Automatic tilt compensation in digital scanning systems

Abstract

The sample may be digitized using the scan in a manner that automatically takes into account a tilt that may cause a partial or full digitized image to be out of focus. This may be accomplished by acquiring a plurality of image data segments and combining the plurality of image data segments into a contiguous digital image of the sample. In such cases, acquiring a plurality of segments of image data may include capturing one or more segments using an initial segment width, detecting tilted image data, and based on detecting tilted image data, determining a narrower segment width, and capturing one or more segments using the narrower segment width.

Description

[0001] Cross-references to related applications

[0002] This application is an international application claiming priority to Provisional Application No. 63 / 540,802 (titled “Automatic Tilt Compensation in Digital Scanning Systems”), filed on September 27, 2023, with the United States Patent and Trademark Office, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] The embodiments described herein generally relate to the control of a slide scanning system, and more specifically to automatic tilt compensation in a slide scanning system. Background Technology

[0004] Digital pathology is an image-based information environment enabled by computer technology that allows for the management of information generated from physical glass slides. Digital pathology is partly enabled by virtual microscopy—the practice of scanning samples on physical glass slides and creating digital slide images that can be stored, viewed, managed, and analyzed on a computer monitor. Leveraging the ability to image entire glass slides, the field of digital pathology has been developed and is currently considered one of the most promising directions in diagnostic medicine, enabling better, faster, and more cost-effective diagnosis, prognosis, and prediction of important diseases such as cancer.

[0005] A primary goal of the digital pathology industry is to provide properly focused images. However, tilting (such as tilting of the slide on which the sample is placed (e.g., due to excessive sealing medium underneath the slide) and / or tilting of the tissue on the slide (e.g., due to improper tissue preparation)) can make this goal difficult to achieve, and excessive tilting can cause partial defocusing of digital images. Therefore, an improved technique is needed to account for tilt when generating digital images using slide scanning systems. Summary of the Invention

[0006] A system, method, and non-transitory computer-readable medium for automatically compensating for tilt when generating digital images of samples using a scanning device are disclosed. This can be achieved by acquiring multiple image data segments (e.g., strips captured by a line scan camera) and combining these multiple image data segments into a continuous digital image of the sample. In such cases, acquiring multiple image data segments may include: capturing one or more segments using an initial segment width, detecting tilted image data, and determining a narrower segment width based on the detected tilted image data, and capturing one or more segments using that narrower segment width. Attached Figure Description

[0007] Details of the disclosed technology, both its structure and operation, can be understood by studying the accompanying drawings, in which the same reference numerals refer to the same parts, wherein:

[0008] Figure 1A An example processor-enabled device is shown that can be used in conjunction with the various embodiments described herein, according to an embodiment.

[0009] Figure 1B An example line scan camera with a single linear array is shown according to an embodiment;

[0010] Figure 1C An example line scan camera with three linear arrays is shown according to an embodiment;

[0011] Figure 1D An example line scan camera with multiple linear arrays is shown according to an embodiment;

[0012] Figure 1E An example side-view configuration of a line scan camera in a scanning system according to an embodiment is shown;

[0013] Figure 1F An example top-view configuration of the imaging sensor relative to the imaging optical path is shown according to an embodiment;

[0014] Figure 1G An example top view configuration of the focusing sensor relative to the focusing optical path is shown according to an embodiment;

[0015] Figure 1H An example focusing sensor according to an embodiment is shown;

[0016] Figure 2A A top view showing image segments that can be generated, such as when creating digital sample images;

[0017] Figure 2B A front view showing image segments that can be generated when creating digital sample images;

[0018] Figure 3 Provides a high-level view of the tilt correction process that can be used in slide scanning systems;

[0019] Figure 4 A front view showing image segments with portions extending beyond the depth of field of the imaging system;

[0020] Figure 5A The result is shown after the width of the image segments used for capture has been halved;

[0021] Figure 5B This illustrates the potential results of calculating a distance that, given a relevant tilt, would cause the edges of an image segment to lie within the depth of field; and

[0022] Figure 6 This illustrates the process of identifying and processing tilt before segments that collectively depict the entire sample are captured. Detailed Implementation

[0023] This document discloses a technique for automatically compensating for tilt during digital slide scanning. Upon reading this specification, those skilled in the art will be able to understand how the invention can be implemented in various alternative embodiments and applications. However, although various embodiments of the invention will be described herein, it should be understood that these embodiments are presented by way of example and illustration only and not as limitations. Therefore, the detailed description of the various embodiments should not be construed as limiting the scope or breadth of the invention as set forth in the appended claims.

[0024] 1. Sample Scanning System

[0025] Figure 1A This is a block diagram illustrating an example processor-enabled slide scanning system 100 that can be used in conjunction with the various embodiments described herein. As those skilled in the art will understand, alternative forms of scanning system 100 may also be used. In the illustrated embodiment, scanning system 100 is proposed as a digital imaging device comprising: 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 (each supporting one or more glass slides 114 having one or more samples 116), one or more illumination systems 118 illuminating the samples 116, imaging system 101 (including imaging optics 103, such as one or more objectives 120, each objective defining an optical path 122 traveling along an optical axis), one or more objective positioners 124, one or more optional incident 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 defining an independent field of view 134 on the sample 116 and / or glass slide 114). Various components of the scanning system 100 are communicatively coupled via one or more communication buses 102. Although there may be multiple components in the scanning system 100, for the sake of simplicity in the following description, these components will be described in singular form, except when appropriate information needs to be expressed in plural form.

[0026] Processor 104 may include, for example, a central processing unit (CPU) and a discrete graphics processing unit (GPU) capable of processing instructions in parallel, or a multi-core processor capable of processing instructions in parallel. Additional discrete processors may also be provided for controlling specific components or performing specific functions (such as image processing). For example, additional processors may include: an auxiliary processor for managing data input; an auxiliary processor for performing floating-point mathematical operations; a dedicated processor (e.g., a digital signal processor) with an architecture suitable for rapidly executing signal processing algorithms; a slave processor subordinate to the master processor (e.g., a back-end processor); and an additional processor for controlling the line scan camera 130, stage 112, objective lens 120, and / or display (e.g., a console including a touchscreen display integrated into the scanning system 100). Such additional processors may be discrete processors or may be integrated into a single processor.

[0027] Memory 106 provides storage for data and instructions for a program executable by processor 104. Memory 106 may include one or more volatile and / or non-volatile computer-readable storage media that store data and instructions. These media may include, for example, random access memory (RAM), read-only memory (ROM), hard disk drive, removable storage drive (e.g., including flash memory), etc. Processor 104 is configured to execute instructions stored in memory 106 and communicate with various components of scanning system 100 via communication bus 102 to perform the overall functions of scanning system 100.

