Automatic tilt compensation in digital scanning systems

Abstract

It is possible to digitize a sample using scanning in a way that automatically takes into account the gradient, otherwise some or all of the digitized image may be out of focus. This may be done by taking the steps of acquiring multiple image data segments and combining the multiple image data segments into a continuous digital image of the sample. In this type of scenario, the step of acquiring multiple image data segments may include taking the steps of capturing one or more segments using an initial segment width, detecting the gradient image data, determining a narrower segment width based on the detection of the gradient image data, and capturing one or more segments using the narrower segment width.

Description

[Technical Field]

[0001] Cross-reference of related applications This application is related to U.S. Provisional Application No. 63 / 540,802, entitled "Automatic Tilt Compensation in a Digital Scanning System," filed with the U.S. Patent and Trademark Office on 27 September 2023, claiming priority under said Provisional Application, the entire disclosure thereof is incorporated herein by reference.

[0002] Background fields The embodiments described herein are generally directed toward the control of a slide scanning system, and more specifically toward automatic tilt compensation in a slide scanning system.

[0003] Related technologies Digital pathology is an image-based information environment made possible by computer technology that enables the management of information generated from physical slides. Digital pathology is partially made possible by virtual microscopy, a technique that scans specimens on physical glass slides and creates digital slide images that can be stored, viewed, managed, and analyzed on a computer monitor. Due to its ability to image entire glass slides, the field of digital pathology is expanding explosively and is now considered one of the most promising means of diagnostic medicine for achieving better, faster, and less expensive diagnosis, prognosis, and prediction of important diseases such as cancer.

[0004] The primary objective of the digital pathology industry is to provide properly focused images. This can be complicated by tilt in the slide on which the specimen is placed (e.g., as a result of excessive mounting medium at the bottom of the slide), and / or tilt in the tissue on the slide (e.g., as a result of inadequate tissue preparation), and excessive tilt can cause parts of the digital image to be out of focus. Therefore, there is a need for improved techniques to account for tilt when generating digital images using slide scanning systems.

[0005] overview A system, method, and non-temporary computer-readable medium are disclosed for automatically compensating for tilt when generating a digital image of a sample using a scanning device. This may be done by acquiring multiple segments of image data (e.g., stripes that can be captured by a line scanning camera) and combining the multiple segments of image data into a continuous digital image of the sample. In this type of scenario, acquiring multiple segments of image data may include capturing one or more segments using an initial segment width, detecting tilted image data, determining narrower segment widths based on the detection of tilted image data, and capturing one or more segments using the narrower segment widths.

[0006] Detailed aspects of both the structure and operation of the disclosed technology may be partially understood by studying the attached drawings. In the attached drawings, the same reference numerals refer to the same part. [Brief explanation of the drawing]

[0007] [Figure 1A] This figure shows an exemplary processor-enabled device that may be used in connection with various embodiments described herein, according to one embodiment. [Figure 1B] This figure shows an exemplary line scanning camera having a single linear array according to one embodiment. [Figure 1C]This figure shows an exemplary line scanning camera having three linear arrays according to one embodiment. [Figure 1D] This figure shows an exemplary line scanning camera having multiple linear arrays according to one embodiment. [Figure 1E] This is a side view showing an exemplary configuration of a line scanning camera in a scanning system according to one embodiment. [Figure 1F] This is a top view showing an exemplary configuration of an imaging sensor relating to the imaging optical path according to one embodiment. [Figure 1G] This is a top view showing an exemplary configuration of a focusing sensor relating to a focusing optical path according to one embodiment. [Figure 1H] This figure shows an exemplary focusing sensor according to one embodiment. [Figure 2A] This is an overview view showing image segments that may be generated when creating digital sample images. [Figure 2B] This is a front view showing an image segment that may be generated when creating a digital sample image. [Figure 3] This is an overall diagram showing a process that can be used for tilt correction in a slide scanning system. [Figure 4] This is a front view showing an image segment that has a portion extending beyond the depth of field of the imaging system. [Figure 5A] This figure shows the result of reducing the width used to capture the image segment by half. [Figure 5B] This figure shows the latent results calculated for the distance at which both ends of an image segment fall within the depth of field, given the relevant slope. [Figure 6] This figure shows the process by which slopes are identified and addressed before segments that comprehensively depict the entire sample are collected.

[0008] Detailed explanation This specification discloses techniques that can be used to automatically compensate for tilt during digital slide scanning. Those skilled in the art will understand how the invention can be implemented in various alternative embodiments and applications. However, while this specification describes various embodiments of the invention, it should be understood that these embodiments are presented for illustrative and illustrative purposes only and are not intended to be limiting. Therefore, the detailed descriptions of these various embodiments should not be construed as limiting the scope or breadth of the invention as described in the appended claims.

[0009] 1. Exemplary Scanning System Figure 1A is a block diagram showing an exemplary processor-based slide scanning system 100 that may be used in connection with various embodiments described herein. As those skilled in the art will understand, alternative forms of the scanning system 100 may be used. In the illustrated embodiment, the scanning system 100 is presented as a digital imaging device including an imaging system 101 which includes 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 for illuminating the samples 116, one or more imaging optical systems 103 such as one or more objective lenses 120 each defining an optical path 122 traveling along the optical axis, one or more objective lens positioning devices 124, one or more optional reflected illumination systems 126 (included in embodiments of fluorescence scanning, for example), one or more focusing optical systems 128, and one or more line scanning cameras 130 and / or one or more area scanning cameras 132 (each of which defines a separate field of view on the sample 116 and / or glass slide 114). Various elements of the scanning system 100 are communicably coupled via one or more communication buses 102. Each of the various elements of the scanning system 100 may exist in multiples, but for the sake of simplifying the following explanation, these elements will be described in the singular unless it is necessary to describe them in multiples in order to convey appropriate information.

[0010] The processor 104 can include, for example, a central processing unit (CPU) capable of parallel processing instructions and a separate graphics processing unit (GPU), or can include a multi-core processor capable of parallel processing instructions. Additional separate processors may be provided to control specific components or perform specific functions such as image processing. For example, the additional processors may include an auxiliary processor that manages data input, an auxiliary processor that performs floating-point operations, a special-purpose processor (e.g., a digital signal processor) having an architecture suitable for high-speed execution of signal processing algorithms, a slave processor subordinate to the main processor (e.g., a back-end processor), and an additional processor for controlling the line scan camera 130, the stage 112, the objective lens 120, and / or a display (e.g., a console including a touch panel display incorporated in the scanning system 100). Such additional processors may be separate discrete processors, or may be integrated into a single processor.

[0011] The memory 106 provides storage for data and instructions for programs executable by the processor 104. The memory 106 can include one or more volatile and / or non-volatile computer-readable storage media that store data and instructions. These storage media can include, for example, random access memory (RAM), read-only memory (ROM), a hard disk drive, a removable storage drive (e.g., including flash memory), and / or the like. The processor 104 is configured to execute instructions stored in the memory 106 and communicate with various elements of the scanning system 100 via the communication bus 102 to perform the overall functions of the scanning system 100.

