Automatic tilt compensation in a digital scanning system

Abstract

It is possible to digitize a sample using a scanning in a manner which automatically accounts for tilt which may otherwise result in some or all of a digitized image being out of focus. This may be done by obtaining a plurality of segments of image data and combining the plurality of segments of image data into a contiguous digital image of the sample. In this type of scenario, obtaining the plurality of segments of image data may comprise capturing one or more segments using an initial segment width, detecting tilted image data and, based on detecting the tilted image data, determining a narrower segment width and capturing one or more segments using the narrower segment width.

Description

AUTOMATIC TILT COMPENSATION IN A DIGITAL SCANNING SYSTEMCROSS REFERENCE TO RELATED APPLICATIONS[1] This is an international application of, and claims the benefit of, provisional application 63 / 540,802, filed in the United States Patent Office on September 27, 2023 for “Automatic Tilt Compensation in a Digital Scanning System,” the disclosure of which is hereby incorporated by reference in its entirety.BACKGROUND[2] Field[3] The embodiments described herein are generally directed to control of a slide-scanning system, and, more particularly, to automatic tilt compensation in a slide-scanning system.[4] Related Art[5] Digital pathology is an image-based information environment, which is enabled by computer technology that allows for the management of information generated from a physical slide. Digital pathology is enabled in part by virtual microscopy, which is the practice of scanning a specimen on a physical glass slide, and creating a digital slide image that can be stored, viewed, managed, and analyzed on a computer monitor. With the capability of imaging an entire glass slide, the field of digital pathology has exploded, and is currently regarded as one of the most promising avenues of diagnostic medicine in order to achieve even better, faster, and cheaper diagnosis, prognosis, and prediction of important diseases, such as cancer.[6] A primary objective for the digital pathology industry is to provide properly focused images. This may be complicated by tilt, such as tilt in a slide on which a sample is disposed (e.g., as a result of excessive mounting medium under the slide) and / or in the tissue on the slide (e.g., as a result of poor tissue preparation), and excessive tilt may cause portions of a digital image to be out of focus. Accordingly, there is a need for improved technology for accounting for tilt when generating digital images using a slide scanning system.SUMMARY[7] Systems, methods, and non-transitory computer-readable media are disclosed for automatically compensating for tilt when generating a digital image of a sample using a scanning apparatus. This may be done by obtaining a plurality of segments of image data (e.g., stripes such as may be captured by a line scanning camera) and combining the plurality of segments of image data into a contiguous digital image of the sample. In this type of scenario, obtaining the plurality of segments of image data may comprise capturing one or more segments using an initial segment width, detecting tilted image data and, based on detecting the tilted image data, determining a narrower segment width and capturing one or more segments using the narrower segment width.BRIEF DESCRIPTION OF THE DRAWINGS[8] The details of aspects of the disclosed technology, both as to its structure and operation, may be gleaned in part by study of the accompanying drawings, in which like reference numerals refer to like parts, and in which:[9] FIG. 1 A illustrates an example processor-enabled device that may be used in connection with the various embodiments described herein, according to an embodiment;

[0010] FIG. IB illustrates an example line-scan camera having a single linear array, according to an embodiment;

[0011] FIG. 1C illustrates an example line-scan camera having three linear arrays, according to an embodiment;

[0012] FIG. ID illustrates an example line-scan camera having a plurality of linear arrays, according to an embodiment;

[0013] FIG. IE illustrates an example side view configuration of line-scan cameras in a scanning system, according to an embodiment;

[0014] FIG. IF illustrates an example top view configuration of an imaging sensor with respect to an imaging optical path, according to an embodiment;

[0015] FIG. 1G illustrates an example top view configuration of a focusing sensor, with respect to a focusing optical path, according to an embodiment;

[0016] FIG. 1H illustrates an example focusing sensor, according to an embodiment;

[0017] FIG. 2A illustrates an overhead view of an image segment such as may be generated when creating a digital sample image;

[0018] FIG. 2B illustrates a front view of an image segment such as may be generated when creating a digital sample image;

[0019] FIG. 3 provides a high level view of a process which can be used for tilt correction in a slide scanning system;

[0020] FIG. 4 illustrates a front view of an image segment having a portion extending out of a depth of field of an imaging system;

[0021] FIG. 5 A illustrates a result of a width used for capturing image segments being reduced by half;

[0022] FIG. 5B illustrates a potential result of calculating a distance which, given the relevant tilt, would result in edges of an image segment being within the depth of view; and

[0023] FIG. 6 illustrates a process in which tilt is identified and addressed before segments collectively depicting an entire sample have been collected.DETAILED DESCRIPTION

[0024] Disclosed herein is technology which can be used to automatically compensate for tilt during digital slide scanning. After reading this description, it will become apparent to one skilled in the art how to implement the invention in various alternative embodiments and alternative applications. However, although various embodiments of the present invention will be described herein, it is understood that these embodiments are presented by way of example and illustration only, and not limitation. As such, this detailed description of various embodiments should not be construed to limit the scope or breadth of the present invention as set forth in the appended claims.

[0025] 1. Example Scanning System

[0026] FIG. 1A is a block diagram illustrating an example processor-enabled slide-scanning system 100 that may be used in connection with various embodiments described herein. Alternative forms of scanning system 100 may also be used as will be understood by the skilled artisan. In the illustrated embodiment, scanning system 100 is presented as a digital imagingdevice that comprises one or more processors 104, one or more memories 106, one or more motion controllers 108, one or more interface systems 110, one or more movable stages 112 that each support one or more glass slides 114 with one or more samples 116, one or more illumination systems 118 that illuminate sample 116, an imaging system 101 that comprises imaging optics 103 such as one or more objective lenses 120 that each define an optical path 122 that travels along an optical axis, one or more objective lens positioners 124, one or more optional epi-illumination systems 126 (e.g., included in a fluorescence-scanning embodiment), one or more focusing optics 128, and one or more line-scan cameras 130, and / or one or more area-scan cameras 132, each of which define a separate field of view 134 on sample 116 and / or glass slide 114. The various elements of scanning system 100 are communicatively coupled via one or more communication busses 102. Although there may be a plurality of each of the various elements of scanning system 100, for simplicity in the description that follows, these elements will be described in the singular, except when needed to be described in the plural to convey the appropriate information.

[0027] Processor 104 may include, for example, a central processing unit (CPU) and a separate graphics processing unit (GPU) capable of processing instructions in parallel, or a multicore processor capable of processing instructions in parallel. Additional separate processors may also be provided to control particular components or perform particular functions, such as image processing. For example, additional processors may include an auxiliary processor to manage data input, an auxiliary processor to perform floating-point mathematical operations, a special-purpose processor having an architecture suitable for fast execution of signal-processing algorithms (e.g., digital-signal processor), a slave processor subordinate to the main processor (e.g., back-end processor), an additional processor for controlling line-scan camera 130, stage 112, objective lens 120, and / or a display (e.g., a console comprising a touch panel display integral to scanning system 100). Such additional processors may be separate discrete processors or may be integrated into a single processor.