[0028] The communication bus 102 can be configured to transmit analog electrical signals and / or digital data. Therefore, communication between the processor 104, motion controller 108, and / or interface system 110 via the communication bus 102 can include both electrical signals and digital data. The processor 104, motion controller 108, and / or interface system 110 can also be configured to communicate with one or more of the various components of the scanning system 100 via a wireless communication link.

[0029] The motion control system 108 is configured to precisely control and coordinate the X, Y, and / or Z movements of the stage 112 (e.g., in the XY plane), the X, Y, and / or Z movements of the objective lens 120 (e.g., via the objective lens positioner 124 along a Z-axis orthogonal to the XY plane), the rotational movement of the turntable described elsewhere herein, the lateral movement of the push / pull assembly described elsewhere herein, and / or any other moving components of the scanning system 100. For example, in a fluorescence scanning embodiment including the incident illumination system 126, the motion control system 108 may be configured to coordinate the movement of optical filters and / or similar elements in the incident illumination system 126.

[0030] Interface system 110 allows scanning system 100 to interface with other systems and operators. For example, interface system 110 may include a console (e.g., a touchscreen display) for providing information directly to operators via a graphical user interface, and / or allowing operators to input directly via touch sensors. Interface system 110 may also be configured to facilitate communication and data transfer between scanning system 100 and one or more external devices (e.g., printers, removable storage media, etc.) directly connected to scanning system 100, and / or with one or more external devices (e.g., via one or more networks) indirectly connected to scanning system 100 (e.g., image storage systems, scanner manager (SAM) servers and / or other management servers, operator workstations, user workstations, etc.).

[0031] 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 may include a variable intensity halogen light source having a concave mirror for maximizing light output and a KG-1 filter for suppressing heat. The light source may include any type of arc lamp, laser, or other light source. In one embodiment, illumination system 118 illuminates sample 116 in a transmission mode, such that line scan camera 130 and / or area scan camera 132 sense the light energy transmitted through sample 116. Alternatively or additionally, illumination system 118 may be configured to illuminate sample 116 in a reflection mode, such that line scan camera 130 and / or area scan camera 132 sense the light energy reflected from sample 116. Illumination system 118 may be configured to be adapted for detecting sample 116 in any known optical microscopy mode.

[0032] In one embodiment, the scanning system 100 includes an epi-illumination system 126 to optimize the scanning system 100 for fluorescence scanning. It should be understood that the epi-illumination system 126 can be omitted if the scanning system 100 does not support fluorescence scanning. Fluorescence scanning involves scanning a sample 116 that includes fluorescent molecules (i.e., photon-sensitive molecules) that absorb light (i.e., are excited) at a specific wavelength. These photon-sensitive molecules also emit light (i.e., emit light) at higher wavelengths. Because this photoluminescence phenomenon is very inefficient, the amount of emitted light is typically very low. This low emission often makes conventional techniques for scanning and digitizing the sample 116 (e.g., transmission mode microscopy) inadequate.

[0033] Advantageously, in embodiments of the scanning system 100 utilizing fluorescence scanning, the light sensitivity of the line scan camera 130 is enhanced by using a line scan camera 130 comprising multiple linear sensor arrays (e.g., a time-delay integration (TDI) line scan camera) by exposing the same region of the sample 116 to each of the multiple linear sensor arrays of the line scan camera 130. This is particularly useful when scanning weakly fluorescent samples with low light emission levels. Therefore, in fluorescence scanning embodiments, the 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 on the sample 116. As those skilled in the art will understand, fluorescent samples can be labeled with a variety of fluorescent dyes that emit light at different wavelengths (also referred to as “channels”).

[0034] Furthermore, since the low-end and high-end signal levels of various fluorescent samples exhibit a wide range of wavelengths for the line scan camera 130 to sense, it is desirable that the line scan camera 130 can sense a similarly wide range of low-end and high-end signal levels. Therefore, in a fluorescence scanning embodiment, the line scan camera 130 may include a monochrome 10-bit 64-linear array TDI line scan camera. It should be noted that line scan cameras 130 of various bit depths can be used for such embodiments.

[0035] The movable stage 112 is configured to perform precise XY movement under the control of the processor 104 or motion controller 108. The movable stage 112 can also be configured to perform Z movement under the control of the processor 104 or motion controller 108. The movable stage 112 is configured to position the sample 116 at a desired location during image data capture by the in-line scanning camera 130 and / or the area scanning camera 132. The movable stage 112 is also configured to accelerate the sample 116 to a substantially constant speed in the scanning direction and then maintain this substantially constant speed during image data capture by the in-line scanning camera 130. In one embodiment, the scanning system 100 may employ a high-precision and tightly coordinated XY grid to assist in positioning the sample 116 on the movable stage 112. In one embodiment, the movable stage 112 is a linear motor-based XY stage employing high-precision encoders on both the X and Y axes. For example, a very precise nanoencoder can be used on the axis of the scanning direction and on an axis located perpendicular to the scanning direction and in the same plane as the scanning direction. The stage 112 is also configured to support a glass slide 114 on which the sample 116 is placed.

[0036] Sample 116 can be any object that can be examined by optical microscopy. For example, glass microscope slides 114 are commonly used as observation substrates for samples including tissues and cells, chromosomes, deoxyribonucleic acid (DNA), proteins, blood, bone marrow, urine, bacteria, microbeads, biopsy material, or any other type of biological material or substance (whether dead or alive, stained or unstained, labeled or unlabeled). Sample 116 can also be an array of any type of DNA or DNA-related material, such as complementary DNA (cDNA) or ribonucleic acid (RNA), or proteins deposited on any type of slide or other substrate, including any and all samples commonly referred to as microarrays. Sample 116 can be a microtiter plate (e.g., a 96-well plate). Other examples of sample 116 include integrated circuit boards, electrophoresis records, petri dishes, films, semiconductor materials, forensic materials, and machined parts.

[0037] Objective lens 120 is mounted on objective lens positioner 124, which in one embodiment employs a highly 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 50-nanometer encoder. The relative positions of stage 112 and objective lens 120 on the 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, which employs memory 106 to store information and instructions, including computer-executable programming steps for the overall operation of scanning system 100.

[0038] In one embodiment, objective 120 is a plan apochromatic (APO) infinity-corrected objective suitable for transmission-mode illumination microscopy, reflection-mode illumination microscopy, and / or incident-illumination-mode fluorescence microscopy (e.g., Olympus 40x, 0.75NA or 20x, 0.75NA). Advantageously, objective 120 is capable of correcting chromatic aberration and spherical aberration. Since objective 120 is infinity-corrected, focusing optics 128 can be placed above objective 120 in the optical path 122 through which the light beam passing through objective 120 is collimated. Focusing optics 128 focuses the light signal captured by objective 120 onto the photosensitive elements of line scan camera 130 and / or area scan camera 132, and may include optical elements such as filters, magnification conversion lenses, etc. Objective 120, in combination with focusing optics 128, provides total magnification for scanning system 100. In one embodiment, focusing optics 128 may include a tube and an optional 2x magnification converter. Advantageously, the 2x magnification converter allows the native 20x objective 120 to scan the sample 116 at 40x magnification.