[0012] Communication bus 102 may be configured to transmit analog electrical signals and / or digital data. Accordingly, communications from processor 104, motion controller 108, and / or interface system 110 via communication bus 102 can include both electrical signals and digital data. Processor 104, motion controller 108, and / or interface system 110 may be configured to communicate with one or more of the various elements of scanning system 100 via a wireless communication link.

[0013] Motion control system 108 is configured to precisely control and coordinate X, Y, and / or Z direction movement of stage 112 (e.g., movement in the X-Y plane), X, Y, and / or Z direction movement of objective lens 120 (e.g., movement along the 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 movable component of scanning system 100. For example, in embodiments of a fluorescence scanning scheme including 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.

[0014] The interface system 110 enables the scanning system 100 to interface with other systems and human operators. For example, the interface system 110 may include a console (e.g., a touch panel display) that provides information directly to the operator via a graphical user interface and / or a console that allows direct input from the operator via a touch sensor. The interface system 110 may be configured to facilitate communication and data transfer between the scanning system 100 and one or more external devices directly connected to the scanning system 100 (e.g., a printer, removable storage media, etc.) and / or one or more external devices indirectly connected to the scanning system 100 via, for example, one or more networks (e.g., an image storage system, a scanner management manager (SAM) server, and / or other management servers, an operator station, a user station, etc.).

[0015] The illumination system 118 is configured to illuminate at least a portion of the sample 116. The illumination system 118 may include, for example, one or more light sources and illumination optics. The light source may be a variable-intensity halogen light source equipped with a concave mirror to maximize light output and a KG-1 filter to suppress heat. The light source may be an arc lamp, a laser, or any other type of light source. In one embodiment, the illumination system 118 illuminates the sample 116 in transmission mode, thereby allowing the line scanning camera 130 and / or area scanning camera 132 to sense the light energy transmitted through the sample 116. Alternatively or additionally, the illumination system 118 may be configured to illuminate the sample 116 in reflection mode, thereby allowing the line scanning camera 130 and / or area scanning camera 132 to sense the light energy reflected from the sample 116. The illumination system 118 may be configured to be suitable for observation of the sample 116 in any known optical microscope mode.

[0016] In one embodiment, the scanning system 100 includes an epi-illumination system 126 that optimizes the scanning system 100 for fluorescence scanning. It should be understood that the epi-illumination system 126 may be omitted if fluorescence scanning is not supported by the scanning system 100. Fluorescence scanning is the scanning of a sample 116 containing fluorescent molecules, which are photon-sensitive molecules that can absorb light of a specific wavelength (i.e., excitation light). These photon-sensitive molecules also emit light of higher wavelengths (emission light). Because the efficiency of this emission phenomenon is very low, the amount of emission is often very small. This low amount of emission typically hinders conventional techniques for scanning and digitizing the sample 116 (e.g., transmission mode microscopy).

[0017] Advantageously, in embodiments of the scanning system 100 utilizing fluorescence scanning, the use of a line scanning camera 130 including multiple linear sensor arrays (e.g., a time-delay integral (TDI) line scanning camera) enhances the sensitivity of the line scanning camera 130 to light by exposing the same area of ​​the sample 116 to each of the multiple linear sensor arrays of the line scanning camera 130. This is particularly useful when scanning weakly fluorescent samples with low emission levels. Therefore, in embodiments of the fluorescence scanning method, the line scanning camera 130 is preferably a monochrome TDI line scanning camera. Monochrome images are ideal for fluorescence microscopy because they can more accurately represent the actual signals from the various channels present on the sample 116. As those skilled in the art will understand, a fluorescent sample can be labeled with multiple fluorescent dyes that emit at different wavelengths, and these fluorescent dyes are also referred to as "channels".

[0018] Furthermore, since the lowest and highest level signals of various fluorescent samples present a broad wavelength spectrum for the line scanning camera 130 that senses them, it is desirable that the lowest and highest level signals that the line scanning camera 130 can sense are also similarly broad. Therefore, in embodiments of the fluorescence scanning method, the line scanning camera 130 may include a monochrome 10-bit 64 linear array TDI line scanning camera. It should be noted that in use with such embodiments, various bit depths can be used for the line scanning camera 130.

[0019] The movable stage 112 is configured to move precisely in the XY direction under the control of the processor 104 or the motion controller 108. The movable stage 112 may also be configured to move in the Z direction under the control of the processor 104 or the motion controller 108. The movable stage 112 is configured to position the sample 116 to a desired position while image data is being captured by the 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 while image data is being captured by the line scanning camera 130. In one embodiment, the scanning system 100 can use 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 with high-precision encoders used on both the X and Y axes. For example, a very high-precision nanometer encoder can be used on the axis in the scanning direction, on an axis perpendicular to the scanning direction, and on an axis coplanar with the scanning direction. The stage 112 is also configured to support a glass slide 114 on which a sample 116 is placed.

[0020] Sample 116 can be anything that can be observed by an optical microscope. For example, glass microscope slides 114 are frequently used as observation substrates for specimens containing tissues or cells, chromosomes, deoxyribonucleic acid (DNA), proteins, blood, bone marrow, urine, bacteria, beads, biopsy material, or any other type of biological material or substance, whether living or dead, stained or unstained, labeled or unlabeled. Sample 116 may also be an array of DNA or DNA-related material or protein, such as complementary DNA (cDNA) or ribonucleic acid (RNA), deposited on any type of slide or other substrate, including any sample generally known as a microarray. 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, films, semiconductor materials, forensic materials, and machined parts.

[0021] The objective lens 120 is mounted on an objective lens positioning device 124, which in one embodiment uses a highly precise linear motor to move the objective lens 120 along the optical axis defined by the objective lens 120. For example, the linear motor of the objective lens positioning device 124 may include a 50-nanometer encoder. The relative positions of the stage 112 and the objective lens 120 in the X, Y, and / or Z axis directions are controlled in a closed-loop manner using a motion controller 108 under the control of a processor 104, which uses memory 106 to store information and instructions, including computer-executable program steps for the overall operation of the scanning system 100.

[0022] In one embodiment, the objective lens 120 is a planar apochromatic ("APO") infinity-corrected objective lens suitable for transmission, reflection, and / or epi-illumination fluorescence microscopes (e.g., an Olympus 40x / 0.75NA or 20x / 0.75NA). Advantageously, the objective lens 120 can correct for chromatic and spherical aberrations. Because the objective lens 120 is infinity-corrected, the focusing optics 128 can be positioned in the optical path 122 above the objective lens 120, where the light beam passing through the objective lens 120 becomes a parallel ray. The focusing optics 128 focuses the light signal captured by the objective lens 120 onto the photosensitive elements of the line scanning camera 130 and / or area scanning camera 132. The focusing optics 128 may further include optical components such as filters, magnification-changing lenses, and / or similar. The objective lens 120, in combination with the focusing optical system 128, provides the overall magnification of the scanning system 100. In one embodiment, the focusing optical system 128 may include a tube lens and an optional 2x magnification change mechanism. Advantageously, the 2x magnification change mechanism allows the objective lens 120, which is originally 20x, to scan the sample 116 at 40x magnification.

