Leica Biosystems Imaging, Inc.

Leica Biosystmes Imaging, Inc.

Yunlu Zou

Allen Olson

Peyman Najmabadi

Greg J Crandall

Gregory J Crandall

Leng-Chun Chen

Nicholas Newberg

Kiran Saligrama

Aaron Alan Stearrett

Ruby Chen

Bharat Annaldas

Andrew Garvey

Philip Nguyen

An input device allows a user to manipulate an image displayed by a user interface (UI) of a computer. The input device includes a housing, a first rotatable control knob supported by the housing, and a second rotatable control knob supported by the housing. The first and second rotatable control knobs allow the user to perform at least zooming and panning manipulations of the image on the UI. The input device can further include a third rotatable control knob and a touch pad. The input device can be configured as a keyboard.

Input device with rotatable control knobs

Input device

A slide scanning device comprises a plurality of line sensors (), each comprising a plurality of pixel sensors. Each line sensor is offset from an adjacent line sensor by a fraction of a length of each pixel sensor, and generates a line image of the same field of view at its respective offset. For each of a plurality of positions on a sample, a processor combines the line images of the same field of view, generated by the plurality of line sensors at their respective offsets, to produce a plurality of subpixels for each of at least a subset of pixels within the line images of the same field of view, and generates an up-sampled line image of the position comprising the plurality of subpixels. Then, the processor combines the up-sampled line images of each of the plurality of positions on the sample into an image.

Subpixel line scanning

Physical calibration slide comprising a plurality of etched features. The etched features may comprise two or more of a slanted Ronchi ruling feature comprising at least one set of parallel lines that are slanted with respect to a long and short axis of the slide, a straight Ronchi ruling feature comprising at least one set of parallel lines that are parallel to either the long or short axis, a star target feature comprising a circle with a plurality of wedge pairs, a crosshair feature comprising at least one crosshair, a clear area, a letter-O feature comprising a circle, a resolution target feature comprising one or more resolution targets, a bullseye feature comprising a two-dimensional array of bullseyes, a triangle feature comprising at least one isosceles triangle, or a symmetric corers feature comprising two symmetric sets of geometric shapes arranged in an L-shape.

Physical calibration slide

Real-time autofocus. In an embodiment, a scanning apparatus includes an imaging sensor, a focusing sensor, an objective lens, and processor(s) configured to analyze image data captured by the imaging and focusing sensors, and move the objective lens. Real-time autofocus during scanning of a sample is achieved by determining a true-Z value for the objective lens for a point on a sample and for each of a plurality of regions on the sample. The true-Z values and/or surfaces calculated therefrom are used to determine a predicted-Z value for an unscanned region of the sample. The objective lens is adjusted to the predicted-Z value at the beginning of the unscanned region. After scanning the region, a true-Z value is determined for the region and compared to the predicted-Z value. A rescan of the region is initiated if the comparison exceeds a predetermined threshold.

Real-time autofocus scanning

Systems and methods for capturing a digital image of a slide using an imaging line sensor and a focusing line sensor. In an embodiment, a beam-splitter is optically coupled to an objective lens and configured to receive one or more images of a portion of a sample through the objective lens. The beam-splitter simultaneously provides a first portion of the one or more images to the focusing sensor and a second portion of the one or more images to the imaging sensor. A processor controls the stage and/or objective lens such that each portion of the one or more images is received by the focusing sensor prior to it being received by the imaging sensor. In this manner, a focus of the objective lens can be controlled using data received from the focusing sensor prior to capturing an image of a portion of the sample using the imaging sensor.

Real-time focusing in line scan imaging

Real-time focusing in a slide-scanning system. In an embodiment, focus points are added to an initialized focus map while acquiring a plurality of image stripes of a sample on a glass slide. For each image stripe, a plurality of frames, collectively representing the image stripe, may be acquired using both an imaging line-scan camera and a tilted focusing line-scan camera. Focus points, representing positions of best focus for trusted frames, are added to the focus map. Outlying focus points are removed from the focus map. In some cases, one or more image stripes may be reacquired. Finally, the image stripes are assembled into a composite image of the sample.

Real-time focusing in a slide-scanning system

A digital scanning apparatus is provided that includes imaging and focusing sensors and a processor to analyze the image data captured by the imaging and focusing sensors and adjust the focus of the scanning apparatus in real time during a scanning operation. The individual pixels of the imaging sensor are all in the same image plane with respect to the optical path of the digital scanning apparatus. The individual pixels of the focusing sensor are each in a different image plane with respect to the optical path, and one pixel of the focusing sensor is on the same image plane as the image sensor. The processor analyzes image data from the imaging sensor and the focusing sensor and determines a distance and direction to adjust the relative position of an objective lens and a stage of the digital scanning apparatus to achieve optimal focus during the scanning operation.

Real-time autofocus focusing algorithm

System for acquiring a digital image of a sample on a microscope slide. In an embodiment, the system comprises a stage configured to support a sample, an objective lens having a single optical axis that is orthogonal to the stage, an imaging sensor, and a focusing sensor. The system further comprises at least one beam splitter optically coupled to the objective lens and configured to receive a field of view corresponding to the optical axis of the objective lens, and simultaneously provide at least a first portion of the field of view to the imaging sensor and at least a second portion of the field of view to the focusing sensor. The focusing sensor may simultaneously acquire image(s) at a plurality of different focal distances and/or simultaneously acquire a pair of mirrored images, each comprising pixels acquired at a plurality of different focal distances.

A digital pathology imaging apparatus includes a single line scan camera sensor optically coupled with first and second optical paths. In a first embodiment, transmission mode illumination and oblique mode illumination are simultaneously used during a single stage movement that captures a low resolution macro image of the entire sample area and the entire label area of the slide via the first optical path. In a second embodiment, transmission mode illumination is used during a first stage movement that captures a low resolution macro image of at least the entire sample area via the first optical path and oblique mode illumination is used during a second stage movement that captures a low resolution macro image of at least the entire label area via the first optical path.

Low resolution slide imaging and slide label imaging and high resolution slide imaging using dual optical paths and a single imaging sensor

Two-pass capture of a macro image. In an embodiment, a scanning apparatus comprises a stage, a high-resolution camera, and a lens that provides a field of view, substantially equal in width to a slide width, to the high-resolution camera. The apparatus also comprises a first illumination system for transmission-mode illumination, and a second illumination system for reflection-mode illumination. Processor(s) move the stage in a first direction to capture a first macro image of a specimen during a single pass while the field of view is illuminated by the first illumination system, and move the stage in a second direction to capture a second macro image of the specimen during a single pass while the field of view is illuminated by the second illumination system. The processor(s) identify artifacts in the second macro image, and, based on those artifacts, correct the first macro image to generate a modified first macro image.

Two pass macro image

Apparatus and methods for scanning a 2D or 3D image of a specimen without relative Z-axis motion between the specimen and the objective lens. In an embodiment, the apparatus includes a tilted camera having individual lines of pixels. Each line of pixels can be separately processed and is at a different image plane with respect to the stage. The depth of field of each line of pixels abuts, slightly overlaps, or is slightly spaced apart from the adjacent lines of pixels in the tilted camera. The angle of the tilt determines the relationship (abut, overlapping, or spaced) of the adjacent lines of pixels. The individual image lines produced by each line of pixels can be combined into a 3D volume image of a sample. Also, the highest-contrast line at each X-Y location can be combined into an in-focus 2D image of the sample.

Growing community of inventors

San Diego, CA, United States of America

Yunlu Zou