[0039] Line scan camera 130 includes a linear array of at least one image element 142 (“pixels”). Line scan camera 130 can be monochrome or color. Color line scan cameras typically have at least three linear arrays, while monochrome line scan cameras can have a single linear array or multiple linear arrays. Any type of singular or complex linear array can also be used, whether as part of the camera package or custom-integrated into the imaging electronics module. For example, a three-linear-array (“red-green-blue” or RGB”) color line scan camera or a 96-linear-array monochrome TDI can also be used. TDI line scan cameras typically provide a significantly better signal-to-noise ratio (“SNR”) in the output signal by summing the intensity data of previously imaged areas of the sample; the improvement in SNR is proportional to the square root of the integral series. TDI line scan cameras contain multiple linear arrays. For example, TDI line scan cameras are available with 24, 32, 48, 64, 96, or more linear arrays. The scanning system 100 also supports linear arrays manufactured in various formats, including some arrays with 512 pixels, some arrays with 1024 pixels, and others with up to 4096 pixels. Similarly, the scanning system 100 also supports linear arrays of various pixel sizes. A significant requirement for selecting any type of line scan camera 130 is that the movement of the stage 112 can be synchronized with the line rate of the line scan camera 130 so that the stage 112 can be in motion relative to the line scan camera 130 during digital image capture of the sample 116.

[0040] In one embodiment, image data generated by the line scan camera 130 is stored in a portion of memory 106 and processed by processor 104 to generate a continuous digital image of at least a portion of sample 116. This continuous digital image may be further processed by processor 104, and the processed continuous digital image may also be stored in memory 106.

[0041] In embodiments having two or more line scan cameras 130, at least one line scan camera 130 may be configured as a focus sensor, operating in conjunction with at least one other line scan camera 130 configured as an imaging sensor 130A. The focus sensor may be logically positioned on the same optical axis as the imaging sensor 130A, or the focus sensor may be logically positioned before or after the imaging sensor 130A relative to the scanning direction of the scanning system 100. In such embodiments where at least one line scan camera 130 serves as the focus sensor, image data generated by the focus sensor may be stored in a portion of memory 106 and processed by processor 104 to generate focus information, thereby allowing the scanning system 100 to adjust the relative distance between the sample 116 and the objective lens 120 during scanning to maintain focus on the sample 116. Furthermore, in one embodiment, at least one line scan camera 130 serving as the focus sensor may be oriented such that each of the plurality of individual pixels 142 of the focus sensor is positioned at a different logical height along the optical path 122.

[0042] In operation, various components of the scanning system 100 and a programming module stored in memory 106 enable the automatic scanning and digitization of a sample 116 placed on a glass slide 114. The glass slide 114 is securely positioned on a movable stage 112 of the scanning system 100 for scanning the sample 116. Under the control of the processor 104, the movable stage 112 accelerates the sample 116 to a substantially constant speed for sensing by the line scan camera 130, wherein the speed of the stage 112 is synchronized with the line rate of the line scan camera 130. After scanning a segment of image data, the movable stage 112 decelerates and brings the sample 116 to a substantially complete stop. The movable stage 112 then moves orthogonally to the scanning direction to position the sample 116 for scanning subsequent segments of image data (e.g., adjacent segments). Additional segments are then scanned until the entire portion or the entire sample 116 has been scanned.

[0043] For example, during a digital scan of sample 116, consecutive digital images of sample 116 are acquired as multiple consecutive fields of view, which are combined to form image segments. Such image segments are as follows: Figure 2A Top view and Figure 2B The front view is shown. As these figures show, each segment can be considered to have a center line 201 parallel to the scanning direction, and a first edge 202 and a second edge 203, which are also parallel to the scanning direction and separated from each other along an axis perpendicular to the scanning direction and the optical axis 204 of the imaging system by the width of the image segment. It should be noted that although the first edge 202 and the second edge 203 of the segment are in Figure 2AWhat may appear as merely parallel edges in the top view shown are actually displaced relative to the optical axis 204 of the imaging system when viewed from the front perspective. Figure 2B In the figure shown, this displacement will be equal to the width of the segment multiplied by the tilt of the segment (e.g., it can be determined using an image mapping and / or contrast ratio from a real-time focusing technique described in U.S. Patent Application 2022 / 0159171, filed June 16, 2021, entitled "Real-time Focusing in a Carrier Slice Scanning System," the disclosure of which is incorporated herein by reference in its entirety). Therefore, any point on the first edge 202 (in...) Figure 2A (shown as the first point 205) and any point on the second edge 203 (in) Figure 2A Point 206 (shown in the diagram) can be considered as being separated from each other at a certain distance along the optical axis of the imaging system. Preferably, this separation should be less than or equal to the depth of field of the imaging system, but if this is not satisfied, some embodiments may be configured to modify the width of the image segments to ensure that the tilt multiplied by the (narrowed) width is within the depth of field (e.g., using the method discussed below). Figure 3 (The method shown).

[0044] Just as multiple adjacent fields of view can be combined to form a single continuous image segment, multiple adjacent image segments can also be similarly combined to form a continuous digital image of part or all of sample 116. Scanning sample 116 may include acquiring vertical or horizontal image segments. Scanning sample 116 can be top-down, bottom-up, or both (i.e., bidirectional), and can begin at any point on sample 116. Alternatively, scanning sample 116 can be left-to-right, right-to-left, or both (i.e., bidirectional), and can begin at any point on sample 116. Image segments do not need to be acquired in an adjacent or continuous manner. Furthermore, the resulting image of sample 116 can be an image of the entire sample 116 or only a portion of sample 116.

[0045] In one embodiment, computer-executable instructions (e.g., programming modules and software) are stored in memory 106 and, when executed, cause scanning system 100 to perform various functions described herein (e.g., displaying a graphical user interface, performing disclosed processes, controlling components of scanning system 100, etc.). In this specification, the term "computer-readable storage medium" is used to refer to any medium used to store and provide computer-executable instructions for execution by processor 104 of scanning system 100. Examples of such media include memory 106 and any removable or external storage media (not shown) that are communicatively coupled to scanning system 100 directly (e.g., via a universal serial bus (USB), wireless communication protocols, etc.) or indirectly (e.g., via wired and / or wireless networks).

[0046] Figure 1B A line scan camera 130 with a single linear array 140 is shown, which can be implemented as a charge-coupled device (“CCD”) or complementary metal-oxide-semiconductor (“CMOS”) array. The single linear array 140 includes a plurality of individual pixels 142. In the illustrated embodiment, the single linear array 140 has 4096 pixels 142. In alternative embodiments, the linear array 140 may have more or fewer pixels. For example, common linear array formats include 512, 1024, and 4096 pixels. The pixels 142 are arranged linearly to define a field of view 134 for the linear array 140. The size of the field of view 134 varies depending on the magnification of the scanning system 100.