[0028] Memory 106 provides storage of data and instructions for programs that can be executed by processor 104. Memory 106 may include one or more volatile and / or non-volatile computer-readable storage mediums that store the data and instructions. These mediums may include, for example, random-access memory (RAM), read-only memory (ROM), a hard disk drive, a removable storage drive (e.g., comprising flash memory), and / or the like. Processor 104is configured to execute instructions that are stored in memory 106, and communicate via communication bus 102 with the various elements of scanning system 100 to carry out the overall function of scanning system 100.

[0029] Communication bus 102 may be configured to convey analog electrical signals and / or digital data. Accordingly, communications from processor 104, motion controller 108, and / or interface system 110, via communication bus 102, may include both electrical signals and digital data. Processor 104, motion controller 108, and / or interface system 110 may also be configured to communicate with one or more of the various elements of scanning system 100 via a wireless communication link.

[0030] Motion control system 108 is configured to precisely control and coordinate X, Y, and / or Z movement of stage 112 (e.g., within an X-Y plane), X, Y, and / or Z movement of objective lens 120 (e.g., along a Z axis orthogonal to the X-Y plane, via objective lens positioner 124), rotational movement of a carousel described elsewhere herein, lateral movement of a push / pull assembly described elsewhere herein, and / or any other moving component of scanning system 100. For example, in a fluorescence-scanning embodiment comprising epi-illumination system 126, motion control system 108 may be configured to coordinate movement of optical filters and / or the like in epi-illumination system 126.

[0031] Interface system 110 allows scanning system 100 to interface with other systems and human operators. For example, interface system 110 may include a console (e.g., a touch panel display) to provide information directly to an operator via a graphical user interface and / or allow direct input from an operator via a touch sensor. Interface system 110 may also be configured to facilitate communication and data transfer between scanning system 100 and one or more external devices that are directly connected to scanning system 100 (e.g., a printer, removable storage medium, etc.), and / or one or more external devices that are indirectly connected to scanning system 100, for example, via one or more networks (e.g., an image storage system, a Scanner Administration Manager (SAM) server and / or other administrative server, an operator station, a user station, etc.).

[0032] Illumination system 118 is configured to illuminate at least a portion of sample 116.Illumination system 118 may include, for example, one or more light sources and illumination optics. The light source(s) could comprise a variable intensity halogen light source with a concavereflective mirror to maximize light output and a KG-1 filter to suppress heat. The light source(s) could comprise any type of arc-lamp, laser, or other source of light. In an embodiment, illumination system 118 illuminates sample 116 in transmission mode, such that line-scan camera 130 and / or area-scan camera 132 sense optical energy that is transmitted through sample 116. Alternatively or additionally, illumination system 118 may be configured to illuminate sample 116 in reflection mode, such that line-scan camera 130 and / or area-scan camera 132 sense optical energy that is reflected from sample 116. Illumination system 118 may be configured to be suitable for interrogation of sample 116 in any known mode of optical microscopy.

[0033] In an embodiment, scanning system 100 includes an epi-illumination system 126 to optimize scanning system 100 for fluorescence scanning. It should be understood that, if fluorescence scanning is not supported by scanning system 100, epi-illumination system 126 may be omitted. Fluorescence scanning is the scanning of samples 116 that include fluorescence molecules, which are photon-sensitive molecules that can absorb light at a specific wavelength (i.e., excitation). These photon-sensitive molecules also emit light at a higher wavelength (i.e., emission). Because the efficiency of this photoluminescence phenomenon is very low, the amount of emitted light is often very low. This low amount of emitted light typically frustrates conventional techniques for scanning and digitizing sample 116 (e.g., transmission-mode microscopy).

[0034] Advantageously, in an embodiment of scanning system 100 that utilizes fluorescence scanning, use of a line-scan camera 130 that includes multiple linear sensor arrays (e.g., a timedelay-integration (TDI) line-scan camera) increases the sensitivity to light of line-scan camera 130 by exposing the same area of sample 116 to each of the plurality of linear sensor arrays of linescan camera 130. This is particularly useful when scanning faint fluorescence samples with low levels of emitted light. Accordingly, in a fluorescence-scanning embodiment, line-scan camera 130 is preferably a monochrome TDI line-scan camera. Monochrome images are ideal in fluorescence microscopy because they provide a more accurate representation of the actual signals from the various channels present on sample 116. As will be understood by those skilled in the art, a fluorescence sample can be labeled with multiple florescence dyes that emit light at different wavelengths, which are also referred to as “channels.”

[0035] Furthermore, because the low-end and high-end signal levels of various fluorescence samples present a wide spectrum of wavelengths for line-scan camera 130 to sense, it is desirable for the low-end and high-end signal levels that line-scan camera 130 can sense to be similarly wide. Accordingly, in a fluorescence-scanning embodiment, line-scan camera 130 may comprise a monochrome 10-bit 64-linear-array TDI line-scan camera. It should be noted that a variety of bit depths for line-scan camera 130 can be employed for use with such an embodiment.

[0036] Movable stage 112 is configured for precise X-Y movement under control of processor 104 or motion controller 108. Movable stage 112 may also be configured for Z movement under control of processor 104 or motion controller 108. Movable stage 112 is configured to position sample 116 in a desired location during image data capture by line-scan camera 130 and / or areascan camera 132. Movable stage 112 is also configured to accelerate sample 116 in a scanning direction to a substantially constant velocity, and then maintain the substantially constant velocity during image data capture by line-scan camera 130. In an embodiment, scanning system 100 may employ a high-precision and tightly coordinated X-Y grid to aid in the location of sample 116 on movable stage 112. In an embodiment, movable stage 112 is a linear-motor-based X-Y stage with high-precision encoders employed on both the X and the Y axes. For example, very precise nanometer encoders can be used on the axis in the scanning direction and on the axis that is in the direction perpendicular to the scanning direction and on the same plane as the scanning direction. Stage 112 is also configured to support glass slide 114 upon which sample 116 is disposed.

[0037] Sample 116 can be anything that may be interrogated by optical microscopy. For example, glass microscope slide 114 is frequently used as a viewing substrate for specimens that include tissues and cells, chromosomes, deoxyribonucleic acid (DNA), protein, blood, bone marrow, urine, bacteria, beads, biopsy materials, or any other type of biological material or substance that is either dead or alive, stained or unstained, labeled or unlabeled. Sample 116 may also be an array of any type of DNA or DNA-related material, such as complementary DNA (cDNA) or ribonucleic acid (RNA), or protein that is deposited on any type of slide or other substrate, including any and all samples commonly known as microarrays. Sample 116 may be a microtiter plate (e.g., a 96-well plate). Other examples of sample 116 include integrated circuit boards, electrophoresis records, petri dishes, film, semiconductor materials, forensic materials, and machined parts.

[0038] Objective lens 120 is mounted on objective positioner 124, which, in an embodiment, employs a very precise linear motor to move objective lens 120 along the optical axis defined by objective lens 120. For example, the linear motor of objective lens positioner 124 may include a fifty-nanometer encoder. The relative positions of stage 112 and objective lens 120 in X, Y, and / or Z axes are coordinated and controlled in a closed-loop manner using motion controller 108 under the control of processor 104 that employs memory 106 for storing information and instructions, including the computer-executable programmed steps for overall operation of scanning system 100.