[0023] The line scanning camera 130 includes a linear array of at least one pixel. The line scanning camera 130 may be monochrome or color. A color line scanning camera typically has at least three linear arrays, while a monochrome line scanning camera may have one or more linear arrays. Any type of single or multiple linear arrays can be used, whether packaged as part of the camera or custom integrated into the imaging electronics module. For example, a color line scanning camera with three linear arrays ("red-green-blue" or "RGB") or a monochrome TDI with 96 linear arrays can be used. A TDI line scanning camera typically provides a significantly improved signal-to-noise ratio ("SNR") in the output signal by adding intensity data from areas imaged ahead of the sample, resulting in an improvement in SNR proportional to the square root of the number of integration stages. A TDI line scanning camera includes multiple linear arrays. For example, TDI line scanning cameras are available with linear arrays of 24, 32, 48, 64, 96, or more pixels. The scanning system 100 also supports linear arrays manufactured in various formats, including those with 512 pixels, 1024 pixels, and even up to 4096 pixels. Similarly, linear arrays of various pixel sizes can be used with the scanning system 100. An important requirement for selecting any type of line scanning camera 130 is that the movement of the stage 112 can be synchronized with the line rate of the line scanning camera 130, thereby allowing the stage 112 to move in relation to the line scanning camera 130 during digital image acquisition of the sample 116.

[0024] In one embodiment, image data generated by the line scanning camera 130 is stored in a portion of the memory 106 and processed by the processor 104 to generate a continuous digital image of at least a portion of the sample 116. This continuous digital image can be further processed by the processor 104, and this processed continuous digital image can also be stored in the memory 106.

[0025] In embodiments having two or more line scanning cameras 130, at least one line scanning camera 130 may be configured to function as a focus sensor operating in conjunction with at least one other line scanning camera 130 configured to function as an image sensor 130A. This focus sensor may be logically positioned on the same optical axis as the image sensor 130A, or it may be logically positioned in front of or behind the image sensor 130A with respect to the scanning direction of the scanning system 100. In such embodiments where at least one line scanning camera 130 functions as a focus sensor, image data generated by the focus sensor may be stored in part of the memory 106 and further processed by the processor 104 to generate focus information, allowing the scanning system 100 to adjust the relative distance between the sample 116 and the objective lens 120 to maintain focus on the sample 116 during scanning. Additionally, in one embodiment, at least one line scanning camera 130 functioning as a focus sensor may be oriented such that each of the multiple individual pixels 142 of the focus sensor is positioned at a different logical height along the optical path 122.

[0026] During operation, various components of the scanning system 100 and program modules stored in memory 106 enable the automatic scanning and digitization of the sample 116 placed on the glass slide 114. The glass slide 114 is firmly placed on the 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 nearly constant speed for sensing by the line scanning camera 130, where the speed of the stage 112 is synchronized with the line rate of the line scanning camera 130. After scanning the image data segment, the movable stage 112 decelerates, bringing the sample 116 to a nearly complete stop. The movable stage 112 then moves in a direction perpendicular to the scanning direction, positioning the sample 116 for scanning the next image data segment (e.g., adjacent segment). Additional segments are scanned sequentially until part of the entire sample 116 or the entire sample 116 has been scanned.

[0027] For example, during the digital scanning of sample 116, a series of digital images of sample 116 are acquired as multiple consecutive fields of view that are combined together to form an image segment. Such image segments may be as shown in the top view of Figure 2A and the front view of Figure 2B. As shown in these drawings, each segment is considered to have a center line 201 parallel to the scanning direction and first and second edges 202, 203 parallel to the scanning direction and spaced apart by the width of the image segment along an axis perpendicular to the scanning direction and the optical axis 204 of the imaging system. It should be noted that while the first and second edges 202, 203 of the segment may appear as simply parallel edges in an overhead view as shown in Figure 2A, when viewed in a front perspective view, those edges may appear displaced relative to the optical axis 204 of the imaging system. In a drawing such as that shown in Figure 2B, this displacement would be equal to the segment width multiplied by the segment inclination (which could be determined, for example, using the image map and / or contrast ratio from the real-time focusing technique described in U.S. Patent Application Publication No. 2022 / 0159171, “Real-Time Focusing in a Slide-Scanning System,” filed June 16, 2021, the disclosure of which is incorporated herein by reference in its entirety). Thus, it can be noted that any point on the first edge 202 (shown as the first point 205 in Figure 2A) and any point on the second edge 203 (shown as the second point 206 in Figure 2A) are spaced apart from each other by a distance along the optical axis of the imaging system. Preferably, this separation distance is less than or equal to the depth of field of the imaging system; however, if not, some embodiments may be configured to modify the width of the image segment to ensure that the product of the slope and the (narrowed) width falls within the depth of field (for example, using a method as shown in Figure 3, described later).

[0028] Just as multiple adjacent fields of view may be combined to form a single continuous image segment, multiple adjacent image segments may also be combined to form a continuous digital image of part or all of the sample 116. Scanning of the sample 116 may include acquiring vertical or horizontal image segments. Scanning of the sample 116 may be performed from top to bottom, bottom to top, or both (i.e., bidirectional), and can be started from any point on the sample 116. Alternatively, scanning of the sample 116 may be performed from left to right, right to left, or both (i.e., bidirectional), and can be started from any point on the sample 116. Image segments do not need to be acquired adjacently or continuously. Furthermore, the resulting image of the sample 116 may be an image of the entire sample 116 or an image of only a part of the sample 116.

[0029] In one embodiment, computer-executable instructions (e.g., programmed modules or software) are stored in memory 106, and when they are executed, they enable the scanning system 100 to perform various functions described herein (e.g., displaying a graphical user interface, executing a disclosed process, controlling components of the scanning system 100, etc.). In this description, the term “computer-readable storage medium” refers to any medium used to store computer-executable instructions and provide them to the scanning system 100 for execution by the processor 104. Examples of these mediums include memory 106, as well as any removable storage medium or external storage medium (not shown) that is communicably coupled to the scanning system 100 directly (e.g., via USB (universal serial bus), wireless communication protocols, etc.) or indirectly (e.g., via wired and / or wireless networks).

[0030] Figure 1B shows a line scanning camera 130 having a single linear array 140, which may be implemented as a charge-coupled device (CCD) array or a 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 other embodiments, the linear array 140 may have more or fewer pixels. For example, common linear array formats include 512, 1024, and 4096 pixels. These pixels 142 are linearly arranged 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.

[0031] Figure 1C shows a line scanning camera 130 having three linear arrays 140, each of which may be implemented as a CCD array. The three linear arrays 140 are combined to form a single color array 150. In one embodiment, each individual linear array within the color array 150 detects the intensity of a different color, such as red, green, or blue. The color image data from each individual linear array 140 within the color array 150 are combined to form a single field of view 134 color image data.