[0047] Figure 1C A line scan camera 130 with three linear arrays 140 is shown, each of which can be implemented as a CCD array. The three linear arrays 140 are combined to form a color array 150. In one embodiment, each individual linear array in the color array 150 detects a different color intensity, including, for example, red, green, or blue. The color image data of each individual linear array 140 in the color array 150 are combined to form color image data of a single field of view 134.

[0048] Figure 1D A line scan camera 130 with multiple linear arrays 140 is shown, each of which can be implemented as a CCD array. The multiple linear arrays 140 are combined to form a TDI array 160. Advantageously, the TDI line scan camera provides a significantly better SNR in its output signal by summing intensity data from previously imaged areas of the sample; the improvement in SNR is proportional to the square root of the number of linear arrays 140 (also known as the integral series). TDI line scan cameras can include a wider variety of numbers of linear arrays 140. For example, common TDI line scan camera formats include 24, 32, 48, 64, 96, 120, or even more linear arrays 140.

[0049] Figure 1EAn example side-view configuration of a line scan camera 130 in a scanning system 100 according to an embodiment is shown. In the illustrated embodiment, the scanning system 100 includes a glass slide 114 with a tissue sample 116, which is placed on a motorized stage 112, illuminated by an illumination system 118, and moved in a scanning direction 170. An objective lens 120 has an optical field of view 134 trained on the slide 114 and provides an optical path 122 for light from the illumination system 118 passing through the sample 116 on the slide 114, being reflected from the sample 116 on the slide 114, emitting fluorescence from the sample 116 on the slide 114, or otherwise passing through the objective lens 120. The light travels along the optical path 122 to a beam splitter 174, which allows a portion of the light to pass through a lens 176 to reach a main imaging sensor 130A. The light may optionally be bent by a mirror 178, as shown in the illustrated embodiment. The imaging sensor 130A can be, for example, a linear charge-coupled device (CCD).

[0050] Other light travels from beam splitter 174 through lens 180 to focusing sensor 130B. Focusing sensor 130B can also be, for example, a linear CCD array. The light traveling to imaging sensor 130A and focusing sensor 130B preferably represents the complete optical field of view 134 from objective lens 120. Based on this configuration of scanning system 100, the scanning direction 170 of slide 114 is logically oriented relative to imaging sensor 130A and focusing sensor 130B, such that logical scanning direction 172 causes the optical field of view 134 of objective lens 120 to pass through the respective imaging sensor 130A and focusing sensor 130B.

[0051] Figure 1F An example top view showing the configuration of the imaging sensor 130A relative to the imaging optical path 122A according to an embodiment is shown. Similarly, Figure 1G An example top view showing the configuration of the focusing sensor 130B relative to the focusing optical path 122B according to an embodiment is shown. Figure 1G As shown, the focusing sensor 130B is tilted at an angle θ relative to the direction perpendicular to the focusing optical path 122B.

[0052] Figure 1H An example focusing sensor 130B according to an embodiment is shown. In the illustrated embodiment, within the focusing range (d) (e.g., 20 μm) of the tissue sample, the focusing sensor 130B includes a plurality of sensor pixels 142, which can be positioned such that the entire focusing range (d) on the Z-axis is converted by optics into an array of focusing sensors 130B on the Y-axis (orthogonal to the X-axis, i.e., the scanning direction 170), as shown. The position of each sensor pixel 142 is directly related to the Z-position of the objective lens 120. Figure 1HAs shown, each dashed line (i.e., p1, p2, ... p1, ... p1) spans the projected focusing range (d). n () represents different focus values ​​and corresponds to the focus height (i.e., Z height) of objective lens 120. The pᵢ with optimal focus (e.g., highest contrast index) 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.

[0053] The relationship between the expected focusing range (d) on focusing sensor 130B and the focusing range (z) on sample 116 is as follows:

[0054] ,

[0055] Where M focusing This is the optical magnification factor of the focusing optical path. For example, if z = 20μm and M... focusing = 20, then d = 8mm.

[0056] In order for the tilted focusing sensor 130B (including the linear array 140) to cover the entire expected focusing range (d), the tilt angle θ should satisfy the following relationship:

[0057] sinθ = d / L,

[0058] Where L is the length of the linear array 140 of the focus sensor 130B. Using d = 8 mm and L = 20.48 mm, θ = 23.0°. θ and L can vary as long as the tilted focus sensor 130B can cover the entire focusing range (d).

[0059] The focusing resolution, or the minimum step size Δz for objective lens height movement, is a function of the sensor pixel size 142, e = minimum(ΔL). From the above formula, we can derive:

[0060] ,

[0061] For example, if e = 10 μm, L = 20.48 mm, and z = 20 μm, then Δz = 0.0097 μm < 10 nm.

[0062] The objective lens height Z of the focal point i on the focusing sensor 130B i With focus position L i The relationship between them is:

[0063]

[0064] If, based on the analysis of data from the focusing sensor 130B, the focusing height is determined from L1 to L2 in a certain way (by a mean from L1 to L2), then the height of the objective lens 120 needs to be moved from Z1 to Z2 based on the following formula:

[0065]

[0066] Although the field of view (FOV) 134 on the Y-axis of the focusing sensor 130B and the imaging sensor 130A may be different, the centers of the two sensors 130A and 130B are preferably aligned with each other along the Y-axis.

[0067] 2. Overview of the tilt correction process

[0068] The following describes in detail an embodiment of a process for addressing errors caused by tilting during slide scanning. It should be understood that the process can be embodied in one or more software modules executed by one or more hardware processors 104 within the scanning system 100. The process can be implemented as instructions in the form of source code, object code, and / or machine code. These instructions can be executed directly by the hardware processor, or alternatively, by a virtual machine operating between the object code and the hardware processor.

[0069] Alternatively, the process can be implemented as a hardware component (e.g., a 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.), a combination of hardware components, or a combination of hardware and software components. To clearly illustrate the interchangeability of hardware and software, the various illustrative components, blocks, modules, circuits, and steps described herein are generally described in terms of their functionality. Whether this functionality is implemented in hardware or software depends on the specific application and the design constraints imposed on the system as a whole. Those skilled in the art can implement the functionality in different ways for each specific application, but such implementation decisions should not be construed as departing from the scope of the invention. Furthermore, functions are grouped into components, blocks, modules, circuits, or steps for ease of description. A particular function or step can be moved from one component, block, module, circuit, or step to another without departing from the invention.

