Other

Genetic Microsystems, Inc.

Affymetrix, Inc.

Xrl, Inc.

James W Overbeck

Jean I Montagu

Peter D Honkanen

Myles L Mace

Roger F Steinert

Peter Flowers

Peter T Flowers

A laser system for treating an eye having a cornea, the laser system including a laser beam source capable of generating a laser beam, an eye position detector which includes at least a corneal tracker, the corneal tracker being responsive to movement of an anterior portion of the cornea, the corneal tracker constructed to detect movement of the cornea based on a set of spaced apart optical manifestations from the outer surface of the anterior portion of the cornea, and a beam controller, the beam controller being responsive to the eye position detector to direct the laser beam with controlled energy from the laser beam source to a desired location on the eye.

Laser system for vision correction

A wide field of view scanning microscope includes a light source, a light detector, optics, a scanning assembly, a translation system, and a data collection control and processing unit. The scanning assembly is constructed to provide from the light source a light beam in a scanning motion to an examined surface. The optics includes an objective lens associated with the scanning assembly arranged to provide an optical path to the light detector. The translation system is constructed to produce a movement of the examined surface. The data collection control and processing unit is arranged to collect data during the scanning motion and process the collected data.

Wide field of view and high speed scanning microscopy

Microscopes, including viewing and other microscopic systems, employ a hinged, tiltable plate to adjust focus on a flat object such as a microscope slide or biochip by motion, achieved by tilting, which is substantially normal to the focus point on the plane of the object. By employing two such tiltable arrangements, relatively long scan lines of e.g., flying objective, single pixel on-axis scanning can be accommodated. The tilting support plate is specifically constructed to provide tailored locations for different objects in series along the Y axis of the plate. The plate can accommodate beaters and cooled plates and/or the flat object being examined. In a fluorescence scanning microscope, locations are specifically adapted to receive microscope slides and biochip cartridges such as Affymetrix's 'Gene Chip&#xae;'. A scanning microscope under computer control, employing such a focusing action, enables unattended scanning of biochips with a simple and economical instrument. Also shown are flexure-mounting of a support plate to define the hinge axis, techniques for automatically determining position and focus, and a rotatably oscillating flying micro-objective scanner combined with the tilting plane focus system. Construction and control techniques are shown that realize simple and accurate focusing. Methods of examination of biological materials are disclosed. Simple and efficient focused scanning with a flying micro-objective of ordered arrays of nucleotides and nucleic acid fragments carried upon a microscope slide or other substrate is disclosed. Quantified fluorescence imaging is economically achieved by combined use of the described scanning and focusing arrangement and use of simple and accurate calibration modules respectively for example for Affymetrix's 'Gene Chip' microarray modules and for microscope slides.

Focusing of microscopes and reading of microarrays

High speed, wide area microscopic scanning or laser positioning is accomplished with an inertia-less deflector (for example an acousto-optic or electro-optic deflector) combined with a high speed wide area microscopic scanning mechanism or laser positioner mechanism that has inertia, the motion of the inertia-less deflector specially controlled to enable a focused spot to stabilize, for example to stop and dwell or be quickly aimed. It leads to improved data acquisition from extremely small objects and higher speed operation. In the case of fluorescence reading of micro-array elements, dwelling of fluorophore-exciting radiation in a spot that is relatively large enables obtaining the most fluorescent photons per array element, per unit time, a winning criterion for reducing fluorophore saturation effects. The same inertia-less deflector performs stop and dwell scanning, edge detection and raster scans. Automated mechanism for changing laser spot size enables selection of spot size optimal for the action being performed.

Scanning microscopy, fluorescence detection, and laser beam positioning

For depositing fluid dots in an array, e.g., for microscopic analysis, a deposit device, e.g. a pin, cooperating with a fluid source defines a precisely sized drop of fluid of small diameter on a drop carrying surface. Transport mechanism positions the device precisely over the receiving surface and drive mechanism moves the deposit device toward and away from the surface. By repeated action, minute drops of fluid can be deposited precisely in a dense array, preferably under computer control. The drop-carrying surface shown has a diameter less than 375, preferably less than 300, preferably between about 15 and 250 micron, and is bound by a sharp rim that defines the perimeter of the fluid drop. The deposit device is compliant in the direction of deposition motion, e.g. by overcoming resistance of a resilient member. When depositing, the deposit device is laterally constrained to a reference position, e.g. by flexure mounting or the deposit device is mounted to displace from its mounting upon engagement with the receiving surface, and is subject to a lateral force or turning moment that engages the device with a lateral reference surface. A mobile-fluid storage device resupplies the deposit device along the array, e.g. in the immediate vicinity of the deposit locations. Mobile annular storage rings are lowered and raised to obtain a supply of fluid, or a mobile multiwell plate is used. Cleaning mechanism, sampling plans, and array products on microscope slides and fragile or soft membranes are disclosed as are many types of fluid and uses, e.g., in biotechnology, analysis and process control.