[0032] Figure 1D shows a line scanning camera 130 having multiple linear arrays 140, each of which may be implemented as a CCD array. The multiple linear arrays 140 are combined to form a TDI array 160. Advantageously, the TDI line scanning camera can provide a significantly improved SNR in its output signal by adding intensity data from areas imaged ahead of the sample, resulting in an improvement in SNR proportional to the square root of the number of linear arrays 140 (also called integration stages). The TDI line scanning camera can include a wider variety of linear arrays 140. For example, common formats for TDI line scanning cameras include not only 24, 32, 48, 64, 96, and 120 linear arrays 140, but also many more.

[0033] Figure 1E shows a side view of an exemplary configuration of a line scanning camera 130 in a scanning system 100 according to one embodiment. In the illustrated embodiment, the scanning system 100 includes a glass slide 114 having a tissue sample 116 placed on a motorized stage 112 that is illuminated by an illumination system 118 and moves in a scanning direction 170. An objective lens 120 has an optical field of view 134 directed onto the slide 114 and provides an optical path 122 for light from the illumination system 118 that passes through the sample 116 on the slide 114, reflects off the sample 116 on the slide 114, fluoresces from the sample 116 on the slide 114, or otherwise passes through the objective lens 120. The light travels along the optical path 122 to a beam splitter 174, which may allow a portion of the light to pass through a lens 176 to a main imaging sensor 130A. This light may be optionally refracted by a mirror 178, as shown in the illustrated embodiment. The imaging sensor 130A may be, for example, a line charge-coupled device (CCD).

[0034] Other light from the beam splitter 174 travels through the lens 180 to the focusing sensor 130B. The focusing sensor 130B may be, for example, a line CCD. The light traveling to the imaging sensor 130A and the focusing sensor 130B preferably represents the full optical field 134 from the objective lens 120. Based on this configuration of the scanning system 100, the scanning direction 170 of the slide 114 is logically oriented with respect to the imaging sensor 130A and the focusing sensor 130B, so that the optical field 134 of the objective lens 120 passes over the respective imaging sensor 130A and focusing sensor 130B in the logical scanning direction 172.

[0035] Figure 1F shows a top view of an exemplary configuration of the imaging sensor 130A with respect to the imaging optical path 122A according to one embodiment. Similarly, Figure 1G is a top view of an exemplary configuration of the focusing sensor 130B with respect to the focusing optical path 122B according to one embodiment. As can be seen in Figure 1G, the focusing sensor 130B is inclined by an angle θ with respect to the direction perpendicular to the focusing optical path 122B.

[0036] Figure 1H shows an exemplary focusing sensor 130B according to one embodiment. In the illustrated embodiment, within a focusing range (d) (e.g., 20 μm) on a tissue sample, the focusing sensor 130B includes a plurality of sensor pixels 142 and may be positioned such that the entire focusing range (d) in the Z-axis direction is transmitted by the optical system to the entire focusing sensor 130B array in the Y-axis direction (the X-axis, i.e., the direction perpendicular to the scanning direction 170), as shown in the figure. The location of each sensor pixel 142 is directly correlated with the Z position of the objective lens 120. As shown in Figure 1H, each dashed line (i.e., p1, p2…p) spans the projected focusing range (d). i ...p n ) represents different focus values ​​and corresponds to the focus height (i.e., Z height) of the objective lens 120. p has the optimal focus (e.g., the best contrast index) for a given part of the sample 116. i This can be used by the scanning system 100 to determine the optimal focus height for that portion of the sample 116.

[0037] The relationship between the focusing range (d) projected on the focusing sensor 130B and the focusing range (z) on the sample 116 is as follows: d=z * M focusing 2 where M focusing is the optical magnification of the focusing path. For example, when z=20μm and M focusing =20, d=8mm.

[0038] In order to cover the entire projected focusing range (d) by the inclined focusing sensor 130B including the linear array 140, the inclination angle θ should follow the following relationship: sinθ=d / L Here, L is the length of the linear array 140 of the focusing sensor 130B. When d=8mm and L=20.48mm are used, θ=23.0°. θ and L can be varied as long as the inclined focusing sensor 130B covers the entire focusing range (d).

[0039] The focusing resolution, or the minimum step Δz of the objective lens height movement, is a function of the sensor pixel 142 size e=minimum(ΔL). From the above formula, the following formula is derived: Δz=e * z / L For example, if e=10μm, L=20.48mm, and z=20μm, then Δz=0.0097μm<10nm.

[0040] The relationship between the objective lens height Z at the focusing point i i and the focusing position L on the focusing sensor 130B i is as follows: L i =Z i * M focusing 2 / sinθ

[0041] ​If the focusing height is determined by the average value from L1 to L2 according to the data analysis from the focusing sensor 130B, then the height of the objective lens 120 is based on the following formula: Z2 = Z1 + (L2 - L1) * sinθ / M focusing 2 It needs to be moved from Z1 to Z2.

[0042] The field of view (FOV) 134 in the Y-axis for the focusing sensor 130B and the imaging sensor 130A may be different, but it is preferable that the centers of both sensors 130A and 130B coincide with each other along the Y-axis.

[0043] 2. Overview of the tilt correction process Embodiments of processes for addressing errors caused by tilt during slide scanning are described in detail below. It should be understood that the processes described may be implemented in one or more software modules executed by one or more hardware processors 104 within the scanning system 100. The processes described 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 or by a virtual machine operating between the object code and the hardware processor.

[0044] Alternatively, the processes described may be implemented as hardware components (e.g., general-purpose processors, integrated circuits (ICs), application-specific integrated circuits (ASICs), digital signal processors (DSPs), field-programmable gate arrays (FPGAs) or other programmable logic devices, discrete gates or transistor logic, etc.), combinations of hardware components, or combinations of hardware components and software components. To clearly demonstrate hardware-software compatibility, various descriptive components, blocks, modules, circuits, and steps are schematically described in terms of their functionality. Whether such functionality is implemented as hardware or software depends on the design constraints imposed on the particular application and the overall system. A person skilled in the art may implement the described functionality in various ways for each specific application, but such implementation decisions should not be construed as departures from the scope of the invention. Additionally, grouping of functionality within components, blocks, modules, circuits, or steps is for the sake of clarity. Certain functionality or steps can be moved from one component, block, module, circuit, or step to another without departing from the invention.

[0045] Furthermore, although the processes described herein are shown in a predetermined arrangement and order of steps, each process may be implemented with fewer steps, more steps, or different steps and different arrangements and / or orders. Additionally, it should be understood that any step may be performed before, after, or in parallel with other independent steps, even if such step is described or depicted in a particular order, as long as no step depends on the completion of another step.