[0070] Furthermore, while the processes described herein are illustrated with a specific sequence of steps, each process may be implemented with fewer, more, or different steps, as well as different sequences and / or orders of steps. Moreover, it should be understood that any step that does not depend on another step may be performed before, after, or in parallel with that other independent step, even if those steps are described or illustrated in a specific order.

[0071] As a specific example Figure 3 A high-level view is provided of the process for tilt correction that can be used in a slide scanning system. In this process, as shown in Figure 1, the scanner can initially acquire (301) multiple segments of image data. This can include capturing (302) one or more segments of image data using an initial segment width. For example, this can be done by capturing segments of a sample on a slide using a real-time or macro-focusing scanning method described in U.S. Patent Application 2022 / 0159171 (filed June 16, 2021, entitled “Real-time Focusing in a Slide Scanning System,” the disclosure of which is incorporated herein by reference in its entirety). After capturing (302) one or more segments using the initial segment width, tilted image data can be detected (303) within the captured segments. This can be done by checking if any segment has a tilt exceeding a fixed tilt threshold. For example, on a scanner with an initial segment width of 1 mm, a threshold of ±2 μm / mm can be used, meaning that image segments with a tilt exceeding 2 μm / mm can be considered tilted image data.

[0072] Of course, other methods are also possible, and those skilled in the art can implement these methods with reference to this disclosure. For example, in some cases, tilted image data can be detected by comparing the detected tilt with a configurable tilt threshold specified by the user using a management interface. As another example, in some cases, calculations (e.g., multiplying the tilt by the segment width and comparing the product with the depth of field) can be performed to detect whether points on the relative edges of (304) image data segments (e.g., the segment with the maximum tilt) are separated from each other along the optical axis of the scanner imaging system by a distance greater than the depth of field of the imaging system. Figure 4 To illustrate this situation, a frontal view is provided of a segment tilted large enough to cause portion 401 of the slide to extend beyond the field of view of the imaging system. Therefore, the description using thresholds should be understood as exemplary only and not as a limitation.

[0073] Regardless of how the tilted image data is detected, after the tilted image data is detected... Figure 3The method continues to determine (305) a segment width narrower than the initial segment width, which can be used to capture one or more additional image data segments. Similar to the detection of tilted image data (303), this determination (305) can be performed in several ways. For example, in some cases, determining (305) a narrower segment width can be achieved by simply halving the segment width (306). Alternatively, in some cases, determining (305) a narrower segment width may include calculating (307) the distance along the segment width between the first and second edges, a distance that, when the width is set to this distance, would separate the first and second edges by no more than the depth of field of the imaging system (e.g., by dividing the tilt by the depth of field). When performing such calculations, the width can be set to a value equal to or less than the calculated value, thereby ensuring that the segments can be rescanned in a way that keeps all image data in focus, while preventing the rescanning process from becoming too slow by avoiding an unnecessary increase in the number of segments requiring rescanning. Examples of results from these two methods for determining (305) a narrower segment width are provided in Figure 5A and Figure 5B middle, Figure 5A The result of halving the width (306) is depicted. Figure 5B The potential result of calculating (307) a distance that, given a tilt, would keep both the first and second edges of the narrowed segment within the depth of field.

[0074] After determining (305) a narrower segment width, one or more image data segments can be captured (308) using a segment width that is narrower than the initial segment width—for example, after capturing each segment, moving a distance equal to the narrower segment width in a direction orthogonal to the scanning direction before capturing the next segment. This can be done by first narrowing (309) the field of view of the imaging system to match the determined segment width (e.g., by configuring the imaging camera to read only the central portion of the sensor array), and then capturing (308) segments in a manner similar to the initial capture (302) of one or more segments using the initial segment width. Alternatively, capturing (308) one or more segments using a narrower segment width can be achieved by capturing (310) data across the initial segment width and then discarding (311) data that is more than half the narrower segment width from the centerline of each segment. In either case, after capturing all the necessary segments, these segments can be combined (312) into a sample of continuous digital images. To illustrate how this is accomplished, consider the following scenario: a first set of segments covering the entire sample is captured (302) using an initial segment width, and then, after detecting (303) tilted image data in these segments, a second set of segments is captured (308) using a segment width narrower than the initial segment width. In this scenario, combining (312) the segments into a continuous digital image may include: discarding (313) the first set of segments, and then (314) combining the second set of segments into a continuous digital image of the sample, thereby providing a complete continuous digital image of the sample in which all portions of the segments (even those at the boundaries of highly tilted segments) are in focus.

[0075] To achieve Figure 3 Other methods of tilt correction shown are also feasible and can be implemented by those skilled in the art without much experimentation, referring to this disclosure. For example, while some embodiments may perform this by first capturing (302) segments covering the entire sample using an initial segment width, and then detecting (303) tilted image data after the entire dataset has been acquired. Figure 3 The process shown may also involve detecting tilted image data before the image segments that collectively depict the entire sample are captured (303). For illustration, consider... Figure 6 The figure illustrates the process of identifying and processing tilt before segments that collectively depict the entire sample are collected. Figure 6 During the process, after capturing (302) each segment with an initial segment width, it is possible to check whether there is tilted image data. Once the tilted image is detected (303), it can transition to capturing (308) segments with a narrower segment width, and start recapturing the data covered by the segment where the tilted image data was detected (303).

[0076] In addition, such as Figure 6 As shown, in some implementations, further variations can be made during the process of acquiring (301) image data segments. For example, after capturing (308) segments using a narrower segment width, an inspection can be performed to determine whether a (601) tilt change is detected in the captured data. This can be done using calculations similar to those described for detecting (303) tilted image data, and if no tilt change is detected, the process can continue capturing (602) segments at the current width until a (601) tilt change is detected, or enough segments are captured to form an image covering the sample. Alternatively, if a (601) tilt change is detected, the (603) changed segment width can be determined. This can be done using calculations similar to those previously described for calculating (307) the distance between the segments that keep both edges within the depth of field for a given tilt. However, it should be noted that in some cases, this determination (603) may also include determining a new width larger than the currently used width to reduce the total number of segments, thereby reducing the time required to scan the sample. For example, in some cases, it is implemented to perform Figure 6 The system of the method shown can detect (601) a tilt change when: the tilt increases to the point that a portion of the segment exceeds the depth of field of the imaging system, or the tilt decreases to the point that the width can be increased to reduce the total number of segments in the fully imaged sample without causing any portion of the segment to exceed the depth of field. In this case, if the (601) tilt change is detected due to the decrease in tilt, the segment width can be changed to the maximum field of view of the imaging system, or to the maximum width of the entire segment within the depth of field, whichever is smaller.

[0077] Regardless of the changed segment width, once the change (603) is determined, the changed segment width can be used to capture (604) the segments. Furthermore, in some cases, data indicating the number of strips used in the scanned sample can be updated (605) for subsequent use when combining (312) the segments into a continuous digital image. The scanning process can continue in this manner until a tilt change (601) is detected (in which case the segment width can be further modified) or enough image data segments have been captured to cover the entire sample. At this point, the step of acquiring (301) multiple image data segments can be considered complete, and these segments can be combined (312) into a continuous digital image.