[0039] In an embodiment, objective lens 120 is a plan apochromatic (“APO”) infinity- corrected objective lens which is suitable for transmission-mode illumination microscopy, reflection-mode illumination microscopy, and / or epi-illumination-mode fluorescence microscopy (e.g., an Olympus 40X, 0.75NA or 20X, 0.75 NA). Advantageously, objective lens 120 is capable of correcting for chromatic and spherical aberrations. Because objective lens 120 is infinity- corrected, focusing optics 128 can be placed in optical path 122 above objective lens 120 where the light beam passing through objective lens 120 becomes a collimated light beam. Focusing optics 128 focus the optical signal captured by objective lens 120 onto the light-responsive elements of line-scan camera 130 and / or area-scan camera 132, and may include optical components such as filters, magnification changer lenses, and / or the like. Objective lens 120, combined with focusing optics 128, provides the total magnification for scanning system 100. In an embodiment, focusing optics 128 may contain a tube lens and an optional 2X magnification changer. Advantageously, the 2X magnification changer allows a native 20X objective lens 120 to scan sample 116 at 40X magnification.

[0040] Line-scan camera 130 comprises at least one linear array of picture elements 142 (“pixels”). Line-scan camera 130 may be monochrome or color. Color line-scan cameras typically have at least three linear arrays, while monochrome line-scan cameras may have a single linear array or plural linear arrays. Any type of singular or plural linear array, whether packaged as part of a camera or custom-integrated into an imaging electronic module, can also be used. For example, a three linear array (“red-green-blue” or “RGB”) color line-scan camera or a ninety-six linear array monochrome TDI may also be used. TDI line-scan cameras typically provide a substantially better signal-to-noise ratio (“SNR”) in the output signal by summing intensity datafrom previously imaged regions of a specimen, yielding an increase in the SNR that is in proportion to the square-root of the number of integration stages. TDI line-scan cameras comprise multiple linear arrays. For example, TDI line-scan cameras are available with 24, 32, 48, 64, 96, or even more linear arrays. Scanning system 100 also supports linear arrays that are manufactured in a variety of formats including some with 512 pixels, some with 1,024 pixels, and others having as many as 4,096 pixels. Similarly, linear arrays with a variety of pixel sizes can also be used in scanning system 100. The salient requirement for the selection of any type of line-scan camera 130 is that the motion of stage 112 can be synchronized with the line rate of line-scan camera 130, so that stage 112 can be in motion with respect to line-scan camera 130 during the digital image capture of sample 116.

[0041] In an embodiment, the image data generated by line-scan camera 130 is stored in a portion of memory 106 and processed by processor 104 to generate a contiguous digital image of at least a portion of sample 116. The contiguous digital image can be further processed by processor 104, and the processed contiguous digital image can also be stored in memory 106.

[0042] In an embodiment with two or more line-scan cameras 130, at least one of the line-scan cameras 130 can be configured to function as a focusing sensor that operates in combination with at least one of the other line-scan cameras 130 that is configured to function as an imaging sensor 130A. The focusing sensor can be logically positioned on the same optical axis as the imaging sensor 130A or the focusing sensor may be logically positioned before or after the imaging sensor BOA with respect to the scanning direction of scanning system 100. In such an embodiment with at least one line-scan camera 130 functioning as a focusing sensor, the image data generated by the focusing sensor may be stored in a portion of memory 106 and processed by processor 104 to generate focus information, to allow scanning system 100 to adjust the relative distance between sample 116 and objective lens 120 to maintain focus on sample 116 during scanning. Additionally, in an embodiment, the at least one line-scan camera 130 functioning as a focusing sensor may be oriented such that each of a plurality of individual pixels 142 of the focusing sensor is positioned at a different logical height along the optical path 122.

[0043] In operation, the various components of scanning system 100 and the programmed modules stored in memory 106 enable automatic scanning and digitizing of sample 116, which is disposed on glass slide 114. Glass slide 114 is securely placed on movable stage 112 of scanningsystem 100 for scanning sample 1 16. Under control of processor 104, movable stage 1 12 accelerates sample 116 to a substantially constant velocity for sensing by line-scan camera 130, where the speed of stage 112 is synchronized with the line rate of line-scan camera 130. After scanning a segment of image data, movable stage 112 decelerates and brings sample 116 to a substantially complete stop. Movable stage 112 then moves orthogonal to the scanning direction to position sample 116 for scanning of a subsequent segment of image data (e.g., an adjacent segment). Additional segments are subsequently scanned until an entire portion of sample 116 or the entire sample 116 is scanned.

[0044] For example, during digital scanning of sample 116, a contiguous digital image of sample 116 is acquired as a plurality of contiguous fields of view that are combined together to form an image segment. Such image segments may be as shown in the overhead view of FIG. 2A and the front view of FIG. 2B. As shown in those figures, each segment may be considered as having a center line 201 which is parallel to the scanning direction, and first and second edges 202 203 which are also parallel to the scanning direction and are separated from each other along an axis which is perpendicular to the scanning direction as well as to the optical axis 204 of the imaging system by the width of the image segment. It should be noted that, while the first and second edges 202203 of a segment may be seen as simply parallel edges in an overhead view such as shown in FIG. 2A, when viewed from a front perspective, those edges may be seen as displaced relative to the optical axis 204 of the imaging system. In a figure such as shown in FIG. 2B, this displacement would be equal to the width of the segment multiplied by the tilt of the segment (e.g., as could be determined using an image map and / or contrast ratios from the real time focusing technology described in U.S. published patent application 2022 / 0159171, filed June 16, 2021 for Real-Time Focusing in a Slide-Scanning System, the disclosure of which is hereby incorporated by reference in its entirety). Thus, any arbitrary point on the first edge 202 (illustrated in FIG. 2 A as a first point 205) and any arbitrary point on the second edge 203 (illustrated in FIG. 2A as a second point 206) can be said to be separated from each other by a distance along the optical axis of the imaging system. Preferably, this separation will be less than or equal to the depth of field of the imaging system, though, if it is not, some embodiments may be configured to modify the width of the image segment to ensure that the tilt multiplied by the (narrowed) width was within the depth of field (e.g., using a method such as illustrated in FIG. 3, discussed below).

[0045] Just as a plurality of adjacent fields of view may be combined to form a single contiguous image segment, a plurality of adjacent image segments may be similarly combined together to form a contiguous digital image of a portion or the entire sample 116. The scanning of sample 116 may include acquiring vertical image segments or horizontal image segments. The scanning of sample 116 may be either top-to-bottom, bottom-to-top, or both (i.e., bi-directional), and may start at any point on sample 116. Alternatively, the scanning of sample 116 may be either left-to-right, right-to-left, or both (i.e., bi-directional), and may start at any point on sample 116. It is not necessary that image segments be acquired in an adjacent or contiguous manner. Furthermore, the resulting image of sample 116 may be an image of the entire sample 116 or only a portion of the sample 116.

[0046] In an embodiment, computer-executable instructions (e.g., programmed modules and software) are stored in memory 106 and, when executed, enable scanning system 100 to perform the various functions (e.g., display the graphical user interface, execute the disclosed processes, control the components of scanning system 100, etc.) described herein. In this description, the term “computer-readable storage medium” is used to refer to any media used to store and provide computer-executable instructions to scanning system 100 for execution by processor 104. Examples of these media include memory 106 and any removable or external storage medium (not shown) communicatively coupled with scanning system 100 either directly (e.g., via a universal serial bus (USB), a wireless communication protocol, etc.) or indirectly (e.g., via a wired and / or wireless network).