[0046] For a more specific illustration, Figure 3 provides an overall diagram of a process that can be used for tilt correction in a slide scanning system. First, in this process, a scanner, such as the one shown in Figure 1, can acquire multiple segments of image data in step 301. This may include step 302, which captures one or more image data segments using an initial segment width. This may be done, for example, by capturing segments of a sample on a slide using a real-time or macro-focus scanning approach described in U.S. Patent Application Publication No. 2022 / 0159171, “Real-Time Focusing in a Slide-Scanning System,” filed June 16, 2021, the disclosure of which is incorporated herein by reference in its entirety. After one or more segments have been captured in step 302 using an initial segment width, tilt image data may be detected within the captured segments in step 303. This may be done by checking whether any of the segments have a tilt greater than a fixed tilt threshold. For example, a threshold of ±2 μm / mm may be used as the threshold on a scanner with an initial segment width of 1 mm, which means that any image segment with a slope greater than 2 μm / mm can be treated as sloped image data.

[0047] Of course, other approaches are possible and can be implemented in light of this disclosure by those skilled in the art. For example, in some cases, the tilt image data may be detected based on a comparison of the detected tilt with a configurable tilt threshold identified by the user using a management interface. As another example, in some cases, a calculation (e.g., multiplying the tilt by the segment width and comparing the result of this multiplication with the depth of field) may be performed to detect in step 304 whether points on opposing edges of an image data segment (e.g., the segment with the greatest tilt) are spaced apart from each other by a distance greater than the depth of field of the scanner's imaging system, along the optical axis of the imaging system. An illustration of this situation is shown in Figure 4, which provides a front view of a segment with a tilt large enough to cause a portion of the slide 401 outside the depth of field of the imaging system to lift up. Thus, the explanation of using a threshold should be understood as merely illustrative and not as an limitation.

[0048] However, after the detection of the tilted image data, the method in Figure 3 proceeds with step 305, which determines a segment width narrower than the initial segment width, and this segment width can be used to capture one or more additional image data segments. Similar to the detection of the tilted image data in step 303, this determining step 305 can be performed in various ways. For example, in some cases, step 305, which determines a narrower segment width, may be performed by step 306, which simply reduces the segment width by half. Alternatively, in some cases, step 305, which determines a narrower segment width, may include step 307, which calculates the distance between a first edge and a second edge along the segment width, such that if the segment width were set to this distance, the first and second edges would be separated by less than the depth of field of the imaging system (for example, by dividing the tilt by the depth of field). When performing this type of calculation, the width may be set to a value less than or equal to the calculated value, thereby avoiding delays in the rescan process by unnecessarily increasing the number of segments that need to be rescanned, while ensuring that all image data remains in focus even when segments are rescanned. Examples of the results of both of these approaches for step 305, which determines a narrower segment width, are presented in Figures 5A and 5B, where Figure 5A shows the result of the width being reduced by half in step 306, and Figure 5B shows the potential result of step 307, which calculates the distance at which both the first and second edges of a segment with a reduced width fall within the depth of field, given a slope.

[0049] After a narrower segment width is determined in step 305, one or more image data segments may be captured in step 308 using a segment width narrower than the initial segment width determined in step 305. For example, after capturing each segment, before capturing the next segment, the image data is moved a distance equal to the narrower segment width in a direction orthogonal to the scanning direction. This may be done by first reducing the field of view of the imaging system to the determined segment width (for example, by configuring the imaging camera to read only the central portion of the sensor array) in step 309, and then by capturing the segments in a manner similar to that of step 302, which initially captures one or more segments using the initial segment width as described above. Alternatively, step 308, which captures one or more segments using a narrower segment width, may be performed by capturing data across the initial segment width in step 310 and discarding data that is more than half the narrower segment width away from the center line of each segment in step 311. In either case, after all the required segments have been captured, those segments can be combined into a continuous digital image of the sample in step 312. To illustrate how this method may be performed, consider a case in which a first set of segments covering the entire sample is captured in step 302 using an initial segment width, and then, after gradient image data is detected within those segments in step 303, a second set of segments is captured in step 308 using a segment width narrower than the initial segment width. In this type of case, step 312, which combines the segments into a continuous digital image, may include step 312, which discards the first set of segments, and then step 314, which combines 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 parts of the image are in focus, including even the boundaries of the segments with high gradients.

[0050] Other approaches to implementing the tilt correction method shown in Figure 3 are also possible and can be carried out by those skilled in the art without any additional experimentation in light of this disclosure. For example, in some embodiments, the process can be carried out by first capturing segments that cover the entire sample using an initial segment width, as shown in Figure 3, and then by detecting tilt image data in step 303 after the entire dataset has been collected. However, it is also possible to perform step 303 to detect tilt image data before image segments that collectively depict the entire sample are captured. For illustrative purposes, Figure 6 is considered to show a process in which tilt is identified and processed before segments that collectively depict the entire sample are captured. In the process of Figure 6, after the step of capturing each segment using an initial segment width, it is possible to check whether tilt image data exists, and as soon as tilt image is detected in step 303, it may be possible to proceed to step 308, which captures segments using a narrower segment width, starting by recapturing the data covered by the segments that the tilt image data covers in step 303.

[0051] Additionally, as shown in Figure 6, in some embodiments, further modifications may be made during the process of acquiring image data segments in step 301. For example, after segments are captured in step 308 using a narrower segment width, an inspection may be performed to determine whether a slope change is detected in the captured data in step 601. This may be done using calculations similar to those described for detecting sloped image data in step 303. If no slope change is present, step 602 can be continued to capture segments at their current width until a slope change is detected in step 601 or enough segments are captured to form an image covering the sample. Alternatively, if a slope change is detected, a modified segment width can be determined in step 603. This may be done using calculations similar to those described earlier for step 307, which calculates the distance of a segment width such that, given a slope, both ends fall within the depth of field. However, it should be noted that in some cases, this determining step 603 may involve determining a new width wider than the width that was then being used in order to reduce the total number of segments and, consequently, the time required to scan the sample. For example, in some cases, a system implemented to perform the method shown in Figure 6 can detect a change in tilt in step 601 whenever the tilt increases and part of the segment falls outside the depth of field of the imaging system, or whenever the tilt decreases and the width is increased, leading to a reduction in the total number of segments required for imaging the entire sample without any part of the segment falling outside the depth of field. In this case, if a change in tilt due to a decrease in tilt is detected in step 601, the segment width can be changed to the smaller of either the maximum field of view of the imaging system or the maximum width that allows the entire width of the segment to fall within the depth of field.

[0052] Regardless of the value of the modified segment width, after the change is determined in step 603, the segment can be captured in step 604 using this modified segment width. Additionally, in some cases, data indicating the number of stripes used in scanning the sample may be updated in step 605, which will later be used in step 312 to combine the segments into a continuous digital image. The scanning process can continue in this manner until a change in slope is detected in step 601 (in this case, the segment width may be further modified), or until enough image data segments to cover the entire sample have been captured. At this point, step 301, which involves acquiring multiple image data segments, can be considered complete, and the segments can be combined into a continuous digital image in step 312.

