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: 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: 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: Optical scanner system approaches are described in which novel focusing approaches are provided. A control algorithm accounts for geometric variation of successive scans in opposite directions across a microarray slide or substrate in order to provide optimized focus. The feedback approach taught may involve PI or PID terms. In either type of control approach, a projected slope of the slide is calculated and followed back and forth outside a scan region of the array in exiting and entering fully adaptive focusing zones, respectively. During turn-around, the system may track a setpoint between the periods of following the extrapolated slope. Also provided are methods of using the subject system in a biopolymer array based application, including genomic and proteomic applications.

Abstract: A method and system for preventing signal clipping in a molecular array scanner by adding an offset signal to the signal generated by the photodetectors and initial stages of signal processing within a molecular array scanner in order to promote the signal above the level where signal information is lost during analog-to-digital signal conversion and/or digital signal integration. A portion of the offset is then subtracted from the digital signal or integrated digital signals, leaving a smaller, constant offset that is reported to the user, stored in a data file, or otherwise made available for further correction during later molecular array data processing.

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: 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: 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: Optical scanner system approaches are described in which novel focusing approaches are provided. A control algorithm accounts for geometric variation of successive scans in opposite directions across a microarray slide or substrate in order to provide optimized focus. The feedback approach taught may involve PI or PID terms. In either type of control approach, a projected slope of the slide is calculated and followed back and forth outside a scan region of the array in exiting and entering fully adaptive focusing zones, respectively. During turn-around, the system may track a setpoint between the periods of following the extrapolated slope. Also provided are methods of using the subject system in a biopolymer array based application, including genomic and proteomic applications.

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: 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: A method and system for preventing signal clipping in a molecular array scanner by adding an offset signal to the signal generated by the photodetectors and initial stages of signal processing within a molecular array scanner in order to promote the signal above the level where signal information is lost during analog-to-digital signal conversion and/or digital signal integration. A portion of the offset is then subtracted from the digital signal or integrated digital signals, leaving a smaller, constant offset that is reported to the user, stored in a data file, or otherwise made available for further correction during later molecular array data processing.

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: 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: System for large dynamic range light detection. In one aspect, the system includes a hybrid counting/integrating system for processing a signal from a photomultiplier tube. In another aspect, large dynamic range is achieved in a cascaded detector system utilizing at least one asymmetric beam splitter for delivering a larger fraction of incident light to one photomultiplier tube and for delivering a smaller fraction of the incident light to another photomultiplier tube.

Abstract: A laser generates a collimated laser beam which passes through a lens off-axis. The beam is focused at a focal plane on a substrate surface. A first position sensitive detector receives the laser beam reflected from the substrate surface through the lens to generate a first signal proportional to lateral beam offset. A beam splitter may be provided to direct a portion of the laser beam before passing through the lens toward a second position sensitive detector to generate a second signal proportional to laser beam pointing instability. Apparatus computes the difference between the first and second signals, the difference being a defocused error signal. It is preferred that the first position sensitive detector be located at a distance from the lens that is at least twice the lens focal length.