[0047] FIG. IB illustrates a line-scan camera 130 having a single linear array 140, which may be implemented as a charge-coupled device (“CCD”) or complimentary metal-oxide semiconductor (“CMOS”) array. Single linear array 140 comprises a plurality of individual pixels 142. In the illustrated embodiment, the single linear array 140 has 4,096 pixels 142. In alternative embodiments, linear array 140 may have more or fewer pixels. For example, common formats of linear arrays include 512, 1,024, and 4,096 pixels. Pixels 142 are arranged in a linear fashion to define a field of view 134 for linear array 140. The size of field of view 134 varies in accordance with the magnification of scanning system 100.

[0048] FIG. 1C illustrates a line-scan camera 130 having three linear arrays 140, each of which may be implemented as a CCD array. The three linear arrays 140 combine to form a color array150. In an embodiment, each individual linear array in color array 150 detects a different color intensity, including, for example, red, green, or blue. The color image data from each individual linear array 140 in color array 150 is combined to form a single field of view 134 of color image data.

[0049] FIG. ID illustrates a line-scan camera 130 having a plurality of linear arrays 140, each of which may be implemented as a CCD array. The plurality of linear arrays 140 combine to form a TDI array 160. Advantageously, a TDI line-scan camera may provide a substantially better SNR in its output signal by summing intensity data from previously imaged regions of a specimen, yielding an increase in the SNR that is in proportion to the square-root of the number of linear arrays 140 (also referred to as integration stages). A TDI line-scan camera may comprise a larger variety of numbers of linear arrays 140. For example, common formats of TDI line-scan cameras include 24, 32, 48, 64, 96, 120, and even more linear arrays 140.

[0050] FIG. IE illustrates an example side view configuration of line-scan cameras 130 in scanning system 100, according to an embodiment. In the illustrated embodiment, scanning system 100 comprises a glass slide 114, with a tissue sample 116 that is placed on motorized stage 112, illuminated by illumination system 118, and moved in a scanning direction 170. Objective lens 120 has an optical field of view 134 that is trained on slide 114 and provides an optical path 122 for light from illumination system 118 that passes through sample 116 on slide 114, reflects off of sample 116 on slide 114, fluoresces from sample 116 on slide 114, or otherwise passes through objective lens 120. The light travels on optical path 122 to a beam splitter 174 that allows some of the light to pass through lens 176 to main imaging sensor 130A. The light may optionally be bent by a mirror 178 as shown in the illustrated embodiment. Imaging sensor I30A may be, for example, a line charge-coupled device (CCD).

[0051] Other light travels from beam splitter 174 through lens 180 to a focusing sensor DOB. Focusing sensor BOB may also be, for example, a line CCD. The light that travels to imaging sensor BOA and focusing sensor BOB preferably represents the complete optical field of view 134 from objective lens 120. Based on this configuration of scanning system 100, scanning direction 170 of slide 114 is logically oriented with respect to imaging sensor BOA and focusing sensor BOB, such that the logical scanning direction 172 causes optical field of view 134 of objective lens 120 to pass over the respective imaging sensor BOA and focusing sensor BOB.

[0052] FIG. IF illustrates an example top view of the configuration of imaging sensor 130A with respect to an imaging optical path 122A, according to an embodiment. Similarly, FIG. 1G illustrates an example top view of the configuration of focusing sensor 130B, with respect to a focusing optical path 122B, according to an embodiment. As can be seen in FIG. 1G, focusing sensor 13 OB is tilted at an angle 0 with respect to a direction that is perpendicular to focusing optical path 122B.

[0053] FIG. 1H illustrates an example focusing sensor 13 OB, according to an embodiment. In the illustrated embodiment, within a range of focusing (d) (e.g., 20pm) on a tissue sample, focusing sensor BOB comprises a plurality of sensor pixels 142 and may be positioned at a location where the entire focusing range (d) in the Z axis is transferred by optics to the entire focusing sensor BOB array in the Y axis (orthogonal to the X axis, i.e., scan direction 170), as shown. The location of each sensor pixel 142 is directly correlated to a Z position of objective lens 120. As illustrated in FIG. 1H, each dashed line (i.e., pi, p2,...pi,...pn) across projected focusing range (d) represents a different focus value and corresponds to a focus height (i.e., Z height) of objective lens 120. The pi having the optimal focus (e.g., highest contrast metric) for a given portion of sample 116 can be used by scanning system 100 to determine the optimal focus height for that portion of sample 116.

[0054] The relationship between the projected focusing range (d) on focusing sensor BOB and the focusing range (z) on sample 116 is as follows: d—Z * Mfocusing^, wherein Mfocusing is the optical magnification of the focusing path. For instance, if z = 20pm and Mfocusing= 20, then d = 8mm.

[0055] In order to cover the entire projected focusing range (d) by a tilted focusing sensor BOB that comprises a linear array 140, the tilting angle 0 should follow the relationship: sin0=d / L, wherein L is the length of linear array 140 of focusing sensor BOB. Using d = 8mm and L = 20.48mm, 0 = 23.0°. 0 and L can vary as long as tilted focusing sensor BOB covers the entire focusing range (d).

[0056] The focusing resolution, or the minimum step of objective height motion Az, is a function of the size of sensor pixel 142, e=minimum(AL). Derived from the above formulas:Az=e*z / L.For instance, if e=10p.m, L=20.48mm, and z=20pm, then Az=0.0097|j.m<10nm.

[0057] The relationship between the objective height Zi and the focus location Li on focusing sensor 130B of focus point z is:Li = Zi * Mfocusing2 / sin0

[0058] If the focus height is determined by a mean from Li to L2, according to analysis of the data from focusing sensor BOB, the height of objective lens 120 needs to be moved from Zi to Z2 based on:Z2 = Z i + (L2-L1) * sinO / Mfocusing2

[0059] Although the field of view (FOV) 134 in the Y axis of focusing sensor BOB and imaging sensor BOA can be different, the centers of both sensors BOA and BOB are preferably aligned to each other along the Y axis.

[0060] 2. Tilt Correction Process Overview

[0061] Embodiments of processes for addressing errors caused by tilt during slide-scanning are described below in detail. It should be understood that the described processes may be embodied in one or more software modules that are executed by one or more hardware processors 104 within scanning system 100. The described processes may be implemented as instructions represented in source code, object code, and / or machine code. These instructions may be executed directly by the hardware processor(s), or alternatively, may be executed by a virtual machine operating between the object code and the hardware processors.

[0062] Alternatively, the described processes may be implemented as a hardware component (e.g., general-purpose processor, integrated circuit (IC), application-specific integrated circuit (ASIC), digital signal processor (DSP), field-programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, etc.), combination of hardware components, or combination of hardware and software components. To clearly illustrate the interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps are described herein generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. Skilled persons can implement the described functionality in varying ways for each particular application, but such implementation decisionsshould not be interpreted as causing a departure from the scope of the invention. In addition, the grouping of functions within a component, block, module, circuit, or step is for ease of description. Specific functions or steps can be moved from one component, block, module, circuit, or step to another without departing from the invention.