[0053] 3. Additional non-limiting embodiments The above description of the disclosed embodiments is provided so that anyone skilled in the art can practice or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art. Furthermore, the general principles set forth herein are applicable to other embodiments without departing from the spirit or scope of the invention. Accordingly, it should be understood that the descriptions and drawings presented herein represent currently preferred embodiments of the invention and are therefore representative of the broadly envisioned protected subject matter. Moreover, it should be understood that the scope of the invention fully encompasses other embodiments that may be apparent to those skilled in the art, and therefore the scope of the invention is not limited. Other variations are also possible and will be immediately apparent to those skilled in the art in light of this disclosure. For example, the following embodiments are provided as specific (but not limiting) descriptions of various approaches that may be taken when practicing the disclosed technology.

[0054] Example 1 A method for automatically digitizing a sample by executing instructions stored on a non-temporary computer-readable medium using a scanner, the method comprising the steps of acquiring a plurality of image data segments using an imaging system, the steps of which include a substep of capturing one or more image data segments using an initial segment width, a substep of detecting tilted image data that is tilted with respect to the optical axis of the imaging system, a substep of determining a segment width narrower than the initial segment width based on the detection of the tilted image data, a substep of 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 center line parallel to the scanning direction.

[0055] Example 2 The method according to Example 1, wherein detecting tilt image data includes detecting a tilt image data segment, the tilt image data segment having a first edge and a second edge, each of which is parallel to the scanning direction, the tilt segment having a first point placed on its first edge and a second point placed on its second edge, the first point and the second point being spaced apart from each other along the optical axis of the imaging system by a distance wider than the depth of field of the imaging system.

[0056] Example 3 The method described in Example 2, wherein determining a segment width narrower than the initial segment width includes, given a slope, calculating the distance between a first edge and a second edge along an axis perpendicular to the scanning direction, wherein the first and second points are spaced apart from each other along the optical axis of the imaging system by a distance not exceeding the depth of field of the imaging system.

[0057] Example 4 The method described in Example 1 or 2, wherein a segment width narrower than the initial segment width is half the initial segment width.

[0058] Example 5 A method according to any one of Examples 1 to 4, wherein the step of acquiring a plurality of image data segments includes a substep of acquiring a first set of image data segments, wherein each segment from the first set of image data segments has one or more adjacent image data segments composed of the first set of image data segments, the first set of image data segments provides a first continuous digital image of a sample, and for each segment from the first set of segments, the center line of the segment is spaced by an initial segment width from the center lines of its adjacent segments, and the substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of acquiring a second set of image data segments, wherein each of the second set of image data segments A segment has one or more adjacent image data segments composed of a second set of image data segments, and a center line extending parallel to the scanning direction and containing the center of the segment, wherein the center line of the segment is spaced from the center lines of its adjacent segments by a segment width narrower than the initial segment width, the second set of image data segments provides a second continuous digital image of the sample, and for each segment from the second set of segments, the center line of the segment is spaced from the center lines of its adjacent segments by a segment width narrower than the initial segment width, and the step of combining multiple image data segments into a continuous digital image of the sample includes a substep of discarding a first set of image data segments and a substep of combining a second set of image data segments into a second continuous digital image of the sample.

[0059] Example 6 A method according to any one of Examples 1 to 4, wherein a substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of capturing segments containing at least a portion of the gradient image data using a segment width narrower than the initial segment width before an image segment that collectively depicts the entire sample is captured, and the multiple image data segments collectively depict the entire sample.

[0060] Example 7 The method according to Example 6, the step of acquiring multiple image data segments, includes a substep of detecting a change in slope after capturing one or more image data segments using a segment width narrower than the initial segment width; a substep of determining a modified segment width different from the segment width narrower than the initial segment width based on the substep of detecting the change in slope; and a substep of capturing one or more image data segments using the modified segment width.

[0061] Example 8 The method described in Example 7, wherein the modified segment width is narrower than the initial segment width and narrower than the segment width.

[0062] Example 9 The method described in Example 7, wherein the modified segment width is wider than a segment width that is narrower than the initial segment width.

[0063] Example 10 The method described in Example 9, wherein the modified segment width is equal to the initial segment width.

[0064] Example 11 A method according to any one of Examples 6 to 10, the method comprising the step of updating data indicating the number of segments used to collectively depict the entire sample whenever the segment width used to capture segments from multiple strips changes.

[0065] Example 12 A method according to any one of Examples 1 to 11, the method comprising the step of reducing the field of view of an 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, the substep of capturing one or more image data segments using a segment width narrower than the initial segment width, and the substep of capturing one or more segments using the imaging system after the field of view of the imaging system has been reduced.

[0066] Example 13 A method according to any one of Examples 1 to 11, wherein a substep of capturing one or more image data segments using a segment width narrower than an initial segment width includes, for each of the one or more image data segments, a substep of capturing the image data segment using the imaging system while the field of view of the imaging system is equal to the initial segment width, and a substep of discarding image data consisting of the segment that is not within a distance equal to half of the segment width narrower than the initial segment width of the segment's centerline.

[0067] Example 14 An automatic scanner, the automatic scanner is an imaging system, the imaging system having depth of field, a field of view having a width along an axis perpendicular to the scanning direction, an optical axis perpendicular to the scanning direction and an axis perpendicular to the scanning direction, a stage movable in the scanning direction, a processor, and a non-temporary computer-readable medium, the non-temporary computer-readable medium, when executed, captures an image of a sample placed on a slide supported by the stage, the following steps: a plurality of image data segments, each having a center line parallel to the scanning direction, the following substep: a substep of capturing one or more image data segments using an initial segment width, and an image inclined with respect to the optical axis of the imaging system. A non-temporary computer-readable medium stores instructions that enable it to be operated to acquire data by performing an operation that includes a substep of determining whether data exists within one or more captured segments; an operation that includes, in the event that tilted image data exists within one or more captured segments, a substep of capturing one or more image data segments using a segment width narrower than an initial segment width; an operation that includes, a substep of capturing one or more image data segments using a segment width narrower than an initial segment width; and an operation that includes combining the multiple image data segments into an image of a sample.

[0068] Example 15 The scanner according to Example 14, wherein the substep for detecting tilted image data includes the substep for detecting a tilted image data segment, the tilted image data segment having a first edge and a second edge, each of which is parallel to the scanning direction, the tilted segment having a first point placed on the first edge and a second point placed on the second edge, the first point and the second point being spaced apart from each other at a distance wider than the depth of field of the imaging system along the optical axis of the imaging system.

[0069] Example 16 The scanner according to Example 15, wherein a substep for determining a segment width narrower than the initial segment width includes a substep for calculating the distance along the width of the inclined segment between a first edge and a second edge, given an inclination, wherein the first and second points are spaced apart from each other along the optical axis of the imaging system by the depth of field of the imaging system.

[0070] Example 17 The scanner according to Example 14 or 15, wherein a segment width narrower than the initial segment width is half the initial segment width.