[0078] 3. Other non-restrictive examples

[0079] The above description of the disclosed embodiments is provided to enable those skilled in the art to make or use the invention. Various modifications to these embodiments will be 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. Therefore, it should be understood that the description and drawings presented herein represent currently preferred embodiments of the invention and thus represent the broad subject matter covered by the invention. It should be further understood that the scope of the invention fully covers other embodiments that may become apparent to those skilled in the art, and the scope of the invention is therefore not limited. Other variations are also possible and will become immediately apparent to those skilled in the art with reference to this disclosure. For example, the following examples are provided as specific (but not limiting) illustrations of various methods that may be employed when implementing the disclosed technology.

[0080] Example 1

[0081] A method for automatically digitizing a sample, executed by a scanner by executing instructions stored on a non-transitory computer-readable medium, the method comprising: acquiring a plurality of image data segments using an imaging system, wherein acquiring the plurality of image data segments includes: capturing one or more image data segments using an initial segment width; detecting tilted image data, wherein the tilted image data is tilted relative to the optical axis of the imaging system; based on the detected tilted image data: determining a segment width narrower than the initial segment width; and capturing one or more image data segments using a segment width narrower than the initial segment width; and combining the plurality of image data segments 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 the scanning direction; and each image data segment includes a centerline parallel to the scanning direction.

[0082] Example 2

[0083] As in Example 1, the method includes: detecting tilted image data includes detecting tilted image data segments; the tilted image data segments have a first edge and a second edge, each 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 at a distance greater than the depth of field of the imaging system.

[0084] Example 3

[0085] As in Example 2, determining a segment width narrower than the initial segment width includes: calculating the distance between the first edge and the second edge along an axis orthogonal to the scanning direction, such that, given an inclination, the first point and the second point are separated from each other along the optical axis of the imaging system at a distance not exceeding the depth of field of the imaging system.

[0086] Example 4

[0087] The method in either of Examples 1-2 is such that the width of the segment that is narrower than the initial segment width is half the width of the initial segment.

[0088] Example 5

[0089] The method of any one of Examples 1-4, wherein: acquiring multiple image data segments includes acquiring a first set of image data segments, wherein: each segment in the first set of image data segments has one or more adjacent image data segments included in the first set of image data segments; and the first set of image data segments provides a first continuous digital image of samples, wherein for each segment in the first set of segments, the centerline of the segment is separated from the centerlines of its adjacent segments by an initial segment width; capturing one or more image data segments using a segment width narrower than the initial segment width includes acquiring a second set of image data segments, wherein: the second image Each segment in the data segment set has one or more adjacent image data segments included in the second image data segment set; and a centerline extending parallel to the scanning direction and including the center of the segment; and the second image data segment set provides a second continuous digital image of the sample, wherein for each segment in the second segment set, the centerline of the segment is separated from the centerlines of its adjacent segments by a segment width narrower than the initial segment width; and combining multiple image data segments into a sample of the continuous digital image includes: discarding the first image data segment set; and combining the second image data segment set into a sample of the second continuous digital image.

[0090] Example 6

[0091] The method of any of Examples 1-4, wherein: capturing one or more image data segments with a segment width narrower than the initial segment width includes: capturing segments comprising at least a portion of tilted image data with a segment width narrower than the initial segment width before capturing image segments that collectively depict the entire sample; and multiple image data segments collectively depicting the entire sample.

[0092] Example 7

[0093] As in Example 6, the method for acquiring multiple image data segments includes: after capturing one or more image data segments with a segment width narrower than the initial segment width, detecting a tilt change; based on the detected tilt change, determining a segment width after the change, which is different from the segment width narrower than the initial segment width; and capturing one or more image data segments using the changed segment width.

[0094] Example 8

[0095] As in Example 7, the changed segment width is narrower than the initial segment width.

[0096] Example 9

[0097] As in Example 7, the changed segment width is wider than the segment width that is narrower than the initial segment width.

[0098] Example 10

[0099] As in Example 9, the changed segment width is equal to the initial segment width.

[0100] Example 11

[0101] The method of any of Examples 6-10 includes: updating data indicating the number of segments used to collectively depict the entire sample whenever the segment width used when capturing segments in multiple stripes changes.

[0102] Example 12

[0103] The method of any one of Examples 1-11, wherein: the method includes: reducing the width of the field of view of the imaging system from an initial segment width to a segment width narrower than the initial segment width based on the detection of tilted image data; and capturing one or more image data segments using a segment width narrower than the initial segment width includes: capturing one or more segments using the imaging system after the width of the field of view of the imaging system is reduced.

[0104] Example 13

[0105] The method of any of Examples 1-11, wherein capturing one or more image data segments with a segment width narrower than the initial segment width for each of one or more image data segments comprises: capturing the image data segment using the imaging system when the width of the field of view of the imaging system is equal to the initial segment width; and discarding image data included in the segment that is not located within a distance equal to half the segment width narrower than the initial segment width and is not located on the center line of the segment.

[0106] Example 14

[0107] An automatic scanner includes: an imaging system having: a depth of field; a field of view having a width along an axis orthogonal to the scanning direction; and an optical axis orthogonal to and perpendicular to the scanning direction; a stage movable in the scanning direction; a processor; and a non-transitory computer-readable medium having instructions stored thereon, which, when executed, are operable to acquire an image of a sample placed on a slide supported by the stage by performing the following actions: acquiring a plurality of image data segments, each image data segment having a centerline parallel to the scanning direction; capturing one or more image data segments using an initial segment width; determining whether there is image data tilted relative to the optical axis of the imaging system in the captured one or more segments; and if there is tilted image data in the captured one or more segments: determining a segment width narrower than the initial segment width; and capturing one or more image data segments using a segment width narrower than the initial segment width; and combining the plurality of image data segments into an image of the sample.

[0108] Example 15

[0109] As in the scanner of Example 14, the detection of tilted image data includes detecting tilted image data segments; the tilted segments have a first edge and a second edge, each parallel to the scanning direction; the tilted segments have 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 at a distance greater than the depth of field of the imaging system.

[0110] Example 16

[0111] As in the scanner of Example 15, determining a segment width narrower than the initial segment width includes: calculating the distance between the first edge and the second edge along the width of the inclined segment, wherein, given the inclination, the first point and the second point are separated from each other along the optical axis of the imaging system with respect to the depth of field of the imaging system.

[0112] Example 17

[0113] The scanner is as shown in any of Examples 14-15, where the width of the segment that is narrower than the initial segment width is half the initial segment width.