[0063] Furthermore, while the processes, described herein, are illustrated with a certain arrangement and ordering of steps, each process may be implemented with fewer, more, or different steps and a different arrangement and / or ordering of steps. In addition, it should be understood that any step, which does not depend on the completion of another step, may be executed before, after, or in parallel with that other independent step, even if the steps are described or illustrated in a particular order.

[0064] As a concrete illustration, FIG. 3 provides a high level view of a process which can be used for tilt correction in a slide scanning system. Initially in that process scanner such as shown in FIG. 1 could obtain 301 a plurality of segments of image data. This could include capturing 302 one or more segments of image data using an initial segment width. This may be done, for example, by capturing segments of a sample on a slide using the real time or macro focus scanning approaches described in U.S. published patent application 2022 / 0159171, filed June 16, 2021 for Real-Time Focusing in a Slide-Scanning System, the disclosure of which is hereby incorporated by reference in its entirety. After one or more segments have been captured 302 using the initial segment width, tilted image data may be detected 303 in the captured segment(s). This may be done, by checking if any of the segments had a tilt greater than a fixed tilt threshold. For instance, a threshold of + / - 2 pm / mm may be used as a threshold on a scanner having an initial segment width of 1 mm, meaning that if an image segment with a tilt greater than 2 pm / mm could be treated as tilted image data.

[0065] Of course, other approaches are also possible, and could be implemented by those of ordinary skill in the art in light of this disclosure. For example, in some cases, tilted image data may be detected based on comparing detected tilt with a configurable tilt threshold specified by a user using an administrative interface. As another example, in some cases, a calculation (e.g., multiplying tilt by segment width and comparing the result of that multiplication with the depth of field) may be performed to detect 304 if points on opposite edges of a segment of image data (e.g., the segment having the greatest tilt) were separated from each other along the optical axis of thescanner’s imaging system by a distance which is greater than the imaging system’s depth of field. An illustration of this situation is shown in FIG. 4, which provides a front view of a segment with a tilt great enough to raise a potion 401 of the slide outside of the imaging system’s field of view. Accordingly, the description of using a threshold should be understood as being illustrative only, and should not be treated as limiting.

[0066] However it takes place, after the tilted image data is detected, the method of FIG. 3 continues with determining 305 a segment width which is narrower than the initial segment width, and which can be used for capturing one or more additional segments of image data. As with the detection 303 of tilted image data, this determination 305 can be performed in a variety of manners. For example, in some cases, determining 305 the narrower segment width may be performed by simply reducing 306 the segment width by half. Alternatively, in some cases, determining 305 the narrower segment width may comprise calculating 307 a distance between the first and second edge along the segment’s width which, if the width were set to that distance, would result in the first and second edge being separated by no more than the imaging system’s depth of field (e.g., by dividing the tilt by the depth of field). When this type of calculation is performed, the width may be set at a value less than or equal to the calculated value, thereby ensuring that the segment could be rescanned in a manner that would keep all of its image data in focus while avoiding slowing down the rescanning process through unnecessarily increasing the number of segments which would have to be rescanned. Examples of results of both of these approaches to determining 305 a narrower segment width are provided in FIGS. 5A and 5B, with FIG. 5A depicting the result of the width being reduced 306 by half, and FIG. 5B showing a potential result of calculating 307 a distance which, given the tilt, would result in the first and second edges of segment having the reduced width both being within the depth of field.

[0067] After the narrower segment width has been determined 305, one or more segments of image data may be captured 308 using the determined 305 segment width which is narrower than the initial segment width - e.g., after capturing each segment, moving in a direction orthogonal to the scanning direction a distance equal to the narrower segment width before capturing the next segment. This may be done by first reducing 309 the field of view of the imaging system to match the determined segment width (e.g., by configuring the imaging camera for reading out only the center portion of the sensor array) and then capturing 308 segments in a manner similar to thatdescribed previously for initially capturing 302 one or more segments using the initial segment width. Alternatively, capturing 308 one or more segments using the narrower segment width may be performed by capturing 310 data across the initial segment width and then discarding 311 data which is more than half of the narrower segment width away from the center line of each segment. In either case, after all of the necessary segments had been captured, the segments could be combined 312 into a contiguous digital image of the sample. To illustrate how this may be done, consider a case in which a first set of segments covering the entire sample is captured 302 using the initial segment width, and then, after tilted image data is detected 303 in those segments, a second set of segments is captured 308 using a segment width which is narrower than the initial segment width. In this type of case, combining 312 the segments into a contiguous digital image may comprise discarding 313 the first set of segments, and then combining 314 the second set of segments into a contiguous digital image of the sample, thereby providing a complete contiguous digital image of the sample in which all portions of the image are in focus, even those portions at the boundaries of high tilt segments.

[0068] Other approaches to implementing a tilt correction method such as that shown in FIG. 3 are also possible, could be implemented without undue experimentation by those of skill in the art in light of this disclosure. For example, while it is possible that some embodiments may perform a process as shown in FIG. 3 by first capturing 302 segments covering the entire sample using the initial segment width, then detecting 303 tilted image data after that entire dataset was collected, it is also possible that detecting 303 the tilted image data may take place before image segments which collectively depict the entire sample have been captured. To illustrate, consider FIG. 6, which shows a process in which tilt is identified and addressed before segments collectively depicting the entire sample have been collected. In the process of FIG. 6, whether there is tilted image data can be checked after each segment with the initial segment width is captured 302, and as soon as tilted image was detected 303, the transition to capturing 308 segments using a narrower segment width could take place, starting with recapturing the data covered by the segment in which the tilted image data was detected 303.

[0069] Additionally, as shown in FIG. 6, in some implementations, there may be further changes made during the process of obtaining 301 the image data segments. For example, after a segment was captured 308 using the narrower segment width, a check may be made to determineif a tilt change was detected 601 in the captured data. This may be done, using calculations similar to those described for detecting 303 tilted image data and, if there was no tilt change, then the process could continue with capturing 602 segments at its then current width until either a tilt change was detected 601, or sufficient segments had been captured to form an image covering the sample. Alternatively, if a tilt change was detected 601, then a changed segment width could be determined 603. This may be done using calculations similar to those described previously for calculating 307 a distance for the width of the segment which would result in both edges being within the depth of view given the tilt. It should be noted though, that in some cases, this determination 603 may also include a determination of a new width which was wider than the width then being used, in order to reduce the total number of segments and therefore the time needed to scan the sample. For instance, in some cases, a system implemented to perform a method as shown in FIG. 6 may detect a tilt change 601 whenever there tilt had increased such that a portion of the segment was outside of the imaging system’s depth of field, or whenever the tilt had decreased such that the width could be increased to the point that it would reduce the total number of segments to fully image the sample without causing any portion of a segment to be outside the depth of field. In this case, if a tilt change was detected 601 due to a decrease in tilt, then the segment width could be changed to either the maximum field of view of the imaging system, or the maximum width which would result in the entire width of the segment being within the depth of field, whichever was less.

[0070] Whatever the changed segment width happened to be, after the change was determined 603, a segment could be captured with the changed segment width 604. Additionally, in some cases, data indicating the number of stipes which would be used in scanning the sample may be updated 605, for later use in combining 312 the segments into a contiguous digital image. The scanning process may continue in this manner until a tilt change was detected 601 (in which case the segment width may be further modified) or sufficient segments of image data had been captured to cover the entire sample, at which point the step of obtaining 301 the plurality of segments of image data could be treated as complete and the segments could be combined 312 into a contiguous digital image.

