some, but not all available data. Subsequent scans of the same area are taken at lower sensitivity settings (in terms of detector gain and/or excitation light source gain or attenuation) and data from at least the previously saturated regions is obtained. If system sensitivity is set too low to produce useful results, optional features may adjust sensitivity upward and follow with an increased sensitivity scan as a remedial measure. Full signal sensitivity is better preserved as most needed in taking data for the weakest signals first with the high-level scan. Data for sample producing stronger signals that can better tolerate photobleaching is then taken in one way or another.

Maximum sensitivity optical scanning system

A method of interrogating an addressable array having a plurality of different chemical features. The method may include simultaneously illuminating different regions of the array with light of different intensities (which, for example, can, but need not be, also of a same waveband). Light emitted from the different regions in response to the illuminating (which light, for example, can, but need not be, of a same waveband) may be simultaneously detected with different detectors. An apparatus, addressable array unit, and related methods are further provided.

Simultaneously reading different regions of a chemical array

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 may include 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. The light emitted from respective features in response to the interrogating light may be detected, which detected light has passed from the front surface, through the substrate and out the back surface. In one arrangement the 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 in a gas or a vacuum which is in contact with the dry array. Other methods and a package containing an addressable array are also provided.

Reading dry chemical arrays through the substrate

Optical scanner system approaches are described in which signal saturation data is produced in real-time. The data generated may be used for tuning a subsequent scan, in protection of optical detector components from damage or otherwise. Approaches for obtaining and storing or expressing the data are also disclosed. Also provided are methods of using the subject system is biopolymer array based application, including genomic and proteomic applications.

Biopolymer array scanner with real-time saturation detection

A method and system for employing pixel-based, signal-intensity data contained within areas of a scanned image of a molecular array corresponding to features and feature backgrounds in order to determine whether or not the features or feature backgrounds have non-uniform signal intensities and are thus outlier features and outlier feature backgrounds. A calculated, estimated variance for the signal intensities within a feature or feature background is compared to a maximum allowable variance calculated for the feature or feature background based on a signal intensity variance model. When the experimental variance is less than or equal to the maximum allowable variance, the feature or feature background is considered to have acceptable signal-intensity uniformity. Otherwise, the feature or feature background is flagged as an outlier feature or outlier feature background.

Method and system for automated outlying feature and outlying feature background detection during processing of data scanned from a molecular array

A self-calibrating scanning system and method are used in the analysis of biomolecules on a microarray. The self-calibrating scanning system comprises an excitation light source, an optical portion, a detection portion and a calibration portion that includes a calibration apparatus and compensation portion. The calibration apparatus comprises a light source having a highly reproducible or calibrated light based on a preselected or reference light level. The calibration apparatus emits the calibrated light that is measured by the detection portion of the scanning equipment. If the detection components are stable, the components will measure a constant output value for the calibrated light over time. As a detection component changes with time, the output value will change for the same calibrated light. The method comprises the steps of initially calibrating the detection portion of the scanning system and subsequently calibrating the detection portion to compensate for sensitivity changes.

Scanning system with calibrated detection and method

High quantum efficiency point detector system. The system includes a light source generating a light beam having an area and includes a CCD detector with a cell size comparable to the light beam area. The CCD cell may include a single pixel or at least two pixels.

Growing community of inventors

Menlo Park, CA, United States of America

Andreas N Dorsel