[0114] Example 18

[0115] A scanner as described in any of Examples 14-17, wherein: acquiring multiple image data segments includes acquiring a first set of image data segments, wherein: each segment in the first set of image data segments has one or more adjacent image data segments included in the first set of image data segments; and the first set of image data segments provides a first continuous digital image of the sample, wherein for each segment in the first set of segments, the centerline of the segment is separated from the centerlines of its adjacent segments by an initial segment width; capturing one or more image data segments using a segment width narrower than the initial segment width includes acquiring a second set of image data segments, wherein: the second Each segment in the image data segment set has one or more adjacent image data segments included in the second image data segment set; and a centerline extending parallel to the scanning direction and including the center of the segment; and the second image data segment set provides a second continuous digital image of the sample, wherein for each segment in the second segment set, the centerline of the segment is separated from the centerlines of its adjacent segments by a segment width narrower than the initial segment width; and combining multiple image data segments into a sample of the continuous digital image includes: discarding the first image data segment set; and combining the second image data segment set into a sample of the second continuous digital image.

[0116] Example 19

[0117] A scanner such as any of Examples 14-17, wherein: capturing one or more image data segments with a segment width narrower than the initial segment width includes: capturing segments comprising at least a portion of tilted image data with a segment width narrower than the initial segment width before capturing image segments that collectively depict the entire sample; and multiple image data segments collectively depicting the entire sample.

[0118] Example 20

[0119] As in the scanner of Example 19, acquiring multiple image data segments includes: after capturing one or more image data segments with a segment width narrower than the initial segment width, detecting whether there is a tilt change in the one or more image data segments captured with a segment width narrower than the initial segment width; if there is a tilt change, determining the segment width after the change; and capturing one or more image data segments with the changed segment width.

[0120] Example 21

[0121] As in the scanner of Example 20, determining the changed segment width includes: if the tilt change causes the distance along the imaging axis between the first and second edges of the most recently captured segment to exceed the depth of field of the imaging system, determining the changed segment width to be narrower than the segment width used when capturing the segment in which the tilt change was detected; and if the tilt change is a decrease in the absolute value of the tilt in the segment in which the tilt change was detected, determining the changed segment width to be larger than the segment width used when capturing the segment in which the tilt change was detected.

[0122] Example 22

[0123] As in the scanner of Example 21, where the changed segment width is determined to be a larger segment width than the segment width used when capturing a segment in which a tilt change is detected, the changed segment width is defined as equal to the initial segment width.

[0124] Example 23

[0125] A scanner such as any of Examples 19-22, wherein the method includes: updating data indicating the number of segments used to collectively depict the entire sample whenever the segment width used when capturing segments in multiple strips changes.

[0126] Example 24

[0127] A scanner as described in any of Examples 14-23, wherein: the method includes: if tilted image data exists in one or more captured segments, reducing the width of the field of view of the imaging system from an initial segment width to a segment width narrower than the initial segment width; and capturing one or more image data segments using a segment width narrower than the initial segment width includes: capturing one or more segments using the imaging system after the width of the field of view of the imaging system has been reduced.

[0128] Example 25

[0129] A scanner, such as any of Examples 14-23, wherein capturing one or more image data segments with a segment width narrower than the initial segment width for each of one or more image data segments comprises: capturing the image data segment using an imaging system when the width of the field of view of the imaging system is equal to the initial segment width; and discarding image data included in the segment that is not located within a distance equal to half the segment width narrower than the initial segment width and is not located on the center line of the segment.

[0130] 4. Explanation

[0131] Any examples or illustrations set forth herein shall not be construed as limiting the scope of the claims included in this document or any related documents. Rather, the protection provided by this document or any related documents shall be understood as being defined by the claims of the related documents, where terms in those claims that are expressly defined herein are given their express definitions, and terms that are not expressly defined shall be given the broadest reasonable interpretation available in a general dictionary.

[0132] The combinations described herein, 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", all include any combination of A, B, and / or C, and may include multiple A, multiple B, or multiple 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 only A, only B, only C, 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 constituent parts A, B, and / or C. For example, a combination of A and B may include one A and multiple B, multiple A and one B, or multiple A and multiple B.

[0133] A statement that something is “based on” another should be understood as meaning that the thing is at least partially determined by the thing it is “based on.” While a “based on” relationship includes situations where one thing is entirely determined by another, it should not be understood as limited to situations where one thing is entirely determined by another, unless the phrase used is “based on only.”

Claims

1. A method for the automatic digitization of a sample by a scanner executing instructions stored on a non-transitory computer-readable medium, the method comprising: • Using an imaging system to acquire multiple image data segments, wherein acquiring the multiple image data segments includes: ◦ Capture one or more image data segments using the initial segment width; ◦ Detect tilted image data, wherein the tilted image data is tilted relative to the optical axis of the imaging system; Based on the detected tilted image data: ▪ Determine a segment width that is narrower than the initial segment width; and ▪ Capture one or more image data segments using a segment width narrower than the initial segment width; and • Combine the multiple image data segments into the image of the sample; in: • The imaging system has a depth of field and a field of view, the field of view having a width along an axis orthogonal to the scanning direction; and • Each image data segment includes a center line parallel to the scanning direction.

2. The method according to claim 1, wherein: - Detecting the tilted image data includes detecting tilted image data segments; - The tilted image data segments each have a first edge and a second edge parallel to the scanning direction; - The inclined 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 at a distance greater than the depth of field of the imaging system.

3. The method according to claim 2, wherein, Determining a segment width narrower than the initial segment width includes: calculating the distance between the first edge and the second edge along an axis orthogonal to the scanning direction, such that, given an inclination, the first point and the second point are separated from each other along the optical axis of the imaging system at a distance not exceeding the depth of field of the imaging system.

4. The method according to any one of claims 1-2, wherein, The width of a segment that is narrower than the initial segment width is half the initial segment width.

5. The method according to any one of claims 1 to 4, wherein: • Obtaining the plurality of image data segments includes obtaining a first set of image data segments, wherein: ◦ Each segment in the first image data segment set has one or more adjacent image data segments included in the first image data segment set; and ◦The first set of image data segments provides a first continuous digital image of the sample, wherein for each segment in the first set of segments, the centerline of the segment is separated from the centerline of its adjacent segment by the initial segment width; • Capturing one or more image data segments using a segment width narrower than the initial segment width includes obtaining a second set of image data segments, wherein: ◦ Each segment in the second set of image data segments has: ▪ The second set of image data segments includes one or more adjacent image data segments; and ▪ A centerline extending parallel to the scanning direction and including the center of the segment; and ◦ The second set of image data segments provides a second continuous digital image of the sample, wherein for each segment in the second set of segments, the centerline of the segment is separated from the centerline of its adjacent segment by a segment width narrower than the initial segment width; and • Combining the multiple image data segments into a continuous digital image of the sample includes: ◦ Discard the first set of image data segments; and ◦ Combine the second set of image data segments into a second continuous digital image of the sample.