[0071] 3. Additional Non-Limiting Examples

[0072] The above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles described herein can be applied to other embodiments without departing from the spirit or scope of the invention. Thus, it is to be understood that the description and drawings presented herein represent a presently preferred embodiment of the invention and are therefore representative of the subject matter which is broadly contemplated by the present invention. It is further understood that the scope of the present invention fully encompasses other embodiments that may become obvious to those skilled in the art and that the scope of the present invention is accordingly not limited. Other variations are also possible, and will be immediately apparent to those of skill in the art in light of this disclosure. For instance, the following examples are provided as concrete (though non-limiting) illustrations of various approaches which could be taken when implementing the disclosed technology.

[0073] Example 1

[0074] A method for automatic digitization of a sample performed by a scanner through execution of instructions stored on a non-transitory computer readable medium, the method comprising: obtaining, using an imaging system, a plurality of segments of image data, wherein obtaining the plurality of segments of image data comprises: capturing one or more segments of image data using an initial segment width; detecting tilted image data, wherein the tilted image data is tilted relative to an optical axis of the imaging system; based on detecting the tilted image data: determining a segment width which is narrower than the initial segment width; and capturing one or more segments of image data using the segment width which is narrower than the initial segment width; and combining the plurality of segments of image data into an image of the sample; wherein: the imaging system has a depth of field and a field of view having a width along an axis orthogonal to a scanning direction; and* each segment of image data comprises a center line parallel to the scanning direction.

[0075] Example 2

[0076] The method of example 1, wherein: detecting the tilted image data comprises detecting a tilted segment of image data; the tilted segment of image data has a first edge and a second edge, each of which is parallel to the scanning direction; the tilted segment has a first point disposed onits first edge, and a second point disposed on its second edge; and the first point and the second point are separated from each other along the optical axis of the imaging system by a distance which is greater than the depth of field of the imaging system.

[0077] Example 3

[0078] The method of example 2, wherein determining the segment width which is narrower than the initial segment width comprises calculating a distance along the axis orthogonal to the scanning direction between first edge and the second edge for which, given the tilt, the first point and the second point are separated from each other along the optical axis of the imaging system by no more than the depth of field of the imaging system.

[0079] Example 4

[0080] The method of any of examples 1-2, wherein the segment width which is narrower than the initial segment width is half of the initial segment width.

[0081] Example s

[0082] The method of any of examples 1-4, wherein: obtaining the plurality of segments of image data comprises obtaining a first set of segments of image data, wherein: each segment from the first set of segments of image data has one or more adjacent segments of image data comprised by the first set of segments of image data; and the first set of segments of image data provides a first contiguous digital image of the sample in which, for each segment from the first set of segments, the center line of that segment is separated from the center line(s) of its adjacent segment(s) by the initial segment width; capturing the one or more segments of image data using the segment width which is narrower than the initial segment width comprises obtaining a second set of segments of image data, wherein: each segment from the second set of segments of image data has one or more adjacent segments of image data comprised by the second set of segments of image data; and a center line which runs parallel to the scanning direction and comprises a center of that segment; and the second set of segments of image data provides a second contiguous digital image of the sample in which, for each segment from the second set of segments, the center line of that segment is separated from the center line(s) of its adjacent segment(s) by the segment width which is narrower than the initial segment width; and combining the plurality of segments of image data into the contiguous digital image of the sample comprises: discarding the first set of segmentsof image data; and combining the second set of segments of image data into the second contiguous digital image of the sample.

[0083] Example 6

[0084] The method of any of examples 1-4, wherein capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises capturing a segment comprising at least part of the tilted image data using the segment width which is narrower than the initial segment width before image segments which collectively depict the entire sample have been captured; and the plurality of segments of image data collectively depict the entire sample.

[0085] Example 7

[0086] The method of example 6, wherein obtaining the plurality of segments of image data comprises: after capturing one or more segments of image data using the segment width which is narrower than the initial segment width, detecting a tilt change; based on detecting the tilt change, determining a changed segment width which is different from the segment width which is narrower than the initial segment width; and capturing one or more segments of image data using the changed segment width.

[0087] Example 8

[0088] The method of example 7, wherein the changed segment width is narrower than the segment width which is narrower than the initial segment width.

[0089] Example 9

[0090] The method of example 7, wherein the changed segment width is greater than the segment width which is narrower than the initial segment width.

[0091] Example 10

[0092] The method of example 9, wherein the changed segment width is equal to the initial segment width.

[0093] Example 11

[0094] The method of any of examples 6-10, wherein the method comprises, each time the segment width used in capturing the segments from the plurality strips changes, updating data indicating a number of segments used to collectively depict the entire sample.

[0095] Example 12

[0096] The method of any of examples 1-11, wherein: the method comprises, based on detecting the tilted image data, reducing the width of the field of view of the imaging system from the initial segment width to the segment width which is narrower than the initial segment width; and capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises capturing one or more segments using the imaging system after the width of the imaging system’s field of view has been reduced.

[0097] Example 13

[0098] The method of any of examples 1-11, wherein capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises, for each of the one or more segments of image data: capturing that segment of image data using the imaging system while the width of the imaging system’s field of view is equal to the initial segment width; and discarding image data comprised by that segment which is not within a distance equal to half of the segment width which is narrower than the initial segment width of that segment’s center line.

[0099] Example 14

[0100] An automatic scanner comprising: an imaging system having: a depth of field; a field of view having a width along an axis orthogonal to a scanning direction; and an optical axis which is orthogonal to the scanning direction and the axis orthogonal to the scanning direction; a stage which is moveable in a scanning direction; a processor; and a non-transitory computer readable medium having stored thereon instructions operable to, when executed, obtain an image of a sample disposed on a slide supported by the stage by performing a method comprising: obtaining a plurality of segments of image data, each of which has a center line parallel to the scanning direction, by performing acts comprising: capturing one or more segments of image data using the initial segment width; determining whether image data which is tilted relative to the optical axis of the imaging system exists in the captured one or more segments; and in the event that tilted image data exists in the captured one or more segments: determining a segment width which is narrower than the initial segment width; and capturing one or more segments of image data using the segment width which is narrower than the initial segment width; combining the plurality of segments of image data into the image of the sample.

[0101] Example 15

[0102] The scanner of example 14, wherein: detecting the tilted image data comprises detecting a tilted segment of image data; the tilted segment has a first edge and a second edge, each of which is parallel to the scanning direction; the tilted segment has a first point disposed on the first edge, and a second point disposed on the second edge; and the first point and the second point are separated from each other along the optical axis of the imaging system by a distance which is greater than the depth of field of the imaging system.

[0103] Example 16

[0104] The scanner of example 15, wherein determining the segment width which is narrower than the initial segment width comprises calculating a distance along the width of the tilted segment between the first edge and the second edge for which, given the tilt, the first point and the second point are separated from each other along the optical axis of the imaging system by the depth of field of the imaging system.