Depositing fluid specimens on substrates, resulting ordered arrays, techniques for analysis of deposited arrays

Limited rotation, micro-lens scanning of DNA arrays, microscope slides, biological materials, etc., is performed by arcuate and translational motion. A scanning system includes an objective lens located on a low moment of inertia oscillating arm, which provides optical coupling to a light source or a light detector arranged for transmission, reflection, or fluorescence microscopy.

Depositing fluid specimens on substrates, resulting ordered arrays, techniques for deposition of arrays

Wide angle, limited rotation, on-axis scanning with a micro objective lens, which is preferably aspheric, and is mounted on a rigid rotary structure that oscillates about a limited arc while a translation system translates the object under the arcuate scan. The micro objective lens communicates optically with a stationary optical system via a light path which, in part, extends along the axis of rotation of the rigid rotary structure. The rotary micro objective lens is shown to cooperate with stationary optics. Predetermined defocusing of some wavelengths relative to others in opposite sense to chromatic aberration of a micro objective lens enable focus by the micro objective lens of multiple wavelengths on the same point. Data collection in a rotary, on-axis scanner is controlled by detecting the actual position of the rotating structure, which may move at constant speed during data collection. Interpolation of arcuate scan data to a raster pattern is achieved by data sampling at positions that correspond with rectilinear rows of the raster pattern and averaging the sampled data points of a row that straddle a raster point. This results in fast, economical interpolation. Novel microscope processes use features provided by the instruments described.

Wide angle, limited rotation, on-axis scanning with a micro lens that preferably is aspheric. Predetermined defocusing of some wavelengths relative to others in opposite sense to chromatic aberration of a micro lens, enable focus by the micro lens of multiple wavelengths on the same point. Data collection in a rotary, on-axis scanner is controlled by detecting the actual position of the rotating structure. Scan efficiency of an on-axis limited rotation lens is improved by coordinated deflection of the light path to different portions of the lens. A flexure-mounted dither mirror effectively makes this correction. Interpolation of arcuate scan data to a raster pattern is achieved by timing the data sampling to correspond with rows of the raster pattern; averaging the straddling data points in the column results in fast, economical interpolation. High speed, limited rotation scanning microscopes operating in transmission and reflectance modes are described, as well as very efficient fluorescence readers. Novel microscope processes use features provided by the instruments described.

By adding an acousto-optic deflector to an existing design of laser marker the laser marker's throughput is increased by a large factor, typically a factor of 5. Galvanometer driven mirrors, which in existing laser markers are used to trace out the strokes in characters are, in this invention, used only to scan smoothly along lines of characters. The acousto-optic deflector, being much faster than the galvanometers, is used to trace out the individual strokes in the characters. Marking rates of 1000 characters per second are achieved in the case of characters for which capital letters are 2 millimeters high and a 2 millimeter long stroke contains 13 laser-produced craters. This performance is achieved over fields as large as 300 millimeters square. The quality of marked characters is improved because the deleterious effects of mirror inertia on character quality, commonly seen when a laser marker is pushed for speed, are eliminated.

Faster laser marker employing acousto-optic deflection

An apparatus for accurately positioning a laser beam on a semiconductor surface, for example for repairing an integrated circuit, has a translational beam positioning apparatus and a galvanometer based beam positioning apparatus. The translational beam positioning apparatus has first and second platform members, the second platform member moving relative to the first platform member and supporting the galvanometer system. The galvanometer beam positioning system thus moves with the second platform member to cover the surface of an integrated circuit on which 'repair' is to be performed. The second platform member further supports an optical system positioned relative to the galvanometer beam positioning system so that a small and uniform spot size can be achieved, at high speed, using small galvanometer mirrors. Thereby, the galvanometer beam positioning system provides high speed movement of a laser beam over a relatively small area and the translational system provides broad, highly accurate, but slower movement of the entire system across the entire integrated circuit. A method for calibrating the galvanometer system employs apparatus for measuring the exact position of the translational system. A comparison of feature measurements using both the translational system and the galvanometer system enables accurate and reliable calibration of the galvanometer system.

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Hingham, MA, United States of America

James W Overbeck