6. The method according to any one of claims 1 to 4, wherein: • Capturing one or more image data segments using a segment width narrower than the initial segment width includes: capturing segments comprising at least a portion of the tilted image data using a segment width narrower than the initial segment width before capturing image segments that collectively depict the entire sample; and • The multiple image data segments together depict the entire sample.

7. The method according to claim 6, wherein, Obtaining the multiple image data segments includes: • After capturing one or more image data segments using a segment width narrower than the initial segment width, detect tilt changes; • Based on the detected tilt change, determine a segment width after the change, which is different from a segment width narrower than the initial segment width; and • Use the changed segment width to capture one or more image data segments.

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

9. The method according to claim 7, wherein, The changed segment width is greater than the segment width that is narrower than the initial segment width.

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

11. The method according to any one of claims 6 to 10, wherein, The method includes updating data indicating the number of segments used to collectively depict the entire sample whenever the segment width used when capturing segments in multiple strips changes.

12. The method according to any one of claims 1 to 11, wherein: • The method includes: 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 a segment width narrower than the initial segment width; and • Capturing one or more image data segments using a segment width narrower than the initial segment width includes: capturing one or more segments using the imaging system after the field of view of the imaging system has been reduced.

13. The method according to any one of claims 1 to 11, wherein, For each of the one or more image data segments, capturing one or more image data segments using a segment width narrower than the initial segment width includes: • When the width of the field of view of the imaging system is equal to the initial segment width, the imaging system is used to capture the image data segments; and • Discard image data that is not located on the center line of the segment and is within a distance equal to half the width of the segment, which is narrower than the initial segment width.

14. An automatic scanner, comprising: • Imaging system, having: ◦ Depth of field; ◦ A field of view with a width along an axis orthogonal to the scanning direction; and ◦ Optical axis, which is orthogonal to the scanning direction and an axis orthogonal to the scanning direction; • A stage that can move in the scanning direction; •processor; and • A non-transitory computer-readable medium having instructions stored thereon, which, when executed, are operable to obtain an image of a sample placed on a slide supported by the stage by performing methods including: ◦ Multiple image data segments are acquired by performing the following actions, each image data segment having a centerline parallel to the scanning direction: ▪ Capture one or more image data segments using the initial segment width; ▪ Determine whether there is image data tilted relative to the optical axis of the imaging system in one or more captured segments; and ▪ If tilted image data exists in one or more of the captured segments: ▫Determine a segment width that is narrower than the initial segment width; and ▫Capture one or more image data segments using a segment width narrower than the initial segment width; ◦ The multiple image data segments are combined to form the image of the sample.

15. The scanner according to claim 14, wherein: - Detecting the tilted image data includes detecting tilted image data segments; - The inclined segments each have a first edge and a second edge parallel to the scanning direction; - The inclined 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 at a distance greater than the depth of field of the imaging system.

16. The scanner according to claim 15, wherein, Determining a segment width narrower than the initial segment width includes: calculating the distance between the first edge and the second edge along the width of the inclined segment, wherein, given the inclination, the first point and the second point are separated from each other along the optical axis of the imaging system with respect to the depth of field of the imaging system.

17. The scanner according to any one of claims 14-15, wherein, The width of a segment that is narrower than the initial segment width is half the initial segment width.

18. The scanner according to any one of Examples 14 to 17, wherein: • Obtaining the plurality of image data segments includes obtaining a first set of image data segments, wherein: ◦ Each segment in the first image data segment set has one or more adjacent image data segments included in the first image data segment set; and ◦The first set of image data segments provides a first continuous digital image of the sample, wherein for each segment in the first set of segments, the centerline of the segment is separated from the centerline of its adjacent segment by the initial segment width; • Capturing one or more image data segments using a segment width narrower than the initial segment width includes obtaining a second set of image data segments, wherein: ◦ Each segment in the second image data segment set has ▪ The second set of image data segments includes one or more adjacent image data segments; and ▪ A centerline extending parallel to the scanning direction and including the center of the segment; and ◦ The second set of image data segments provides a second continuous digital image of the sample, wherein for each segment in the second set of segments, the centerline of the segment is separated from the centerline of its adjacent segment by a segment width narrower than the initial segment width; and • Combining the multiple image data segments into a continuous digital image of the sample includes: ◦ Discard the first set of image data segments; and ◦ Combine the second set of image data segments into a second continuous digital image of the sample.

19. The scanner according to any one of claims 14 to 17, wherein: • Capturing one or more image data segments using a segment width narrower than the initial segment width includes: capturing segments comprising at least a portion of the tilted image data using a segment width narrower than the initial segment width before capturing image segments that collectively depict the entire sample; and • The multiple image data segments together depict the entire sample.

20. The scanner according to claim 19, wherein, Obtaining the multiple image data segments includes: • After capturing one or more image data segments using a segment width narrower than the initial segment width, detect whether there is a tilt change in the one or more image data segments captured using a segment width narrower than the initial segment width; • If the aforementioned tilt change exists, determine the segment width after the change; and • Use the changed segment width to capture one or more image data segments.

21. The scanner of claim 20, wherein determining the changed segment width comprises: • If the tilt change causes the distance along the imaging axis between the first and second edges of the most recently captured segment to exceed the depth of field of the imaging system, the changed segment width is determined to be a segment width that is narrower than the segment width used when capturing the segment in which the tilt change is detected. and • If the tilt change is a decrease in the absolute value of the tilt in the segment where the tilt change is detected, the width of the changed segment is determined to be a larger segment width than the segment width used when capturing the segment where the tilt change is detected.

22. The scanner according to claim 21, wherein, Determining the changed segment width to be a larger segment width than the segment width used when capturing a segment in which the tilt change is detected is equivalent to defining the changed segment width as equal to the initial segment width.

23. The scanner according to any one of claims 19 to 22, wherein the method comprises: Whenever the segment width used when capturing segments in multiple stripes changes, update the data indicating the number of segments used to collectively depict the entire sample.

24. The scanner according to any one of claims 14 to 23, wherein: • The method includes: if the tilted image data exists in one or more of the captured segments, reducing the width of the imaging system's field of view from the initial segment width to a segment width narrower than the initial segment width; and • Capturing one or more image data segments using a segment width narrower than the initial segment width includes: capturing one or more segments using the imaging system after the field of view of the imaging system has been reduced.

25. The scanner according to any one of claims 14 to 23, wherein, For each of the one or more image data segments, capturing one or more image data segments using a segment width narrower than the initial segment width includes: • When the width of the field of view of the imaging system is equal to the initial segment width, the imaging system is used to capture the image data segments; and • Discard image data that is not located on the center line of the segment and is within a distance equal to half the width of the segment, which is narrower than the initial segment width.

Images