[0071] Example 18 A scanner according to any one of Examples 14 to 17, wherein the step of acquiring a plurality of image data segments includes a substep of acquiring a first set of image data segments, wherein each segment from the first set of image data segments has one or more adjacent image data segments composed of the first set of image data segments, the first set of image data segments provides a first continuous digital image of a sample, and for each segment from the first set of segments, the center line of the segment is spaced by an initial segment width from the center lines of its adjacent segments, and the substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of acquiring a second set of image data segments, wherein from the second set of image data segments Each segment has one or more adjacent image data segments, which are composed of a second set of image data segments, and a center line that extends parallel to the scanning direction and includes the center of the segment, wherein the center line of the segment is spaced from the center line of its adjacent segments by a segment width narrower than the initial segment width, the second set of image data segments provides a second continuous digital image of the sample, and for each segment from the second set of segments, the center line of the segment is spaced from the center line of its adjacent segments by a segment width narrower than the initial segment width, and the step of combining multiple image data segments into a continuous digital image of the sample includes a substep of discarding the first set of image data segments and a substep of combining the second set of image data segments into a second continuous digital image of the sample.

[0072] Example 19 A scanner according to any one of Examples 14 to 17, wherein a substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of capturing segments containing at least a portion of tilted image data using a segment width narrower than the initial segment width before an image segment that collectively depicts the entire sample is captured, and the multiple image data segments collectively depict the entire sample.

[0073] Example 20 The scanner according to Example 19, the step of acquiring multiple image data segments includes a substep of capturing one or more image data segments using a segment width narrower than the initial segment width, detecting whether a slope change exists in the one or more image data segments captured using a segment width narrower than the initial segment width, determining a modified segment width if a slope change exists, and capturing one or more image data segments using the modified segment width.

[0074] Example 21 The scanner according to Example 20, the substep for determining the modified segment width includes, if the change in tilt causes the distance along the imaging axis separating the first and second edges of the most recently captured segment to exceed the depth of field of the imaging system, the substep for determining the modified segment width as a segment width narrower than the segment width used when capturing the segment in which the tilt change was detected; and if the change in tilt is a decrease in the absolute value of the tilt in the segment in which the tilt change was detected, the substep for determining the modified segment width as a segment width wider than the segment width used when capturing the segment in which the tilt change was detected.

[0075] Example 22 In the scanner described in Example 21, a substep in which the modified segment width is determined to be a segment width wider than the segment width used when capturing the segment in which the slope change was detected is to define the modified segment width as equal to the initial segment width.

[0076] Example 23 A scanner according to any one of Examples 19 to 22, the method comprising the step of updating data indicating the number of segments used to collectively depict the entire sample whenever the segment width used to capture segments from multiple strips changes.

[0077] Example 24 A scanner according to any one of Examples 14 to 23, the method comprising the step of reducing the field of view of an imaging system from an initial segment width to a segment width narrower than the initial segment width when tilt image data is located within one or more segments that have been captured, and a substep of capturing one or more image data segments using a segment width narrower than the initial segment width further comprising the substep of capturing one or more segments using the imaging system after the field of view of the imaging system has been reduced.

[0078] Example 25 A scanner according to any one of Examples 14 to 23, wherein a substep of capturing one or more image data segments using a segment width narrower than an initial segment width includes, for each of the one or more image data segments, a substep of capturing the image data segment using the imaging system while the field of view of the imaging system is equal to the initial segment width, and a substep of discarding image data composed of the segment that is not within a distance equal to half of the segment width narrower than the initial segment width of the segment's centerline.

[0079] 4. Interpretation None of the examples or descriptions contained herein should be construed as limiting the scope of any claims contained herein or in any related specification. Rather, the scope of protection provided by herein or in any related specification should be understood as defined by the claims of such specification, in which the terms explicitly defined herein are given their explicit definitions, and the terms not explicitly defined are given the broadest and most reasonable interpretations provided by general dictionaries.

[0080] 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,” “A, B, C, or any combination thereof,” include any combination of A, B, and / or C, and may include multiple A's, multiple B's, or multiple C's. Specifically, the 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” are either 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 include one or more of its constituent A, B, and / or C. For example, a combination of A and B may consist of one A and multiple B, multiple A and one B, or multiple A and multiple B.

[0081] The expression "based on" something should be understood as meaning that the thing is determined, at least partially, by the object on which it is based. While the relationship of "based on" includes cases where one thing is completely determined by another, unless the expression is "based exclusively on," the relationship of "based on" should not be interpreted as being limited to cases where one thing is completely determined by another.

Claims

1. A method for the automated digitization of a sample, performed by a scanner by the execution of instructions stored on a non-temporary computer-readable medium, wherein the method is: A step of acquiring multiple image data segments using an imaging system, wherein the step of acquiring the multiple image data segments is: A substep to capture one or more image data segments using the initial segment width, A substep of detecting tilted image data that is tilted with respect to the optical axis of the imaging system, Based on the detection of the aforementioned fixed image data, A substep of determining a segment width narrower than the initial segment width, This includes a substep of capturing one or more image data segments using a segment width narrower than the initial segment width. Steps and The steps include combining multiple image data segments into an image of the sample and Includes, The imaging system has a depth of field and a field of view having a width along an axis perpendicular to the scanning direction. Each image data segment includes a center line parallel to the scanning direction.

2. The substep for detecting the tilt image data includes a substep for detecting the tilt image data segment, The inclined image data segment has a first edge and a second edge, each of which is parallel to the scanning direction. The inclined segment has a first point placed on its first edge and a second point placed on its second edge. The method according to claim 1, wherein the first point and the second point are spaced apart from each other along the optical axis of the imaging system by a distance wider than the depth of field of the imaging system.

3. The method according to claim 2, wherein the substep of determining a segment width narrower than the initial segment width includes, given a slope, a substep of calculating the distance between a first edge and a second edge along an axis perpendicular to the scanning direction, wherein the first point and the second point are spaced apart from each other along the optical axis of the imaging system by a distance not exceeding the depth of field of the imaging system.

4. The method according to claim 1 or 2, wherein a segment width narrower than the initial segment width is half the initial segment width.

5. The step of obtaining the plurality of image data segments includes a substep of obtaining a first set of image data segments, where, Each segment from the first set of image data segments has one or more adjacent image data segments that are composed of the first set of image data segments. The first set of image data segments provides a first continuous digital image of the sample, and for each segment from the first set of segments, the center line of the segment is spaced by an initial segment width from the center line of its adjacent segment. A substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of obtaining a second set of image data segments, where, Each segment from the second set of image data segments is: One or more adjacent image data segments, which are composed of the second set of the image data segments, It has a center line that extends parallel to the scanning direction and includes the center of the segment, The center line of the aforementioned segment is spaced from the center line of its adjacent segment by a segment width narrower than the initial segment width. The second set of image data segments provides a second continuous digital image of the sample, and for each segment from the second set of segments, the center line of the segment is spaced from the center line of its adjacent segment by a segment width narrower than the initial segment width. The step of combining multiple image data segments into a continuous digital image of the sample is: A substep of discarding the first set of image data segments, A substep of combining the second set of image data segments into a second continuous digital image of the sample. The method according to any one of claims 1 to 4, including.