[0105] Example 17

[0106] The scanner of any of examples 14-15, wherein the segment width which is narrower than the initial segment width is half of the initial segment width

[0107] Example 18

[0108] The scanner of any of examples 14-17, wherein: obtaining the plurality of segments of image data comprises obtaining a first set of segments of image data, wherein: each segment from the first set of segments of image data has one or more adjacent segments of image data comprised by the first set of segments of image data; and the first set of segments of image data provides a first contiguous digital image of the sample in which, for each segment from the first set of segments, the center line of that segment is separated from the center line(s) of its adjacent segment(s) by the initial segment width; capturing the one or more segments of image data using the segment width which is narrower than the initial segment width comprises obtaining a second set of segments of image data, wherein: each segment from the second set of segments of image data has one or more adjacent segments of image data comprised by the second set of segments of image data; and a center line which runs parallel to the scanning direction and comprises a center of that segment; and the second set of segments of image data provides a second contiguous digital image of the sample in which, for each segment from the second set of segments, the center line of that segment is separated from the center line(s) of its adjacent segment(s) by the segment widthwhich is narrower than the initial segment width; and combining the plurality of segments of image data into the contiguous digital image of the sample comprises: discarding the first set of segments of image data; and combining the second set of segments of image data into the second contiguous digital image of the sample.

[0109] Example 19

[0110] The scanner of any of examples 14-17, wherein: capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises capturing a segment comprising at least part of the tilted image data using the segment width which is narrower than the initial segment width before image segments which collectively depict the entire sample have been captured; and the plurality of segments of image data collectively depict the entire sample.

[0111] Example 20

[0112] The scanner of example 19, wherein obtaining the plurality of segments of image data comprises: after capturing one or more segments of image data using the segment width which is narrower than the initial segment width, detecting if a tilt change is present in the one or more segments of image data captured using the segment width which is narrower than the initial segment width; in the event that the tilt change is present, determining a changed segment width; and capturing one or more segments of image data using the changed segment width.

[0113] Example 21

[0114] The scanner of example 20, wherein determining the changed segment width comprises: in the event the tilt change causes a distance along the imaging axis separating the first edge from the second edge of the most recently captured segment to exceed the depth of field of the imaging system, determining the changed segment width as a segment width which is narrower than that used when capturing a segment in which the tilt change was detected; and in the event the tilt change is a decrease in an absolute value of tilt in segment in which the tilt change was detected, determining the changed segment width as a segment width which is greater than that used when capturing the segment in which the tilt change was detected.

[0115] Example 22

[0116] The scanner of example 21, wherein determining the changed segment width as the segment width which is greater than that used when capturing the segment in which the tilt change was detected is defining the changed segment width as equal to the initial segment width.

[0117] Example 23

[0118] The scanner of any of examples 19-22, wherein the method comprises, each time the segment width used in capturing the segments from the plurality strips changes, updating data indicating a number of segments used to collectively depict the entire sample.

[0119] Example 24

[0120] The scanner of any of examples 14-23, wherein: the method comprises, in the event that tilted image data exists in the captured one or more segments, reducing the width of the field of view of the imaging system from the initial segment width to the segment width which is narrower than the initial segment width; and capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises capturing one or more segments using the imaging system after the width of the imaging system’s field of view has been reduced.

[0121] Example 25

[0122] The scanner of any of examples 14-23, wherein capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises, for each of the one or more segments of image data: capturing that segment of image data using the imaging system while the width of the imaging system’s field of view is equal to the initial segment width; and discarding image data comprised by that segment which is not within a distance equal to half of the segment width which is narrower than the initial segment width of that segment’s center line.

[0123] 4. Interpretation

[0124] None of the examples or illustrations set forth herein should be understood as implying limitations on the scope of any claims included in this document or any related document. Instead, the protection provided by this document or any related document, should be understood as being defined by the relevant document’s claims, when the terms in those claims which are explicitly defined herein are given their explicit definitions, and the terms which are not explicitly defined are given their broadest reasonable interpretation as provided by a general purpose dictionary.

[0125] Combinations, described herein, such as “at least one of A, B, or C,” “one or more ofA, B, or C,” “at least one of A, B, and C,” “one or more of A, B, and C,” and “A, B, C, or any combination thereof’ include any combination of A, B, and / or C, and may include multiples of A, multiples of B, or multiples of C. Specifically, combinations such as “at least one of A, B, or C,” “one or more of A, B, or C,” “at least one of A, B, and C,” “one or more of A, B, and C,” and “A,B, C, or any combination thereof’ may be A only, B only, C only, A and B, A and C, B and C, or A and B and C, and any such combination may contain one or more members of its constituents A, B, and / or C. For example, a combination of A and B may comprise one A and multiple B’s, multiple A’s and one B, or multiple A’s and multiple B’s.

[0126] A statement that something is “based on” something else should be understood as meaning that that thing is determined at least in part by that which it is “based on.” While the “based on” relationship includes scenarios in which one thing is completely determined by another, the “based on” relationship should not be understood as being limited to only scenarios in which one thing is completely determined by another unless the phrase used is “based exclusively on.”

Claims

CLAIMSWhat is claimed is:

1. A method for automatic digitization of a sample performed by a scanner through execution of instructions stored on a non-transitory computer readable medium, the method comprising:• obtaining, using an imaging system, a plurality of segments of image data, wherein obtaining the plurality of segments of image data comprises:° capturing one or more segments of image data using an initial segment width;° detecting tilted image data, wherein the tilted image data is tilted relative to an optical axis of the imaging system;° based on detecting the tilted image data:■ determining a segment width which is narrower than the initial segment width; and■ capturing one or more segments of image data using the segment width which is narrower than the initial segment width; and• combining the plurality of segments of image data into an image of the sample; wherein:• the imaging system has a depth of field and a field of view having a width along an axis orthogonal to a scanning direction; and• each segment of image data comprises a center line parallel to the scanning direction.

2. The method of claim 1, wherein: detecting the tilted image data comprises detecting a tilted segment of image data; the tilted segment of image data has a first edge and a second edge, each of which is parallel to the scanning direction;the tilted segment has a first point disposed on its first edge, and a second point disposed on its second edge; and the first point and the second point are separated from each other along the optical axis of the imaging system by a distance which is greater than the depth of field of the imaging system.

3. The method of claim 2, wherein determining the segment width which is narrower than the initial segment width comprises calculating a distance along the axis orthogonal to the scanning direction between first edge and the second edge for which, given the tilt, the first point and the second point are separated from each other along the optical axis of the imaging system by no more than the depth of field of the imaging system.

4. The method of any of claims 1-2, wherein the segment width which is narrower than the initial segment width is half of the initial segment width.

5. The method of any of claims 1-4, wherein:• obtaining the plurality of segments of image data comprises obtaining a first set of segments of image data, wherein:° each segment from the first set of segments of image data has one or more adjacent segments of image data comprised by the first set of segments of image data; and° the first set of segments of image data provides a first contiguous digital image of the sample in which, for each segment from the first set of segments, the center line of that segment is separated from the center line(s) of its adjacent segment(s) by the initial segment width;• capturing the one or more segments of image data using the segment width which is narrower than the initial segment width comprises obtaining a second set of segments of image data, wherein:° each segment from the second set of segments of image data has■ one or more adjacent segments of image data comprised by the second set of segments of image data; and■ a center line which runs parallel to the scanning direction and comprises a center of that segment; and° the second set of segments of image data provides a second contiguous digital image of the sample in which, for each segment from the second set of segments, the center line of that segment is separated from the center line(s) of its adjacent segment(s) by the segment width which is narrower than the initial segment width; and• combining the plurality of segments of image data into the contiguous digital image of the sample comprises:° discarding the first set of segments of image data; and° combining the second set of segments of image data into the second contiguous digital image of the sample.

