Abstract: 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.

Abstract: Array units and methods are provided which have constructions to reduce or take advantage of Fresnel reflection. The array units may have a subtantially unreflective substrate. In one arrangement a transparent spacer layer is provided while in another an anti-reflective layer is present.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: An optical scanner system scheme is described that enables better detection limits to be reached at the highest resolution of a fluorescent imager. In a scanner that has asymmetric scan qualities, measurement errors are eliminated by a factor that is greater than expected for simply handling random errors through additional sampling. Systematic asymmetries in scan direction are factored out by averaging pixel results obtained from opposite direction scans of the same line and binning them together at the same resolution.

Abstract: 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. In the subject methods, a scanner is employed in which the interrogating light and detector gain are modulated in a manner sufficient to maintain constant scale factor in the scanner despite reductions in laser power resulting from laser degradation.

Abstract: Apparatus and method for scanning a surface. An optical system generates a light beam to illuminate a surface. A carrier supports the surface for reciprocating motion with respect to the light beam to form one axis of a raster. A propulsion system moves the carrier at a substantially constant speed and a position sensor provides an output signal representing the surface position with respect to the light beam. A control system responsive to the output signal modulates a sample period reciprocally to carrier speed to achieve substantially constant scan length per sample and to control data acquisition timing.

Abstract: Array units and methods are provided which have constructions to reduce or take advantage of Fresnel reflection. The array units may have a subtantially unreflective substrate. In one arrangement a transparent spacer layer is provided while in another an anti-reflective layer is present.

Abstract: A method and system for calibrating molecular arrays to a reference molecular array, and for subsequently calibrating the molecular arrays to maintain a constant signal-intensity-to-label-concentration ratio. In the first step of the two-step calibration method, a reference array coated with the fluorophore or chromophore used to label probe molecules is employed, while in the second step of the two-step method, a reference array coated with a stable dye is employed.

Abstract: 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.

Abstract: 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.

Abstract: Apparatus and method for scanning a surface. An optical system generates a light beam to illuminate a surface. A carrier supports the surface for reciprocating motion with respect to the light beam to form one axis of a raster. A propulsion system moves the carrier at a substantially constant speed and a position sensor provides an output signal representing the surface position with respect to the light beam. A control system responsive to the output signal modulates a sample period reciprocally to carrier speed to achieve substantially constant scan length per sample and to control data acquisition timing.

Abstract: The system includes a confocal optical system to illuminate an object at an intended detection plane and to focus light from the object onto a pinhole. An opaque obstacle is disposed within the confocal optical system, the obstacle selected to suppress light originating outside the intended detection plane from passing through the pinhole. It is preferred that the obstacle size and location be selected to achieve a desired level of suppression. A design goal is a 100-fold reduction in background with a 10% or less loss of signal.