6. A substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of capturing segments containing at least a portion of the gradient image data using a segment width narrower than the initial segment width, before an image segment collectively depicting the entire sample is captured. The method according to any one of claims 1 to 4, wherein the plurality of image data segments collectively depict the entire sample.

7. The step of acquiring the aforementioned multiple image data segments is: A substep of detecting a change in slope after capturing one or more image data segments using a segment width narrower than the initial segment width, A substep that determines a modified segment width different from the initial segment width based on the substep that detects the change in slope, The method according to claim 6, further comprising a substep of capturing one or more image data segments using a modified segment width.

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

9. The method according to claim 7, wherein the modified segment width is wider than a segment width narrower than the initial segment width.

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

11. The method according to any one of claims 6 to 10, further comprising the step of updating data indicating the number of segments used to collectively depict the entire sample whenever the segment width used to capture segments from the plurality of strips changes.

12. The method includes the step of reducing the field of view of the imaging system from the initial segment width to a segment width narrower than the initial segment width, based on the detection of the tilted image data. The method according to any one of claims 1 to 11, wherein the substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of capturing one or more segments using the imaging system after the field of view of the imaging system has been reduced.

13. The substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes, for each of the one or more image data segments: A substep of capturing the image data segment using the imaging system while the field of view width of the imaging system is equal to the initial segment width, The method according to any one of claims 1 to 11, further comprising the substep of discarding image data composed of a segment that is not within a distance equal to half of a segment width narrower than the initial segment width of the center line of the segment.

14. An automatic scanner, said automatic scanner, An imaging system, Depth of field and, A field of view having a width along an axis perpendicular to the scanning direction, An optical axis perpendicular to the scanning direction and an axis perpendicular to the scanning direction An imaging system having, A stage that can move in the scanning direction, Processor and A non-temporary computer-readable medium, which, when executed, displays an image of a sample placed on a slide supported by the stage in the following steps: Multiple image data segments, each having a center line parallel to the scanning direction, are processed in the following substeps: A substep of capturing one or more image data segments using the initial segment width, A substep of determining whether image data tilted with respect to the optical axis of the imaging system exists within one or more captured segments, If the tilt image data is present within one or more of the captured segments, A substep of capturing one or more image data segments using a segment width narrower than the initial segment width, Steps obtained by performing an action that includes, The steps include combining multiple image data segments into an image of the sample and A non-temporary computer-readable medium that stores within itself instructions that can be operated to be obtained by performing a method including, An automatic scanner that includes this.

15. The substep for detecting the tilt image data includes a substep for detecting the tilt image data segment, The inclined image data segment has a first edge and a second edge, each of which is parallel to the scanning direction. The inclined segment has a first point placed on a first edge and a second point placed on a second edge. The scanner according to claim 14, wherein the first point and the second point are spaced apart from each other along the optical axis of the imaging system by a distance greater than the depth of field of the imaging system.

16. The scanner according to claim 15, wherein a substep for determining a segment width narrower than the initial segment width includes a substep for calculating the distance along the width of the inclined segment between a first edge and a second edge, given an inclination, wherein the first point and the second point are spaced apart from each other along the optical axis of the imaging system by the depth of field of the imaging system.

17. The scanner according to claim 14 or 15, wherein a segment width narrower than the initial segment width is half the initial segment width.

18. The step of obtaining the plurality of image data segments includes a substep of obtaining a first set of image data segments, where, Each segment from the first set of image data segments has one or more adjacent image data segments that are composed of the first set of image data segments. The first set of image data segments provides a first continuous digital image of the sample, and for each segment from the first set of segments, the center line of the segment is spaced by an initial segment width from the center line of its adjacent segment. A substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of obtaining a second set of image data segments, where, Each segment from the second set of image data segments is: One or more adjacent image data segments, which are composed of the second set of the image data segments, It has a center line that extends parallel to the scanning direction and includes the center of the segment, The center line of the aforementioned segment is spaced from the center line of its adjacent segment by a segment width narrower than the initial segment width. The second set of image data segments provides a second continuous digital image of the sample, and for each segment from the second set of segments, the center line of the segment is spaced from the center line of its adjacent segment by a segment width narrower than the initial segment width. The step of combining multiple image data segments into a continuous digital image of the sample is: A substep of discarding the first set of image data segments, A substep of combining the second set of image data segments into a second continuous digital image of the sample. A scanner according to any one of claims 14 to 17.

19. A substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of capturing segments containing at least a portion of the gradient image data using a segment width narrower than the initial segment width, before an image segment collectively depicting the entire sample is captured. The scanner according to any one of claims 14 to 17, wherein the plurality of image data segments collectively depict the entire sample.

20. The step of acquiring the aforementioned multiple image data segments is: A substep of capturing one or more image data segments using a segment width narrower than the initial segment width, and then detecting whether a change in slope exists in the one or more image data segments captured using a segment width narrower than the initial segment width, If a change in slope exists, a substep is performed to determine the changed segment width, The scanner according to claim 19, further comprising a substep of capturing one or more image data segments using a modified segment width.

21. The substep for determining the changed segment width is: If, due to the aforementioned tilt change, the distance along the imaging axis separating the first and second edges of the most recently captured segment exceeds the depth of field of the imaging system, the modified segment width is determined to be narrower than the segment width used when capturing the segment in which the tilt change was detected. The scanner according to claim 20, further comprising the substep of determining the modified segment width as a segment width wider than the segment width used when capturing the segment in which the change in inclination was detected, if the change in inclination is a decrease in the absolute value of the inclination in the segment in which the change in inclination was detected.

22. The scanner according to claim 21, wherein the substep of determining the modified segment width as a segment width wider than the segment width used when capturing the segment in which the slope change was detected is to define the modified segment width as equal to the initial segment width.

23. The scanner according to any one of claims 19 to 22, wherein the method includes updating data indicating the number of segments used to collectively depict the entire sample whenever the segment width used to capture segments from the plurality of strips changes.

24. The method includes, when tilt image data is present within one or more captured segments, reducing the field of view of the imaging system from the initial segment width to a segment width narrower than the initial segment width, The scanner according to any one of claims 14 to 23, wherein the substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes a substep of capturing one or more segments using the imaging system after the field of view of the imaging system has been reduced.

25. The substep of capturing one or more image data segments using a segment width narrower than the initial segment width includes, for each of the one or more image data segments: A substep of capturing the image data segment using the imaging system while the field of view width of the imaging system is equal to the initial segment width, The scanner according to any one of claims 14 to 23, further comprising the substep of discarding image data composed of a segment that is not within a distance equal to half a segment width narrower than the initial segment width of the center line of the segment.

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