6. The method of any of claims 1-4, wherein:• capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises capturing a segment comprising at least part of the tilted image data using the segment width which is narrower than the initial segment width before image segments which collectively depict the entire sample have been captured; and• the plurality of segments of image data collectively depict the entire sample.

7. The method of claim 6, wherein obtaining the plurality of segments of image data comprises:• after capturing one or more segments of image data using the segment width which is narrower than the initial segment width, detecting a tilt change;• based on detecting the tilt change, determining a changed segment width which is different from the segment width which is narrower than the initial segment width; and• capturing one or more segments of image data using the changed segment width.

8. The method of claim 7, wherein the changed segment width is narrower than the segment width which is narrower than the initial segment width.

9. The method of claim 7, wherein the changed segment width is greater than the segment width which is narrower than the initial segment width.

10. The method of claim 9, wherein the changed segment width is equal to the initial segment width.

11. The method of any of claims 6-10, wherein the method comprises, each time the segment width used in capturing the segments from the plurality strips changes, updating data indicating a number of segments used to collectively depict the entire sample.

12. The method of any of claims 1-11, wherein:• the method comprises, based on detecting the tilted image data, reducing the width of the field of view of the imaging system from the initial segment width to the segment width which is narrower than the initial segment width; and• capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises capturing one or more segments using the imaging system after the width of the imaging system’s field of view has been reduced.

13. The method of any of claims 1-11, wherein capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises, for each of the one or more segments of image data:• capturing that segment of image data using the imaging system while the width of the imaging system’s field of view is equal to the initial segment width; and• discarding image data comprised by that segment which is not within a distance equal to half of the segment width which is narrower than the initial segment width of that segment’s center line.

14. An automatic scanner comprising:• an imaging system having:° a depth of field;° a field of view having a width along an axis orthogonal to a scanning direction; and° an optical axis which is orthogonal to the scanning direction and the axis orthogonal to the scanning direction;• a stage which is moveable in a scanning direction;• a processor; and• a non-transitory computer readable medium having stored thereon instructions operable to, when executed, obtain an image of a sample disposed on a slide supported by the stage by performing a method comprising:° obtaining a plurality of segments of image data, each of which has a center line parallel to the scanning direction, by performing acts comprising:■ capturing one or more segments of image data using the initial segment width;■ determining whether image data which is tilted relative to the optical axis of the imaging system exists in the captured one or more segments; and■ in the event that tilted image data exists in the captured one or more segments:° determining a segment width which is narrower than the initial segment width; and° capturing one or more segments of image data using the segment width which is narrower than the initial segment width; o combining the plurality of segments of image data into the image of the sample.

15. The scanner of claim 14, wherein: detecting the tilted image data comprises detecting a tilted segment of image data; the tilted segment has a first edge and a second edge, each of which is parallel to the scanning direction; the tilted segment has a first point disposed on the first edge, and a second point disposed on the second edge; and the first point and the second point are separated from each other along the optical axis of the imaging system by a distance which is greater than the depth of field of the imaging system.

16. The scanner of claim 15, wherein determining the segment width which is narrower than the initial segment width comprises calculating a distance along the width of the tilted segment between the first edge and the second edge for which, given the tilt, the first point and the second point are separated from each other along the optical axis of the imaging system by the depth of field of the imaging system.

17. The scanner of any of claims 14-15, wherein the segment width which is narrower than the initial segment width is half of the initial segment width.

18. The scanner of any of examples 14-17, wherein:• obtaining the plurality of segments of image data comprises obtaining a first set of segments of image data, wherein:° each segment from the first set of segments of image data has one or more adjacent segments of image data comprised by the first set of segments of image data; and° the first set of segments of image data provides a first contiguous digital image of the sample in which, for each segment from the first set of segments, the center line of that segment is separated from the center line(s) of its adjacent segment(s) by the initial segment width;• capturing the one or more segments of image data using the segment width which is narrower than the initial segment width comprises obtaining a second set of segments of image data, wherein:° each segment from the second set of segments of image data has■ one or more adjacent segments of image data comprised by the second set of segments of image data; and■ a center line which runs parallel to the scanning direction and comprises a center of that segment; and° the second set of segments of image data provides a second contiguous digital image of the sample in which, for each segment from the second set of segments, the center line of that segment is separated from the center line(s) of its adjacent segment(s) by the segment width which is narrower than the initial segment width; and• combining the plurality of segments of image data into the contiguous digital image of the sample comprises:° discarding the first set of segments of image data; and° combining the second set of segments of image data into the second contiguous digital image of the sample.

19. The scanner of any of claims 14-17, wherein:• capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises capturing a segment comprising at least part of the tilted image data using the segment width which is narrower than the initial segment width before image segments which collectively depict the entire sample have been captured; and• the plurality of segments of image data collectively depict the entire sample.

20. The scanner of claim 19, wherein obtaining the plurality of segments of image data comprises:• after capturing one or more segments of image data using the segment width which is narrower than the initial segment width, detecting if a tilt change is present in the one or more segments of image data captured using the segment width which is narrower than the initial segment width;• in the event that the tilt change is present, determining a changed segment width; and• capturing one or more segments of image data using the changed segment width.

21. The scanner of claim 20, wherein determining the changed segment width comprises:• in the event the tilt change causes a distance along the imaging axis separating the first edge from the second edge of the most recently captured segment to exceed the depth of field of the imaging system, determining the changed segment width as a segment width which is narrower than that used when capturing a segment in which the tilt change was detected; and• in the event the tilt change is a decrease in an absolute value of tilt in segment in which the tilt change was detected, determining the changed segment width as a segment width which is greater than that used when capturing the segment in which the tilt change was detected.

22. The scanner of claim 21, wherein determining the changed segment width as the segment width which is greater than that used when capturing the segment in which the tilt change was detected is defining the changed segment width as equal to the initial segment width.

23. The scanner of any of claims 19-22, wherein the method comprises, each time the segment width used in capturing the segments from the plurality strips changes, updating data indicating a number of segments used to collectively depict the entire sample.

24. The scanner of any of claims 14-23, wherein:• the method comprises, in the event that tilted image data exists in the captured one or more segments, reducing the width of the field of view of the imaging system from the initial segment width to the segment width which is narrower than the initial segment width; and• capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises capturing one or more segments using the imaging system after the width of the imaging system’s field of view has been reduced.

25. The scanner of any of claims 14-23, wherein capturing one or more segments of image data using the segment width which is narrower than the initial segment width comprises, for each of the one or more segments of image data:• capturing that segment of image data using the imaging system while the width of the imaging system’s field of view is equal to the initial segment width; and• discarding image data comprised by that segment which is not within a distance equal to half of the segment width which is narrower than the initial segment width of that segment’s center line.

Images